|
Compound was tested for analgesic activity in mice by phenylquinone writhing test at dose of 200 mg/kg, po
|
Mus musculus
|
45.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of 2,2'-diaminobiphenyl derivatives.
Year : 1981
Volume : 24
Issue : 5
First Page : 632
Last Page : 634
Authors : Calcinari R, Case N, Guerrato A, Milanino R, Passarella E, Perchinunno M, Tamburini B, Sparatore F.
|
Compound was tested for antiinflammatory activity in rats adjuvant arthritis test after peroral administration of 50 mg/kg dose
|
Rattus norvegicus
|
66.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of 2,2'-diaminobiphenyl derivatives.
Year : 1981
Volume : 24
Issue : 5
First Page : 632
Last Page : 634
Authors : Calcinari R, Case N, Guerrato A, Milanino R, Passarella E, Perchinunno M, Tamburini B, Sparatore F.
|
Compound was tested for antiinflammatory activity in rats by carrageenam edema test after peroral administration of 200 mg/kg dose
|
Rattus norvegicus
|
42.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of 2,2'-diaminobiphenyl derivatives.
Year : 1981
Volume : 24
Issue : 5
First Page : 632
Last Page : 634
Authors : Calcinari R, Case N, Guerrato A, Milanino R, Passarella E, Perchinunno M, Tamburini B, Sparatore F.
|
Analgesic activity was determined using acetic acid writing test at a dose of 50 mg/kg perorally in rats. (p<0.01)
|
Rattus norvegicus
|
82.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antiinflammatory, analgesic activity of 3,3'-(1,2-ethanediyl)-bis[2-aryl-4-thiazolidinone] chiral compounds. Part 10.
Year : 2001
Volume : 11
Issue : 21
First Page : 2791
Last Page : 2794
Authors : Vigorita MG, Ottanà R, Monforte F, Maccari R, Trovato A, Monforte MT, Taviano MF.
Abstract : In this note, the synthesis and structure-activity relationships of a new series of 2R,2'R/2S,2'S and 2R,2'S-meso 3,3'-(1,2-ethanediyl)-bis[2-aryl-4-thiazolidinones] are described. Antiinflammatory activity was investigated by the carrageenin-induced paw edema test and analgesic activity by acetic acid writhing and hot plate tests in rats. All compounds displayed ulcerogenic effects and acute toxicity much lower than indomethacin and phenylbutazone. Meso isomers (b) showed better pharmacological profiles than corresponding racemates (a). Methoxy substitution patterns of the aryls on stereogenic carbons are generally the most favorable on the pharmacological profile.
|
Antiinflammatory activity of compound expressed as percentage inhibition of carrageenan edema 4 hr after an oral dose of 10 mg/kg.
|
Rattus norvegicus
|
35.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of metabolites of piroxicam.
Year : 1981
Volume : 24
Issue : 1
First Page : 39
Last Page : 42
Authors : Lombardino JG.
Abstract : Four possible pyridine monohydroxylated metabolites of the antiinflammatory agent piroxicam have been synthesized for comparison with a natural pyridine-hydroxylated metabolite of this compound. In addition, another metabolite of piroxicam, derived from dehydration of the parent drug, has been made and characterized. The antiinflammatory activity of these compounds and four other known metabolites of piroxicam has been measured in the carrageenan-induced rat paw edema model and all are found to be less active than piroxicam itself.
|
Antiinflammatory activity of compound expressed as percentage inhibition of carrageenan edema 4 hr after an oral dose of 33 mg/kg.
|
Rattus norvegicus
|
50.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of metabolites of piroxicam.
Year : 1981
Volume : 24
Issue : 1
First Page : 39
Last Page : 42
Authors : Lombardino JG.
Abstract : Four possible pyridine monohydroxylated metabolites of the antiinflammatory agent piroxicam have been synthesized for comparison with a natural pyridine-hydroxylated metabolite of this compound. In addition, another metabolite of piroxicam, derived from dehydration of the parent drug, has been made and characterized. The antiinflammatory activity of these compounds and four other known metabolites of piroxicam has been measured in the carrageenan-induced rat paw edema model and all are found to be less active than piroxicam itself.
|
Antiinflammatory activity by carrageenan-induced rat paw edema assay after 3 hr at 100 mg/kg concentration administered perorally.
|
Rattus norvegicus
|
43.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of some 2-(substituted-pyridinyl)benzimidazoles.
Year : 1980
Volume : 23
Issue : 7
First Page : 734
Last Page : 738
Authors : Tsukamoto G, Yoshino K, Kohno T, Ohtaka H, Kagaya H, Ito K.
Abstract : A series of 2-(2-pyridinyl)benzimidazoles was synthesized and evaluated for antiinflammatory activity by the carrageenan-induced rat paw edema assay. Among several active derivatives, 2-(5-ethylpyridin-2-yl)benzimidazole (6) was selected for further study. A comparison of compound 6 with phenylbutazone and tiaramide revealed that 6 possesses stronger activity in acute inflammatory models possibly with slightly less gastrointestinal irritation than both phenylbutazone and tiaramide.
|
Antiinflammatory efficacy is measured by the percent inhibition of paw volume during the 3 week adjuvant arthritis test at 0.08 mM/kg (24.6 mg)
|
Rattus norvegicus
|
66.0
%
|
|
Journal : J. Med. Chem.
Title : Bulky amine analogues of ketoprofen: potent antiinflammatory agents.
Year : 1984
Volume : 27
Issue : 12
First Page : 1682
Last Page : 1690
Authors : Schlegel DC, Zenitz BL, Fellows CA, Laskowski SC, Behn DC, Phillips DK, Botton I, Speight PT.
Abstract : Replacement of the carboxyl group of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) with various bulky amines has produced a series of highly active antiinflammatory agents that have reduced intestinal ulcerogenicity and have better therapeutic ratios in the 21-day adjuvant arthritis assay in rats than currently marketed nonsteroidal antiinflammatory drugs. Activity is maintained on reduction of these 2-(3-benzoylphenyl)propyl bulky amines to the corresponding alcohols or methylene analogues, on conversion of the ketone function to a primary amine or oxime, and on introduction of a 4-halo substitutent (Cl or F) on the terminal aromatic ring. Removal of the alpha-CH3 group greatly reduces the antiinflammatory activity of the series. These compounds have been synthesized by the reductive amination of 2-(3-bromophenyl)propionaldehyde with the respective amine followed by lithiation of this product and condensation with the appropriate benzonitrile.
|
Compound was evaluated for its antiinflammatory activity in the cotton pellet induced granuloma(CPG) in normal rats at the dose 50 mg/kg p.o.
|
Rattus norvegicus
|
38.0
%
|
|
Journal : J. Med. Chem.
Title : 3-Alkyl-2-aryl-3H-naphth[1,2-d]imidazoles, a novel class of nonacidic antiinflammatory agents.
Year : 1984
Volume : 27
Issue : 5
First Page : 610
Last Page : 616
Authors : Toja E, Selva D, Schiatti P.
Abstract : Novel 3-alkyl-2-aryl-3H- naphth [1,2-d]imidazoles were synthesized and evaluated as antiinflammatory agents in the carrageenin-induced paw edema, cotton pellet induced granuloma, and adjuvant-induced polyarthritis assays in rats. The analgesic, antipyretic, and gastroulcerogenic effects were also tested. Structure-activity relationships are discussed. One of the compounds, 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H- naphth [1,2-d]imidazole (35), was selected for clinical trials as a nonacidic antiinflammatory and analgesic agent.
|
The mean increase in paw volume was compared between drug treated groups and placebo to calculate the percent inhibition in rats at 0.08 mmol/kg by carrageenan Edema Assay; 40-49
|
Rattus norvegicus
|
40.0
%
|
|
Journal : J. Med. Chem.
Title : Bulky amine analogues of ketoprofen: potent antiinflammatory agents.
Year : 1984
Volume : 27
Issue : 12
First Page : 1682
Last Page : 1690
Authors : Schlegel DC, Zenitz BL, Fellows CA, Laskowski SC, Behn DC, Phillips DK, Botton I, Speight PT.
Abstract : Replacement of the carboxyl group of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) with various bulky amines has produced a series of highly active antiinflammatory agents that have reduced intestinal ulcerogenicity and have better therapeutic ratios in the 21-day adjuvant arthritis assay in rats than currently marketed nonsteroidal antiinflammatory drugs. Activity is maintained on reduction of these 2-(3-benzoylphenyl)propyl bulky amines to the corresponding alcohols or methylene analogues, on conversion of the ketone function to a primary amine or oxime, and on introduction of a 4-halo substitutent (Cl or F) on the terminal aromatic ring. Removal of the alpha-CH3 group greatly reduces the antiinflammatory activity of the series. These compounds have been synthesized by the reductive amination of 2-(3-bromophenyl)propionaldehyde with the respective amine followed by lithiation of this product and condensation with the appropriate benzonitrile.
|
The percent inhibition was calculated from the average differences in hind paw volume between the adjuvant injected controls and the adjuvant-injected medicated rats at 0.08 mmol/kg; 60-69
|
Rattus norvegicus
|
60.0
%
|
|
Journal : J. Med. Chem.
Title : Bulky amine analogues of ketoprofen: potent antiinflammatory agents.
Year : 1984
Volume : 27
Issue : 12
First Page : 1682
Last Page : 1690
Authors : Schlegel DC, Zenitz BL, Fellows CA, Laskowski SC, Behn DC, Phillips DK, Botton I, Speight PT.
Abstract : Replacement of the carboxyl group of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) with various bulky amines has produced a series of highly active antiinflammatory agents that have reduced intestinal ulcerogenicity and have better therapeutic ratios in the 21-day adjuvant arthritis assay in rats than currently marketed nonsteroidal antiinflammatory drugs. Activity is maintained on reduction of these 2-(3-benzoylphenyl)propyl bulky amines to the corresponding alcohols or methylene analogues, on conversion of the ketone function to a primary amine or oxime, and on introduction of a 4-halo substitutent (Cl or F) on the terminal aromatic ring. Removal of the alpha-CH3 group greatly reduces the antiinflammatory activity of the series. These compounds have been synthesized by the reductive amination of 2-(3-bromophenyl)propionaldehyde with the respective amine followed by lithiation of this product and condensation with the appropriate benzonitrile.
|
Percentage inhibition of Carrageenan-induced rat paw edema at a concentration of 32 mg/kg
|
Rattus norvegicus
|
47.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis of 5-aryl-2H-tetrazoles, 5-aryl-2H-tetrazole-2-acetic acids, and [(4-phenyl-5-aryl-4H-1,2,4-triazol-3-yl)thio]acetic acids as possible superoxide scavengers and antiinflammatory agents.
Year : 1984
Volume : 27
Issue : 12
First Page : 1565
Last Page : 1570
Authors : Maxwell JR, Wasdahl DA, Wolfson AC, Stenberg VI.
Abstract : A series of 5-aryl-2H-tetrazoles, 5-aryl-2H-tetrazole-2-acetic acids, and [(4-phenyl-5-aryl-4H-1,2,4-triazol-3-yl)thio]acetic acids were synthesized and tested in vitro for superoxide scavenging activity, in vivo in the carrageenan-induced rat paw edema assay, and in the reverse passive Arthus reaction. The hydroxy-substituted compounds were effective as in vitro scavengers of superoxide but were not effective as in vivo antiinflammatory agents.
|
In vitro inhibitory activity against ovine cyclooxygenase-1 (COX-1) at 200 uM; Inactive
|
None
|
50.0
%
|
|
Journal : J. Med. Chem.
Title : Novel cyclooxygenase-1 inhibitors discovered using affinity fingerprints.
Year : 2004
Volume : 47
Issue : 20
First Page : 4875
Last Page : 4880
Authors : Hsu N, Cai D, Damodaran K, Gomez RF, Keck JG, Laborde E, Lum RT, Macke TJ, Martin G, Schow SR, Simon RJ, Villar HO, Wick MM, Beroza P.
Abstract : We used protein affinity fingerprints to discover structurally novel inhibitors of cyclooxygenase-1 (COX-1) by screening a selected number of compounds, thus providing an alternative to extensive screening. From the affinity fingerprints of 19 known COX-1 inhibitors, a computational model for COX-1 inhibition was constructed and used to select candidate inhibitors from our compound library to be tested in the COX-1 assay. Subsequent refinement of the model by including affinity fingerprints of inactive compounds identified three molecules that were more potent than ibuprofen, a commonly used COX-1 inhibitor. These compounds are structurally distinct from those used to build the model and were discovered by testing only 62 library compounds. The discovery of these leads demonstrates the efficiency with which affinity fingerprints can identify novel bioactive chemotypes from known drugs.
|
Percent inhibition of cyclooxygenase activity of compound at 10 uM concentration
|
Oryctolagus cuniculus
|
89.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis of some newer analogues of substituted dibenzoyl phenol as potent anti-inflammatory agents.
Year : 2004
Volume : 14
Issue : 21
First Page : 5351
Last Page : 5355
Authors : Khanum SA, D VT, Shashikanth S, Firdouse A.
Abstract : Benzoylation of hydroxybenzophenones 1a-f affords substituted benzoyl phenyl benzoates 3a-f, which on Fries rearrangement using microwave irradiation led to a facile synthesis of solely dibenzoyl phenols 4a-f in excellent yield. The newly synthesized compounds were screened for their anti-inflammatory activity and were compared with standard drugs. Out of the compounds studied, the compound 4e showed more potent activity than the standard drugs at all doses tested.
|
Antiinflammatory activity in Wistar Albino rat assessed as inhibition of carrageenan-induced paw oedema at 20 mg/kg after 1 hr relative to control
|
Rattus norvegicus
|
21.24
%
|
|
Journal : Eur. J. Med. Chem.
Title : Studies on synthesis and pharmacological activities of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues.
Year : 2007
Volume : 42
Issue : 6
First Page : 823
Last Page : 840
Authors : Mathew V, Keshavayya J, Vaidya VP, Giles D.
Abstract : Several 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues were synthesized from hetero aromatic acids and hetero aromatic aldehydes, respectively, by microwave-assisted dry media and conventional methods. Elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data elucidated the structures of all newly synthesized compounds. Synthesized compounds are studied for their antibacterial, antifungal, anti-inflammatory and analgesic activities. Some of the tested compounds showed significant pharmacological activities.
|
Antiinflammatory activity in Wistar Albino rat assessed as inhibition of carrageenan-induced paw oedema at 20 mg/kg after 2 hrs relative to control
|
Rattus norvegicus
|
33.59
%
|
|
Journal : Eur. J. Med. Chem.
Title : Studies on synthesis and pharmacological activities of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues.
Year : 2007
Volume : 42
Issue : 6
First Page : 823
Last Page : 840
Authors : Mathew V, Keshavayya J, Vaidya VP, Giles D.
Abstract : Several 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues were synthesized from hetero aromatic acids and hetero aromatic aldehydes, respectively, by microwave-assisted dry media and conventional methods. Elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data elucidated the structures of all newly synthesized compounds. Synthesized compounds are studied for their antibacterial, antifungal, anti-inflammatory and analgesic activities. Some of the tested compounds showed significant pharmacological activities.
|
Antiinflammatory activity in Wistar Albino rat assessed as inhibition of carrageenan-induced paw oedema at 20 mg/kg after 3 hrs relative to control
|
Rattus norvegicus
|
40.81
%
|
|
Journal : Eur. J. Med. Chem.
Title : Studies on synthesis and pharmacological activities of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues.
Year : 2007
Volume : 42
Issue : 6
First Page : 823
Last Page : 840
Authors : Mathew V, Keshavayya J, Vaidya VP, Giles D.
Abstract : Several 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues were synthesized from hetero aromatic acids and hetero aromatic aldehydes, respectively, by microwave-assisted dry media and conventional methods. Elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data elucidated the structures of all newly synthesized compounds. Synthesized compounds are studied for their antibacterial, antifungal, anti-inflammatory and analgesic activities. Some of the tested compounds showed significant pharmacological activities.
|
Antiinflammatory activity in Wistar Albino rat assessed as inhibition of carrageenan-induced paw oedema at 20 mg/kg after 4 hrs relative to control
|
Rattus norvegicus
|
45.4
%
|
|
Journal : Eur. J. Med. Chem.
Title : Studies on synthesis and pharmacological activities of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues.
Year : 2007
Volume : 42
Issue : 6
First Page : 823
Last Page : 840
Authors : Mathew V, Keshavayya J, Vaidya VP, Giles D.
Abstract : Several 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues were synthesized from hetero aromatic acids and hetero aromatic aldehydes, respectively, by microwave-assisted dry media and conventional methods. Elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data elucidated the structures of all newly synthesized compounds. Synthesized compounds are studied for their antibacterial, antifungal, anti-inflammatory and analgesic activities. Some of the tested compounds showed significant pharmacological activities.
|
Antiinflammatory activity against carrageenan-induced paw edema in Albino rat assessed as oedema inhibition relative to control at 20 mg/kg, po
|
Rattus norvegicus
|
30.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and crystallographic analysis of benzophenone derivatives--the potential anti-inflammatory agents.
Year : 2007
Volume : 15
Issue : 10
First Page : 3505
Last Page : 3514
Authors : Venu TD, Shashikanth S, Khanum SA, Naveen S, Firdouse A, Sridhar MA, Shashidhara Prasad J.
Abstract : Fries rearrangement of substituted phenyl benzoates 1a-j to substituted hydroxy benzophenones 2a-j was achieved in excellent yield. Further benzoylation of 2a-j to benzoyloxy benzophenones 4a-n, a benzophenone analogue was achieved in good yield. All the newly synthesized compounds were evaluated for their anti-inflammatory activity and were compared with standard drugs. Out of the compounds studied, the compounds 4c, 4e, 4g, 4h and 4k with chloro and methyl substituents at para position showed more potent activity than the standard drugs at all doses tested.
|
Antiinflammatory activity against carrageenan-induced paw edema in Albino rat assessed as oedema inhibition relative to control at 40 mg/kg, po
|
Rattus norvegicus
|
33.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and crystallographic analysis of benzophenone derivatives--the potential anti-inflammatory agents.
Year : 2007
Volume : 15
Issue : 10
First Page : 3505
Last Page : 3514
Authors : Venu TD, Shashikanth S, Khanum SA, Naveen S, Firdouse A, Sridhar MA, Shashidhara Prasad J.
Abstract : Fries rearrangement of substituted phenyl benzoates 1a-j to substituted hydroxy benzophenones 2a-j was achieved in excellent yield. Further benzoylation of 2a-j to benzoyloxy benzophenones 4a-n, a benzophenone analogue was achieved in good yield. All the newly synthesized compounds were evaluated for their anti-inflammatory activity and were compared with standard drugs. Out of the compounds studied, the compounds 4c, 4e, 4g, 4h and 4k with chloro and methyl substituents at para position showed more potent activity than the standard drugs at all doses tested.
|
Antiinflammatory activity against carrageenan-induced paw edema in Albino rat assessed as oedema inhibition relative to control at 80 mg/kg, po
|
Rattus norvegicus
|
55.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and crystallographic analysis of benzophenone derivatives--the potential anti-inflammatory agents.
Year : 2007
Volume : 15
Issue : 10
First Page : 3505
Last Page : 3514
Authors : Venu TD, Shashikanth S, Khanum SA, Naveen S, Firdouse A, Sridhar MA, Shashidhara Prasad J.
Abstract : Fries rearrangement of substituted phenyl benzoates 1a-j to substituted hydroxy benzophenones 2a-j was achieved in excellent yield. Further benzoylation of 2a-j to benzoyloxy benzophenones 4a-n, a benzophenone analogue was achieved in good yield. All the newly synthesized compounds were evaluated for their anti-inflammatory activity and were compared with standard drugs. Out of the compounds studied, the compounds 4c, 4e, 4g, 4h and 4k with chloro and methyl substituents at para position showed more potent activity than the standard drugs at all doses tested.
|
Inhibition of rabbit microsomal COX at 10 uM
|
Oryctolagus cuniculus
|
85.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and crystallographic analysis of benzophenone derivatives--the potential anti-inflammatory agents.
Year : 2007
Volume : 15
Issue : 10
First Page : 3505
Last Page : 3514
Authors : Venu TD, Shashikanth S, Khanum SA, Naveen S, Firdouse A, Sridhar MA, Shashidhara Prasad J.
Abstract : Fries rearrangement of substituted phenyl benzoates 1a-j to substituted hydroxy benzophenones 2a-j was achieved in excellent yield. Further benzoylation of 2a-j to benzoyloxy benzophenones 4a-n, a benzophenone analogue was achieved in good yield. All the newly synthesized compounds were evaluated for their anti-inflammatory activity and were compared with standard drugs. Out of the compounds studied, the compounds 4c, 4e, 4g, 4h and 4k with chloro and methyl substituents at para position showed more potent activity than the standard drugs at all doses tested.
|
Decrease in histamine-induced capillary permeability in Wistar rat assessed as inhibition of pontamine sky blue 6BX dye leakage at 50 ug treated topically relative to control
|
Rattus norvegicus
|
11.1
%
|
|
Journal : J. Nat. Prod.
Title : A comparative study on anti-inflammatory activities of the enantiomers, shikonin and alkannin.
Year : 1986
Volume : 49
Issue : 3
First Page : 466
Last Page : 469
Authors : Tanaka S, Tajima M, Tsukada M, Tabata M.
Abstract : A pharmacological comparison between the enantiomers, shikonin (R) and alkannin (S), was made with regard to their inhibitory effects on the increased capillary permeability and thermal edema in rats, using phenylbutazone as a positive control in both models. The results of experiments have shown that there is no significant difference in the anti-inflammatory activity between the two compounds.
|
Antiinflammatory activity against carrageenan-induced paw edema in Swiss mouse at 80 mg/kg, po administered 1 hr before carrageenan challenge measured after 3 hrs
|
Mus musculus
|
51.4
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory activity of two flavonoids from Tanacetum microphyllum.
Year : 1993
Volume : 56
Issue : 7
First Page : 1164
Last Page : 1167
Authors : Abad MJ, Bermejo P, Villar A, Valverde S.
Abstract : The CH2Cl2 extract of Tanacetum microphyllum aerial parts exhibited anti-inflammatory activity and yielded two anti-inflammatory flavonoids: 5,7,3'-trihydroxy-3,6,4'-trimethoxyflavone (centaureidin) [1], and 5,3'-dihydroxy-4'-methoxy-7-carbomethoxyflavonol [2]. This is the first report of the chemical composition of Ta. microphyllum and of the isolation of centaureidin from the genus Tanacetum.
|
Antiinflammatory activity against carrageenan-induced paw edema in Swiss mouse at 80 mg/kg, po administered 1 hr before carrageenan challenge measured after 5 hrs
|
Mus musculus
|
47.2
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory activity of two flavonoids from Tanacetum microphyllum.
Year : 1993
Volume : 56
Issue : 7
First Page : 1164
Last Page : 1167
Authors : Abad MJ, Bermejo P, Villar A, Valverde S.
Abstract : The CH2Cl2 extract of Tanacetum microphyllum aerial parts exhibited anti-inflammatory activity and yielded two anti-inflammatory flavonoids: 5,7,3'-trihydroxy-3,6,4'-trimethoxyflavone (centaureidin) [1], and 5,3'-dihydroxy-4'-methoxy-7-carbomethoxyflavonol [2]. This is the first report of the chemical composition of Ta. microphyllum and of the isolation of centaureidin from the genus Tanacetum.
|
Antiinflammatory activity in albino mouse assessed as inhibition of carrageenan-induced paw edema at 100 mg/kg, po administered 1 hr before carrageenan challenge measured after 3 hrs
|
Mus musculus
|
47.7
%
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory compounds from Sideritis javalambrensis n-hexane extract.
Year : 1989
Volume : 52
Issue : 5
First Page : 1088
Last Page : 1091
Authors : Alcaraz MJ, Jimenez MJ, Valverde S, Sanz J, Rabanal RM, Villar A.
Abstract : The anti-inflammatory activities of the n-hexane extract of Sideritis javalambrensis and several purified fractions were investigated using the carrageenan mouse paw edema test. Progressive fractionation led to the isolation of the active principles ent-16-hydroxy-13-epimanoyl oxide [1] and esters of tyrosol with palmitic, stearic, behenic, and lignoceric acids.
|
Antiinflammatory activity in rat assessed as inhibition of carrageenan-induced edema at 100 mg/kg
|
Rattus norvegicus
|
64.0
%
|
|
Journal : J. Nat. Prod.
Title : A pentacyclic triterpene with anti-inflammatory and analgesic activity from the roots of Commiphora merkeri.
Year : 1989
Volume : 52
Issue : 5
First Page : 1129
Last Page : 1131
Authors : Fourie TG, Snyckers FO.
Abstract : A new pentacyclic triterpene [1] with anti-inflammatory activity was isolated from the roots of Commiphora merkeri. The structure was established on the basis of spectral data and conversion to its triacetate.
|
Antiinflammatory activity against CF1 mouse assessed as inhibition of carrageenan-induced paw edema at 50 mg/kg administered 30 mins before carrageenan challenge measured after 3 hrs relative to control
|
Mus musculus
|
47.0
%
|
|
Journal : J. Nat. Prod.
Title : Hypolipidemic, anti-inflammatory, and antineoplastic activity and cytotoxicity of flavonolignans isolated from Hydnocarpus wightiana seeds.
Year : 1991
Volume : 54
Issue : 5
First Page : 1298
Last Page : 1302
Authors : Sharma DK, Hall IH.
Abstract : Flavonolignans isolated from Hydnocarpus wightiana seeds, namely hydnowightin, hydnocarpin, and neohydnocarpin, demonstrated potent hypolipidemic activity in mice, lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day ip. Hydnowightin demonstrated the best lipid-lowering effect of the three compounds. Good anti-inflammatory and antineoplastic activity was demonstrated by hydnocarpin in mice in vivo. The other two derivatives were not as active in these screens. Cytotoxicity against the growth of murine and human tissue cultured cells was shown. All three compounds were moderately active against murine L-1210 leukemia growth. All three compounds demonstrated good activity against the growth of human KB nasopharynx, colon adenocarcinoma, osteosarcoma, and HeLa-S3 uterine growth. Hydnocarpin was the only compound of the three which was active against glioma growth. Hydnocarpin and neohydnocarpin demonstrated significant activity against Tmolt3 leukemia cell growth.
|
Antiinflammatory activity against carrageenan-induced acute paw edema in albino rat assessed as reduction of edema at 20 mg/kg, po after 3 hrs relative to control
|
Rattus norvegicus
|
29.6
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines.
Year : 2008
Volume : 18
Issue : 15
First Page : 4409
Last Page : 4412
Authors : Venu TD, Khanum SA, Firdouse A, Manuprasad BK, Shashikanth S, Mohamed R, Vishwanth BS.
Abstract : Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a-f in excellent yield. The newly synthesized heterocycles were characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.
|
Antiinflammatory activity against carrageenan-induced acute paw edema in albino rat assessed as reduction of edema at 40 mg/kg, po after 3 hrs relative to control
|
Rattus norvegicus
|
34.1
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines.
Year : 2008
Volume : 18
Issue : 15
First Page : 4409
Last Page : 4412
Authors : Venu TD, Khanum SA, Firdouse A, Manuprasad BK, Shashikanth S, Mohamed R, Vishwanth BS.
Abstract : Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a-f in excellent yield. The newly synthesized heterocycles were characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.
|
Antiinflammatory activity against carrageenan-induced acute paw edema in albino rat assessed as reduction of edema at 80 mg/kg, po after 3 hrs relative to control
|
Rattus norvegicus
|
51.9
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines.
Year : 2008
Volume : 18
Issue : 15
First Page : 4409
Last Page : 4412
Authors : Venu TD, Khanum SA, Firdouse A, Manuprasad BK, Shashikanth S, Mohamed R, Vishwanth BS.
Abstract : Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a-f in excellent yield. The newly synthesized heterocycles were characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.
|
Inhibition of rabbit distal colon cyclooxygenase at 10 uM
|
Oryctolagus cuniculus
|
89.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines.
Year : 2008
Volume : 18
Issue : 15
First Page : 4409
Last Page : 4412
Authors : Venu TD, Khanum SA, Firdouse A, Manuprasad BK, Shashikanth S, Mohamed R, Vishwanth BS.
Abstract : Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a-f in excellent yield. The newly synthesized heterocycles were characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.
|
Inhibition of rat PLA2 using [14C]oleate labeled autoclaved Escherichia coli at 10 ug
|
Rattus norvegicus
|
85.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines.
Year : 2008
Volume : 18
Issue : 15
First Page : 4409
Last Page : 4412
Authors : Venu TD, Khanum SA, Firdouse A, Manuprasad BK, Shashikanth S, Mohamed R, Vishwanth BS.
Abstract : Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a-f in excellent yield. The newly synthesized heterocycles were characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.
|
Antiinflammatory activity in albino rat assessed as inhibition of carrageenan-induced paw edema at 20 mg/kg, po administered 30 mins prior to challenge relative to control
|
Rattus norvegicus
|
31.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-aryloxy methyl oxazolines.
Year : 2008
Volume : 18
Issue : 16
First Page : 4597
Last Page : 4601
Authors : Khanum SA, Khanum NF, Shashikanth M.
Abstract : A series of potential biologically active 2-aryloxy methyl oxazolines 3a-n have been synthesized from substituted hydroxybenzenes 1a-n with good chemical yield. The compounds 3a-n were screened for their anti-inflammatory, ulcerogenic, cyclooxygenase activities and also for their acute toxicity. The potency of the compounds was compared with that of the standard drugs, aspirin and phenyl butazone. The outcome indicates that compounds 3b (48.2%), 3h (48.5%) and 3l (46.5%) offered significant anti-inflammatory activity with low ulcerogenic activity than the standard drugs.
|
Antiinflammatory activity in albino rat assessed as inhibition of carrageenan-induced paw edema at 40 mg/kg, po administered 30 mins prior to challenge relative to control
|
Rattus norvegicus
|
35.5
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-aryloxy methyl oxazolines.
Year : 2008
Volume : 18
Issue : 16
First Page : 4597
Last Page : 4601
Authors : Khanum SA, Khanum NF, Shashikanth M.
Abstract : A series of potential biologically active 2-aryloxy methyl oxazolines 3a-n have been synthesized from substituted hydroxybenzenes 1a-n with good chemical yield. The compounds 3a-n were screened for their anti-inflammatory, ulcerogenic, cyclooxygenase activities and also for their acute toxicity. The potency of the compounds was compared with that of the standard drugs, aspirin and phenyl butazone. The outcome indicates that compounds 3b (48.2%), 3h (48.5%) and 3l (46.5%) offered significant anti-inflammatory activity with low ulcerogenic activity than the standard drugs.
|
Antiinflammatory activity in albino rat assessed as inhibition of carrageenan-induced paw edema at 80 mg/kg, po administered 30 mins prior to challenge relative to control
|
Rattus norvegicus
|
57.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-aryloxy methyl oxazolines.
Year : 2008
Volume : 18
Issue : 16
First Page : 4597
Last Page : 4601
Authors : Khanum SA, Khanum NF, Shashikanth M.
Abstract : A series of potential biologically active 2-aryloxy methyl oxazolines 3a-n have been synthesized from substituted hydroxybenzenes 1a-n with good chemical yield. The compounds 3a-n were screened for their anti-inflammatory, ulcerogenic, cyclooxygenase activities and also for their acute toxicity. The potency of the compounds was compared with that of the standard drugs, aspirin and phenyl butazone. The outcome indicates that compounds 3b (48.2%), 3h (48.5%) and 3l (46.5%) offered significant anti-inflammatory activity with low ulcerogenic activity than the standard drugs.
|
Inhibition of cyclooxygenase in rabbit colon microsomes assessed as reduction in conversion of arachidonic acid to PGE2 at 10 uM by liquid scintillation spectrometry relative to control
|
Oryctolagus cuniculus
|
60.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and anti-inflammatory activity of 2-aryloxy methyl oxazolines.
Year : 2008
Volume : 18
Issue : 16
First Page : 4597
Last Page : 4601
Authors : Khanum SA, Khanum NF, Shashikanth M.
Abstract : A series of potential biologically active 2-aryloxy methyl oxazolines 3a-n have been synthesized from substituted hydroxybenzenes 1a-n with good chemical yield. The compounds 3a-n were screened for their anti-inflammatory, ulcerogenic, cyclooxygenase activities and also for their acute toxicity. The potency of the compounds was compared with that of the standard drugs, aspirin and phenyl butazone. The outcome indicates that compounds 3b (48.2%), 3h (48.5%) and 3l (46.5%) offered significant anti-inflammatory activity with low ulcerogenic activity than the standard drugs.
|
Antiinflammatory activity against Swiss mouse assessed as inhibition of carrageenan-induced paw volume at 100 mg/kg, po administered 1 hr prior to carrageenan challenge measured after 1 hr
|
Mus musculus
|
54.0
%
|
|
Journal : J. Nat. Prod.
Title : A glycosyl analogue of diacylglycerol and other antiinflammatory constituents from Inula viscosa.
Year : 1999
Volume : 62
Issue : 4
First Page : 601
Last Page : 604
Authors : Máñez S, Recio MC, Gil I, Gómez C, Giner RM, Waterman PG, Ríos JL.
Abstract : Some extracts from Inula viscosa were examined for acute antiinflammatory activity in vivo. Three flavonoids: rhamnocitrin (1), 7-O-methylaromadendrin (3), and 3-O-acetylpadmatin (4); a sesquiterpene lactone, inuviscolide (2); a sesquiterpene acid, ilicic acid (5); and a digalactosyl-diacylglycerol, inugalactolipid A (6), were isolated from the CH2Cl2 extract, identified by spectroscopic methods, and characterized as the topical antiinflammatory principles of this species. All these compounds proved to be effective against 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice, although lacking activity against arachidonic acid-induced edema. In addition, compounds 5 and, markedly, 6 showed notable effects on a multiple-dose murine chronic dermatitis model. This is the first attempt to establish a rationale concerning the documented use of the plant on various skin diseases.
|
Antiinflammatory activity against Swiss mouse assessed as inhibition of carrageenan-induced paw volume at 100 mg/kg, po administered 1 hr prior to carrageenan challenge measured after 3 hrs
|
Mus musculus
|
58.0
%
|
|
Journal : J. Nat. Prod.
Title : A glycosyl analogue of diacylglycerol and other antiinflammatory constituents from Inula viscosa.
Year : 1999
Volume : 62
Issue : 4
First Page : 601
Last Page : 604
Authors : Máñez S, Recio MC, Gil I, Gómez C, Giner RM, Waterman PG, Ríos JL.
Abstract : Some extracts from Inula viscosa were examined for acute antiinflammatory activity in vivo. Three flavonoids: rhamnocitrin (1), 7-O-methylaromadendrin (3), and 3-O-acetylpadmatin (4); a sesquiterpene lactone, inuviscolide (2); a sesquiterpene acid, ilicic acid (5); and a digalactosyl-diacylglycerol, inugalactolipid A (6), were isolated from the CH2Cl2 extract, identified by spectroscopic methods, and characterized as the topical antiinflammatory principles of this species. All these compounds proved to be effective against 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice, although lacking activity against arachidonic acid-induced edema. In addition, compounds 5 and, markedly, 6 showed notable effects on a multiple-dose murine chronic dermatitis model. This is the first attempt to establish a rationale concerning the documented use of the plant on various skin diseases.
|
Antiinflammatory activity against Swiss mouse assessed as inhibition of carrageenan-induced paw volume at 100 mg/kg, po administered 1 hr prior to carrageenan challenge measured after 5 hrs
|
Mus musculus
|
43.0
%
|
|
Journal : J. Nat. Prod.
Title : A glycosyl analogue of diacylglycerol and other antiinflammatory constituents from Inula viscosa.
Year : 1999
Volume : 62
Issue : 4
First Page : 601
Last Page : 604
Authors : Máñez S, Recio MC, Gil I, Gómez C, Giner RM, Waterman PG, Ríos JL.
Abstract : Some extracts from Inula viscosa were examined for acute antiinflammatory activity in vivo. Three flavonoids: rhamnocitrin (1), 7-O-methylaromadendrin (3), and 3-O-acetylpadmatin (4); a sesquiterpene lactone, inuviscolide (2); a sesquiterpene acid, ilicic acid (5); and a digalactosyl-diacylglycerol, inugalactolipid A (6), were isolated from the CH2Cl2 extract, identified by spectroscopic methods, and characterized as the topical antiinflammatory principles of this species. All these compounds proved to be effective against 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice, although lacking activity against arachidonic acid-induced edema. In addition, compounds 5 and, markedly, 6 showed notable effects on a multiple-dose murine chronic dermatitis model. This is the first attempt to establish a rationale concerning the documented use of the plant on various skin diseases.
|
Antiinflammatory activity in Charles-Foster albino rat assessed as inhibition of carrageenan-induced hind paw edema at 50 mg/kg, po relative to control
|
Rattus norvegicus
|
36.8
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and anti-inflammatory activity of newer quinazolin-4-one derivatives.
Year : 2009
Volume : 44
Issue : 1
First Page : 83
Last Page : 90
Authors : Kumar A, Rajput CS.
Abstract : 2-Methyl-3-aminosubstituted-3H-quinazolin-4-ones (1-2), 2-methyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (3-10), 2-bromomethyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (11-18), 2-(5'-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (19-26), 3-(3-chloro-2-oxo-4-substituted-aryl-azetidin-1-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (27-34) and 3-(4-oxo-2-substituted-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (35-42) were synthesized in present study. All the compounds exhibited anti-inflammatory activity at the dose 50 mg/kg p.o. varying degree from 16.3 to 36.3% inhibition of oedema. Compound 40 showed same activity at 25, 50 and 100 mg/kg p.o. like standard drugs. The structure of all these newly synthesized compounds was confirmed by their analytical (C, H, N) and spectral (IR and (1)H NMR) data.
|
Antiinflammatory activity in Charles-Foster albino rat assessed as inhibition of carrageenan-induced hind paw edema at 25 mg/kg, po relative to control
|
Rattus norvegicus
|
25.4
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and anti-inflammatory activity of newer quinazolin-4-one derivatives.
Year : 2009
Volume : 44
Issue : 1
First Page : 83
Last Page : 90
Authors : Kumar A, Rajput CS.
Abstract : 2-Methyl-3-aminosubstituted-3H-quinazolin-4-ones (1-2), 2-methyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (3-10), 2-bromomethyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (11-18), 2-(5'-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (19-26), 3-(3-chloro-2-oxo-4-substituted-aryl-azetidin-1-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (27-34) and 3-(4-oxo-2-substituted-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (35-42) were synthesized in present study. All the compounds exhibited anti-inflammatory activity at the dose 50 mg/kg p.o. varying degree from 16.3 to 36.3% inhibition of oedema. Compound 40 showed same activity at 25, 50 and 100 mg/kg p.o. like standard drugs. The structure of all these newly synthesized compounds was confirmed by their analytical (C, H, N) and spectral (IR and (1)H NMR) data.
|
Antiinflammatory activity in Charles-Foster albino rat assessed as inhibition of carrageenan-induced hind paw edema at 100 mg/kg, po relative to control
|
Rattus norvegicus
|
66.4
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and anti-inflammatory activity of newer quinazolin-4-one derivatives.
Year : 2009
Volume : 44
Issue : 1
First Page : 83
Last Page : 90
Authors : Kumar A, Rajput CS.
Abstract : 2-Methyl-3-aminosubstituted-3H-quinazolin-4-ones (1-2), 2-methyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (3-10), 2-bromomethyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (11-18), 2-(5'-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (19-26), 3-(3-chloro-2-oxo-4-substituted-aryl-azetidin-1-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (27-34) and 3-(4-oxo-2-substituted-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (35-42) were synthesized in present study. All the compounds exhibited anti-inflammatory activity at the dose 50 mg/kg p.o. varying degree from 16.3 to 36.3% inhibition of oedema. Compound 40 showed same activity at 25, 50 and 100 mg/kg p.o. like standard drugs. The structure of all these newly synthesized compounds was confirmed by their analytical (C, H, N) and spectral (IR and (1)H NMR) data.
|
Antiinflammatory activity in albino Charles-Foster rat assessed as inhibition of carrageenan-induced paw oedema at 50 mg/kg, po measured before 1 hr and after 3 hrs of carrageenan challenge relative to control
|
Rattus norvegicus
|
36.8
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents.
Year : 2008
Volume : 43
Issue : 11
First Page : 2323
Last Page : 2330
Authors : Bhati SK, Kumar A.
Abstract : Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5-b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h), and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4-thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present study. The structure of these newly synthesized compounds were confirmed by their analytical and spectral data. These compounds were also evaluated for their anti-inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most active anti-inflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin.
|
Antiinflammatory activity in albino Charles-Foster rat assessed as inhibition of carrageenan-induced paw oedema at 25 mg/kg, po measured before 1 hr and after 3 hrs of carrageenan challenge relative to control
|
Rattus norvegicus
|
26.76
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents.
Year : 2008
Volume : 43
Issue : 11
First Page : 2323
Last Page : 2330
Authors : Bhati SK, Kumar A.
Abstract : Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5-b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h), and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4-thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present study. The structure of these newly synthesized compounds were confirmed by their analytical and spectral data. These compounds were also evaluated for their anti-inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most active anti-inflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin.
|
Antiinflammatory activity in albino Charles-Foster rat assessed as inhibition of carrageenan-induced paw oedema at 100 mg/kg, po measured before 1 hr and after 3 hrs of carrageenan challenge relative to control
|
Rattus norvegicus
|
64.68
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents.
Year : 2008
Volume : 43
Issue : 11
First Page : 2323
Last Page : 2330
Authors : Bhati SK, Kumar A.
Abstract : Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5-b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h), and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4-thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present study. The structure of these newly synthesized compounds were confirmed by their analytical and spectral data. These compounds were also evaluated for their anti-inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most active anti-inflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin.
|
Antiinflammatory activity against rat assessed as inhibition of carrageenan-induced edema at 75 mg/kg
|
Rattus norvegicus
|
81.0
%
|
|
Journal : J. Nat. Prod.
Title : A flavone with antiinflammatory activity from the roots of Rhus undulata.
Year : 1984
Volume : 47
Issue : 6
First Page : 1057
Last Page : 1058
Authors : Fourie TG, Snyckers FO.
|
Antiinflammatory activity in Albino mouse assessed as inhibition of carrageenan-induced foot paw edema at 100 mg/kg, po administered 1 hr before carrageenan challenge measured after 2 hrs
|
Mus musculus
|
53.28
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Benzophenone-N-ethyl piperidine ether analogues--synthesis and efficacy as anti-inflammatory agent.
Year : 2009
Volume : 19
Issue : 7
First Page : 1887
Last Page : 1891
Authors : Khanum SA, Girish V, Suparshwa SS, Khanum NF.
Abstract : A sequence of substituted benzophenone-N-ethyl piperidine ether analogues has been synthesized and evaluated as orally active anti-inflammatory agents with reduced side effects. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin, and phenylbutazone. These analogues showed an interesting anti-inflammatory activity in carrageenan-induced foot pad edema assay. In the air-pouch test, some of the analogues reduced the total number of leukocytes of the exudate, which indicates inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, in the liver and stomach. None of the compounds illustrated significant side effects compared with standard drugs like indomethacin and naproxen.
|
Inhibition of hyaluronidase activity at 71.68 mM
|
None
|
50.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : In vitro and QSAR studies of cucurbitacins on HepG2 and HSC-T6 liver cell lines.
Year : 2011
Volume : 19
Issue : 8
First Page : 2757
Last Page : 2766
Authors : Bartalis J, Halaweish FT.
Abstract : The aim of this study was to evaluate cucurbitacins (Cucs) liver protective activity in vitro and conduct QSAR studies against lipophilicity and ab initio descriptors. Nine Cucs were isolated from Cucurbitaceae plants and eight prepared by C2-alkylation or C16-acylation. Ten Cucs demonstrated protective activity on human hepatocyte-derived HepG2 cells exposed to CCl(4) (EC(50)=2.4-45.3 μM) with good margin to toxicity (T/A). All Cucs exhibited anti-proliferative effect on serum-activated rat stellate cells, HSC-T6 (EC(50)=0.02-4.12 μM) with high T/A. While silybin is nontoxic, its protection is lower compared to Cuc D (3), iso-D (4), I (5), B (11), E (12), I-Me (6), L-Me (7), and E-Me (13) on both cell lines. Strong correlations were found for lipophilicity with both protection and toxicity on HepG2. Lipophilicity correlated only with toxicity on HSC-T6. Consequently, we suggest that Cucs are potential hepatoprotective agents against fibrosis that deserve further examination.
|
TP_TRANSPORTER: inhibition of PAH uptake (PAH: 2 uM, Phenylbutazone: 1000 uM) in Xenopus laevis oocytes
|
Xenopus laevis
|
98.8
%
|
|
Journal : Mol. Pharmacol.
Title : Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes.
Year : 1999
Volume : 55
Issue : 1
First Page : 847
Last Page : 854
Authors : Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H.
Abstract : Organic anion transporter 1 (OAT1) is the para-aminohippurate (PAH) transporter in the basolateral membrane of the proximal tubule. The present study investigated whether or not nonsteroidal anti-inflammatory drugs (NSAIDs) are transported by OAT1. All of the NSAIDs tested inhibited [14C]PAH uptake via OAT1 expressed in Xenopus laevis oocytes. Ibuprofen, indomethacin, salicylurate, and naproxen showed the strongest potency to inhibit [14C]PAH uptake (Ki approximately 2-10 microM); acetylsalicylate, salicylate, and phenacetin exhibited moderate potency (Ki approximately 300-400 microM), and acetaminophen (paracetamol) exhibited the weakest inhibitory potency (Ki approximately 2 mM). Radiolabeled acetylsalicylate, salicylate, and indomethacin were taken up by OAT1 and the uptake rate of these three NSAIDs was enhanced by the outwardly directed dicarboxylate gradient. The efflux of the preloaded [14C]PAH from the oocytes via OAT1 was trans-stimulated by PAH and glutarate added to the media. The addition of salicylate, acetylsalicylate, or salicylurate into the media also trans-stimulated the efflux of PAH, whereas indomethacin did not. The present study indicates that OAT1 is responsible for the renal uptake and secretion of NSAIDs.
|
Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting
|
Homo sapiens
|
25.1
%
|
|
Journal : J. Med. Chem.
Title : Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Year : 2012
Volume : 55
Issue : 10
First Page : 4740
Last Page : 4763
Authors : Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P.
Abstract : The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
Inhibition of human liver OATP1B3 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E17-betaG uptake at 20 uM incubated for 5 mins by scintillation counting
|
Homo sapiens
|
17.0
%
|
|
Journal : J. Med. Chem.
Title : Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Year : 2012
Volume : 55
Issue : 10
First Page : 4740
Last Page : 4763
Authors : Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P.
Abstract : The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
Inhibition of human liver OATP2B1 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E3S uptake at 20 uM incubated for 5 mins by scintillation counting
|
Homo sapiens
|
15.1
%
|
|
Journal : J. Med. Chem.
Title : Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Year : 2012
Volume : 55
Issue : 10
First Page : 4740
Last Page : 4763
Authors : Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P.
Abstract : The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
Anti-inflammatory activity in albino Rattus norvegicus (rat) assessed as inhibition of carrageenan-induced paw edema at 100 mg/kg, po administered 1 hr prior to carrageenan-challenge measured after 1 to 3 hr relative to control
|
Rattus norvegicus
|
70.0
%
|
|
Journal : Med Chem Res
Title : Synthesis and pharmacological evaluation of newer thiazolo [3,2-a] pyrimidines for anti-inflammatory and antinociceptive activity
Year : 2010
Volume : 19
Issue : 9
First Page : 1245
Last Page : 1258
Authors : Alam O, Khan SA, Siddiqui N, Ahsan W
|
Anti-inflammatory activity in albino Rattus norvegicus (rat) assessed as inhibition of carrageenan-induced paw edema at 50 mg/kg, po administered 1 hr prior to carrageenan-challenge measured after 1 to 3 hr relative to control
|
Rattus norvegicus
|
55.0
%
|
|
Journal : Med Chem Res
Title : Synthesis and pharmacological evaluation of newer thiazolo [3,2-a] pyrimidines for anti-inflammatory and antinociceptive activity
Year : 2010
Volume : 19
Issue : 9
First Page : 1245
Last Page : 1258
Authors : Alam O, Khan SA, Siddiqui N, Ahsan W
|
Anti-inflammatory activity in albino Rattus norvegicus (rat) assessed as inhibition of carrageenan-induced paw edema at 25 mg/kg, po administered 1 hr prior to carrageenan-challenge measured after 1 to 3 hr relative to control
|
Rattus norvegicus
|
43.0
%
|
|
Journal : Med Chem Res
Title : Synthesis and pharmacological evaluation of newer thiazolo [3,2-a] pyrimidines for anti-inflammatory and antinociceptive activity
Year : 2010
Volume : 19
Issue : 9
First Page : 1245
Last Page : 1258
Authors : Alam O, Khan SA, Siddiqui N, Ahsan W
|
Antiinflammatory activity in ip dosed Wistar albino rat assessed as inhibition of carrageenan-induced paw edema administered 1 hr prior to carrageenan challenge measured at 3 hrs by plethysmometric analysis
|
Rattus norvegicus
|
0.22
mmol/Kg
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.
Year : 2013
Volume : 63
First Page : 645
Last Page : 654
Authors : Ragab FA, Abdel Gawad NM, Georgey HH, Said MF.
Abstract : Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.
|
Antiinflammatory activity in Wistar albino rat assessed as inhibition of carrageenan-induced paw edema at 0.16 mmol/kg, ip administered 1 hr prior to carrageenan challenge measured at 3 hrs by plethysmometric analysis relative to control
|
Rattus norvegicus
|
42.1
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.
Year : 2013
Volume : 63
First Page : 645
Last Page : 654
Authors : Ragab FA, Abdel Gawad NM, Georgey HH, Said MF.
Abstract : Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.
|
Antiinflammatory activity in Wistar albino rat assessed as inhibition of carrageenan-induced paw edema at 0.08 mmol/kg, ip administered 1 hr prior to carrageenan challenge measured at 3 hrs by plethysmometric analysis relative to control
|
Rattus norvegicus
|
20.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.
Year : 2013
Volume : 63
First Page : 645
Last Page : 654
Authors : Ragab FA, Abdel Gawad NM, Georgey HH, Said MF.
Abstract : Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.
|
Antiinflammatory activity in Wistar albino rat assessed as inhibition of carrageenan-induced paw edema at 0.32 mmol/kg, ip administered 1 hr prior to carrageenan challenge measured at 3 hrs by plethysmometric analysis relative to control
|
Rattus norvegicus
|
70.55
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.
Year : 2013
Volume : 63
First Page : 645
Last Page : 654
Authors : Ragab FA, Abdel Gawad NM, Georgey HH, Said MF.
Abstract : Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.
|
Antiinflammatory activity in Wistar albino rat assessed as inhibition of carrageenan-induced paw edema at 0.32 mmol/kg, ip administered 1 hr prior to carrageenan challenge measured at 2 hrs by plethysmometric analysis relative to control
|
Rattus norvegicus
|
57.28
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.
Year : 2013
Volume : 63
First Page : 645
Last Page : 654
Authors : Ragab FA, Abdel Gawad NM, Georgey HH, Said MF.
Abstract : Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.
|
Antiinflammatory activity in mouse assessed as inhibition of carrageenan-induced increase in paw volume at 100 mg/kg, ip administered 1 hr prior to carrageenan challenge measured after 3 hrs relative to control
|
Mus musculus
|
70.9
%
|
|
Journal : Eur. J. Med. Chem.
Title : Biological activity, design, synthesis and structure activity relationship of some novel derivatives of curcumin containing sulfonamides.
Year : 2013
Volume : 64
First Page : 579
Last Page : 588
Authors : Lal J, Gupta SK, Thavaselvam D, Agarwal DD.
Abstract : Five series of curcumin derivatives with sulfonamides 3a-3e, 4a-4e, 5a-5e, 6a-6e and 7a-7e have been synthesized and evaluated for in vitro antibacterial activity against selected medically important gram-(+) and gram-(-) bacterial species viz. Staphylococcus aureus, Bacillus cereus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli, and antifungal activity against few pathogenic fungal species viz. Aspergillus niger, Aspergillus flavus, Trichoderma viride and Curvularia lunata. The cytotoxicity has been determined by measuring IC50 values against human cell lines HeLa, Hep G-2, QG-56 and HCT-116. Among the compounds screened, 3a-3e showed the most potent biological activity against tested bacteria and fungi. Compounds 3a-3e displayed higher cytotoxicity than curcumin. The curcumin derivatives were also evaluated for in vivo anti-inflammatory activity. In contrast, the compounds 6a-6e and 7a-7e showed dramatically decrease in biological activity.
|
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
70.89
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
62.24
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Antiinflammatory activity in rat assessed as inhibition of carrageenan-induced paw edema at 50 mg/kg, po preincubated for 1 hr followed by carrageenan challenge relative to control
|
Rattus norvegicus
|
43.4
%
|
|
Journal : J. Med. Chem.
Title : Syntheses and antiinflammatory actions of 4,5,6,7-tetrahydroindazole-5-carboxylic acids.
Year : 1979
Volume : 22
Issue : 1
First Page : 48
Last Page : 52
Authors : Nagakura M, Ota T, Shimidzu N, Kawamura K, Eto Y, Wada Y.
Abstract : A novel series of 1-aryl-4,5,6,7-tetrahydro-1H-indazole-5-carboxylic acids and 2-aryl-4,5,6,7-tetrahydro-2H-indazole-5-carboxylic acids were synthesized via condensation between a phenylhydrazine and a 2-(hydroxymethylene)cyclohexanone-4-carboxylate, and the antiinflammatory activity was determined. In the carrageenan edema test, 1-aryl-4,5,6,7-tetrahydro-1H-indazole-5-carboxylic acids exhibited fairly high antiinflammatory activity. However, the 2-aryl isomers were far less active than the former. The most active compound of the series was 1-phenyl-4,5,6,7-tetrahydro-1H-indazole-5-carboxylic acid, which had an ED50 value of 3.5 mg/kg.
|
Antiinflammatory activity in Sprague-Dawley rat assessed as inhibition of carrageenan-induced paw edema at 150 mg/kg, po after 3 hrs
|
Rattus norvegicus
|
51.0
%
|
|
Journal : J. Med. Chem.
Title : Bicyclic pyrazolines, potential central nervous system depressants and antiinflammatory agents.
Year : 1979
Volume : 22
Issue : 2
First Page : 207
Last Page : 210
Authors : Krapcho J, Turk CF.
Abstract : The synthesis and CNS activity of a series of 34 substituted bicyclic pyrazolines are described. Ten of these compounds were also screened for antiinflammatory activity. One of the compounds (15) exhibited significant antiinflammatory activity in the carrageenan-induced edema test.
|
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 100 mg/kg, po pretreated for 30 mins followed by carrageenan challenge measured after 3 hrs relative to control
|
Rattus norvegicus
|
40.6
%
|
|
Journal : J. Med. Chem.
Title : A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds.
Year : 1979
Volume : 22
Issue : 1
First Page : 53
Last Page : 58
Authors : Takaya M, Sato M, Terashima K, Tanizawa H, Maki Y.
Abstract : In order to examine analgesic and antinflammatory activities, various 2-alkyl- or 2-alkenyl-4-alkoxy-5-(substituted amino)-3(2H)-pyridazinones were prepared. Among the compounds prepared, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (8) was evaluated to be the most attractive compound as an analgesic-antiinflammatory agent. Compound 8 was shown to be more potent in analgesic and antiinflammatory activities and less potent in toxicity than aminopyrine and phenylbutazone. Some pyridazinone derivatives in which possible active sites of 8 are eliminated and altered were prepared, and their activities were evaluated by means of analogous assays. On the basis of available data, the structure-activity relationship in a series of 4-alkoxy-2-substituted-5-(substituted amino)-3(2H)-pyridazinones was also discussed.
|
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 50 mg/kg, po pretreated for 30 mins followed by carrageenan challenge measured after 3 hrs relative to control
|
Rattus norvegicus
|
35.0
%
|
|
Journal : J. Med. Chem.
Title : A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds.
Year : 1979
Volume : 22
Issue : 1
First Page : 53
Last Page : 58
Authors : Takaya M, Sato M, Terashima K, Tanizawa H, Maki Y.
Abstract : In order to examine analgesic and antinflammatory activities, various 2-alkyl- or 2-alkenyl-4-alkoxy-5-(substituted amino)-3(2H)-pyridazinones were prepared. Among the compounds prepared, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (8) was evaluated to be the most attractive compound as an analgesic-antiinflammatory agent. Compound 8 was shown to be more potent in analgesic and antiinflammatory activities and less potent in toxicity than aminopyrine and phenylbutazone. Some pyridazinone derivatives in which possible active sites of 8 are eliminated and altered were prepared, and their activities were evaluated by means of analogous assays. On the basis of available data, the structure-activity relationship in a series of 4-alkoxy-2-substituted-5-(substituted amino)-3(2H)-pyridazinones was also discussed.
|
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 25 mg/kg, po pretreated for 30 mins followed by carrageenan challenge measured after 3 hrs relative to control
|
Rattus norvegicus
|
18.0
%
|
|
Journal : J. Med. Chem.
Title : A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds.
Year : 1979
Volume : 22
Issue : 1
First Page : 53
Last Page : 58
Authors : Takaya M, Sato M, Terashima K, Tanizawa H, Maki Y.
Abstract : In order to examine analgesic and antinflammatory activities, various 2-alkyl- or 2-alkenyl-4-alkoxy-5-(substituted amino)-3(2H)-pyridazinones were prepared. Among the compounds prepared, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (8) was evaluated to be the most attractive compound as an analgesic-antiinflammatory agent. Compound 8 was shown to be more potent in analgesic and antiinflammatory activities and less potent in toxicity than aminopyrine and phenylbutazone. Some pyridazinone derivatives in which possible active sites of 8 are eliminated and altered were prepared, and their activities were evaluated by means of analogous assays. On the basis of available data, the structure-activity relationship in a series of 4-alkoxy-2-substituted-5-(substituted amino)-3(2H)-pyridazinones was also discussed.
|
Antiinflammatory activity in Sprague-Dawley rat assessed as inhibition of carrageenan-induced paw edema at 30 mg/kg, po
|
Rattus norvegicus
|
39.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
Year : 1978
Volume : 21
Issue : 9
First Page : 965
Last Page : 978
Authors : Clark RL, Pessolano AA, Shen TY, Jacobus DP, Jones H, Lotti VJ, Flataker LM.
Abstract : In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.
|
Antiarthritic activity in Lewis rat assessed as inhibition of adjuvant-induced paw swelling at 50 mg/kg, po qd for 13 days measured on day 14
|
Rattus norvegicus
|
78.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
Year : 1978
Volume : 21
Issue : 9
First Page : 965
Last Page : 978
Authors : Clark RL, Pessolano AA, Shen TY, Jacobus DP, Jones H, Lotti VJ, Flataker LM.
Abstract : In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.
|
Antiinflammatory activity in rat assessed as inhibition of carrageenan-induced paw edema at 150 mg/kg
|
Rattus norvegicus
|
59.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of cis-4,5,6,7,8,8a,9-hexahydro-alpha-methyl-5H-fluorene-2-acetic acid.
Year : 1977
Volume : 20
Issue : 5
First Page : 726
Last Page : 728
Authors : Sprague PW, Heikes JE.
|
Antiinflammatory activity in rabbit assessed as inhibition of edema at 200 ug per site by reversed passive arthus test
|
Oryctolagus cuniculus
|
44.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of cis-4,5,6,7,8,8a,9-hexahydro-alpha-methyl-5H-fluorene-2-acetic acid.
Year : 1977
Volume : 20
Issue : 5
First Page : 726
Last Page : 728
Authors : Sprague PW, Heikes JE.
|
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw swelling at 2 x 100 mg/kg, po administered 0.5 to 3 hrs prior to carrageenan challenge measured after 2.5 hrs by plethysmographic analysis relative to control
|
Rattus norvegicus
|
50.0
%
|
|
Journal : J. Med. Chem.
Title : Potential antiinflammatory compounds. 1. Antiinflammatory phenylpiperidine derivatives.
Year : 1979
Volume : 22
Issue : 12
First Page : 1460
Last Page : 1464
Authors : Hicks TA, Smith CE, Williamson WR, Day EH.
Abstract : The syntheses of a number of amines and their derivatives, based on the phenylpiperidine nucleus, are described. Their activities on the rat paw carrageenan test are also reported. Activities comparable to that of phenylbutazone were obtained for some of the amines, notably 4-piperidino-beta-methylphenethylamine.
|
Antiinflammatory activity in rat assessed as reduction of carrageenan-induced foot edema at 50 mg/kg, po administered as two doses
|
Rattus norvegicus
|
30.0
%
|
|
Journal : J. Med. Chem.
Title : Potential antiinflammatory compounds. 3. Compounds derived from acenaphthene and indan.
Year : 1979
Volume : 22
Issue : 12
First Page : 1464
Last Page : 1469
Authors : Smith CE, Williamson WR, Cashin CH, Kitchen EA.
Abstract : Compounds having acenaphthene and indan as their parent nuclei were synthesized for antiinflammatory testing. Compounds which showed activity were 1-phenyl-5-acenaphthenylacetic acid and its alpha-methyl derivative (carrageenan rat paw edema) and the same alpha-methylacenaphthenylacetic acid and 2-(4-chlorobenzylidene)-3-oxo-5-indanacetic acid and its alpha-methyl derivative (rat adjuvant arthritis). None of the compounds was more active than the control compounds phenylbutazone and indomethacin.
|
Antiinflammatory activity against rat adjuvant arthritis model assessed as reduction of swelling in non-injected foot at 33 mg/kg, po administered for 16 days
|
Rattus norvegicus
|
42.0
%
|
|
Journal : J. Med. Chem.
Title : Potential antiinflammatory compounds. 3. Compounds derived from acenaphthene and indan.
Year : 1979
Volume : 22
Issue : 12
First Page : 1464
Last Page : 1469
Authors : Smith CE, Williamson WR, Cashin CH, Kitchen EA.
Abstract : Compounds having acenaphthene and indan as their parent nuclei were synthesized for antiinflammatory testing. Compounds which showed activity were 1-phenyl-5-acenaphthenylacetic acid and its alpha-methyl derivative (carrageenan rat paw edema) and the same alpha-methylacenaphthenylacetic acid and 2-(4-chlorobenzylidene)-3-oxo-5-indanacetic acid and its alpha-methyl derivative (rat adjuvant arthritis). None of the compounds was more active than the control compounds phenylbutazone and indomethacin.
|
Antiinflammatory activity against rat adjuvant arthritis model assessed as reduction of swelling in non-injected foot at 50 mg/kg, po administered for 16 days
|
Rattus norvegicus
|
50.0
%
|
|
Journal : J. Med. Chem.
Title : Potential antiinflammatory compounds. 3. Compounds derived from acenaphthene and indan.
Year : 1979
Volume : 22
Issue : 12
First Page : 1464
Last Page : 1469
Authors : Smith CE, Williamson WR, Cashin CH, Kitchen EA.
Abstract : Compounds having acenaphthene and indan as their parent nuclei were synthesized for antiinflammatory testing. Compounds which showed activity were 1-phenyl-5-acenaphthenylacetic acid and its alpha-methyl derivative (carrageenan rat paw edema) and the same alpha-methylacenaphthenylacetic acid and 2-(4-chlorobenzylidene)-3-oxo-5-indanacetic acid and its alpha-methyl derivative (rat adjuvant arthritis). None of the compounds was more active than the control compounds phenylbutazone and indomethacin.
|
Antiinflammatory activity in rat assessed as inhibition of carrageenan-induced paw edema at 50 mg/kg, po administered as two doses 3 and 0.5 hr prior to challenge measured 2.5 hrs post challenge
|
Rattus norvegicus
|
39.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of some 2-aryl-6-benzoxazoleacetic acid derivatives.
Year : 1977
Volume : 20
Issue : 6
First Page : 797
Last Page : 801
Authors : Dunwell DW, Evans D.
Abstract : Various approaches to the synthesis of 2-aryl-6-substituted benzoxazoles are described. The products, which included the 6-methyl derivative 4a, ethylamines 10 and 19, ethanols 12 and 14, the acetic and alpha-methylacetic acids 9 and 16a--f, and the acetic ester 11, were screened for antiinflammatory activity on the carrageenan-induced rat paw edema test. Some of the compounds possessed activity superior to that of phenylbutazone and of the same order as that of benoxaprofen.
|
Antiinflammatory activity in adrenalectomized rat assessed as inhibition of carrageenan-induced paw edema at 100 mg/kg, po administered as two doses 3 and 0.5 hr prior to challenge measured 2.5 hrs post challenge
|
Rattus norvegicus
|
60.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory activity of some 2-aryl-6-benzoxazoleacetic acid derivatives.
Year : 1977
Volume : 20
Issue : 6
First Page : 797
Last Page : 801
Authors : Dunwell DW, Evans D.
Abstract : Various approaches to the synthesis of 2-aryl-6-substituted benzoxazoles are described. The products, which included the 6-methyl derivative 4a, ethylamines 10 and 19, ethanols 12 and 14, the acetic and alpha-methylacetic acids 9 and 16a--f, and the acetic ester 11, were screened for antiinflammatory activity on the carrageenan-induced rat paw edema test. Some of the compounds possessed activity superior to that of phenylbutazone and of the same order as that of benoxaprofen.
|
Antiinflammatory activity in fasted male rat assessed as decrease in carrageenan-induced pleural fluid at 10 mg/kg, po after 5 hrs by Evans blue carrageenan pleural effusion assay relative to control
|
Rattus norvegicus
|
10.5
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.
Year : 1979
Volume : 22
Issue : 9
First Page : 1074
Last Page : 1079
Authors : Welstead WJ, Moran HW, Stauffer HF, Turnbull LB, Sancilio LF.
Abstract : The synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid are described. This compound was postulated to be an active metabolite of 7-benzoylindoline in order to explain the unexpected antiinflammatory activity of the latter compound. Metabolism studies on 14C-labeled 7-benzoylindoline did not confirm this hypothesis. Nevertheless, 2-amino-3-benzoylphenylacetic acid, its ethyl ester, and the sodium salt show potent antiinflammatory activity in pharmacological models.
|
Antiinflammatory activity in fasted male rat assessed as decrease in carrageenan-induced pleural fluid at 50 mg/kg, po after 5 hrs by Evans blue carrageenan pleural effusion assay relative to control
|
Rattus norvegicus
|
24.2
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.
Year : 1979
Volume : 22
Issue : 9
First Page : 1074
Last Page : 1079
Authors : Welstead WJ, Moran HW, Stauffer HF, Turnbull LB, Sancilio LF.
Abstract : The synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid are described. This compound was postulated to be an active metabolite of 7-benzoylindoline in order to explain the unexpected antiinflammatory activity of the latter compound. Metabolism studies on 14C-labeled 7-benzoylindoline did not confirm this hypothesis. Nevertheless, 2-amino-3-benzoylphenylacetic acid, its ethyl ester, and the sodium salt show potent antiinflammatory activity in pharmacological models.
|
Antiinflammatory activity in fasted male rat assessed as decrease in carrageenan-induced pleural fluid at 2 mg/kg, po after 5 hrs by Evans blue carrageenan pleural effusion assay relative to control
|
Rattus norvegicus
|
0.0
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.
Year : 1979
Volume : 22
Issue : 9
First Page : 1074
Last Page : 1079
Authors : Welstead WJ, Moran HW, Stauffer HF, Turnbull LB, Sancilio LF.
Abstract : The synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid are described. This compound was postulated to be an active metabolite of 7-benzoylindoline in order to explain the unexpected antiinflammatory activity of the latter compound. Metabolism studies on 14C-labeled 7-benzoylindoline did not confirm this hypothesis. Nevertheless, 2-amino-3-benzoylphenylacetic acid, its ethyl ester, and the sodium salt show potent antiinflammatory activity in pharmacological models.
|
Antiinflammatory activity in fasted male rat assessed as decrease in carrageenan-induced pleural fluid at 20 mg/kg, po after 5 hrs by Evans blue carrageenan pleural effusion assay relative to control
|
Rattus norvegicus
|
19.4
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.
Year : 1979
Volume : 22
Issue : 9
First Page : 1074
Last Page : 1079
Authors : Welstead WJ, Moran HW, Stauffer HF, Turnbull LB, Sancilio LF.
Abstract : The synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid are described. This compound was postulated to be an active metabolite of 7-benzoylindoline in order to explain the unexpected antiinflammatory activity of the latter compound. Metabolism studies on 14C-labeled 7-benzoylindoline did not confirm this hypothesis. Nevertheless, 2-amino-3-benzoylphenylacetic acid, its ethyl ester, and the sodium salt show potent antiinflammatory activity in pharmacological models.
|
Antiinflammatory activity in fasted male rat assessed as decrease in carrageenan-induced pleural fluid at 100 mg/kg, po after 5 hrs by Evans blue carrageenan pleural effusion assay relative to control
|
Rattus norvegicus
|
31.0
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.
Year : 1979
Volume : 22
Issue : 9
First Page : 1074
Last Page : 1079
Authors : Welstead WJ, Moran HW, Stauffer HF, Turnbull LB, Sancilio LF.
Abstract : The synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid are described. This compound was postulated to be an active metabolite of 7-benzoylindoline in order to explain the unexpected antiinflammatory activity of the latter compound. Metabolism studies on 14C-labeled 7-benzoylindoline did not confirm this hypothesis. Nevertheless, 2-amino-3-benzoylphenylacetic acid, its ethyl ester, and the sodium salt show potent antiinflammatory activity in pharmacological models.
|
Antiinflammatory activity in Holtzman rat assessed as inhibition of carrageenan-induced paw edema at 50 mg/kg, po administered at 0.5 and 2.5 hrs prior to carrageenan-challenge relative to control
|
Rattus norvegicus
|
50.0
%
|
|
Journal : J. Med. Chem.
Title : Biologically oriented organic sulfur chemistry. 14. Antiinflammatory properties of some aryl sulfides, sulfoxides, and sulfones.
Year : 1976
Volume : 19
Issue : 6
First Page : 798
Last Page : 802
Authors : Brannigan LH, Hodge RB, Field L.
Abstract : To extend earlier work, to examine the possibility that certain sulfoxides might serve as counterparts of amines in receptor-site interactions, and to add to the little information available about sulfoxides in medicinal chemistry, sulfoxides were prepared of the general structure XArS(O)C6H4(CHR)nCO2H, together with the sulfides and some of the sulfones. The products were evaluated as antiinflammatory agents by carrageenan-edema inhibition and uv-erythema inhibition. Four of the compounds had activity roughly comparable to aspirin or phenylbutazone in one or the other of these assays (2a-c, 3b). Sulfoxides did not seem especially promising as a class and usually were less active than the corresponding sulfides. The two most interesting compounds in these assays, o-(phenylthio)phenylacetic acid (2b) and its sulfoxide 3b, had no significant activity in adjuvant arthritis. Hydrogen-bonding effects are indicated in certain of the acids by their absence in the corresponding esters.
|
Antiinflammatory activity in Wistar rat assessed as reduction in carrageenan-induced paw edema at 50 mg/kg, po treated 2 hrs before carrageenan challenge measured after 3 hrs
|
Rattus norvegicus
|
51.0
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory activity of some 2,3-dihydrobenzofuran-5-acetic acids and related compounds.
Year : 1976
Volume : 19
Issue : 2
First Page : 303
Last Page : 308
Authors : Hirose N, Kuriyama S, Kato Y, Toyoshima S.
Abstract : A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and alpha-(7-chloro-2,2-dimethyl-2,3-dihydrobenzofuran)-alpha-methyl-5-acetic acid (13a) showed the most potent activity in this series.
|
Antiinflammatory activity in Wistar rat assessed as reduction in carrageenan-induced paw edema at 10 mg/kg, po treated 2 hrs before carrageenan challenge measured after 3 hrs
|
Rattus norvegicus
|
24.0
%
|
|
Journal : J. Med. Chem.
Title : Antiinflammatory activity of some 2,3-dihydrobenzofuran-5-acetic acids and related compounds.
Year : 1976
Volume : 19
Issue : 2
First Page : 303
Last Page : 308
Authors : Hirose N, Kuriyama S, Kato Y, Toyoshima S.
Abstract : A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and alpha-(7-chloro-2,2-dimethyl-2,3-dihydrobenzofuran)-alpha-methyl-5-acetic acid (13a) showed the most potent activity in this series.
|
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced hind paw edema at 100 mg/kg, po administered as gum arabic suspension 30 mins prior to carrageenin injection measured 3 hrs post-carrageenin injection
|
Rattus norvegicus
|
54.5
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiinflammatory and hypnotic activity of 5-alkoxy-3-(N-substituted carbamoyl)-1-phenylpyrazoles.
Year : 1977
Volume : 20
Issue : 1
First Page : 80
Last Page : 85
Authors : Sugiura S, Ohno S, Ohtani O, Izumi K, Kitamikado T, Asai H, Kato K.
Abstract : 5-Alkoxy-3-(N-substituted carbamoly)-1-phenylpyrazoles were prepared and tested for antiinflammatory and hypnotic activity. Four compounds showed antiinflammatory activity and three possessed hypnotic properties.
|
Antiinflammatory activity in Wistar albino rat assessed as inhibition of adjuvant-induced arthritis at 30 mg/kg, po administered for 14 days prior to adjuvant challenge relative to control
|
Rattus norvegicus
|
71.0
%
|
|
Journal : J. Med. Chem.
Title : 6,11-Dihydro-11-oxodibenz [b,e] oxepinacetic acids with potent antiinflammatory activity.
Year : 1976
Volume : 19
Issue : 7
First Page : 941
Last Page : 946
Authors : Ueno K, Kubo S, Tagawa H, Yoshioka T, Tsukada W.
Abstract : A series of 6,11-dihydro-11-oxodibenz[b,e]oxepinacetic acids was synthesized and the antiinflammatory activity determined. Studies on 29 compounds revealed certain structure-activity relationships. In the carrageenan edema test, eight compounds exhibited higher antiinflammatory activities than did indomethacin. Several compounds (2, 9, 14, 22, 25) also proved to have activities superior or comparable to indomethacin in suppressing chronic as well as acute inflammation and carrageenan-induced hyperesthesia. Gastric irritation and lethality rates were less frequently observed with these compounds.
|
Antiinflammatory activity in Wistar albino rat assessed as inhibition of adjuvant-induced arthritis at 30 mg/kg, po administered for 14 days followed by adjuvant challenge relative to control
|
Rattus norvegicus
|
58.0
%
|
|
Journal : J. Med. Chem.
Title : 6,11-Dihydro-11-oxodibenz [b,e] oxepinacetic acids with potent antiinflammatory activity.
Year : 1976
Volume : 19
Issue : 7
First Page : 941
Last Page : 946
Authors : Ueno K, Kubo S, Tagawa H, Yoshioka T, Tsukada W.
Abstract : A series of 6,11-dihydro-11-oxodibenz[b,e]oxepinacetic acids was synthesized and the antiinflammatory activity determined. Studies on 29 compounds revealed certain structure-activity relationships. In the carrageenan edema test, eight compounds exhibited higher antiinflammatory activities than did indomethacin. Several compounds (2, 9, 14, 22, 25) also proved to have activities superior or comparable to indomethacin in suppressing chronic as well as acute inflammation and carrageenan-induced hyperesthesia. Gastric irritation and lethality rates were less frequently observed with these compounds.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
-0.21
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Inhibition of NAPRT (unknown origin)
|
Homo sapiens
|
0.1
nM
|
|
Title : Sensitization of cancer cells to nampt inhibitors by nicotinic acid phosphoribosyltransferase neutralization
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-6.635
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.07
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.07
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
