|
Inhibition of mast cell degranulation was assessed in female albino rats at a dose of 2 umol/kg iv
|
Rattus norvegicus
|
22.0
%
|
|
Journal : J. Med. Chem.
Title : 1-(2-pyridinyl)piperazine derivatives with antianaphylactic, antibronchospastic, and mast cell stabilizing activities.
Year : 1987
Volume : 30
Issue : 1
First Page : 13
Last Page : 19
Authors : Catto A, Motta G, Tajana A, Cazzulani P, Nardi D, Leonardi A.
Abstract : New 1-(2-pyridinyl)piperazine derivatives were synthesized and tested as inhibitors of the reaginic passive cutaneous anaphylaxis in the rat (PCA), of the histamine-induced bronchospasm in the guinea pig, and of the rat mesenteric mast cell degranulation induced by compound 48/80. On the basis of test results, a series of N-(substituted phenyl)-omega-[4-(2-pyridinyl)-1-piperazinyl]alkanamides was prepared. The nature of substituents at the anilide ring strongly influenced mast cell stabilizing activity, whereas it was less determining in the case of the other two tests. No clear correlation between the most common physicochemical parameters (pi, sigma, Vw volume) of substituents and activity could be detected. With regard to the position of substituents at the anilide ring, the rank order of potency, in the PCA and bronchoconstriction tests, was para greater than meta greater than ortho. Introduction of substituents in the 1-(2-pyridinyl)piperazinyl moiety of the N-(substituted phenyl)propanamide derivatives hardly affected activity, or the effect was deleterious. Some of the new compounds exhibited a simultaneous remarkable activity in all the three assays employed.
|
Inhibition of guinea pig ALA at a dose of 1 mg/kg 1 hr after postdosing intraperitoneally
|
Cavia porcellus
|
82.0
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of guinea pig ALA at a dose of 1 mg/kg 1 hr after postdosing orally
|
Cavia porcellus
|
68.0
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of guinea pig ALA at a dose of 1 mg/kg 24 hr after postdosing intraperitoneally
|
Cavia porcellus
|
6.5
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of guinea pig ALA at a dose of 1 mg/kg 24 hr after postdosing orally
|
Cavia porcellus
|
37.0
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of guinea pig ALA at a dose of 1 mg/kg 7 hr after postdosing intraperitoneally
|
Cavia porcellus
|
68.0
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of guinea pig ALA at a dose of 1 mg/kg 8 hr after postdosing orally
|
Cavia porcellus
|
73.0
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of slow reacting substance of anaphylaxis (SRS-A) release from sensitized guinea pig chopped lung upon antigen challenge at 10 ug/mL
|
Cavia porcellus
|
38.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic benzophenones and related compounds.
Year : 1987
Volume : 30
Issue : 8
First Page : 1321
Last Page : 1327
Authors : Evans D, Cracknell ME, Saunders JC, Smith CE, Williamson WR, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Anti-histaminic activity was measured in guinea pig trachea
|
Cavia porcellus
|
1.6
nM
|
|
Journal : J. Med. Chem.
Title : Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure-activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acryl amides.
Year : 1989
Volume : 32
Issue : 3
First Page : 583
Last Page : 593
Authors : Nishikawa Y, Shindo T, Ishii K, Nakamura H, Kon T, Uno H.
Abstract : A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (3-pyridyl)acrylamide] against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase. Particularly, (E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (6-methyl-3-pyridyl)acrylamide (17p) showed an ED50 value of 3.3 mg/kg po in the rat PCA test, which was one-fifth of ketotifen and oxatomide. As compared with ketotifen and oxatomide, compound 17p (AL-3264) possessed a better balance of antiallergic properties due to inhibition of chemical mediator release, inhibition of 5-lipoxygenase, and antagonism of histamine.
|
Compound was tested for the inhibition of guinea pig active lung anaphylaxis (ALA) at 0.001 mg/kg iv
|
Cavia porcellus
|
57.0
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of histamine release from sensitized guinea pig chopped lung upon antigen challenge at 10 ug/mL.
|
Cavia porcellus
|
37.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic benzophenones and related compounds.
Year : 1987
Volume : 30
Issue : 8
First Page : 1321
Last Page : 1327
Authors : Evans D, Cracknell ME, Saunders JC, Smith CE, Williamson WR, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Histamine induced in lethality in guinea pigs at 8 hr after oral dose of 0.02 mg/kg
|
Cavia porcellus
|
10.0
%
|
|
Journal : J. Med. Chem.
Title : Amphoteric drugs. 3. Synthesis and antiallergic activity of 3-[(5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11- ylidene)piperidino]propionic acid derivatives and related compounds.
Year : 1995
Volume : 38
Issue : 3
First Page : 496
Last Page : 507
Authors : Iwasaki N, Ohashi T, Musoh K, Nishino H, Kado N, Yasuda S, Kato H, Ito Y.
Abstract : An important approach to the design of antiallergic agents with reduced penetration into the central nervous system (CNS) is described. A series of 3-[(5,11- dihydro[1]benzoxepino[4,3-b]-pyridin-11-ylidene)piperidino]propion ic acid derivatives (31-47) and related compounds (48-54) were synthesized and evaluated for antiallergic activity and penetration of a compound into the CNS in comparison with the corresponding 6H-dibenz[b,e]oxepin derivative (3). Combination of zwitterionization and introduction of a pyridine component resulted in an increase in antiallergic activity and a great reduction of penetration into the CNS, which was evaluated by the selectivity (B/A) of antihistaminic activities in the central system [ID50 value (B) for ex vivo H1 binding to mouse brain membranes] and in the peripheral system [ED50 value (A) for inhibitory effect on histamine-induced increase in vascular permeability in mice]. This surprising reduction of penetration into the CNS could be considered on the basis of an increase in hydrophilicity caused by both of the zwitterionization and the introduction of a pyridine component. 3-[4-(8-Fluoro-5,11-dihydro[1]benzoxepino[4,3- b]pyridin-11-ylidene)piperidino]propionic acid (33) exhibited a strong antiallergic effect in various experimental models and very low penetration into the CNS. Compound 33 (HSR-609) is now under clinical trial as a promising antiallergic agent with greatly reduced penetration into the CNS.
|
Ability to inhibit histamine-induced contractions of isolated guinea pig ileum
|
Cavia porcellus
|
6.4
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis, structure-activity relationships, and pharmacological evaluation of pyrrolo[3,2,1-ij]quinoline derivatives: potent histamine and platelet activating factor antagonism and 5-lipoxygenase inhibitory properties. Potential therapeutic application in asthma.
Year : 1995
Volume : 38
Issue : 4
First Page : 669
Last Page : 685
Authors : Paris D, Cottin M, Demonchaux P, Augert G, Dupassieux P, Lenoir P, Peck MJ, Jasserand D.
Abstract : A series of pyrrolo[3,2,1-ij]quinoline derivatives was synthesized and evaluated for their in vitro and in vivo activities against histamine, platelet activating factor (PAF), and leukotrienes which are recognized to be of importance in asthma. The structure-activity relationship studies have shown that the optimum moiety on the 1-position of the pyrroloquinoline nucleus is a 2-[4-(4-methyl-2-pyridinyl)-1-piperazinyl]ethyl chain in conjunction with a methyl group on the 2-position for potent antagonism of both histamine and PAF. The introduction of substituents on the 8- and 4-positions was also investigated in order to increase the potency of 5-lipoxygenase inhibition while retaining or improving the activities against histamine and PAF. This series is exemplified by 4-n-butyl-5,6-dihydro-8-hydroxy-2-methyl-1- [2-[4-(4-methyl-2-pyridinyl)-1-piperazinyl]ethyl]-4H-pyrrolo[3,2,1- ij]quinoline (24, KC 11404) which was found to be active against all three of the selected mediators. Compound 24 was found to be orally active in guinea pig models against the histaminic phase of antigen-induced bronchospasm and PAF-induced bronchoconstriction (ED50 = 1.9 and 2.1 mumol/kg, respectively). When tested against the leukotriene-dependent phase of the antigen-induced bronchoconstriction, compound 24 showed the same potency as zileuton.
|
H1-antihistamine activity in guinea pig ileum
|
Cavia porcellus
|
0.3162
nM
|
|
Journal : J. Med. Chem.
Title : Studies on 1,2,3-triazoles. 13. (Piperazinylalkoxy) [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties.
Year : 1986
Volume : 29
Issue : 11
First Page : 2262
Last Page : 2267
Authors : Buckle DR, Rockell CJ, Smith H, Spicer BA.
Abstract : Several N-benzylpiperazino derivatives of [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-one and its 5-methyl homologue have been prepared and evaluated for H1-antihistamine activity on guinea pig ileum. The most potent compounds were also evaluated for their ability to stabilize mast cells in the rat passive peritoneal anaphylaxis (PPA) system and were shown to inhibit histamine release at concentrations below those required to inhibit extravasation, suggesting that this might be relevant to their antianaphylactic activity in this system. The compound tested with the most potent H1-antihistamine activity was 6-[3-[4-(4-chlorobenzyl)-1-piperazinyl]propoxy][1]benzopyrano[2,3- d]-1,2,3-triazol-9(1H)-one, 28, which had a pA2 of 9.1 against histamine on guinea pig ileum, comparable to that of mepyramine, and inhibited histamine release in the rat PPA system with an IC50 value of 5.4 X 10(-6) M.
|
The compound was tested in vitro for binding affinity against histamine H1 receptor from guinea pig cerebellum, using [3H]pyrilamine as radioligand at 0.1 uM
|
Cavia porcellus
|
0.31
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiallergic activity of 11-(aminoalkylidene)-6,11-dihydrodibenz[b,e]oxepin derivatives.
Year : 1992
Volume : 35
Issue : 11
First Page : 2074
Last Page : 2084
Authors : Ohshima E, Otaki S, Sato H, Kumazawa T, Obase H, Ishii A, Ishii H, Ohmori K, Hirayama N.
Abstract : A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin-2-carboxylic acid derivatives was synthesized and demonstrated to be orally active antiallergic agents. These compounds are structurally related to 1 (KW-4994), which we had reported previously to be a new antiallergic agent. Most compounds synthesized exhibited potent inhibitory effects on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea pigs. Additionally, compounds possessing a terminal carboxyl group at the 2-position of the dibenz[b,e]oxepin ring system exhibited inhibitory effects on specific [3H]pyrilamine binding to guinea pig cerebellum histamine H1 receptors, whereas these demonstrated negligible effects on specific [3H]QNB binding to rat striatum muscarinic acetylcholine M1 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and (3) a dibenzoxepin ring system. Among the compounds synthesized, (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid hydrochloride (16) was selected for further evaluation. It had an ED50 value of 0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in inhibiting anaphylactic bronchoconstriction in guinea pigs. Furthermore, it had a Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited negligible CNS side effects up to a dose of 600 mg/kg po. Compound 16 is now under clinical evaluation as KW-4679.
|
H1-antihistamine activity on guinea pig ileum
|
Cavia porcellus
|
0.3162
nM
|
|
Journal : J. Med. Chem.
Title : N-benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties.
Year : 1984
Volume : 27
Issue : 11
First Page : 1452
Last Page : 1457
Authors : Buckle DR, Outred DJ, Smith H, Spicer BA.
Abstract : In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.
|
Binding affinity for Muscarinic acetylcholine receptor M1 from rat striatum, using [3H]quinuclidinyl benzilate as radioligand at 10 uM.
|
None
|
55.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and antiallergic activity of 11-(aminoalkylidene)-6,11-dihydrodibenz[b,e]oxepin derivatives.
Year : 1992
Volume : 35
Issue : 11
First Page : 2074
Last Page : 2084
Authors : Ohshima E, Otaki S, Sato H, Kumazawa T, Obase H, Ishii A, Ishii H, Ohmori K, Hirayama N.
Abstract : A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin-2-carboxylic acid derivatives was synthesized and demonstrated to be orally active antiallergic agents. These compounds are structurally related to 1 (KW-4994), which we had reported previously to be a new antiallergic agent. Most compounds synthesized exhibited potent inhibitory effects on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea pigs. Additionally, compounds possessing a terminal carboxyl group at the 2-position of the dibenz[b,e]oxepin ring system exhibited inhibitory effects on specific [3H]pyrilamine binding to guinea pig cerebellum histamine H1 receptors, whereas these demonstrated negligible effects on specific [3H]QNB binding to rat striatum muscarinic acetylcholine M1 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and (3) a dibenzoxepin ring system. Among the compounds synthesized, (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid hydrochloride (16) was selected for further evaluation. It had an ED50 value of 0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in inhibiting anaphylactic bronchoconstriction in guinea pigs. Furthermore, it had a Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited negligible CNS side effects up to a dose of 600 mg/kg po. Compound 16 is now under clinical evaluation as KW-4679.
|
Compound was tested for percent inhibition, at 0.37 mg/kg administered intraperitoneally against histamine
|
Rattus norvegicus
|
64.6
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Compound was tested for percent inhibition, at 0.37 mg/kg administered intraperitoneally against serotonin by Dunnett's test
|
Rattus norvegicus
|
14.8
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Compound was tested for percent inhibition, at 3.3 mg/kg administered intraperitoneally against histamine by Dunnett's test
|
Rattus norvegicus
|
62.5
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Compound was tested for percent inhibition, at 3.3 mg/kg administered intraperitoneally against rat passive cutaneous anaphylaxis by Dunnett's test
|
Rattus norvegicus
|
92.4
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Compound was tested for percent inhibition, at 3.3 mg/kg administered intraperitoneally against serotonin by Dunnett's test
|
Rattus norvegicus
|
35.3
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Compound was tested for the inhibition of rat passive cutaneous anaphylaxis (PCA) at 0.37 mg/kg dose ip (1h pretreatment)
|
Rattus norvegicus
|
63.3
%
|
|
Journal : J. Med. Chem.
Title : Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.
Year : 1986
Volume : 29
Issue : 6
First Page : 1118
Last Page : 1121
Authors : Ho CY, Hageman WE, Persico FJ.
Abstract : A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.
|
Inhibition of Histamine mediator release form passively sensitized human lung upon antigen challenge at 10 ug/mL dose
|
Homo sapiens
|
23.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic benzophenones and related compounds.
Year : 1987
Volume : 30
Issue : 8
First Page : 1321
Last Page : 1327
Authors : Evans D, Cracknell ME, Saunders JC, Smith CE, Williamson WR, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Inhibition of Histamine mediator release form passively sensitized human lung upon antigen challenge at 1 ug/mL dose
|
Homo sapiens
|
0.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic benzophenones and related compounds.
Year : 1987
Volume : 30
Issue : 8
First Page : 1321
Last Page : 1327
Authors : Evans D, Cracknell ME, Saunders JC, Smith CE, Williamson WR, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Inhibition of Slow reacting substance of anaphylaxis (SRS-A) mediator release form passively sensitized human lung upon antigen challenge at 10 ug/mL dose
|
Homo sapiens
|
100.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic benzophenones and related compounds.
Year : 1987
Volume : 30
Issue : 8
First Page : 1321
Last Page : 1327
Authors : Evans D, Cracknell ME, Saunders JC, Smith CE, Williamson WR, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Inhibition of Slow reacting substance of anaphylaxis (SRS-A) mediator release form passively sensitized human lung upon antigen challenge at 1 ug/mL dose
|
Homo sapiens
|
51.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic benzophenones and related compounds.
Year : 1987
Volume : 30
Issue : 8
First Page : 1321
Last Page : 1327
Authors : Evans D, Cracknell ME, Saunders JC, Smith CE, Williamson WR, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Antagonist activity against human histamine H1 receptor expressed in CHO cells by FLIPR assay
|
Homo sapiens
|
0.1585
nM
|
|
Journal : J. Med. Chem.
Title : Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.
Year : 2010
Volume : 53
Issue : 21
First Page : 7778
Last Page : 7795
Authors : Gianotti M, Botta M, Brough S, Carletti R, Castiglioni E, Corti C, Dal-Cin M, Delle Fratte S, Korajac D, Lovric M, Merlo G, Mesic M, Pavone F, Piccoli L, Rast S, Roscic M, Sava A, Smehil M, Stasi L, Togninelli A, Wigglesworth MJ.
Abstract : Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.
|
Antagonist activity at human 5HT2A receptor expressed in HEK cells assessed as inhibition of intracellular calcium accumulation by aequorin assay
|
Homo sapiens
|
15.85
nM
|
|
Journal : J. Med. Chem.
Title : Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.
Year : 2010
Volume : 53
Issue : 21
First Page : 7778
Last Page : 7795
Authors : Gianotti M, Botta M, Brough S, Carletti R, Castiglioni E, Corti C, Dal-Cin M, Delle Fratte S, Korajac D, Lovric M, Merlo G, Mesic M, Pavone F, Piccoli L, Rast S, Roscic M, Sava A, Smehil M, Stasi L, Togninelli A, Wigglesworth MJ.
Abstract : Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.
|
Antagonist activity at human 5HT2B receptor expressed in human SH-SY5Y cells by FLIPR assay
|
Homo sapiens
|
31.62
nM
|
|
Journal : J. Med. Chem.
Title : Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.
Year : 2010
Volume : 53
Issue : 21
First Page : 7778
Last Page : 7795
Authors : Gianotti M, Botta M, Brough S, Carletti R, Castiglioni E, Corti C, Dal-Cin M, Delle Fratte S, Korajac D, Lovric M, Merlo G, Mesic M, Pavone F, Piccoli L, Rast S, Roscic M, Sava A, Smehil M, Stasi L, Togninelli A, Wigglesworth MJ.
Abstract : Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.
|
Antagonist activity at human 5HT2C receptor expressed in human SH-SY5Y cells by FLIPR assay
|
Homo sapiens
|
199.53
nM
|
|
Journal : J. Med. Chem.
Title : Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.
Year : 2010
Volume : 53
Issue : 21
First Page : 7778
Last Page : 7795
Authors : Gianotti M, Botta M, Brough S, Carletti R, Castiglioni E, Corti C, Dal-Cin M, Delle Fratte S, Korajac D, Lovric M, Merlo G, Mesic M, Pavone F, Piccoli L, Rast S, Roscic M, Sava A, Smehil M, Stasi L, Togninelli A, Wigglesworth MJ.
Abstract : Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.
|
Displacement of [3H]pyrilamine from human histamine H1 receptor expressed in CHO-K1 cells after 60 mins by scintillation counting
|
Homo sapiens
|
1.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines.
Year : 2011
Volume : 19
Issue : 9
First Page : 3005
Last Page : 3021
Authors : Kubota K, Kurebayashi H, Miyachi H, Tobe M, Onishi M, Isobe Y.
Abstract : A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.
|
Antiinflammatory activity in ovalbumin-sensitized BALB/c mouse biphasic allergic model assessed as immediate type reaction at 10 mg/kg, po administered 1 hr before ovalbumin challenge measured 1 hr after elicitation by ear swelling assay
|
Mus musculus
|
119.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines.
Year : 2011
Volume : 19
Issue : 9
First Page : 3005
Last Page : 3021
Authors : Kubota K, Kurebayashi H, Miyachi H, Tobe M, Onishi M, Isobe Y.
Abstract : A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.
|
Antiinflammatory activity in ovalbumin-sensitized BALB/c mouse biphasic allergic model assessed as late type reaction at 10 mg/kg, po administered 1 hr before ovalbumin challenge measured 24 hrs after elicitation by ear swelling assay
|
Mus musculus
|
3.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines.
Year : 2011
Volume : 19
Issue : 9
First Page : 3005
Last Page : 3021
Authors : Kubota K, Kurebayashi H, Miyachi H, Tobe M, Onishi M, Isobe Y.
Abstract : A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
268.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
838.0
nM
|
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
298.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
468.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
141.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
374.0
nM
|
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
269.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
31.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
8.977
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
820.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
710.0
nM
|
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
324.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
46.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
29.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
160.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
84.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
530.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
872.0
nM
|
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
436.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
667.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
1.188
nM
|
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
0.138
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
Antianaphylactic activity in human chopped lung treated with atopic serum isolated from patients allergic to cocksfoot pollen assessed as inhibition of antigen-induced histamine release at 10 ug/mL after 15 mins relative to control
|
Homo sapiens
|
23.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic agents. 1. 2-(Acylamino)oxazoles.
Year : 1979
Volume : 22
Issue : 4
First Page : 412
Last Page : 417
Authors : Ross WJ, Harrison RG, Jolley MR, Neville MC, Todd A, Verge JP, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 35 2-(acylamino)oxazoles are described. The majority of the compounds inhibit the release of slow-reacting substance of anaphylaxis (SRS-A) in vitro from sensitized guinea pig chopped lung. In addition, several of the compounds inhibited the release of SRS-A from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
Antianaphylactic activity in human chopped lung treated with atopic serum isolated from patients allergic to cocksfoot pollen assessed as inhibition of antigen-induced slow-reacting substance of anaphylaxis release at 10 ug/mL after 15 mins relative to control
|
Homo sapiens
|
100.0
%
|
|
Journal : J. Med. Chem.
Title : Antianaphylactic agents. 1. 2-(Acylamino)oxazoles.
Year : 1979
Volume : 22
Issue : 4
First Page : 412
Last Page : 417
Authors : Ross WJ, Harrison RG, Jolley MR, Neville MC, Todd A, Verge JP, Dawson W, Sweatman WJ.
Abstract : The synthesis and biological properties of 35 2-(acylamino)oxazoles are described. The majority of the compounds inhibit the release of slow-reacting substance of anaphylaxis (SRS-A) in vitro from sensitized guinea pig chopped lung. In addition, several of the compounds inhibited the release of SRS-A from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.
|
DNDI: Malaria in Vitro, 72 hour
|
Plasmodium falciparum
|
750.0
nM
|
|
Title : Antiprotozoal Activity Profiling of Approved Drugs: A Starting Point toward Drug Repositioning
Authors : Kaiser M, Mäser P, Tadoori LP, Ioset JR, Brun R.
Abstract : In this study, a set of 100 registered drugs with drug repositioning potential for neglected tropical diseases was assembled. The compound collection was systematically screened against protozoan parasites, namely T. b. rhodesiense, L. donovani, T. cruzi and P. falciparum. Several drugs and drug classes exhibited in vitro activity and selectivity against one of the protozoan parasites. The results offer opportunities for drug repurposing and the identified compound classes could also be a starting point for new drug discovery projects. See also publication: Antiprotozoal Activity Profiling of Approved Drugs: A Starting Point toward Drug Repositioning. PLoS One. 2015 10(8): e0135556.
