|
Binding affinity at serotonin 5-hydroxytryptamine 2 receptor by [3H]ketanserin displacement.
|
None
|
3.1
nM
|
|
Journal : J. Med. Chem.
Title : Development of a receptor-interaction model for serotonin 5-HT2 receptor antagonists. Predicting selectivity with respect to dopamine D2 receptors.
Year : 1994
Volume : 37
Issue : 7
First Page : 950
Last Page : 962
Authors : Andersen K, Liljefors T, Gundertofte K, Perregaard J, Bøgesø KP.
Abstract : A receptor-interaction model for serotonin 5-HT2 receptor antagonists has been developed by conformational analysis with molecular mechanics (MM2(91)) and superimposition studies of serotonin 5-HT2 receptor antagonists. Substituted 3-(4-piperidinyl)-,1-(4- piperidinyl)-,3-(1,2,3,6-tetrahydropyridin-4-yl)-, and 1-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles, substituted 3-(4-fluorophenyl)-1-(4-piperazinyl)indans, cyprohepatadine derivatives, ritanserin, and danitracene have been used as bases for the model. Other serotonin 5-HT2 receptor antagonists, such as ketanserin and MDL 11,939, are well accommodated into the model. Comparison of the model with a recently described receptor-interaction model for dopamine D2 receptor antagonists suggests a common pharmacophore for dopamine D2 and serotonin 5-HT2 receptor antagonists. Important steric differences between 5-HT2 receptor antagonists with additional high affinity for dopamine D2 receptors and serotonin 5-HT2 receptor antagonists with high selectivity versus D2 receptors are described. The geometry of the receptor-interaction model described is significantly different from that of a recently reported receptor-interaction model for 5-HT2 receptor agonists and antagonists developed by use of (+)-LSD as a template, suggesting the existence of two binding modes at the 5-HT2 receptor.
|
Binding affinity towards 5-hydroxytryptamine 2A receptor using [3H]ketanserin
|
None
|
3.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA).
Year : 2004
Volume : 14
Issue : 9
First Page : 2279
Last Page : 2283
Authors : Peddi S, Roth BL, Glennon RA, Westkaemper RB.
Abstract : The synthesis and 5-HT(2A) receptor affinities of ring altered derivatives of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (4), a structurally unique tetracyclic 5-HT(2A) receptor antagonist, are described. The characteristics of the parent compound prove to be necessary for optimal 5-HT(2A) receptor affinity. However, expansion of the size of the pyrrolidine and central rings produce compounds with reasonably high 5-HT(2A) receptor affinities. In addition, the parent compound is shown to have high 5-HT(2) receptor selectivity.
|
Displacement of [3H]ketanserin from 5-hydroxytryptamine 2A receptor expressed NIH3T3 cells
|
None
|
1.6
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
Year : 2001
Volume : 11
Issue : 5
First Page : 655
Last Page : 658
Authors : Runyon SP, Savage JE, Taroua M, Roth BL, Glennon RA, Westkaemper RB.
Abstract : Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K = 20nM; 5-HT2C, Ki=43nM) versus the dopamine D2 receptor (Ki>10,000nM), as well as the serotonin and norepinephrine transporters (Ki>10,000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.
|
Binding affinity against 5-hydroxytryptamine 2A receptor from rat forebrain using [3H]ketanserin as radioligand
|
None
|
1.6
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Exploring the relationship between binding modes of 9-(aminomethyl)-9,10-dihydroanthracene and cyproheptadine analogues at the 5-HT2A serotonin receptor.
Year : 2001
Volume : 11
Issue : 4
First Page : 563
Last Page : 566
Authors : Westkaemper RB, Runyon SP, Savage JE, Roth BL, Glennon RA.
Abstract : Comparison of the serotonin 5-HT2A receptor affinities of a parallel series of structural analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine cyproheptadine suggests that the two agents bind to the receptor in different fashions. Examination of ligand-receptor model complexes supports the experimental data and suggests a potential origin for the differences in binding modes.
|
Displacement of [3H]ketanserin from 5-hydroxytryptamine 2A receptor of rat brain cortex
|
Rattus norvegicus
|
5.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : 4-(3-furyl)-2-(4-methylpiperazino)pyrimidines: Potent 5-HT2A receptor antagonists
Year : 1997
Volume : 7
Issue : 13
First Page : 1635
Last Page : 1638
Authors : Mokrosz MJ, Duszynska B, Klodzinska A, Deren-Wesolek A, Chojnacka-Wojcik E, Baranowski TC, Abdou IM, Redmore NP, Strekowski L
|
Binding affinity to 5-hydroxytryptamine 2C receptor using [3H]Mesulergine as radioligand in stably transfected NIH3T3 cells
|
None
|
11.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
Year : 2001
Volume : 11
Issue : 5
First Page : 655
Last Page : 658
Authors : Runyon SP, Savage JE, Taroua M, Roth BL, Glennon RA, Westkaemper RB.
Abstract : Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K = 20nM; 5-HT2C, Ki=43nM) versus the dopamine D2 receptor (Ki>10,000nM), as well as the serotonin and norepinephrine transporters (Ki>10,000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.
|
Binding affinity towards 5-hydroxytryptamine 2C receptor using [3H]mesulergine as radioligand
|
None
|
11.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA).
Year : 2004
Volume : 14
Issue : 9
First Page : 2279
Last Page : 2283
Authors : Peddi S, Roth BL, Glennon RA, Westkaemper RB.
Abstract : The synthesis and 5-HT(2A) receptor affinities of ring altered derivatives of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (4), a structurally unique tetracyclic 5-HT(2A) receptor antagonist, are described. The characteristics of the parent compound prove to be necessary for optimal 5-HT(2A) receptor affinity. However, expansion of the size of the pyrrolidine and central rings produce compounds with reasonably high 5-HT(2A) receptor affinities. In addition, the parent compound is shown to have high 5-HT(2) receptor selectivity.
|
Affinity against 5-hydroxytryptamine receptor was determined in rat stomach fundus strip
|
Rattus norvegicus
|
7.943
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : A novel bromopyrrole alkaloid from the sponge Agelas longissima with antiserotonergic activity
Year : 1995
Volume : 5
Issue : 8
First Page : 799
Last Page : 804
Authors : Cafieri F, Fattorusso E, Mangoni A, Taglialatela-Scafati O, Carnuccio R
|
Binding affinity towards 5-hydroxytryptamine 7 receptor
|
None
|
50.12
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : First pharmacophoric hypothesis for 5-HT7 antagonism.
Year : 2000
Volume : 10
Issue : 10
First Page : 1097
Last Page : 1100
Authors : López-Rodríguez ML, Porras E, Benhamú B, Ramos JA, Morcillo MJ, Lavandera JL.
Abstract : In order to make the first contribution to the elucidation of essential structural features for 5-HT7 antagonism, a set of thirty 5-HT7 antagonists were selected from the literature. A pharmacophore model was built using Molecular Modeling studies with Catalyst program. The information contained in this model was validated with new synthesized compounds.
|
Non-selective inhibitory activity was determined against 5-hydroxytryptamine 7 receptor
|
None
|
50.12
nM
|
|
Journal : J. Med. Chem.
Title : Optimization of the pharmacophore model for 5-HT7R antagonism. Design and synthesis of new naphtholactam and naphthosultam derivatives.
Year : 2003
Volume : 46
Issue : 26
First Page : 5638
Last Page : 5650
Authors : López-Rodríguez ML, Porras E, Morcillo MJ, Benhamú B, Soto LJ, Lavandera JL, Ramos JA, Olivella M, Campillo M, Pardo L.
Abstract : We present in this study an optimization of a preliminary pharmacophore model for 5-HT(7)R antagonism, with the incorporation of recently reported ligands and using an efficient procedure with the CATALYST program. The model consists of five features: a positive ionizable atom (PI), a H-bonding acceptor group (HBA), and three hydrophobic regions (HYD). This model has been supported by the design, synthesis, and biological evaluation of new naphtholactam and naphthosultam derivatives of general structure I (39-72). A systematic structure-affinity relationship (SAFIR) study on these analogues has allowed us to confirm that the model incorporates the essential structural features for 5-HT(7)R antagonism. In addition, computational simulation of the complex between compound 56 and a rhodopsin-based 3D model of the 5-HT(7)R transmembrane domain has permitted us to define the molecular details of the ligand-receptor interaction and gives additional support to the proposed pharmacophore model for 5-HT(7)R antagonism: (i) the HBA feature of the pharmacophore model binds Ser(5.42) and Thr(5.43), (ii) the HYD1 feature interacts with Phe(6.52), (iii) the PI feature forms an ionic interaction with Asp(3.32), and (iv) the HYD3 (AR) feature interacts with a set of aromatic residues (Phe(3.28), Tyr(7.43)). These results provide the tools for the design and synthesis of new ligands with predetermined affinities and pharmacological properties.
|
Binding affinity to Dopamine receptor D2 using [3H]spiperone as radioligand in stably transfected NIH3T3 cells
|
None
|
112.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
Year : 2001
Volume : 11
Issue : 5
First Page : 655
Last Page : 658
Authors : Runyon SP, Savage JE, Taroua M, Roth BL, Glennon RA, Westkaemper RB.
Abstract : Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K = 20nM; 5-HT2C, Ki=43nM) versus the dopamine D2 receptor (Ki>10,000nM), as well as the serotonin and norepinephrine transporters (Ki>10,000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.
|
Binding affinity at dopamine D2 receptor by [3H]spiperone displacement.
|
None
|
140.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of a receptor-interaction model for serotonin 5-HT2 receptor antagonists. Predicting selectivity with respect to dopamine D2 receptors.
Year : 1994
Volume : 37
Issue : 7
First Page : 950
Last Page : 962
Authors : Andersen K, Liljefors T, Gundertofte K, Perregaard J, Bøgesø KP.
Abstract : A receptor-interaction model for serotonin 5-HT2 receptor antagonists has been developed by conformational analysis with molecular mechanics (MM2(91)) and superimposition studies of serotonin 5-HT2 receptor antagonists. Substituted 3-(4-piperidinyl)-,1-(4- piperidinyl)-,3-(1,2,3,6-tetrahydropyridin-4-yl)-, and 1-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles, substituted 3-(4-fluorophenyl)-1-(4-piperazinyl)indans, cyprohepatadine derivatives, ritanserin, and danitracene have been used as bases for the model. Other serotonin 5-HT2 receptor antagonists, such as ketanserin and MDL 11,939, are well accommodated into the model. Comparison of the model with a recently described receptor-interaction model for dopamine D2 receptor antagonists suggests a common pharmacophore for dopamine D2 and serotonin 5-HT2 receptor antagonists. Important steric differences between 5-HT2 receptor antagonists with additional high affinity for dopamine D2 receptors and serotonin 5-HT2 receptor antagonists with high selectivity versus D2 receptors are described. The geometry of the receptor-interaction model described is significantly different from that of a recently reported receptor-interaction model for 5-HT2 receptor agonists and antagonists developed by use of (+)-LSD as a template, suggesting the existence of two binding modes at the 5-HT2 receptor.
|
Displacement of [3H]- spiperone radioligand binding at the dopamine binding site of rat caudate
|
None
|
63.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and receptor binding studies relevant to the neuroleptic activities of some 1-methyl-4-piperidylidene-9-substituted-pyrrolo[2,1-b][3]benzazepine derivatives.
Year : 1983
Volume : 26
Issue : 7
First Page : 974
Last Page : 980
Authors : Remy DC, Britcher SF, King SW, Anderson PS, Hunt CA, Randall WC, Bélanger P, Atkinson JG, Girard Y, Rooney CS, Fuentes JJ, Totaro JA, Robinson JL, Risley EA, Williams M.
Abstract : The synthesis of a series of 1-methyl-4-(9-substituted-11H-pyrrolo[2,1-b]benzazepin-11-ylidene)piperidines (4a-f) and 1-methyl-4-(9-substituted-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepin-11-ylidene)piperidines (4g-l) is described. As with th e 3-substituted cyproheptadine compounds 1b-e, atropisomerism exists in 4b-f, but unlike the enantiomers of 1b-e, the pyrrolobenzazepine enantiomers racemize at room temperature. Thus, the bromo compound (+)-4b has a half-life of 128 +/- 1 min at 25 degrees C, while the chloro compound (-)-4c has a half-life of 114 +/- 9 min at 25 degrees C. Compounds 4a-l have been examined for receptor binding affinities in assays that have been recognized as predictive for antipsychotic activity. The displacement of specifically bound tritiated ligands, comprising the dopamine antagonist [3H]spiperone, the dopamine agonist [3H]apomorphine, the muscarinic cholinergic antagonist [3H]quinuclidinyl benzilate (QNB), the alpha-adrenergic antagonist [3H]prazosin, the alpha-adrenergic agonist [3H]clonidine, the serotonin-1 binding agent [3H]serotonin, and the mixed serotonin agonist-antagonist [3H]lysergic acid diethylamide (LSD), by 4a-l has been measured utilizing membrane preparations of mammalian brain. Certain of the features of the receptor binding of these compounds have been shown to be common to several of the receptor sites. Data from these binding studies have been compared to corresponding data previously obtained for a series of chiral 3-substituted cyproheptadine analogues, and the receptor binding data of the two classes of compounds are discussed with respect to their molecular geometries.
|
Binding affinity towards dopamine receptor D2 using [3H]spiperone as radioligand
|
None
|
112.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA).
Year : 2004
Volume : 14
Issue : 9
First Page : 2279
Last Page : 2283
Authors : Peddi S, Roth BL, Glennon RA, Westkaemper RB.
Abstract : The synthesis and 5-HT(2A) receptor affinities of ring altered derivatives of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (4), a structurally unique tetracyclic 5-HT(2A) receptor antagonist, are described. The characteristics of the parent compound prove to be necessary for optimal 5-HT(2A) receptor affinity. However, expansion of the size of the pyrrolidine and central rings produce compounds with reasonably high 5-HT(2A) receptor affinities. In addition, the parent compound is shown to have high 5-HT(2) receptor selectivity.
|
Potency against histamine H1 receptor on guinea pig ileum
|
Cavia porcellus
|
1.0
nM
|
|
Journal : J. Med. Chem.
Title : The histamine H1-receptor antagonist binding site. A stereoselective pharmacophoric model based upon (semi-)rigid H1-antagonists and including a known interaction site on the receptor.
Year : 1995
Volume : 38
Issue : 17
First Page : 3351
Last Page : 3360
Authors : ter Laak AM, Venhorst J, Donné-Op den Kelder GM, Timmerman H.
Abstract : A new pharmacophoric model for the H1-antagonist binding site is derived which reveals that a simple atom to atom matching of compounds is not sufficient; in this model, interacting residues from the receptor need to be included. To obtain this model, the bioactive conformations of several (semi-)rigid classical histamine H1-receptor antagonists have been investigated (cyproheptadine, phenindamine, triprolidine, epinastine, mequitazine, IBF28145, and mianserine). In general, these antihistamines contain two aromatic rings and a basic nitrogen atom. A previously derived pharmacophoric model with the nitrogen position fixed relative to the two aromatic rings is now found not to be suitable for describing the H1-antagonist binding site. A procedure is described which allows for significant freedom in the position of the basic nitrogen of the histamine H1-antagonist. The area accessible to the basic nitrogen is confined to the region accessible to its counterion on the histamine H1-receptor, i.e., the carboxylate group of Asp116. The basic nitrogen is assumed to form an ionic hydrogen bond with this aspartic acid which C alpha- and C beta-carbons are fixed with respect to the protein backbone. Via this hydrogen bond, the direction of the acidic proton of the antagonist is taken into account. Within these computational procedures, an aspartic acid is coupled to the basic nitrogen of each H1-antagonist considered; the carboxylate group is connected to the positively charged nitrogen via geometric H-bonding restraints obtained from a thorough database search (CSD). Also to the basic nitrogen of the pharmacophore is coupled an aspartic acid (to yield our new template). In order to derive a model for the H1-antagonist binding site, the aromatic ring systems of the antagonists and template are matched according to a previously described procedure. Subsequently, the C alpha- and C beta-carbons of the aspartic acid coupled to the H1-antagonists are matched with those of the template in a procedure which allows the antagonist and the carboxylate group to adapt their conformation (and also their relative position) in order to optimize the overlap with the template. A six-point pharmacophoric model is derived which has stereoselective features and is furthermore able to distinguish between the so-called "cis"- and "trans"-rings mentioned in many (Q)SAR studies on H1-antagonists. Due to its stereoselectivity, the model is able to designate the absolute bioactive configuration of antihistamines such as phenindamine (S), epinastine (S), and IBF28145 (R). A further merit of this study is that a model is obtained which includes an amino acid from the receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
|
Inhibition of [3H]mepyramine binding with histamine H1 receptor in guinea pig cerebellum membranes after 30 min
|
Cavia porcellus
|
0.537
nM
|
|
Journal : J. Med. Chem.
Title : The histamine H1-receptor antagonist binding site. A stereoselective pharmacophoric model based upon (semi-)rigid H1-antagonists and including a known interaction site on the receptor.
Year : 1995
Volume : 38
Issue : 17
First Page : 3351
Last Page : 3360
Authors : ter Laak AM, Venhorst J, Donné-Op den Kelder GM, Timmerman H.
Abstract : A new pharmacophoric model for the H1-antagonist binding site is derived which reveals that a simple atom to atom matching of compounds is not sufficient; in this model, interacting residues from the receptor need to be included. To obtain this model, the bioactive conformations of several (semi-)rigid classical histamine H1-receptor antagonists have been investigated (cyproheptadine, phenindamine, triprolidine, epinastine, mequitazine, IBF28145, and mianserine). In general, these antihistamines contain two aromatic rings and a basic nitrogen atom. A previously derived pharmacophoric model with the nitrogen position fixed relative to the two aromatic rings is now found not to be suitable for describing the H1-antagonist binding site. A procedure is described which allows for significant freedom in the position of the basic nitrogen of the histamine H1-antagonist. The area accessible to the basic nitrogen is confined to the region accessible to its counterion on the histamine H1-receptor, i.e., the carboxylate group of Asp116. The basic nitrogen is assumed to form an ionic hydrogen bond with this aspartic acid which C alpha- and C beta-carbons are fixed with respect to the protein backbone. Via this hydrogen bond, the direction of the acidic proton of the antagonist is taken into account. Within these computational procedures, an aspartic acid is coupled to the basic nitrogen of each H1-antagonist considered; the carboxylate group is connected to the positively charged nitrogen via geometric H-bonding restraints obtained from a thorough database search (CSD). Also to the basic nitrogen of the pharmacophore is coupled an aspartic acid (to yield our new template). In order to derive a model for the H1-antagonist binding site, the aromatic ring systems of the antagonists and template are matched according to a previously described procedure. Subsequently, the C alpha- and C beta-carbons of the aspartic acid coupled to the H1-antagonists are matched with those of the template in a procedure which allows the antagonist and the carboxylate group to adapt their conformation (and also their relative position) in order to optimize the overlap with the template. A six-point pharmacophoric model is derived which has stereoselective features and is furthermore able to distinguish between the so-called "cis"- and "trans"-rings mentioned in many (Q)SAR studies on H1-antagonists. Due to its stereoselectivity, the model is able to designate the absolute bioactive configuration of antihistamines such as phenindamine (S), epinastine (S), and IBF28145 (R). A further merit of this study is that a model is obtained which includes an amino acid from the receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
|
Displacement of [3H]- QNB binding at the muscarinic-cholinergic binding site of rat brain S1
|
None
|
4.0
nM
|
|
Journal : J. Med. Chem.
Title : Synthesis and receptor binding studies relevant to the neuroleptic activities of some 1-methyl-4-piperidylidene-9-substituted-pyrrolo[2,1-b][3]benzazepine derivatives.
Year : 1983
Volume : 26
Issue : 7
First Page : 974
Last Page : 980
Authors : Remy DC, Britcher SF, King SW, Anderson PS, Hunt CA, Randall WC, Bélanger P, Atkinson JG, Girard Y, Rooney CS, Fuentes JJ, Totaro JA, Robinson JL, Risley EA, Williams M.
Abstract : The synthesis of a series of 1-methyl-4-(9-substituted-11H-pyrrolo[2,1-b]benzazepin-11-ylidene)piperidines (4a-f) and 1-methyl-4-(9-substituted-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepin-11-ylidene)piperidines (4g-l) is described. As with th e 3-substituted cyproheptadine compounds 1b-e, atropisomerism exists in 4b-f, but unlike the enantiomers of 1b-e, the pyrrolobenzazepine enantiomers racemize at room temperature. Thus, the bromo compound (+)-4b has a half-life of 128 +/- 1 min at 25 degrees C, while the chloro compound (-)-4c has a half-life of 114 +/- 9 min at 25 degrees C. Compounds 4a-l have been examined for receptor binding affinities in assays that have been recognized as predictive for antipsychotic activity. The displacement of specifically bound tritiated ligands, comprising the dopamine antagonist [3H]spiperone, the dopamine agonist [3H]apomorphine, the muscarinic cholinergic antagonist [3H]quinuclidinyl benzilate (QNB), the alpha-adrenergic antagonist [3H]prazosin, the alpha-adrenergic agonist [3H]clonidine, the serotonin-1 binding agent [3H]serotonin, and the mixed serotonin agonist-antagonist [3H]lysergic acid diethylamide (LSD), by 4a-l has been measured utilizing membrane preparations of mammalian brain. Certain of the features of the receptor binding of these compounds have been shown to be common to several of the receptor sites. Data from these binding studies have been compared to corresponding data previously obtained for a series of chiral 3-substituted cyproheptadine analogues, and the receptor binding data of the two classes of compounds are discussed with respect to their molecular geometries.
|
Binding affinity to Norepinephrine transporter using [3H]-nisoxatine as radioligand in stably transfected NIH3T3 cells
|
None
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.
Year : 2001
Volume : 11
Issue : 5
First Page : 655
Last Page : 658
Authors : Runyon SP, Savage JE, Taroua M, Roth BL, Glennon RA, Westkaemper RB.
Abstract : Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K = 20nM; 5-HT2C, Ki=43nM) versus the dopamine D2 receptor (Ki>10,000nM), as well as the serotonin and norepinephrine transporters (Ki>10,000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.
|
Binding affinity towards Norepinephrine transporter using [3H]nisoxitine as radioligand
|
None
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA).
Year : 2004
Volume : 14
Issue : 9
First Page : 2279
Last Page : 2283
Authors : Peddi S, Roth BL, Glennon RA, Westkaemper RB.
Abstract : The synthesis and 5-HT(2A) receptor affinities of ring altered derivatives of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (4), a structurally unique tetracyclic 5-HT(2A) receptor antagonist, are described. The characteristics of the parent compound prove to be necessary for optimal 5-HT(2A) receptor affinity. However, expansion of the size of the pyrrolidine and central rings produce compounds with reasonably high 5-HT(2A) receptor affinities. In addition, the parent compound is shown to have high 5-HT(2) receptor selectivity.
|
Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 10 uM
|
Cavia porcellus
|
83.0
%
|
|
Journal : J. Med. Chem.
Title : [3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
Year : 1985
Volume : 28
Issue : 3
First Page : 381
Last Page : 388
Authors : McNeal ET, Lewandowski GA, Daly JW, Creveling CR.
Abstract : [3H]Batrachotoxinin A benzoate ( [3H]BTX-B) binds with high affinity to sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex. In this preparation, local anesthetics competitively antagonize the binding of [3H]BTX-B. The potencies of some 40 classical local anesthetics and a variety of catecholamine, histamine, serotonin, adenosine, GABA, glycine, acetylcholine, and calcium antagonists, tranquilizers, antidepressants, barbiturates, anticonvulsants, steroids, vasodilators, antiinflammatories, anticoagulants, analgesics, and other agents have been determined. An excellent correlation with the known local anesthetic activity of many of these agents indicate that antagonism of binding of [3H]BTX-B binding provides a rapid, quantitative, and facile method for the screening and investigation of local anesthetic activity.
|
Antiinflammatory activity against PLA2-induced Swiss mouse paw edema at 5 mg/kg, ip administered 30 mins before PLA2 challenge
|
Mus musculus
|
82.0
%
|
|
Journal : J. Nat. Prod.
Title : Griffonianone D, an isoflavone with anti-inflammatory activity from the root bark of Millettia griffoniana.
Year : 2003
Volume : 66
Issue : 9
First Page : 1288
Last Page : 1290
Authors : Yankep E, Njamen D, Fotsing MT, Fomum ZT, Mbanya JC, Giner RM, Recio MC, Máñez S, Ríos JL.
Abstract : A new isoflavone, griffonianone D (1), and the previously known compounds durmillone and odorantin were isolated from a chloroform extract of the root bark of Millettia griffoniana. The structure of 1 was established as (7E)-(6",7"-dihydroxy-3",7"-dimethyloct-2"-enyl)oxy-4'-methoxyisoflavone on the basis of its spectral data. The chloroform extract of the root bark of M. griffoniana and compound 1 showed anti-inflammatory effects in different experimental models of inflammation.
|
Antiinflammatory activity against PLA2-induced Swiss mouse paw edema at 5 mg/kg, ip administered 60 mins before PLA2 challenge
|
Mus musculus
|
82.0
%
|
|
Journal : J. Nat. Prod.
Title : Griffonianone D, an isoflavone with anti-inflammatory activity from the root bark of Millettia griffoniana.
Year : 2003
Volume : 66
Issue : 9
First Page : 1288
Last Page : 1290
Authors : Yankep E, Njamen D, Fotsing MT, Fomum ZT, Mbanya JC, Giner RM, Recio MC, Máñez S, Ríos JL.
Abstract : A new isoflavone, griffonianone D (1), and the previously known compounds durmillone and odorantin were isolated from a chloroform extract of the root bark of Millettia griffoniana. The structure of 1 was established as (7E)-(6",7"-dihydroxy-3",7"-dimethyloct-2"-enyl)oxy-4'-methoxyisoflavone on the basis of its spectral data. The chloroform extract of the root bark of M. griffoniana and compound 1 showed anti-inflammatory effects in different experimental models of inflammation.
|
Antiinflammatory activity against Naja mossambica PLA2-induced Swiss mouse paw edema assessed as inhibition of paw volume at 5 mg/kg, ip administered before 30 mins of PLA2 challenge measured after 30 mins relative to control
|
Mus musculus
|
66.0
%
|
|
Journal : J. Nat. Prod.
Title : Warangalone, the isoflavonoid anti-inflammatory principle of Erythrina addisoniae stem bark.
Year : 2003
Volume : 66
Issue : 6
First Page : 891
Last Page : 893
Authors : Talla E, Njamen D, Mbafor JT, Fomum ZT, Kamanyi A, Mbanya JC, Giner RM, Recio MC, Máñez S, Ríos JL.
Abstract : The prenylisoflavone warangalone has been isolated from the bark of Erythrina addisoniae. This compound, previously recognized as a powerful inhibitor of protein kinase A, showed marked effectiveness as an anti-inflammatory on the phospholipase A(2)-induced paw edema and on the 12-O-tetradecanoylphorbol 13-acetate-induced ear edema in mice, after systemic and local administration, respectively.
|
Antiinflammatory activity against Naja mossambica PLA2-induced Swiss mouse paw edema assessed as inhibition of paw volume at 5 mg/kg, ip administered before 30 mins of PLA2 challenge measured after 60 mins relative to control
|
Mus musculus
|
63.0
%
|
|
Journal : J. Nat. Prod.
Title : Warangalone, the isoflavonoid anti-inflammatory principle of Erythrina addisoniae stem bark.
Year : 2003
Volume : 66
Issue : 6
First Page : 891
Last Page : 893
Authors : Talla E, Njamen D, Mbafor JT, Fomum ZT, Kamanyi A, Mbanya JC, Giner RM, Recio MC, Máñez S, Ríos JL.
Abstract : The prenylisoflavone warangalone has been isolated from the bark of Erythrina addisoniae. This compound, previously recognized as a powerful inhibitor of protein kinase A, showed marked effectiveness as an anti-inflammatory on the phospholipase A(2)-induced paw edema and on the 12-O-tetradecanoylphorbol 13-acetate-induced ear edema in mice, after systemic and local administration, respectively.
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
16.0
nM
|
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
3.943
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
|
35.0
nM
|
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
12.0
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
|
46.0
nM
|
|
DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
9.655
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
|
16.0
nM
|
|
DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
2.186
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
|
3.835
nM
|
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
2.755
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-HT1A radioligand binding (ligand: [3H] 8-OH-DPAT)
|
None
|
122.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: [3H] 8-OH-DPAT)
|
None
|
70.0
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
|
0.973
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
0.278
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-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
241.0
nM
|
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
98.0
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-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
44.0
nM
|
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
80.0
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-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
107.0
nM
|
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
53.0
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-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
283.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
106.0
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
|
38.0
nM
|
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
17.0
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: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
185.0
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: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
564.0
nM
|
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
559.0
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
|
9.441
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
6.008
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
|
2.44
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
1.278
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
|
281.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
130.0
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: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
438.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
426.0
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
|
158.0
nM
|
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
79.0
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 D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
164.0
nM
|
|
DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
55.0
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
|
48.0
nM
|
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
16.0
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
|
3.7
nM
|
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
0.43
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 H2 radioligand binding (ligand: [125I] Aminopotentidine)
|
None
|
198.0
nM
|
|
DRUGMATRIX: Histamine H2 radioligand binding (ligand: [125I] Aminopotentidine)
|
None
|
195.0
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: Imidazoline I2, Central radioligand binding (ligand: [3H] Idazoxan)
|
Rattus norvegicus
|
871.0
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
|
Inhibition of hypersensitive immune responses in rat passive cutaneous anaphylaxis model at 30 mg/kg
|
Rattus norvegicus
|
69.0
%
|
|
Journal : J. Med. Chem.
Title : Bruton's tyrosine kinase inhibitors: approaches to potent and selective inhibition, preclinical and clinical evaluation for inflammatory diseases and B cell malignancies.
Year : 2012
Volume : 55
Issue : 10
First Page : 4539
Last Page : 4550
Authors : Lou Y, Owens TD, Kuglstatter A, Kondru RK, Goldstein DM.
|
Antagonist activity at 5HT2A receptor
|
None
|
0.46
nM
|
|
Journal : J. Med. Chem.
Title : Life beyond kinases: structure-based discovery of sorafenib as nanomolar antagonist of 5-HT receptors.
Year : 2012
Volume : 55
Issue : 12
First Page : 5749
Last Page : 5759
Authors : Lin X, Huang XP, Chen G, Whaley R, Peng S, Wang Y, Zhang G, Wang SX, Wang S, Roth BL, Huang N.
Abstract : Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an "induced-fit" protocol to improve the homology models of 5-HT(2A) receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT(2A) models and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib, has shown unexpected promiscuous 5-HTRs binding affinities, K(i) = 1959, 56, and 417 nM against 5-HT(2A), 5-HT(2B), and 5-HT(2C), respectively. Our preliminary SAR exploration supports the predicted binding mode and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well-known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its "off-target" 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects.
|
Antiallergic activity in in guinea pig ileum strips assessed as inhibition of serotonin-induced anaphylaxis
|
Cavia porcellus
|
0.04
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in guinea pig ileum strips assessed as inhibition of bradykinin-induced anaphylaxis
|
Cavia porcellus
|
2.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in rat stomach strips assessed as inhibition of PGE2-induced anaphylaxis
|
Rattus norvegicus
|
25.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in rat stomach strips assessed as inhibition of PGE2alpha-induced anaphylaxis
|
Rattus norvegicus
|
65.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in guinea pig lung tissue assessed as inhibition of SRS-A production
|
Cavia porcellus
|
1.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in rat stomach strips assessed as inhibition of PGE2-induced anaphylaxis at 25 ug/ml
|
Rattus norvegicus
|
54.0
%
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in rat stomach strips assessed as inhibition of PGE2alpha-induced anaphylaxis at 25 ug/ml
|
Rattus norvegicus
|
33.0
%
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in rat stomach strips assessed as inhibition of PGE2alpha-induced anaphylaxis at 100 ug/ml
|
Rattus norvegicus
|
74.0
%
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in guinea pig lung tissue assessed as inhibition of SRS-A production at 1 ug/ml
|
Cavia porcellus
|
62.0
%
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in adrenalectomized Sprague-Dawley rat assessed as inhibition of egg albumin-induced passive cutaneous anaphylaxis reaction at 10 mg/kg, iv after 30 mins by Evans blue staining
|
Rattus norvegicus
|
51.0
%
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in adrenalectomized Sprague-Dawley rat assessed as inhibition of egg albumin-induced passive cutaneous anaphylaxis reaction at 3 mg/kg, iv after 30 mins by Evans blue staining
|
Rattus norvegicus
|
30.0
%
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Antiallergic activity in in guinea pig ileum strips assessed as inhibition of histamine-induced anaphylaxis
|
Cavia porcellus
|
0.04
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Antiallergic 9-oxo-11-hydroxy-5H,9H-[2]benzopyrano[4,3-g][1]benzopyrans.
Year : 1978
Volume : 21
Issue : 5
First Page : 480
Last Page : 483
Authors : Devlin JP, Bauen A, Possanza GJ, Stewart PB.
Abstract : The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.
|
Displacement of [3H]ketanserin from Sprague-Dawley rat cerebral cortex 5-HT2A receptor after 30 mins by liquid scintillation counting analysis
|
Rattus norvegicus
|
1.6
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Steric structure-activity relationship of cyproheptadine derivatives as inhibitors of histone methyltransferase Set7/9.
Year : 2016
Volume : 24
Issue : 18
First Page : 4318
Last Page : 4323
Authors : Fujiwara T, Ohira K, Urushibara K, Ito A, Yoshida M, Kanai M, Tanatani A, Kagechika H, Hirano T.
Abstract : Set7/9 is a histone lysine methyltransferase, but it is also thought to be involved in a wide variety of pathophysiological functions. We previously identified cyproheptadine, which has a characteristic butterfly-like molecular conformation with bent tricyclic dibenzosuberene and chair-form N-methylpiperidine moieties, as a Set7/9 inhibitor. In this work, we synthesized several derivatives in order to examine the steric structure-inhibitory activity relationship. We found that even a small change of molecular shape due to reduction or replacement of the 10,11-olefinic bond of the tricyclic ring generally resulted in a drastic decrease of the inhibitory activity. Our results should be useful not only for development of more potent and selective inhibitors, but also for the construction of novel inhibitor scaffolds.
|
Antiinflammatory activity in Wistar rat assessed as inhibition of dextran-induced paw edema administered orally 30 mins prior to dextran treatment measured after 3 hrs
|
Rattus norvegicus
|
56.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.
Year : 2017
Volume : 27
Issue : 2
First Page : 176
Last Page : 179
Authors : Lima TC, Lucarini R, Volpe AC, de Andrade CQJ, Souza AMP, Pauletti PM, Januário AH, Símaro GV, Bastos JK, Cunha WR, Borges A, da Silva Laurentiz R, Conforti VA, Parreira RLT, Borges CHG, Caramori GF, Andriani KF, E Silva MLA.
Abstract : (-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK.
|
Displacement of [3H]5-HT from recombinant human 5-HT7 receptor expressed in African green monkey COS7 cells
|
Homo sapiens
|
125.89
nM
|
|
Journal : Eur J Med Chem
Title : Structure-activity relationships of serotonin 5-HT<sub>7</sub> receptors ligands: A review.
Year : 2019
Volume : 183
First Page : 111705
Last Page : 111705
Authors : Thirumaran SL, Lepailleur A, Rochais C.
Abstract : 5-HT<sub>7</sub> receptors are the most recently discovered serotonergic receptors, for which numerous physiological implications in the central and the peripheral nervous systems as well as the endocrine system are described. A current public health challenge is to propose new and more efficient treatments against neuropsychiatric disorders such as epilepsy or Alzheimer's disease. In this context, 5-HT<sub>7</sub> receptors represent an interesting target for the treatment and prevention of those pathologies, as an alternative or in association with other medicines. Thus, numerous chemical series of agonists and antagonists have been developed. Some of these molecules have shown a therapeutic potential in various in vivo studies. This review aims to present an overview of 5-HT<sub>7</sub> receptors and of the medicinal chemistry programs that led to the identification of new, potent and selective 5-HT<sub>7</sub> receptors ligands. Structure-activity relationships studies based on molecular docking and pharmacophoric approaches are also described.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
14.5
%
|
|
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
|
0.03
%
|
|
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
|
0.03
%
|
|
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.
