- Identification of fused bicyclic heterocycles as potent and selective 5-HT2A receptor antagonists for the treatment of insomnia
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A series of fused bicyclic heterocycles was identified as potent and selective 5-HT2A receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation.
- Xiong, Yifeng,Ullman, Brett,Choi, Jin-Sun Karoline,Cherrier, Martin,Strah-Pleynet, Sonja,Decaire, Marc,Feichtinger, Konrad,Frazer, John M.,Yoon, Woo H.,Whelan, Kevin,Sanabria, Erin K.,Grottick, Andrew J.,Al-Shamma, Hussien,Semple, Graeme
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experimental part
p. 1870 - 1873
(2012/04/17)
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- HETEROCYCLIC COMPOUNDS AS CCR1 RECEPTOR ANTAGONISTS
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Disclosed are CCR1 receptor antagonists of the formula (I) wherein Ar1, Ar2, R1-R3, X and L are disclosed herein. Also disclosed are compositions, methods of making and using compounds of the formula (I).
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Page/Page column 46
(2011/06/11)
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- IMIDAZO[L,2-α]PYRIDINE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
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rmidazo[l,2-α]pyridine derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia, dyssomnia, parasomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, thrombosis, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de Ia Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic- related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to methods for the treatment of 5-HT2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.
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Page/Page column 52
(2009/04/25)
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- Pyrrolizidine esters and amides as 5-HT4 receptor agonists and antagonists
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A series of pyrrolizidine esters, amides, and ureas was prepared and tested for 5-HT4 and 5-HT3 receptor binding, 5-HT4 receptor agonism in the rat tunica muscularis mucosae (TMM) assay, and for 5-HT3 receptor-mediated functional antagonism in the Bezold-Jarisch reflex assay. Several pyrrolizidine derivatives were identified with high affinity for the 5-HT4 receptor, including benzamide 12a (SC-53116), a potent and selective 5-HT4 partial agonist that exhibits efficacy in promoting antral contractions and activity in promoting gastric emptying in canine models. Also discovered were 5-HT4 receptor antagonists, including imidazopyridine amide 12h (SC-53606), which is a potent and selective 5-HT4 receptor antagonist with a pA2 value of 8.13 in the rat TMM assay. N-Methyl indole ester 13d was identified as a potent 5-HT 4 antagonist with a pA2 value of 8.93. High selectivity was observed for these pyrrolizidine derivatives versus other monoamine receptors, including 5-HT1, 5-HT2, D1, D 2, α1, α2, and β receptors. 2006 American Chemical Society.
- Becker, Daniel P.,Flynn, Daniel L.,Moormann, Alan E.,Nosal, Roger,Villamil, Clara I.,Loeffler, Richard,Gullikson, Gary W.,Moummi, Chafiq,Yang, Dai-C.
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p. 1125 - 1139
(2007/10/03)
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- Compounds
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This invention relates to nicotinamide derivatives of general formula (I): in which R1, Z and R2 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.
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Page/Page column 28
(2008/06/13)
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- Nicotinamide derivatives useful as PDE4 inhibitors
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This invention relates to nicotinamide derivatives of general formula (I): in which R1, R2 and R3 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.
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- Novel compounds
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This invention relates to nicotinamide derivatives of general formula (I): in which R1, X, Y, Z and R2 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.
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