- PYRIDINE DERIVATIVES AND THEIR USE AS MEDICAMENTS FOR TREATING DISEASES RELATED TO MCH RECEPTOR
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The present invention encompasses novel substituted pyridine compounds of Formula (I), which act as MCH receptor antagonists. These compositions and pharmaceutical compositions thereof are useful in the prophylaxis or treatment of improving memory function, sleeping and arousal, anxiety, depression, mood disorders, seizure, obesity, diabetes, appetite and eating disorders, cardiovascular disease, hypertension, dyslipidemia, myocardial infarction, binge eating disorders including bulimia, anorexia, mental disorders including manic depression, schizophrenia, delirium, dementia, stress, cognitive disorders, attention deficit disorder, substance abuse disorders and dyskinesias including Parkinson's disease, epilepsy, and addiction.
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Page/Page column 89
(2010/10/20)
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- 4-Benzyl and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones: In vitro evaluation of new C-3-amino-substituted and C-5,6-alkyl-substituted analogues against clinically important HIV mutant strains
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In a program to optimize the anti-HIV activity of the 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 9 and 10, lead compounds in a new class of highly potent non-nucleoside type inhibitors of HIV-1 reverse transcriptase, modification of the alkyl substitutents at the C-5 and C-6 positions on the pyridinone ring and of the substitutents on the C-3 amino group has been studied. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L100I + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A], which are clinically relevant. Concerning modulation of the N-3 substituent, 36 new analogues were prepared. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC50's) against all the other mutant strains except K103N + Y181C and F227L + V106A. Two possible, but distinct, modes of binding of these analogues in RT were suggested from molecular modeling studies. The preferred mode of binding for compound 62, corresponding to the predicted "orientation 1", was revealed in the X-ray crystal structure of the compound 62-RT complex.
- Benjahad, Abdellah,Croisy, Martine,Monneret, Claude,Bisagni, Emile,Mabire, Dominique,Coupa, Sophie,Poncelet, Alain,Csoka, Imre,Guillemont, Jér?me,Meyer, Christophe,Andries, Koen,Pauwels, Rudi,De Béthune, Marie-Pierre,Himmel, Daniel M.,Das, Kalyan,Arnold, Eddy,Chi, Hung Nguyen,Grierson, David S.
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p. 1948 - 1964
(2007/10/03)
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- ANTIPRURITICS
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It is intended to provide antipruritics (drugs to control itching, antiitch agents and drugs to stop itching). It is found out that a compound having an agonistic activity to the cannabinoid receptor shows an antipruritics effect.
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Page/Page column 29
(2008/06/13)
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- PYRIDONE DERIVATIVE HAVING AFFINITY FOR CANNABINOID 2-TYPE RECEPTOR
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It was found that the compound having a binding activity to the cannabinoid type 2 receptor represented by the formula (I): wherein R' is a group represented by the formula: -Y1-Y2-Y3Ra wherein Y1 is single bond or the like; Y2 is -C(=O)-NH- or the like; Y3 is optionally substituted aryl or the like; R2 is hydrogen or the like; R3 is alkyl or the like; R4 is alkyl or the like; R5 is optionally substituted alkyl or the like; or R3 and R4 taken together with the adjacent atom form cyclic group or the like.
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Page/Page column 46-47
(2008/06/13)
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- Preparation and Reaction of Pyridones: Steric and Electronic Effects on Cycloadditions with 2(1H)-Pyridones
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The reactions of series of substituted 2(1H)-pyridones with dimethyl butynedioate have been studied.Cycloadditions across the 3,6-positions can be observed in certain instances and are particularly favoured where steric buttressing occurs between the substituent groups of the starting pyridones.The pyridone could not be induced to react with simple olefins, either by intermolecular or, via incorporation of alkenyl substituents, by intramolecular processes.From the results it is shown that 2-pyridones can be encouraged to behave as reactive classical dienes in cycloaddition reactions.
- Gisby, Graham P.,Royall, Sven E.,Sammes, Peter G.
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p. 169 - 174
(2007/10/02)
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