- TACHYKININ RECEPTOR ANTAGONISTS
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The present invention relates to selective NK-1 receptor antagonists of Formula (I) or a pharmaceutically acceptable salt thereof, for the treatment of disorders associated with an excess of tachykinins.
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- Synthesis and structure-activity relationships of trisubstituted phenyl urea derivatives as neuropeptide Y5 receptor antagonists
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1-((1R,2R)-2-Hydroxy-1-methyl-2-phenylethyl)-1-methyl-3-(4-phenoxyphenyl)urea (1) was identified as a hit from the screening of the neuropeptide Y5 (NPY5) receptor. This lead was optimized for in vitro potency by changing the stereochemistry, the phenylethyl segment, the urea portion, and the 4-phenoxyphenyl group on the molecule. Over 40 analogues of 1 were prepared to study the structure-activity relationship for this series. The most potent compounds in this class have IC50S less than 0.1 nM at the NPY5 receptor (e.g., 40f, 44a, and 47). To determine the functional activity for this series of compounds, selected analogues were tested in a cellular assay measuring forskolin-induced cyclic AMP accumulation in 293 cells transfected with the human NPY5 receptor. All urea analogues tested in the functional assay acted as antagonists (e.g., 1, 32, 40a, and 44e).
- Fotsch,Sonnenberg,Chen,Hale,Karbon,Norman
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p. 2344 - 2356
(2007/10/03)
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- DERIVATIVES OF 4-(AMINOMETHYL) PIPERIDINE, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
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Compounds of general formula (I) STR1 in which n is 1 or 2; R represents a linear or branched C 1-C 3-alkyl group; andX represents at least one substituent chosen from hydrogen, halogen, C 1-C 3-alkyl and C 1-C 3-alkoxy, in the form of a free base or an acid addition salt thereof, and their therapeutic application.
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- Comparison of Biological Effects of N-Alkylated Congeners of β-Phenylethylamine Derived from 2-Aminotetralin, 2-Aminoindan, and 6-Aminobenzocycloheptene
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Three series of bicyclic, semirigid congeners of β-phenethylamine have been prepared for evaluation of the effect of ring size (and of concomitant conformational variation) on biological activity in a variety of assays for adrenergic and dopaminergic actions.Pharmacologic activity was associated with 2-aminotetralin and 2-aminoindan derivatives, but was not found with 6-aminobenzocycloheptene derivatives.Noteworthy is the ability of several aminotetralins and aminoindans to increase the hot-plate reaction time without eliciting dopaminergic effects.This action was not blocked by pretreatment with naloxone.
- Cannon, Joseph G.,Perez, Julio A.,Pease, Jonathan P,Long, John Paul,Flynn, Jan R.,et al.
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p. 745 - 749
(2007/10/02)
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