Nicotine addiction reducing heteroaryl fused azapolycyclic...

C - Chemistry – Metallurgy – 07 – D

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C07D 471/08 (2006.01) A61K 31/439 (2006.01) A61P 25/34 (2006.01) C07D 498/08 (2006.01)

Patent

CA 2529193

The present invention provides a compound having the structure of formula (I): wherein R1 is hydrogen, (C1-C6) alkyl, unconjugated (C3-C6) alkenyl, benzyl, YC(=O)(C1-C6) alkyl or -CH2CH2-O-(C1-C4) alkyl; X is CH2 or CH2CH2; Y is (C2- C6) alkylene; Z is (CH2)m, CF2, or C(=O), where m is 0, 1 or 2; R2 and R3 are selected independently from hydrogen, halogen, - (C1-C6) alkyl optionally substituted with from 1 to 7 halogen atoms, and -O(C1-C6) alkyl optionally substituted with from 1 to 7 halogen atoms, or R2 and R3 each together with the atom to which it is connected independently form C(=O), S.fwdarw.O,S(=O)2, or N.fwdarw.O; and Het is a 5- to 7- ~membered monocyclic heteroaryl group selected from pyridinyl, pyridone, pyridazinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, cinnolinyl, triazinyl, oxadiazolyl, thiadiazolyl and furazanyl groups. The compounds can be used to treat disease states mediated by neuronal nicotinic acetylcholine specific receptor sites.

L'invention concerne un composé ayant la structure de formule I, dans laquelle R' est hydrogène, (C¿1?-C¿6?)¿?alkyle, (C¿3?-C¿6?) alkényle non conjugué, YC(=O)(C¿1?-C¿6?) alkyle ou -CH¿2?CH¿2?-O-(C¿1?-C¿4?) alkyle ; X est CH¿2? ou CH¿2?CH¿2 ?; Y est (C¿2?-C¿6?)alkylène ; Z est (CH¿2?)¿m?, CF¿2? ou C(=O), où m est égal à 0, 1 ou 2 ; R?2¿ et R?3¿ sont indépendamment sélectionnés parmi l'hydrogène, les halogènes, -(C¿1?-C¿6?) alkyle facultativement substitué par 1 à 7 atomes d'halogènes, et O(C¿1?-C¿6?) alkyle facultativement substitué par 1 à 7 atomes d'halogènes, ou R?2¿ et R?3¿, associés chacun à l'atome auquel ils sont connectés, forment indépendamment C(=O), S.fwdarw.O, S(=O)¿2? ou N.fwdarw.O ; et Het est un groupe hétéroaryle monocyclique de 5 à 7 maillons sélectionné parmi les groupes pyridinyle, pyridone, pyridazinyle, imidazolyle, pyrimidinyle, pyrazolyle, triazolyle, pyrazinyle, furyle, thiényle, isoxazolyle, thiazolyle, oxazolyle, isothiazolyle, pyrrolyle, cinnolinyle, triazinyle, oxadiazolyle, thiadiazolyle et furazanyle. Ces composés peuvent également être utilisés pour traiter des états pathologiques médiés par les sites récepteurs neuronaux nicotiniques de l'acétylcholine.

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