9-azabicyclo [3.3.1] nonane derivatives as monoamine...

C - Chemistry – Metallurgy – 07 – D

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C07D 451/14 (2006.01) A61K 31/439 (2006.01) A61P 25/24 (2006.01)

Patent

CA 2623359

The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula (I), wherein R1 is H or C1-5alkyl; X is O or NR2, wherein R2 is H, C1- 5alkyl or C2-5acyl and Ar is C6-10aryl or a 5-10 membered heteroaryl ring system, both being optionally substituted with one to three of R3-R5 independently selected from halogen, C1-5alkyl, C1-5alkoxy, C3-6cycloalkyl, C2- 5alkenyl, C2-5alkynyl, CN, NO2, hydroxy, phenyl, phenoxy and phenylC1-2alkoxy, wherein said C1-5alkyl and C1-5alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC1-2alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R3-R5 at adjacent positions together form a methylenedioxy or propylene unit, with the proviso that the compounds exo-9- methyl-3-phenoxy-9-azabicyclo[3.3.1]nonane and N-(9-methyl-9- azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine are excluded, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9- azabicyclo[3.3.1]nonane derivatives and to their use in therapy.

La présente invention concerne un dérivé de 9-azabicyclo[3.3.1]nonane de formule (I), dans laquelle R1 est H ou un C1-5alkyle ; X est O ou NR2, dans laquelle R2 est H, un C1-5alkyle ou un C2-5acyle et Ar est un C6-10aryle ou un système de cycle hétéroaryle de 5 à 10 chaînons, les deux portant facultativement une substitution par de un à trois parmi R3 à R5 indépendamment choisis parmi un halogène, un C1-5alkyle, un C1-5alcoxy, un C3-6cycloalkyle, un C2-5alkényle, un C2-5alkynyle, CN, NO2, un hydroxy, un phényl, un phénoxy et un phénylC1-2alcoxy, lesdits C1-5alkyle et C1-5alcoxy portant facultativement une substitution par de un à trois halogènes et lesdits phényle, phénoxy et phénylC1-2alcoxy portant facultativement une substitution par de un à trois substituants indépendamment choisis parmi un halogène et un méthyle ou deux parmi R3 à R5 en des positions adjacentes formant ensemble une unité méthylène dioxy ou propylène, à condition d'exclure les composés exo-9-méthyl-3-phénoxy-9-azabicyclo[3.3.1]nonane et N-(9-méthyl-9-azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine, ou un de leurs sels ou solvates pharmaceutiquement acceptables. L'invention concerne également des compositions pharmaceutiques comprenant lesdits dérivés de 9-azabicyclo[3.3.1]nonane et leur utilisation thérapeutique.

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