Spiro (piperidine-4, 2 ' -pyrrolidine) -1- (3, 5-...

C - Chemistry – Metallurgy – 07 – D

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C07D 471/10 (2006.01) A61P 25/22 (2006.01) A61P 25/24 (2006.01) A61P 29/00 (2006.01) C07D 498/20 (2006.01)

Patent

CA 2723062

Compounds of formula (I) or a pharmaceutically acceptable salt thereof wherein R is hydrogen or C1-4 alkyl; R1 is hydrogen, C1-4 alkyl, C(O)OH, C(O)NH2 or (C1-4 alkylene)R10; R2 and R3 are independently hydrogen, C1-4 alkyl or R2 together with R3 and together with the carbon atom to which they are attached form a C3- 8 cycloalkyl group; R4 is C1-4 alkyl, C1-4 alkoxy or halogen; R5 and R7 are independently hydrogen, hydroxy, halogen, C(O)NH2, C(O)OH or (C1-4alkylene)R10; R6 and R8 are independently hydrogen or halogen; R9 is hydrogen, (C1-4 alkylene)R10, C(O)NH2, C(O)OH or R9 together with R form a 6 membered heterocyclic ring optionally containing a further heteroatom selected from oxygen, sulphur or nitrogen; R10 is hydrogen, halogen, hydroxy, C(O)NH2, C(O)NH(C1-4alkyl), C(O)N(C1-4alkyl)2 or C(O)OH; n is O, 1 or 2. processes for their preparation, to compositions containing them and to their use in the treatment of diseases and conditions for which antagonism of NK1 is beneficial.

Linvention concerne des composés de formule (I) ou un sel pharmaceutiquement acceptable de ceux-ci, où R est hydrogène ou C 1-4 alkyle ; R1 est hydrogène, C1-4 alkyle, C(O)OH, C(O)NH2 ou (C 1-4 alkylène)R10 ; R2 et R3 sont indépendamment hydrogène, C1-4 alkyle ou R2 avec R3 et avec latome de carbone auquel ils sont attachés constituent un groupe cycloalkyle C3-8 ; R4 est C 1-4 alkyle, C1-4 alcoxy ou halogène ; R5 et R7 sont indépendamment hydrogène, hydroxy, halogène, C(O)NH2, C(O)OH ou (C1-4 allylène) R10 ; R6 et R8 sont indépendamment hydrogène ou halogène ; R9 est hydrogène, (C1-4 alkylène)R10, C(O)NH2, C(O)OH ou R9 avec R constituent un cycle hétérocyclique à 6 éléments contenant éventuellement un hétéroatome supplémentaire sélectionné parmi oxygène, sulfure ou azote ; R10 est hydrogène, halogène, hydroxy, C(O)NH2, C(O)NH(C1-4 alkyl), C(O)N(C1-4 alkyl)2 ou C(O)OH ; n est O, 1 ou 2. Linvention concerne en outre des processus pour leur préparation, des compositions les contenant et leur utilisation dans le traitement de maladies et daffections pour lesquelles lantagonisme de NK1 est avantageux.

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