Anti-inflammatory piperazinyl-benzyl-tetrazole derivatives...

C - Chemistry – Metallurgy – 07 – D

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C07D 257/04 (2006.01) A61K 31/495 (2006.01) C07D 295/155 (2006.01)

Patent

CA 2290501

Tetrazoles and their pharmaceutically acceptable salts which are selective agonists for the delta opioid receptor, particularly useful in the treatment of inflammatory diseases such as arthritis, psoriasis, asthma, inflammatory bowel disease, disorders of respiratory function, gastro-intestinal disorders such as functional bowel disease and functional GI disorders, of formula (I), wherein R1 is H, C2-C6 alkanoyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C7 cycloalkyl, (C3-C7 cycloalkyl)-(C1-C4 alkyl), (C1-C4 alkoxy)-(C1-C4 alkyl), carboxy-(C1-C4 alkyl), aryl-(C1-C4 alkyl) or heteroaryl-(C1-C4 alkyl); R2 and R3 are each independently H or C1-C4 alkyl; R4 is selected from (i) H, (ii) a group of the formula R6-(CH2)m-Z-(CH2)n-, where m is 0, 1, 2 or 3, n is 1, 2 or 3, Z is a direct link or O, and R6 is -CO2H or -CO2(C1-C4 alkyl), and (iii) a group of formula (a) where R7 is H or C1-C4 alkyl; and R5 is hydroxy, C1-C4 alkoxy or -NHSO2(C1-C4 alkyl); with the proviso that when Z is O, m is 1, 2, or 3 and n is 2 or 3.

L'invention concerne des tétrazoles et leurs sels pharmaceutiquement acceptables qui sont des agonistes sélectifs pour le récepteur d'opioïde delta, particulièrement utiles dans le traitement de maladies inflammatoires telles que l'arthrite, la psoriasis, l'asthme, les maladies intestinales inflammatoires, les troubles de la fonction respiratoire, les troubles gastro-intestinaux, tels que la maladie intestinale fonctionnelle et les troubles gastro-intestinaux fonctionnels, ces composé ayant la formule (I) dans laquelle R?1¿ désigne H, alcanoyle C¿2?-C¿6?, alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6?, alcynyle C¿2?-C¿6?, cycloalkyle C¿3?-C¿7?, (cycloalkyle C¿3?-C¿7?)-(alkyle C¿1?-C¿4?), (alcoxy C¿1?-C¿4?)-(alkyle C¿1?-C¿4?), carboxy-(alkyle C¿1?-C¿4?), aryl-(alkyle C¿1?-C¿4?) ou hétéroaryl-(alkyle C¿1?-C¿4?); R?2¿ et R?3¿ désignent chacun indépendamment H ou alkyle C¿1?-C¿4?; R?4¿ est sélectionné parmi (i) H, (ii) un groupe de formule R?6¿-(CH¿2?)¿m?-Z-(CH¿2?)¿n?-, où m est égal à 0, 1, 2 ou 3, n est égal à 1, 2 ou 3, Z désigne une liaison directe ou O et R?6¿ désigne -CO¿2?H ou -CO¿2?(alkyle C¿1?-C¿4?) et (iii) un groupe de formule (a) dans laquelle R?7¿ désigne H ou alkyle C¿1?-C¿4? et R?5¿ désigne un hydroxy, alcoxy C¿1?-C¿4? ou -NHSO¿2?(alkyle C¿1?-C¿4?); à condition que, lorsque Z dé signe O, m désigne 1, 2 ou 3 et n désigne 2 ou 3.

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