摘要 |
The present invention is directed to substituted aza-bicyclic imidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8, including for example, inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold and pulmonary disease aggravated by cold. |
主权项 |
1. A compound of formula (I) wherein R1 is selected from the group consisting of hydrogen, fluoro, chloro, fluorinated C1-4alkyl and fluorinated C1-4alkoxy; R2 is hydrogen;is selected from the group consisting of wherein R3 is selected from the group consisting of hydrogen, chloro, cyano, C1-4alkyl, fluorinated C1-4 alkyl, C1-4alkoxy, fluorinated C1-4alkoxy, —O—(CH2)2—OH, —O—CH2—CO2H, —O—(CH2)2—O—(C1-4 alkyl), —O—CH2-(fluorinated C1-2 alkyl), —O—(CH2)2—NRARB and —NRARB; wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-4alkyl; alternatively RA and RB are taken together with the nitrogen atom to which they are bound to form a ring structure selected form the group consisting of pyrrolidin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methyl-piperidin-1-yl, 4-methyl-piperazin-1-yl and morpholin-4-yl; Q is an optionally substituted ring structure selected from the group consisting of formulas (a) through (h) (a) (b) wherein R5 is C1-4alkyl; R6 is selected from the group consisting of C1-4alkyl and fluorinated C1-4alkyl; and R7 is selected from the group consisting of hydrogen, chloro, fluoro, cyano, C1-4 alkyl and C1-4 alkoxy; (c) wherein R8 and R9 are each independently selected from the group consisting of C1-4alkyl; (d) wherein R10 is C1-4alkyl; and R11 is selected from the group consisting of hydrogen and cyano; (e) wherein R12 and R13 are each independently selected from the group consisting of hydrogen and C1-4alkyl; (f) wherein R14 is C1-4alkyl; (g) wherein R15 is C1-4alkyl; and R16 is selected from the group consisting of hydrogen, chloro and bromo; and (h) wherein R17 is C1-4alkyl; or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. |