Benzoimidazole derivatives and pharmaceutical composition comprising the same

摘要

Disclosed herein are novel benzoimidazole derivatives functioning as antagonists to vanilloid receptor-1, and a pharmaceutical composition comprising the same. They are useful in preventing or treating pain, acute pain, chronic pain, neuropathic pain, postoperative pain, migraines, arthralgia, neuropathy, nerve injury, diabetic neuropathy, neurological illness, neurodermatitis, strokes, bladder hypersensitivity, irritable bowel syndrome, respiratory disorders such as asthma, chronic obstructive pulmonary disease, etc., burns, psoriasis, itching, vomiting, irritation of the skin, eyes, and mucous membranes, gastric-duodenal ulcers, inflammatory intestinal diseases, and inflammatory diseases.

主权项

1. A compound having the following Chemical Formula 1, or a pharmaceutically acceptable salt thereof:wherein:
R1 is 3-methylpyridin-2-yl, unsubstituted pyridinyl, pyridinyl substituted with one or more Ra, or phenyl substituted with a fluoro and a methanesulfonamide group; each Ra is independently selected from a non-substituted lower alkenyl having 2 to 6 carbon atoms; a non-substituted lower alkoxy having 1 to 8 carbon atoms; a non-substituted haloalkyl having 1 to 6 carbon atoms; a non-substituted haloalkoxy having 1 to 6 carbon atoms; a halogen atom; a nitro; a hydroxyl; a cyano; an amino, an amide and a sulfonamide group, wherein the amino, amide and sulfonamide groups are mono- or di-substituted with a non-substituted alkyl having 1 to 6 carbon atoms or are non-substituted; A is O or CO; n is an integer equal to 0 or 1; W is N or CR3; X is N or CR4; R2 is hydrogen; R3 and R4 may be the same or different, and are each independently hydrogen; or a halogen atom; Q1 is N or CR6; Q2 is CR7; Q3 is CR8; Q4 is N or CR9; R6 is hydrogen; a non-substituted lower alkyl having 1 to 8 carbon atoms; a non-substituted lower alkoxy having 1 to 8 carbon atoms; a non-substituted haloalkyl having 1 to 6 carbon atoms; a non-substituted haloalkoxy having 1 to 6 carbon atoms; a halogen atom; an amino which is mono- or di-substituted with a non-substituted lower alkyl having 1 to 6 carbon atoms or is non-substituted; a cyclic group selected from the group consisting of morpholine, thiomorpholine and pyrrolidine; R9 is hydrogen; a non-substituted lower alkyl having 1 to 8 carbon atoms; a non-substituted lower alkoxy having 1 to 8 carbon atoms; a non-substituted haloalkyl having 1 to 6 carbon atoms; a non-substituted haloalkoxy having 1 to 6 carbon atoms; a halogen atom; an amino which is mono- or di-substituted with a non-substituted lower alkyl having 1 to 6 carbon atoms; a cyclic group selected from the group consisting of morpholine, thiomorpholine and pyrrolidine; R7 is hydrogen, or a halogen atom; R8 is hydrogen; a non-substituted lower alkyl having 1 to 8 carbon atoms; a non-substituted lower alkenyl having 2 to 6 carbon atoms; a non-substituted lower alkoxy having 1 to 8 carbon atoms; a non-substituted haloalkyl having 1 to 6 carbon atoms; a non-substituted haloalkoxy having 1 to 6 carbon atoms; a halogen atom; hydroxy; hydroxymethyl; an amino which is mono- or di-substituted with a non-substituted lower alkyl having 1 to 6 carbon atoms; sulfanyl; a cyclic group selected from the group consisting of pyridine, pyrimidine, pyrazole, phenyl, benzyl, imidazole, morpholine, benzodioxole, benzothiazole, indole, pyrazolone, thiophene, thiazole, isothiazole, oxazole, isooxazole, triazole, oxodiazole, thiadiazole, indazole, thiomorpholine, thiazolidine, oxazolidine, pyrrolidine, chromonyl, piperidine, morpholineethyl, and dihydropyrazole, wherein the cyclic group is non-substituted or substituted with one or more Rd; and each Rd is independently selected from a non-substituted lower alkyl having 1 to 8 carbon atoms; a non-substituted lower alkenyl having 2 to 6 carbon atoms; a non-substituted lower alkoxy having 1 to 8 carbon atoms; a non-substituted haloalkyl having 1 to 6 carbon atoms; a non-substituted haloalkoxy having 1 to 6 carbon atoms; a halogen atom; a nitro; a hydroxyl; a cyano; an amino, amide, sulfanyl, and a carboxylic acid which is mono- or di-substituted with a non-substituted lower alkyl having 1 to 6 carbon atoms or is non-substituted.