Transient Receptor Potential antagonists of vanilloides 1 (TRPV1) useful for treating Pain and inflammation

摘要

Item 1: a compound whose characteristics are to respond to formula (1) or a dissolved salt, to produce a salt, or a mixture, from an acceptable pharmaceutical product, wherein R1 represents a group of pharmacists,(b)(C) o (d)Rx, in each case, represents an alternative to any double ring replaceable position selected from a set of bitumen, halogen, halide, Wu, O (bitumen),O (halogen)NH2, n (H) (person)And n (TAR) 2; R is hydrogen or methyl; R2 and R3 are equal or different, and each is an independent hydrogen, C1-5 tar or halogen tar; or R2 and R3, together with the carbon atoms attached to them, form a single cyclic chemical cyclohexane with 3 to 6 carbon atoms, which can be replaced by 1, 2 or 3 carbon atoms. Selected from the bitumen and halogen groups; R4 in each case represents an alternative to any double ring replaceable position selected from the bitumen, halogen, halide or (bitumen) group,O (halogen)[7 - [7 - [7 - (trifluoro-7] - 1 - (3] - 1 - [7 - [7] - 7 - [7] - 7 - [7 1. Dihydro-2h-chromium-4-il] urea; 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1 - (L) - (L) - (n) - - isoquinol-5-ilurea; N - (6-chloro-7-methyl-3, 4-dihydro-2h-chromium-4-1) - n '- 1h-indazol-4-ilurea;3-3-3-3-fluoro-3-3-3-3-6) (1); N - (4-3-3-fluoro-3-3-6 (b) urea; N - (6-methyl-3, 4-dihydro-2h-chromium-4-il) - n '(3-methylisoquinine-5-il); [7] - [i-ethan] - [I-7] - [i-ethan] - [i-ethan] - [7] - [i-ethan] - [3. Trifluoroid-3, 4-dihydro-2h-chromium-4-il;N-1H-indazol-4-yl-N '- [8- (trifluoromethyl) -3,4-dihydro-2H-chromen-4-yl] urea; (-) - N-1H-indazol-4-yl-N '- [7- (trifluoromethyl) -3,4-dihydro-2H-chromen-4-yl] urea; (+) - N-1H-indazol-4-yl-N '- [7- (trifluoromethyl) -3,4-dihydro-2H-chromen-4-yl] urea; N-1H-indazol-4-yl-N '- (8-piperidin-1-yl-3,4-dihydro-2H-chromen-4-yl) urea; N- (8-tert-butyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- [8-Chloro-7- (trifluoromethyl) -3,4-dihydro-2H-chromen-4-yl] -N'-1H-indazol-4-ylurea; (+) - N- (8-tert-butyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; (-) - N- (8-tert-butyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N-1H-indazol-4-yl-N '- [8- (trifluoromethoxy) -3,4-dihydro-2H-chromen-4-yl] urea;N- [8-fluoro-7- (trifluoromethyl) -3,4-dihydro-2H-chromen-4-yl] -N'-1H-indazol-4-ylurea; N-1H-indazol-4-yl-N '- [7- (trifluoromethoxy) -3,4-dihydro-2H-chromen-4-yl] urea; N- (6-fluoro-2-methyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N-1H-indazol-4-yl-N '- (7-methoxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl) urea; N-1H-indazol-4-yl-N '- (7-methoxy-2,2,8-trimethyl-3,4-dihydro-2H-chromen-4-yl) urea; N-1H-indazol-4-yl-N '- (2,2,8-trimethyl-3,4-dihydro-2H-chromen-4-yl) urea; N-1H-indazol-4-yl-N '- (7-methoxy-2,2-dimethyl-8-propyl-3,4-dihydro-2H-chromen-4-yl) urea; N- (2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea;N- (7-fluoro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (7- (3,3-dimethylbutyl) -3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (7-tert-butyl-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (2,2-diethyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl) -N '- (1-methyl-1H-indazol-4-yl) urea; N- (7,8-difluoro-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (7-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (2,2-dibutyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea; N- (2-tert-butyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl) -N'-1H-indazol-4-ylurea;7, 6-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1 -- 3, 4-dihydro-2h-chromium-4-il urea; N - [(4R) - 3, 4-dihydro-2h-chromium-4-il] - n '(7-hydroxy-5, 6, 7, (7-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-4-il) urea; 1 - (7-fluorospiro [croman-2, 1 '- ciciochotan] - 4-il) - 3 - (1h-indazol-4-il) urea;(1 - (1) - 1-1 - (1 - (1 -) (1 1. Urea [cr-2, 1L Cyclohexan] - 4-il) - 3 - (1h-indazol-4-il) urea; 1 - (7-tertbutilesepiro [cr-2], - 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1 '- cyclopentanone] - 4-1) urea; 1 - (7-etoxiespiro [croman-2, 1' - cyclopentanone] - 4-il) - 3 - (1h-indazol-4-il) urea;1]] - 1] - 1 -, 1 - (1 -, 1 - (1 - [(L) 3 - (7-methoxyspiro [cr-2, 1 '- cyclohexane] - 4-il) urea; (+ -) 1 - (3, 4-dihydro-2), - toluene toluene toluene toluene 3 - (benzene toluene toluene toluene toluene toluene - (6) - 1 - (6-methoxy-3,4-dihydro-2,2-dimethyl-2h-1-benzodiazo-4-il) - 3 - (isoquinine-5-il) urokinase;3, 3, 3, 3, 3-methylmethylmethyltoluene-toluene, 3, 3-methyltoluene-an-4-il) - 3 - (1-methylisoquinine-5-il) urea; (+ -) 1 - (6-bromo-3, 4-dihydro-2) Urea; (+ -) 1 - (3,4-dihydro-helix - [2h-1-benzodiazepine-2,1 '- cyclobutan] - 4-il) - 3 - (isoquinolin-5-il) urea;(+) 1- (3,4-dihydro-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (isoquinolin-5-yl) urea; (-) 1- (3,4-dihydro-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (isoquinolin-5-yl) urea; (+ -) 1- (3,4-dihydro-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (8-chloroisoquinolin-5-yl) urea; (+ -) 1- (3,4-Dihydro-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (3-methylisoquinolin-5-yl) urea; (+ -) 1- (3,4-Dihydro-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (1-methylisoquinolin-5-yl) urea; (+ -) 1- (3,4-dihydro-6-methyl-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (isoquinolin-5-yl) urea; (+ -) 1- (3,4-dihydro-7-methyl-spiro- [2H-1-benzopyran-2,1'-cyclobutan] -4-yl) -3- (isoquinolin-5-yl) urea;]],,, [1 - [1 - [3 - [3 - [3 - [3 - [3 - [3 - [3-2h-1-benzopiran-2, 1 '- cyclobutan] - 4-il) - 3 - (isoquinolin-5-il) urea; (+ -) 1 - (3), (1) 1 -------- (1 -------- 1.1-2,1 '- cyclobutan] - 4-il) - 3 - (isoquinolin-5-il) urea;1 - (different from - 1 -) (1 -) (1 -) (different from - 2 h-1-benzopiran-2, 1 '- cyclobutan] - 4-il) - 3 - (3-methylisoquinine-5-il) urea; 1 - (1 -) (1 -) (1 -) (1 -) (1 -) (1 -) (1-1. Dihydro helix - [2h-1-benzodiazo-2, 1 '- cyclohexane] - 4-il) - 3 - (isoquinol-5-il) urea;(1 - (2h-1-benzopiran-2, 1 '- cyclobutan] - 4-il) - 3 - (isoquinolin-5-il) urea; (+ -) 1 - (6-bromo-3), 6] - [6] - [6] - [6] - 1 - [6] - 1-4 - [6 - [6] - 4-4-4-1. Zopiran-2, 1 '- cyclobutan] - 4-il) - 3 - (isoquinolin-5-il) urea;-) (different from - 1 -) (1 -) (1 -) (1 -) (different from from from 5) 1 - (chloro-1 -) (from 3 - [2h-1-benzopiran-2, 1 '- cyclobutan] - 4-il) - 3 - (8-chloroisoquinlin-5-il) urea; (+ -) 1 - (6-fluoro-3)