Trk-INHIBITING COMPOUND

摘要

An object of the present invention is to provide a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I):;;(wherein all symbols represent the same meanings as described in the specification), a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

主权项

1. A compound represented by the general formula (I): wherein: a ring Cy1 represents a C3-10 monocyclic carbocycle or bicyclic carbocycle or a 4- to 10-membered monocyclic heterocycle or bicyclic heterocycle; R1 represents: (1) a halogen; (2) a C1-6 alkyl group optionally substituted with a halogen or an oxo group; (3) a C3-6 cycloalkyl group optionally substituted with a halogen or a C1-3 alkyl group; (4) a C1-6 alkyl group having an oxygen atom substituting for a carbon atom and optionally substituted with a halogen or an oxo group; or (5) a C3-6 cycloalkyl group having an oxygen atom substituting for a carbon atom and optionally substituted with a halogen or a C1-3 alkyl group; R2 represents: (1) a C1-6 alkyl group, a C2-6 alkenyl group or a C2-6 alkynyl group optionally substituted with a substituent selected from the group consisting of:
(i) a halogen;(ii) a hydroxy group;(iii) —NH(C1-3 alkyl);(iv) —N(C1-3 alkyl)2;(v) an amino group;(vi) a cyano group;(vii) a nitro group;(viii) a C1-4 alkylsulfonyl group,(ix) a sulfonamide group;(x) a C1-4 alkylsulfonamide group;(xi) an oxo group;(xii) a carboxyl group;(xiii) —C(O)(O—C1-4 alkyl);(xiv) a phosphonooxy group;(xv) —OP(O)(O—C1-4 alkyl)2;(xvi) a carbamoyl group;(xvii) a C1-4 alkylamide group; and(xviii) a C1-4 alkylcarbamate group; (2) a hydrogen atom; (3) a hydroxy group; (4) a carboxyl group; (5) —C(O)(O—C1-4 alkyl); (6) a phosphonooxy group; (7) —OP(O)(O—C1-4 alkyl)2; (8) an amino group; (9) a cyano group; (10) a nitro group; (11) a C1-4 alkylsulfonyl group; (12) a sulfonamide group; (13) a C1-4 alkylsulfonamide group; (14) an oxo group; (15) a carbamoyl group; (16) a C1-4 alkylamide group; (17) a C1-4 alkylcarbamate group; or (18) wherein an arrow a represents binding to the ring Cy1; X represents a bond, an oxygen atom, C═O or NH; a ring Cy2 represents a C3-10 monocyclic carbocycle or bicyclic carbocycle or a 4- to 10-membered monocyclic heterocycle or bicyclic heterocycle; R6 represents: (1) a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group or a C3-6 cycloalkyl group optionally substituted with a substituent selected from the group consisting of:
(i) a halogen;(ii) a hydroxy group;(iii) an oxo group;(iv) —NH(C1-3 alkyl);(v) —N(C1-3 alkyl)2;(vi) a C1-6 alkoxy group;(vii) an amino group;(viii) a cyano group;(ix) a nitro group;(x) a C1-4 alkylsulfonyl group;(xi) a sulfonamide group;(xii) a C1-4 alkylsulfonamide group;(xiii) a carboxyl group;(xiv) —C(O)(O—C1-4 alkyl);(xv) a phosphonooxy group;(xvi) —OP(O)(O—C1-4 alkyl)2;(xvii) a carbamoyl group;(xviii) a C1-4 alkylamide group; and(xix) a C1-4 alkylcarbamate group; (2) a halogen; (3) a C1-4 alkoxy group; (4) a phosphonooxy group; (5) —OP(O)(O—C1-4 alkyl)2; (6) a sulfonamide group; (7) an oxo group; (8) —NH(C1-3 alkyl); (9) —N(C1-3 alkyl)2; (10) a carboxyl group; (11) —C(O)(O—C1-4 alkyl); (12) a carbamoyl group; (13) a C1-4 alkylamide group; (14) a hydroxy group; (15) an amino group; (16) a cyano group; (17) a nitro group; (18) a C1-4 alkylsulfonyl group; (19) a C1-4 alkylsulfonamide group; or (20) a C1-4 alkylcarbamate group; A1 and A2 respectively and independently represent ═CR3—, ═CH— or ═N—; A3, A4, A5 and A6 respectively and independently represent ═CR4— or ═N—; R3 represents: (1) a halogen; or (2) a C1-3 alkyl group or C1-3 alkoxy group optionally substituted with a halogen; R4 represents (1) a halogen; (2) a C1-3 alkyl group or C1-3 alkoxy group optionally substituted with a halogen; or (3) a hydrogen atom; Y represents an oxygen atom, an optionally oxidized sulfur atom, a methylene group or C═O; Z represents: or a group: having an oxygen atom substituting for a carbon atom forming the ring; R5 represents a halogen, a hydroxy group or a C1-4 alkyl group optionally substituted with a hydroxy group; R7 respectively and independently represents: (1) a C1-6 alkyl group, a C3-6 cycloalkyl group, a C1-6 alkyl group having an oxygen atom substituting for a carbon atom or a C3-6 cycloalkyl group having an oxygen atom substituting for a carbon atom, all of which may be optionally substituted with:
(i) a halogen;(ii) a C3-6 cycloalkyl group;(iii) a hydroxy group;(iv) an oxo group; and(v) a 4- to 6-membered monocyclic heterocycle; or (2) a hydrogen atom; arrows b, c, d and e represent binding to the thiazole ring; p represents an integer of 0 to 5; q represents an integer of 0 to 7; r represents an integer of 0 to 2; w represents an integer of 1 to 5; and u represents an integer of 0 to 2; provided that when p, q, r and u respectively represent an integer of 2 or more, R1, R3, R5 and R6 groups may be respectively and independently the same or different; a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof.