| 摘要 |
The present invention relates to sulfonamide derivatives, of formula (I):;
or a pharmaceutically acceptable salts thereof, wherein X, Z, R1a, R1b, R2, R3, R4 and R5 are as defined in the description, and to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. The compounds of formula (I) are Nav1.7 inhibitors useful in the treatment of a wide range of disorders, particularly pain. |
| 主权项 |
1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein X is —OCH2— or —CH2O—; Z is selected from naphthyl, phenyl or Het1, wherein said naphthyl, phenyl or Het1 is optionally substituted by one to three substituents selected from Y1 or Y2; wherein Y1 and Y2 are each independently selected from:
(i) F;(ii) Cl;(iii) CN;(iv) (C1-C8)alkyl, optionally substituted by (C3-C8)cycloalkyl and/or, by one to eight F;(v) (C3-C8)cycloalkyl, optionally substituted by one to eight F;(vi) NR7R8;(vii) (C1-C8)alkyloxy, optionally substituted by one to three R9, and/or, by one to eight F;(viii) (C3-C8)cycloalkyloxy, optionally substituted by one to eight F and/or by one to three R10, and further optionally fused to a phenyl ring;(ix) phenyl, optionally substituted by one to three substituents selected from F or R10;(x) phenoxy, optionally substituted by one to three substituents selected from F or R10;(xi) Het2;(xii) Het2-oxy; or(xiii) Het3; R1a and R1b are each independently selected from:
(i) H,(ii) (C1-C6)alkyl; or(iii) (C3-C6)cycloalkyl, optionally substituted by one to eight F or, R1a and R1b taken together with the N atom to which they are attached, form a 3- to 8-membered monoheterocycloalkyl, said monoheterocycloalkyl being optionally substituted on a ring carbon atom by one to eight F; R2, R3, and R4 are each independently selected from H, F, CI or —OCH3; R5 is H, CN, F, Cl, Het3, or R6; wherein R6 is selected from (C1-C6)alkyl or (C1-C6)alkyloxy, and said (C1-C6)alkyl and (C1-C6)alkyloxy are optionally substituted by one to eight F; R7 and R8 are each independently selected from:
(i) H;(ii) (C1-C8)alkyl, optionally substituted by one to three R11;(iii) (C3-C8)cycloalkyl, optionally substituted by one to eight F and/or by one to three R10, and further optionally fused to a phenyl ring;(iv) ‘C-linked’ Het2; or(v) C-linked Het3; R9 is selected from:
(i) (C1-C6)alkyloxy;(ii) (C3-C8)cycloalkyl, optionally substituted by one to eight F;(iii) Het2; or(iv) phenyl, optionally substituted by one to three R6; R10 is Cl, CN or R6; R11 is selected from:
(i) F;(ii) (C1-C6)alkyloxy;(iii) (C3-C8)cycloalkyl, optionally substituted by one to eight F;(iv) ‘C-linked’ Het2; or(v) phenyl, optionally substituted by one to three R6; Het1 is a 6-, 9- or 10-membered heteroaryl containing one to three nitrogen atoms; Het2 is a 3- to 8-membered saturated monoheterocycloalkyl containing one or two ring members selected from —NR12— and —O—, said monoheterocycloalkyl being optionally substituted on a ring carbon atom by one to three substituents independently selected from F, (C1-C6)alkyl, (C1-C4)alkyloxy(C0-C4)alkylene or (C3-C8)cycloalkyl; Het3 is a 5- or 6-membered heteroaryl containing one to three nitrogen atoms, said heteroaryl being optionally substituted by one to three substituents selected from F, Cl, CN or R6; and R12 is H, (C1-C6)alkyl or (C3-C8)cycloalkyl, wherein said (C1-C6)alkyl and said (C3-C8)cycloalkyl are optionally substituted by one to eight F; or, when Het2 is ‘N-linked’, R12 is absent. |
