Cysteine protease inhibitors

摘要

Compounds of the formula I;
wherein
R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; orR1a and R1b together define a saturated cyclic amine with 3-6 ring atoms;R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a andR2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl;R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or —CH2C3-C7 cycloalkyl;R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylamino or C1-C6dialkylamino;

for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

主权项

1. A compound of the formula I: wherein
R1a is H; andR1b C1 -C6alkyl, optionally substituted with 1-3 substituents independently selected from: halo, hydroxy, cyano, azido, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkoxycarbonyl, C1-C4alkylcarbonyl, amine, C1-C4alkylamine, C1-C4 dialkylamine, C1-C4alkylsulfonyl, C1-C4alkylsulfonylamino, aminocarbonyl, aminosulphonyl, Carbocyclyl and Het; or R1b is Carbocyclyl or Het; or
R1a and R1b together with the N atom to which they are attached define a saturated cyclic amine with 3-6 ring atoms;wherein the Carbocyclyl, Het or cyclic amine is optionally substituted with 1-3 substituents independently selected from halo, hydroxy, cyano, azido, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkoxycarbonyl, C1-C4alkylcarbonyl, amine, C1-C4alkylamine, C1-C4dialkylamine, C1-C4alkylsulfonyl, C1-C4alkylsulfonylamino, aminocarbonyl, aminosulphonyl, RxOOC—C0-C2alkylene (where Rx is H, C1-C4alkyl or C1-C4haloalkyl), phenyl, benzyl or C3-C6cycloalkylC0-C2alkylene;
wherein the phenyl, benzyl or cycloalkyl moiety is optionally substituted with 1-3 substituents independently selected from halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy);R2a and R2b are independently selected from H, halo, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl;R3 is a C5-C10alkyl, optionally substituted with 1-3 substituents independently selected from halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; or R3 is a C2-C4alkyl chain with at least 2 chloro or 3 fluoro substituents; or R3 is C3-C7cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C1-C4alkyl, halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy;
R4 is C1-C6alkyl, C1-C6dihaloalkyl, C1-C6alkylamino or C1-C6dialkylamino;Het is a stable, monocyclic or bicyclic, saturated, partially saturated or aromatic ring system containing 1-4 heteroatoms independently selected from O, S and N, each ring having 5 or 6 ring atoms;Carbocyclyl is C3-C6cycloalkyl, C5-C6cycloalkenyl or phenyl;or a pharmaceutically acceptable salt, hydrate or N-oxide thereof.