Furo3, 2-B pyrrol-3-ones as cathespin S inhibitors

摘要

A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof,; wherein:one of R³ and R⁴ is H, and the other is selected from C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, and C_6-12-aralkyl;or R³ and R⁴ are each independently selected from C_1-6-alkyl and halo;R⁹ is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group.;Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.