Biologically active compounds

Details Biologically active compounds Biologically active compounds

C - Chemistry, Metallurgy

07

D

C07D 487/04 (2006.01) A61K 31/407 (2006.01) A61P 19/00 (2006.01) A61P 35/00 (2006.01) C07D 498/04 (2006.01)

Patent

CA 2499465

Compounds of general formula (I) wherein: Z = CR3R4, where R3 and R4 are independently chosen from CO-7-alkyl P1 = CR5R6, P2 = O, CR7R8 or NR9, Y = CR10R11-C(O) or CR10R11-C(S) or CR10R11-S(O) or CR10R11-SO2(X)o=.CR16R17 (W)n = 0, S, C(O), S(O) or S(O)2-or NR18 (V)m = C(O), C(S), S(O), S(O)2, S(O)2NH, OC(O), NHC(O), NHS(O), NHS(O)2, OC(O)NH, C(O)NH or CR19R20, C=N-C(O)-OR19 or C=N-C(O)-NHR19, U = a stable. 5- to 7-membered monocyclic or a stable 8- to 11- membered bicyclic ring which is either saturated or unsaturated, and which includes zero to four heteroatoms and their salts, hydrates, solvates, complexes and prodrugs are inhibitors of cathepsin K and other cysteine protease inhibitors and are useful as therapeutic agents, .for example in osteoporosis, Paget's disease gingival diseases such as gingivitis and periodontitis, hypercalaemia of malignancy, metabolic bone disease, diseases involving matrix or cartilage degradation, in particular osteoarthritis and rheumatoid arthritis and neoplastic diseases. The compounds are also useful for validating therapeutic target compounds.

L'invention concerne des composés de formule générale (I) dans laquelle Z=CR?3¿R?4¿, R?3¿ et R?4¿ étant choisis indépendamment l'un de l'autre parmi alkyle C¿0-7?, P¿1?=CR?5¿R?6¿, P¿2?=O,CR?7¿R?8¿ ou NT?9¿, Y=CR?10¿R?11¿-C(O)ou CR?10¿R?11¿-C(S) ou CR?10¿R?11¿-SO¿z?, (X)¿0?=CR?16¿R?17¿, (W)¿0?=O,S,C(O),S(O) ou S(O¿)2?- ou NR?18¿, (V)m=C(O),C(S),S(O),S(O¿)2?,S(O)¿2?NH,OC(O),NHC(O),NHS(O),NHS (O)¿2?,OC(O)NH,C(O)NH ou CR?19¿R?20¿, C=N-C(O)-OR?19¿ ou C=N-C(O)-NHR?19¿, U = un composé monocyclique ayant entre 5 et 7 chaînons ou un composé bicyclique ayant entre 8 et 11 chaînons, qui est saturé ou insaturé et comprend entre zéro et quatre hétéroatomes. Lesdits composés, leurs sels, hydrates, solvates, complexes et promédicaments sont des inhibiteurs de la cathepsine K et d'autres inhibiteurs de cystéine kinase et s'utilisent comme agents thérapeutiques, par exemple dans le traitement de l'ostéoporose, de la maladie de Paget, des affections gingivales telles que la gingivite et la périodontite, de l'hypercalcémie de malignité, de la maladie métabolique osseuse, des affections impliquant une dégradation de matricielle ou cartilagineuse, notamment l'ostéoarthrite et la polyarthrite rhumatoïde et des affections néoplasiques. Ces composés s'utilisent pour valider des composés cibles thérapeutiques.

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