| 摘要 |
Substituted heterocyclic spiro compound (I), is new. Substituted heterocyclic spiro compound of formula (I), is new. Either Ring A, Ring B : saturated or partially saturated 3-11C cycloalkyl (optionally substituted), 3-11 membered heterocycle containing 1-4 heteroatoms of O, S or N (where the heterocycle is unbridged, bridged or annealed, and according to ring size, the cycloalkyl is optionally substituted); or Ring A-B : spiro compound; X : e.g. covalent bond, -O- or -S-; Y1 : e.g. covalent bond, -C(O)-, -S(O)-, -S(O 2)-, -C(NR1)-, -C(S)-, -C(=N-CN)-, -C(=CHNO 2)- or -CH(CF 3)-; R1 : H, -(1-4C)-alkyl or -(0-4C)-alkylen-(3-6C)-cycloalkyl; either R2, R3 : e.g. H, -(1-10C)-alkyl, -(1-6C)-fluoroalkyl, -(0-4C)-alkylen-(3-8C)-cycloalkyl or -(0-4C)-alkylen-aryl (optionally substituted), -(0-4C)-alkylen-Het (where Het is optionally substituted); or CR2R3 : 3-6 membered cycloalkyl ring (optionally substituted) or 3-6 membered heterocycloalkyl ring (optionally substituted); Z : -N(R26)-(C(R24)(R25)) m-CN; R26 : H, -(1-4C)-alkyl or -(0-4C)-alkylene-(3-6C)-cycloalkyl; either R24, R25 : e.g. H, -(1-6C)-alkyl, -(0-4C)-alkylene-(3-6C)-cycloalkyl, -(1-3C)-fluoroalkyl, -(0-4C)-alkylene-aryl (where aryl is optionally substituted) or -(0-4C)-alkylen-Het (where Het is optionally substituted); or CR24R25 : 3-6 membered cycloalkyl ring (optionally substituted) or 3-6 membered cycloalkyl ring (optionally substituted); and m : 1-3. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. An independent claim is included for the preparation of (I). [Image] - ACTIVITY : Osteopathic; Antiallergic; Neuroprotective; Nootropic; Anticoagulant; Thrombolytic; Antiasthmatic; Antiarteriosclerotic; Immunosuppressive; Virucide; Antibacterial; Hemostatic; Vasotropic; Anticonvulsant; Antiinflammatory; Gastrointestinal-Gen; Antidiabetic; Respiratory-Gen; Gynecological; Nephrotropic; Metabolic; Antithyroid; CNS-Gen; Hepatotropic; Anti-HIV; Cytostatic; Dermatological; Antimalarial; Anabolic; Muscular-Gen; Analgesic; Cerebroprotective; Antiarthritic; Antiparkinsonian; Antipsoriatic; Angiogenesis. - MECHANISM OF ACTION : Cathepsins inhibitor; Protease inhibitor. The cathepsin inhibiting activity of (I) was tested using human cathespsin S. The results showed that (I) exhibited K i value of 0.5 nM. |
