Patent EP-2343303-A1 (EP)
Inventor: BREITFELDER STEFFEN
IPC: A61P35/00
Filed: 2005-10-05
Abstract: Thiazolo[4,5-g]indazole derivatives (I) are new. Thiazolo[4,5-g]indazole derivatives (I) of formula (1) and their tautomers, isomers and acid addition salts are new: R 1> : NHRc, NHCORc, NHCOORc, NHCONRcRd or NHCOSRc; R 2> : 1-6C alkyl, 3-8C cycloalkyl, 3- to 8-membered heterocycloalkyl, 6-10C aryl or 5- to 10-membered heteroaryl, all optionally substituted with R 4>; R 3> : 6-10C aryl or 5- to 10-membered heteroaryl, all optionally substituted with Re and/or Rf; R 4> : Ra (optionally substituted with Rc and/or Rb) or Rb; Ra : 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl; Rb : =O, ORc, 1-3C haloalkoxy, OCF 3, =S, SRc, =NRc, =NORc, NRcRc, halo, CF 3, CN, NC, OCN, SCN, NO, NO 2, =N 2, N 3, SORc, SO 2Rc, SO 2ORc, SONRcRc, SO 2NRcRc, OSORc, OSO 2Rc, OSO 2ORc, OSO 2NRcRc, CORc, COORc, CONRcRc, CON(Rg)NRcRc, CON(Rg)ORc CN(Rg)NRcRc, OCORc, OCOORc, OCONRcRc, OCN(Rg)NRcRc, N(Rg)CORc, N(Rg)CSRc, N(Rg)SO 2Rc, N(Rg)SO 2NRcRc, N(SO 2Rc) 2, N(Rg)CORc, N(Rg)CONRcRc or N(Rg)CN(Rg)NRcRc; Rc : H or 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl, all optionally substituted with Rd and/or Re; Rd : H or 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl, all optionally substituted with Re and/or Rf; Re : =O, ORf, 1-3C haloalkoxy, OCF 3, =S, SRf, =NRf, =NORf, NRfRf, halo, CF 3, CN, NC, OCN, SCN, NO, NO 2, =N 2, N 3, SORf, SO 2Rf, SO 2ORf, SONRfRf, SO 2NRfRf, OSORf, OSO 2Rf, OSO 2ORf, OSO 2NRfRf, CORf, COORf, CONRfRf, CON(Rg)NRfRf, CON(Rg)ORf CN(Rg)NRfRf, OCORf, OCOORf, OCONRfRf, OCN(Rg)NRfRf, N(Rg)CORf, N(Rg)CSRf, N(Rg)SO 2Rf, N(Rg)SO 2NRfRf, N(SO 2Rf) 2, N(Rg)CORf, N(Rg)CONRfRf or N(Rg)CN(Rg)NRfRf; Rf : H or 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl, all optionally substituted with Rg; Rg : H, 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl. Independent claims are also included for: (1) 4,5,6,7-tetrahydrobenzothiazol-7-one derivatives of formula (A); (2) pharmaceutical product comprising a compound (I) and at least one other cytostatic or cytotoxic agent. X : Me, OR 4> or SR 4>; Y : phenyl, 5- to 10-membered heteroaryl or COO; Ry : H, NO 2 or 1-6C alkyl. [Image] ACTIVITY : Cytostatic; Virucide; Anti-HIV; Antiinflammatory; Immunosuppressive; Antiarthritic; Neuroprotective; Nootropic; Nephrotropic; Antibacterial; Fungicide; Antiparasitic; Dermatological; Antipsoriatic; Osteopathic; Vasotropic. Various compounds (I), e.g. , had EC 50 values of less than 5 mu M against HCT116 human colon carcinoma cells. MECHANISM OF ACTION : PI3 kinase inhibitor.