Patent EP-2357181-A1 (EP)
Inventor: ZAHN STEPHAN KARL
IPC: A61K31/506
Filed: 2007-05-15
Abstract: 2,4-Diamino pyrimidine compounds (I) and their tautomers, racemates, enantiomers and/or diastereomers, and optionally their acid addition salts, are new. 2,4-Diamino pyrimidine compounds of formula (I) and their tautomers, racemates, enantiomers and/or diastereomers, and optionally their acid addition salts, are new. X : N or CH; R 1>3-10C cycloalkyl (substituted with R 3> and optionally with one or more R 4>); R 2>H, halo, -CN, -NO 2, 1-4C (halo)alkyl, 3-10C cycloalkyl, 4-16C cycloalkylalkyl or 7-16C arylalkyl; R 3>-C(O)Rc, -C(O)ORC, -C(O)NRCRC, -S(O)2RC, -N(Rf)S(O)2Rc, -N(Rf)C(O)Rc, -N(Rf)C(O)ORc or -N(Rf)C(O)NRcRc; R 4>Ra or Rb (where Ra is substituted by Rc and/or Rb); Ra : 1-6C alkyl, 3-10C cycloalkyl, 4-16C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocycloalkyl, 4-14 membered heterocycloalkylalkyl, 5-12 membered heteroaryl or 6-18 membered heteroarylalkyl; Rb : O=, -ORc, 1-3C haloalkyloxy, -OCF 3, =S, -SRc, =NRc, =NORc, -NRcRc, halo, -CF 3, -CN, -NC, -OCN, -SCN, -NO 2, -S(O)Rc, -S(O) 2Rc, -S(O) 2ORc, -S(O)NRcRc, -S(O) 2NRcRc, -OS(O)Rc, -OS(O) 2Rc, -OS(O) 2ORc, -OS(O) 2NRcRc, -C(O)Rc, -C(O)ORc, -C(O)NRcRc, -CN(Rf)NRcRc, -CN(OH)Rc, -CN(OH)NRcRc, -OC(O)Rc, -OC(O)ORc, -OC(O)NRcRc, -OCN(Rf)NRcRc, -N(Rf)C(O)Rc, -N(Rf)C(S)Rc, -N(Rf)S(O) 2Rc, -N(Rf)C(O)ORc, -N(Rf)C(O)NRcRc, -[N(Rf)C(O)] 2Rc, -N[C(O)] 2Rc, -N[C(O)] 2ORc, -[N(Rf)C(O)] 2ORc or -N(Rf)CN(Rf)NRcRc; Rc : H or optionally Rd and/or Re substituted 1-6C alkyl, 3-10C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocycloalkyl, 4-14 membered heterocycloalkylalkyl, 5-12 membered heteroaryl or 6-18 membered heteroarylalkyl; Rd : H or an optionally Re and/or Rf substituted 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocycloalkyl, 4-14 membered heterocycloalkylalkyl, 5-12 membered heteroaryl or 6-18 membered heteroarylalkyl; Re : O=, -OR, 1-3C haloalkyloxy, -OCF 3, =S, -SR , =NR, =NORf, -NRfRf, halo, -CF-3, -CN, -NC, -OCN, -SCN, -NO 2, -S(O)Rf, -S(O) 2Rf, -S(O) 2ORf, -S(O)NRfRf, -S(O) 2NRfRf, -OS(O)Rf, -OS(O) 2Rf, -OS(O) 2ORf, -OS(O) 2NRfRf, -C(O)Rf, -C(O)ORf, -C(O)NRfRf, -CN(Rg)NRfRf, -CN(OH)Rf, -C(NOH)NRfRf, -OC(O)Rf, -OC(O)ORf, -OC(O)NRfRf, -OCN(Rg)NRfRf, -N(Rg)C(O)Rf, -N(Rg)C(S)Rf, -N(Rg)S(O) 2Rf, -N(Rd)C(O)ORf, -N(Rg)C(O)NRfRf or -N(Rg)CN(Rf)NRfRf; Rf : H or optionally Rg substituted 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocycloalkyl, 4-14 membered heterocycloalkylalkyl, 5-12 membered heteroaryl or 6-18 membered heteroarylalkyl; Rg : H, 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocycloalkyl, 4-14 membered heterocycloalkyl, 5-12 membered heteroaryl or 6-18 membered heteroarylalkyl; m : 0 or 1; n : 1-4; and p : 0-2. Provided that 25 compounds are excluded e.g. 4-[4-((1R,2S)-2-isopropylcarbamoyl-cyclopentylamino)-5-trifluoromethylpyrimidine-2-ylamino]-N-( 1-methyl-piperidin-4-yl)-benzamide, 4-[4-((1R,2S)-2-isopropylcarbamoyl-cyclopentylamino)-5-trifluoromethylpyrimidin-2-ylamino]-N-piperidin-4-yl-benzamide, 2-chloro-4-[4-((1R,2S)-2-isopropylcarbamoyl-cyclopentylamino)-5-trifluoromethylpyrimidin-2-ylamino]-N-methyl-N-(1-methyl-piperidin-4-yl)-benzamide, 4-[4-((1R,2S)-2-carbamoyl-cyclopentylamino)-5-methyl-pyrimidin-2-ylamino]-N-(1-methyl-piperidin-4-yl)-benzamide and 4-[4-((1R,2S)-2-carbamoyl-cyclopentylamino)-5-nitro-pyrimidin-2-ylamino]-N-(1-methyl-piperidin-4-yl)-benzamide. An independent claim is included for a pharmaceutical preparation comprising (I) and at least a further cytostatic or cytotoxic active substance. [Image] ACTIVITY : Cytostatic; Antimicrobial; Antiinflammatory; Immunosuppressive; Anti-HIV; Gastrointestinal-Gen; Antiarthritic; Neuroprotective; Nootropic; Nephrotropic; Vulnerary; Dermatological; Antipsoriatic; Cardiovascular-Gen; Vasotropic. MECHANISM OF ACTION : Cell cycle kinase inhibitor.