Patent RU-2378263-C2 (RU)
Inventor: BRJUS AJAN
IPC: A61P9/10
Filed: 2003-02-27
Granted: 2010-01-10
Abstract: FIELD: pharmacology. 
     SUBSTANCE: invention deals with formula I compounds and their sals pharmaceutically relevant in the capacity of phosphatidylinositol 3-kinase inhibitors, their preparation method as well as their application for production of a pharmaceutical preparation, a pharmaceutical compounds based thereon and a therapy method envisaging their application. In a   formula compound R 1  is represented by aminocarbonyl, non-obligatorily displaced with nitrile, or R 1  is represented by C 1 -C 8 -alkylcarbonyl that is non-obligatorily displaced with hydroxi, carboxi, C 1 -C 8 -alcoxicarbonyl, nitrile, phenyl, C 1 -C 8 -halogenalkyl or C 1 -C 8 -alkyl, non-obligatorily displaced with hydroxi or R 1  is represented by C 1 -C 8- alkyl aminocarbonyl alkylcarbonyl that is non-obligatorily displaced with halogen, hydroxi, C 1 -C 8 -alkylanimo, di(C 1 -C 8 -alkyl)amino, carboxi, C 1 -C 8 -alcoxicarbonyl, nitrile, C 1 -C 8 -halogenalkyl or C 1 -C 8 -alkyl, non-obligatorily displaced with hydroxi or R 1  is represented by C 1 -C 8 -alkylaminocarbonyl, non-obligatorily displaced with C 1 -C 8 -cycloalkyl or R 1  is represented by C 1 -C 8 -alkylcarbonyl or C 1 -C 8 -alkylaminocarbonyl, each of them non-obligatorily displaced with C 1 -C 8 -alcoxi, non-obligatorily displaced with hydroxi or R 1  is represented by C 1 -C 8 -alkylaminocarbonyl, displaced with phenyl, additionally displaced with hydroxi or R 1  is represented by C 1 -C 8 -alkylcarbonyl that is non-obligatorily displaced with a 5- or 6-membered heterocyclic ring that has 1-4 cyclic nitrogen heteroatom(s) where the ring is non-obligatorily displaced with C 1 -C 8 -alkyl on condition that the 6-membered heterocyclic ring is no 1-piperidyl or R 1  is represented by C 1 -C 8 -alkylaminocarbonyl that is non-obligatorily displaced with a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen where the ring is non-obligatorily displaced with C 1 -C 8 -alkyl or R 1  is represented by -(C=O)-(NH)a-Het, where a stands to denote 0 or 1 and Het stands to denote a 4-, 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) where the ring is non-obligatorily displaced with hydroxi, C 1 -C 8 -alkyl, C 1 -C 8 -alcoxi or a 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen or R 1  is represented by -(C=O)-(NH) b -T, where b stands to denote 0 or 1 and T stands to denote C 3 -C 8 -cycloalkyl that is non-obligatorily displaced with hydroxi or C 1 -C 8 -alkyl displaced with hydroxi or R 1  is represented by -(C=O)-(NH) b -T, where b stands to denote 1 and T stands to denote phenyl that is non-obligatorily displaced with C 1 -C 8 -alkyl or C 1 -C 8 -alkyl displaced with hydroxi, R 2  is represented by C 1 -C 3 -alkyl; one of R 3  and R 4  is represented by R 6  while the other is represented by R 7 ; R 5  is represented by hydrogen or a halogen; R 6  is represented by hydrogen, hydroxi, amino, -SOR 8 , -SO 2 R 8 , -SO 2 NH 2 , -SO 2 NR 9 R 10 , -COR 8 , -CONHR 8 , -NHSO 2 R 8 , nitrile, carboxi, -OR 8  or C 1 -C 8 -halogenalkyl; R 7  is represented by hydrogen, R 11 , -OR 11 , halogen, -SO 2 R 8 , ciano or C 1 -C 8 -halogenalkyl or, when R 4  is represented by R 7 , R 7  may equally be represented by -NR 12 R 13 ; R 8  and R 11  are independently represented by C 1 -C 8 -alkyl or C 3 -C 8 -cycloalkyl, non-obligatorily displaced with hydroxi, nitrile, amino, C 1 -C 8 -alkylamino or di(C 1 -C 8 -alkyl)amino; any R 9  is represented by C 1 -C 8 -alkyl or C 3 -C 8 -cycloalkyl, non-obligatorily displaced with hydroxi, C 1 -C 8 -alcoxi, nitrile, amino, C 1 -C 8 -akrylamino, di(C 1 -C 8 -alkyl)amino or 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen where the ring where the ring is non-obligatorily displaced with C 1 -C 8 -alkyl, and R 10  is represented by hydrogen or C 1 -C 8 -alkyl or R 9  and R 10  together with the nitrogen atom they are connected to form a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatoms where the ring is non-obligatorily displaced with C 1 -C 8 -alkyl; any R 12  is represented by C 1 -C 8 -alkyl or C 3 -C 8 -cycloalkyl, non-obligatorily displaced with amino, C 1 -C 8 -alkylamino or di(C 1 -C 8 -alkyl)amino and R 13  is represented by halogen or C 1 -C 8 -alkyl or R 12  and R 13  together with the nitrogen atom they are connected to form a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatoms where the ring is non-obligatorily displaced with C 1 -C 8 -alkyl. 
     EFFECT: proposed compounds are to be utilised for treatment of diseases mediated by phosphatidilinozitol 3-kinase such as allergy, psoriasis, diabetes, atherosclerosis, diabetes, cancer. 
     19 cl, 3 tbl, 181 ex