Patent RU-2283311-C2 (RU)
Title: Quinazoline substituted derivatives and their using as inhibitors
Inventor: MORTLOK EHNDRJU
IPC: C07D417/12
Filed: 2001-06-21
Granted: 2006-09-10
Abstract: FIELD: organic chemistry, biochemistry, medicine, pharmacy. 
     SUBSTANCE: invention relates to compound of the formula (IA)   wherein X means -NH; R 5a  represents optionally substituted 5-membered heteroaromatic ring chosen from the group of the following formulae: (a)   (b)   (c)   (d)   (e)   (f)   (g)   (h)   (i)   or (j)   wherein * means the addition position to the group X in the formula (IA); R 60  and R 61  from group of the formula (k)   wherein p and q mean independently 0 or 1; R 1 ' and R 1 '' represent independently hydrogen atom, hydroxy-group wherein T represents C=O, sulfur atom (S), -C(=NOR)CO, -C(O)C(O) wherein R represents hydrogen atom, (C 1 -C 6 )-alkyl and phenyl; V represents independently hydrogen atom, hydroxyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy-, (C 2 -C 6 )-alkenyloxy-group, trifluoromethyl, phenyl optionally substituted with (C 1 -C 6 )-alkoxy- or (C 1 -C 6 )-alkanoyloxy-group or (C 3 -C 7 )-cycloalkyl; or V represents -N(R 63 )R 64  wherein one of R 63  and R 64  is chosen independently from hydrogen atom, (C 1 -C 10 )-alkyl optionally substituted with hydroxy-group, (C 1 -C 6 )-alkoxycarbonyl and (C 1 -C 6 )-alkoxyl; and (C 2 -C 6 )-alkenyl and another represents (C 1 -C 6 )-alkyl optionally substituted 1 or 2 with (C 1 -C 4 )-alkoxyl, cyano-group, (C 1 -C 4 )-alkoxycarbonyl, (C 2 -C 4 )-alkanoyloxy- or hydroxy-group; heteroaryl-(C 1 -C 6 )-alkyl wherein heteroaryl represents 5-6-membered ring comprising 1-2 heteroatoms chosen from oxygen (O), sulfur (S) and nitrogen (N) atoms and optionally substituted with (C 1 -C 6 )-alkyl; phenyl or phenyl-(C 1 -C 6 )-alkyl optionally substituted with 1, 2 or 3 groups chosen from halogen atom, N,N-di-(C 1 -C 6 )-alkyl)-amino-, N-(C 1 -C 6 )-alkyl)-amino-, (C 1 -C 6 )-alkoxy-group, (C 2 -C 6 )-alkanoyl, trifluoromethyl, cyano-group, (C 1 -C 6 )-alkyl optionally substituted with hydroxy- or cyano-group, carbamoyl, hydroxy-, trifluoromethoxy-, nitro-, (C 1 -C 6 )-alkylthio-, amino-group, -O-(C 1 -C 3 )-alkyl-O- and (C 1 -C 6 )-alkylcarbonyl; heteroaryl chosen from pyridyl, furanyl and indolyl optionally substituted with 1 or 2 hydroxy-groups, halogen atom, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkoxy-group; (C 3 -C 7 )-cycloalkyl or (C 3 -C 7 )-cycloalkyl-(C 1 -C 6 )-alkyl optionally substituted with hydroxy-group; or R 63  and R 64  in common with nitrogen atom to which they are bound form 5-6-membered ring that can comprise additionally heteroatom N or O and can be optionally substituted with (C 1 -C 6 )-alkyl, hydroxy-group, hydroxy-(C 1 -C 6 )-alkyl or carbamoyl; R 62  represents hydrogen atom, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxycarbonyl or carbamoyl; R 1'  represents hydrogen atom; R 2'  represents (C 1 -C 5 )-alkoxy-group; R 3'  represents -X 1 R 9  wherein X 1  represents -O- and R 9  is chosen from the following groups: (1) (C 1 -C 5 )-alkyl; (2) (C 1 -C 5 )-alkyl-X 3 R 20  wherein X 3  represents -NR 25 - wherein R 25  represents hydrogen atom or (C 1 -C 3 )-alkyl; R 20  represents (C 1 -C 3 )-alkyl, cyclopentyl and (C 1 -C 3 )-alkyl group can comprise 1 or 2 substitutes  chosen from oxo-, hydroxy-group, halogen atom and (C 1 -C 4 )-alkoxy-group; (3) represents (C 1 -C 5 )-X 4 -(C 1 -C 5 )-alkyl-X 5 R 26  wherein each among X 4  and X 5  represents -NR 31 - wherein R 31  represents hydrogen atom or (C 1 -C 3 )-alkyl; R 26  represents hydrogen atom or (C 1 -C 3 )-alkyl; (4) (C 1 -C 5 )-alkyl-R 32  wherein R 32  represents 5-6-membered saturated heterocyclic group bound through carbon or nitrogen atom with 1-2 heteroatoms chosen independently from O and N and wherein heterocyclic group can comprise 1 or 2 substitutes chosen from hydroxy-group, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-hydroxyalkyl; (5) (C 1 -C 3 )-alkyl-X 9 -(C 1 -C 3 )-alkyl-R 32  wherein X 9  represents -NR 57 - wherein R 57  represents hydrogen atom or (C 1 -C 3 )-alkyl and R 32  is given above; R 4'  represents hydrogen atom; or to its pharmaceutically acceptable salts. Compounds are inhibitors of kinase aurora 2 and can be used for preparing a medicinal agent used in treatment of proliferative diseases, in particular, in cancer treatment. Except for, invention relates to a pharmaceutical composition possessing the abovementioned activity and a method for preparing compounds of the formula (IA). 
     EFFECT: valuable medicinal properties of compounds and pharmaceutical composition. 
     14 cl, 30 tbl, 477 ex