Patent RU-2267489-C2 (RU)
Inventor: EHNNEKEHN LORAN FRANSUA ANDRE
IPC: A61K31/517
Filed: 2001-08-15
Granted: 2006-01-10
Abstract: FIELD: organic chemistry, medicine, oncology, pharmacy. 
     SUBSTANCE: invention relates to new derivatives of quinazoline of the formula (I):  
     
       
     
     wherein m = 0, 1, 2 or 3; each group R 1  that can be similar or different is taken among halogen atom, trifluoromethyl, hydroxy-, amino-group, (C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl, (C 2 -C 8 )-alkynyl, (C 1 -C 6 )-alkoxy-, (C 2 -C 6 )-alkenyloxy-, (C 2 -C 6 )-alkynyloxy-, (C 1 -C 6 )-alkylamino-, di-[(C 1 -C 6 )-alkyl]amino- and (C 2 -C 6 )-alkanoylamino-group, or among the group of the formula:  Q   1   -X   1 - wherein X 1  represents oxygen atom (O); Q 1  represents aryl-(C 1 -C 6 )-alkyl, heteroaryl, heteroaryl-(C 1 -C 6 )-alkyl, heterocyclyl or heterocyclyl-(C 1 -C 6 )-alkyl and wherein neighboring carbon atoms in any (C 2 -C 6 )-alkylene chain in substitute at R 1  are separated optionally by insertion to the chain the group taken among oxygen atom (O) and N(R 5 ) wherein R 5  represents hydrogen atom or (C 1 -C 6 )-alkyl, or when the inserted group represents N(R 5 ); R 5  can represent also (C 2 -C 6 )-alkanoyl and wherein any group -CH 2  or -CH 3  in substitute R 1  carries one or more substitutes in each indicated group -CH 2  or -CH 3  and wherein these substitutes are taken among halogen atom or (C 1 -C 6 )-alkyl, or substitute taken among hydroxy-, amino-group, (C 1 -C 6 )-alkoxy-, (C 1 -C 6 )-alkylthio-group, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylamino-, di-[(C 1 -C 6 )-alkyl]amino-, (C 2 -C 6 )-alkanoyloxy, (C 2 -C 6 )-alkanoylamino- and N-(C 1 -C 6 )-alktyl-(C 2 -C 6 )-alkanoylamino-group, or among the group of the formula:  -X   3   -Q   3  wherein X 3  represents oxygen atom (O) and Q 3  represents heteroaryl, and wherein any aryl, heteroaryl or heterocyclyl group in substitute at R 1  carries optionally 1, 2 or 3 substitutes that can be similar or different and taken among halogen atom, trifluoromethyl, cyano-, hydroxy-, amino-group, carbamoyl, (C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl, (C 2 -C 8 )-alkynyl, (C 1 -C 6 )-alkoxy-, (C 2 -C 6 )-alkenyloxy, (C 2 -C 6 )-alkynyloxy,(C 1 -C 6 )-alkylthio-group, (C 1 -C)-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylamino-, di-[(C 1 -C 6 )-alkyl]amino-group, (C 1 -C 6 )-alkoxycarbonyl, N-(C 1 -C 6 )-alkylcarbamoyl, N,N-di-[(C 1 -C 6 )-alkyl]carbamoyl, (C 2 -C 6 )-alkanoyl, (C 2 -C 6 )-alkanoyloxy-, (C 2 -C)-alkanoylamino- and N-(C 1 -C 6 )-alkyl-(C 2 -C 6 )-alkanoylamino-group, or among the group of the formula:  -X   4   -R   8  wherein X 4  represents a simple bond and R 8  represents hydroxy-(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl, cyano-(C 1 -C 6 )-alkyl, amino-(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylamino-(C 1 -C 6 )-alkyl or di-[(C 1 -C 6 )-alkyl]amino-(C 1 -C 6 )-alkyl, or among the group of the formula:  -X   5   -Q   4  wherein X 5  represents a simple bond or -CO, and Q 4  represents heterocyclyl or heterocyclyl-(C 1 -C 6 )-alkyl that carries optionally 1 or 2 substitutes that can be similar or different and taken among halogen atom, (C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl, (C 2 -C 8 )-alkynyl and (C 1 -C 6 )-alkoxy-group and wherein any heterocyclyl group in substitute at R 1  carries optionally 1 or 2 oxo-substitutes, and wherein any aryl group in the group R 1  represents phenyl; any heteroaryl group in the group R 1  is taken among pyrrolyl, imidazolyl, triazolyl and pyridyl, and any heterocyclyl group in the group R 1  is taken among oxyranyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, 1,1-dioxotetrahydro-1,4-thiazinyl, piperidinyl, homopiperidinyl, piperazinyl and homopiperazinyl; R 2  represents hydrogen atom; n = 0, 1, 2 or 3; R 3  represents halogen atom, trifluoromethyl, cyano-, hydroxy-group, (C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl, (C 2 -C 8 )-alkynyl or (C 1 -C 6 )-alkoxy-group, or its pharmaceutically acceptable salt. Also, invention relates to methods for preparing compounds of the formula (1) and to pharmaceutical composition based on thereof for using as an anti-tumor agent. Invention provides preparing new derivatives of quinazoline possessing an anti-tumor activity. 
     EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition. 
     17 cl, 7 tbl, 7 ex