QUINAZOLINE DERIVATIVES INHIBITING EGFR ACTIVITY Russian patent published in 2014 - IPC C07D239/95 C07D239/72 C07D401/12 C07D403/12 C07D405/12 C07D409/12 C07D413/12 C07D487/04 A61K31/517 A61K31/4427 A61K31/5377 A61K31/381 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to novel quinazoline derivatives of formula , where each of R₁, R₂ and R₅, independently, represents H; one of R₃ and R₄ represents where n - 1 or 2; each R^a represents H, C_1-10alkyl, optionally substituted with substituent, selected from group, including C_1-10alkoxy, C_1-10alkansulfonyl carboxy-group, 5-6-membered monocyclic heterocycloalkyl, which has one or several heteroatoms, selected from O and N, where N atom can be substituted with C_1-10alkyl, phenyl, optionally substituted with halogen, 5-6-membered monocyclic heteroaryl, which has one or several heteroatoms, selected from N and S, 7-membered bicyclic heterocycloalkyl, which has 2 N atoms; C_2-10alkenyl; C_2-10alkinyl; cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms; each of R^b and R^c, independently, represents H or C_1-10alkyl, optionally substituted C_1-10alkoxy, or R^b and R^c, together with atom of nitrogen, with which they are bound, form bicyclic ring of the following formula: , where each of m₁, m₂, m₃, and m₄ is 0, 1 or 2; A is CH; B is NR, where R is H or C_1-10alkyl; and each of R_i, R_ii, R_iii, R_iV, R_v, R_vi, R_vii and R_viii is H; or 6-7-membered monocyclic heterocycloalkyl, containing 1-2 N atoms, optionally substituted with substituent, selected from group, including hydroxy, C_1-10alkyl, optionally substituted C_1-10alkoxy, C_1-10alkyl, optionally substituted with C_3-6cycloalkyl; and each of R^d, R^e, independently represents H, C_2-10alkenyl; C_2-10alkinyl; or C_1-10alkyl, optionally substituted with substituent, selected from group, including C_1-10alkyloxy, hydroxy, CN, 5-6-membered monocyclic heterocycloalkyl, which has 1 or 2 N atoms, optionally substituted with C_1-10alkyl, halogen or 5-6-membered heterocycloalkyl, which has 1 N atom, phenyl, optionally substituted with halogen, cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms, 5-6-membered monocyclic heteroaryl, which has one or 2 N atoms; or R^d and R^e, together with nitrogen atom, with which they are bound, form 5-6-membered saturated heterocycloalkyl, which has 1-2 heteroatoms, selected from N and O, optionally substituted with substituent, selected from group, including C_1-10alkyl (which is optionally substituted with C_3-6cicloalkyl, C_1-10alkoxy, halogen), 5-membered heterocycloalkyl, which has one N atom, halogen, C_1-10alkansulfonyl, C_1-10alkylcarbonyl, optionally substituted with halogen, or R^d and R^e, together with nitrogen, with which they are bound, form 7-10-membered, saturated, bicyclic heterocycloalkyl, containing 1-2 heteroatoms, selected from N and O, optionally substituted with C_1-10alkyl; and the other of R³ and R⁴ represents H, halogen or C_1-10alkoxy; X represents NR^f, where R^f represents phenyl, substituted with C_2-4 alkinyl; and Z represents N. Invention also relates to particular quinazoline derivatives, based on it pharmaceutical composition, and to method of cancer treatment.

EFFECT: novel quinazoline derivatives, inhibiting EGFR activity are obtained.

11 cl, 171 ex