| 摘要 |
FIELD: chemistry.SUBSTANCE: invention relates to novel quinazoline derivatives of formula, where each of R, Rand R, independently, represents H; one of Rand Rrepresentswhere n - 1 or 2; each Rrepresents H, Calkyl, optionally substituted with substituent, selected from group, including Calkoxy, Calkansulfonyl 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 Calkyl, 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; Calkenyl; Calkinyl; cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms; each of Rand R, independently, represents H or Calkyl, optionally substituted Calkoxy, or Rand R, together with atom of nitrogen, with which they are bound, form bicyclic ring of the following formula:, where each of m, m, m, and mis 0, 1 or 2; A is CH; B is NR, where R is H or Calkyl; and each of R, R, R, R, R, R, Rand Ris H; or 6-7-membered monocyclic heterocycloalkyl, containing 1-2 N atoms, optionally substituted with substituent, selected from group, including hydroxy, Calkyl, optionally substituted Calkoxy, Calkyl, optionally substituted with Ccycloalkyl; and each of R, R, independently represents H, Calkenyl; Calkinyl; or Calkyl, optionally substituted with substituent, selected from group, including Calkyloxy, hydroxy, CN, 5-6-membered monocyclic heterocycloalkyl, which has 1 or 2 N atoms, optionally substituted with Calkyl, 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 Rand R, 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 Calkyl (which is optionally substituted with Ccicloalkyl, Calkoxy, halogen), 5-membered heterocycloalkyl, which has one N atom, halogen, Calkansulfonyl, Calkylcarbonyl, optionally substituted with halogen, or Rand R, 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 Calkyl; and the other of Rand Rrepresents H, halogen or Calkoxy; X represents NR, where Rrepresents phenyl, substituted with Calkinyl; 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 |
