| 摘要 |
organic chemistry, heterocyclic compounds. SUBSTANCE: invention relates to novel bicyclic derivatives of pyrimidine or its pharmaceutically acceptable salts, method of inhibition of activity of tyrosine kinase in epidermal growth factor receptors, in part, in treatment of patients with cancer diseases, to pharmaceutical composition eliciting activity inhibiting activity of tyrosine kinase in epidermal growth factor receptors and to composition eliciting contraceptive effect. Proposed compounds correspond to the general formula (I) where 1-2 of radicals A-E mean nitrogen atom and other radicals mean carbon atom, or two adjacent radicals A-E mean heteroatom among the group nitrogen, sulfur atoms and A-E in common with adjacent carbon atoms mean pyridine, pyrimidine, thienyl, pyrrole or imidazole ring; X means groups NH, NHR5 where R5 means lower alkyl with 1-4 carbon atoms; n = 0, 1 or 2; R is absent or means hydrogen atom, alkyl with 1-4 carbon atoms, alkoxyl-group with 1-4 carbon atoms, nitro-group, halogen atom, perfluoroalkyl with 1-4 carbon atoms, hydroxyl, amino-group, mono- or dialkylamino-group with 1-4 carbon atoms in each alkyl-group; Ar is phenyl, thienyl; R1, R2, R3 and R4 each is absent independently or means hydrogen atom, alkyl with 1-4 carbon atoms, alkoxyl-group with 1-4 carbon atoms, acyloxy-group with 1-4 carbon atoms, amino-group, mono- or dialkylamino-group with 1-4 carbon atoms in each alkyl-group, acylamino-group with 1-4 carbon atoms under condition that: a) at least one of radicals R1- R4 has value that is distinct from hydrogen atom, lower alkyl with 1-4 carbon atoms or alkoxyl-group with 1-4 carbon atoms; b) if E and B means nitrogen atom then D and A mean carbon atom and R1 and R4 are absent; R3 is hydrogen atom; X is NH; n = 0, 1 or 2; Ar is phenyl substituted with halogen atom, amino-group or hydroxyl or if n = 1 or 2 and Ar is phenyl substituted with halogen atom, amino-group or hydroxyl or if n = 1 or 2 and Ar is thienyl then R2 has value distinct from hydrogen atom, amino-group or mono- or dialkyl-amino-group with 1-4 carbon atoms in each alkyl moiety, or its pharmaceutically acceptable salt taken in the effective dose. Invention relates to also method of inhibition that involves administration to mammal of the above indicated compound or its pharmaceutically acceptable salt. Proposed compositions have the indicated bicyclic compound taken in effective dose and pharmaceutically or contraceptively acceptable excipient, diluting agent or carrier, respectively. EFFECT: new compounds indicated above, enhanced effectiveness of inhibition, valuable medicinal and pharmacological properties. 54 cl, 17 dwg, 3 tbl, 79 ex
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