TRICYCLIC DIAZEPINE VASOPRESSIN AND OXYTOCIN ANTAGONISTS, METHOD OF THEIR SYNTHESIS, PHARMACEUTICAL COMPOSITION, METHOD OF TREATMENT Russian patent published in 1999 - IPC

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to tricyclic diazepine antagonists of vasopressin and oxytocin of the general formula (I) where Y means -(CH₂)_n where n = 0 or 1; A-B means -NR³-(CH₂)_m- where m = 1 or 2 and fragment means condensed phenyl, 5-membered aromatic (unsaturated) heterocyclic ring containing one sulfur heteroatom. Fragment means 5-membered heterocyclic, unsaturated, condensed ring containing nitrogen atom where D, E and F are taken from carbon or nitrogen atoms and where carbon atoms can be optionally substituted with substituents taken from halogen atom, , -C(O)O-lower-(C₁-C₃)-alkyl and others; substituent R³ means a fragment of the formula where Ar means a residue where R⁵ and R⁷ are hydrogen, lower-(C₁-C₃)-alkyl, lower-(C₁-C₃)-alkoxy-group and halogen atom. Compound is taken from fragments of formulas -NR_aCOAr′,-CONR_aAr′,-NR_aCOCH₂Ar′ and others where R_a is hydrogen, CH₂ or ; q = 1; R_b is CH₃ or C₂H₅; Ar′ is taken from fragments of formulas where W′ means S; R⁸ and R⁹ are taken independently from hydrogen atom, lower-(C₁-C₃)-alkyl, -S-lower-(C₁-C₃)-alkyl, halogen atom, OH, NO₂, -O-lower-(C₁-C₃)-alkyl, CF₃; R¹⁰ is taken from hydrogen, halogen atoms, lower-(C₁-C₃)-alkyl, and its pharmaceutically acceptable salts and prodrugs. Method of synthesis of compounds of the formula (I) involves an interaction of compound of the formula (II) with compound of the formula Ar-C(O)-Q where substituents Y, Q, E, F, Z, Ar and n are given above. A substituent Q means halogen atom or activating group that is synthesized by conversion of arylcarboxylic acid to mixed anhydride or by activation using couple peptide reagent to compound of the formula (I). Invention relates to also a pharmaceutical composition showing antagonistic activity with respect to vasopressin and can be used for treatment of patients with excess absorption of renal water, congestion cardiac failure, liver cirrhosis, nephrotic syndrome, central nervous system damages and others and to treatment of patients with vasopressin-dependent diseases also. EFFECT: improved method of synthesis, enhanced effectiveness of compounds. 13 cl, 13 tbl