SUBSTITUTED 1-PHENYL-3-CARBOXAMIDES AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS, METHOD OF THEIR SYNTHESIS, INTERMEDIATE COMPOUNDS AND PHARMACEUTICAL COMPOSITION BASED ON THEREOF SHOWING AFFINITY TO HUMAN NEUROTENSIN RECEPTORS

摘要

FIELD: organic chemistry, chemical technology, medicine, pharmacy. SUBSTANCE: invention relates to substituted 1-phenylpyrazole-3-carboxamides of the formula (Ia) where R_1x is in position 4 or 5 and means group T-CON-R_aR_b where T means a direct bond or (C₁-C₇-alkylene; NR_aR_b means group taken among: (a) -NR₉(CH₂)_sCR₇R₈(CH₂)_rNR₅R₆; (a), (b) , (c) ; R₅ and R₆ mean independently each of other hydrogen atom, (C₁-C₆)--alkyl, (C₃-C₈)--alkenyl; or R₅ and R₆ in common with nitrogen atom to which they are bound mean heterocycle taken among: pyrrolidine, piperidine, morpholine, piperazine substituted at position 4 with substitute R₉; mean independently each of other (C₁-C₆)-alkyl; R₇ means hydrogen atom, (C₁-C₄)alkyl or benzyl; R₈ means hydrogen atom, (C₁-C₄)-alkyl; or R₇ and R_8/ in common with carbon atom to which they are bound form (C₃-C₅)-cycloalkane; R₁₀ means hydrogen atom, (C₁-C₄)-alkyl; s = 0-3; t = 0-3 under condition that (s + t) in the same group = 1 or above; bivalent radicals A and E in common with carbon atom and nitrogen atom with which they are bound form saturated heterocycle including from 4 to 7 links that, except for, can be substituted with one or some (C₁-C₄)-alkyls; R_2x and R_3x mean independently each of other hydrogen atom, (C₁-C₆)-alkyl, (C₃-C₈)-cycloalkyl, (C₃-C₈)-cycloalkylmethyl under condition that R_2x and R_3x do not hydrogen atom simultaneously; or R_2x and R_3x in common form tetramethylene group; and their pharmaceutically acceptable salts. Also, invention proposes intermediate derivatives of 1-phenylpyrazole-3-carboxylic acid of formulas (II) or (II') where R₁, R₂, R₃ have values corresponding to values R_1x, R_2x and R_3x given for the formula (Ia). Invention relates also to method of synthesis of compounds of the formula (Ia) from indicated intermediate compounds and intermediate derivatives of phenylhydrazine used for synthesis of compounds of formulas (II) and (II'). Compounds of the formula (Ia) show affinity to human neurotensin receptors and they present a base for pharmaceutical composition. EFFECT: improved method of synthesis, valuable medicinal properties of compounds. 8 cl, 7 tbl