TETRAHYDROTRIAZOLOPYRIMIDINE DERIVATIVES AS INHIBITORS OF HUMAN NEUTROPHIL ELASTASE

摘要

FIELD: pharmacology.;SUBSTANCE: invention compounds have the properties of human neutrophil elastase (HNE) inhibitors. In formula I ; ;A represents CH; R₁ is selected from hydrogen; a (C₁-C₆) alkyl; a (C₁-C₆)alkylNR₇R₈group; a (C₁-C₄)alkenyl; a (C₁-C₆)alkylphenyl, where the phenyl ring is possibly substituted by a (C₁-C₆)alkylNR₁₅R₁₆ group or a (C₁-C₆)alkylN⁺R₁₅R₁₆R₁₇group; a -(CH₂)_nCONR₅R₆group; a -CH₂-(CH₂)_nNR₅SO₂R₆group; a -(CH₂)_t-(C₆H₄)-SO₂(C₁-C₄)alkyl group; a -(CH₂)_rSO₂(C₁-C₄)alkyl group, wherein such (C₁-C₄)alkyl is possibly substituted by a -N⁺R₁₅R₁₆R₁₇group; a -SO₂-phenyl group. Such phenyl ring is possibly substituted by a (C₁-C₆)alkylNR₇R₈group; and a -(CH₂)n-W group, where W represents a 6-membered heteroaryl ring with one heteroatom N, which is possibly substituted by a group -SO₂(C₁-C₄)alkyl; n means 1; t means zero, 1; r means 2, 3; R₅ is selected from the group consisting of hydrogen, a (C₁-C₆)alkyl, a (C₁-C₆)alkylNR₁₆R₁₅group and a (C₁-C₆)alkylN⁺R₁₇R₁₅R₁₆group; R₆ represents hydrogen or a (C₁-C₆)alkyl; R₇ is selected from the group consisting of a (C₁-C₆)alkyl, a carbonyl(C₁-C₆)alkyl group, a -SO₂(C₁-C₄)alkyl group and a (C₁-C₆)alkylNR₁₆R₁₅group; R₈ represents a (C₁-C₆ )alkyl; alternatively, R₇ and R₈ can form, together with the nitrogen atom to which they are attached, a (C₅-C₇)heterocycloalkyl ring system, which is possibly substituted by oxo; R₁₆ represents a (C₁-C₆)alkyl; R₁₅ represents a (C₁-C₆)alkyl; R₁₇ represents a (C₁-C₆)alkyl; R₂ represents hydrogen or -SO₂R₄, where R₄ is selected from a (C₁-C₆)alkyl; R₁₄ represents a cyano group or a -C(O)-XR₃group; X is a divalent group selected from -O- and -NH-; R₃ represents a group selected from hydrogen; a (C₁-C₆)alkyl; a group of formula -[Alk¹]-Z, where Alk¹ represents a (C₁-C₄)alkylene radical, and Z represents NR₉R₁₀, where R₉ and R₁₀ independently represent a (C₁-C₆)alkyl. The invention also relates to pharmaceutical compositions and to a method of treating a disease or a condition in which HNE is involved.;EFFECT: new formula compounds obtained, having the properties of human neutrophil elastase inhibitors.;16 cl, 1 tbl, 39 ex