TRICYCLIC 5,6-DIHYDRO-9H-PYRAZOLO-[3,4-C]-1,2,4-TRIAZOLO- -[4,3-A]-PYRIDINES, METHOD OF INHIBITION OF ACTIVITY OF PHOSPHODIESTERASE TYPE IV AND METHOD OF INHIBITION OF TUMOR-SPECIFIC NECROSIS FACTOR PRODUCING

摘要

organic chemistry, biochemistry, medicine. SUBSTANCE: invention describes novel tricyclic 5,6-dihydro-9H-pyrazolo-[3,4-c]- -1,2,4-triazolo-[4,3-a] -pyridines of the general formula (I) or their pharmaceutically acceptable salts where R1 means (C1-C6)-alkyl; R2 means (C1-C14)-alkyl, (C3-C7)-cycloalkyl, saturated or unsaturated (C4-C7)-heterocyclic (CH2)n-group where n = 0 or 1 that has oxygen, sulfur or nitrogen atom as heteroatom or the group NR4 where R4 is hydrogen atom or (C1-C4)-alkyl; or the group of the formula (II) where a is the whole number 1 or 2; b and c = 0 or 1; R3 means (C1-C6)-alkyl, (C3-C7)-cycloalkyl or phenyl optionally substituted with substituents taken among the group including hydroxy-group, (C1-C5)-alkyl, (C1-C5)-alkoxy-group, halogen atom and trifluoromethyl group; R5 means hydrogen atom, (C1-C5)-alkyl, (C1-C5)-alkoxy-group, trifluoromethyl group or halogen atom; Z means oxygen atom; Y means (C1-C5)-alkoxy-group; R9 and R10 mean hydrogen atom being each of alkyl, cycloalkyl or heterocyclic group can has 1-2 substituents taken among the group including (C1-C2)-alkyl, trifluoromethyl group or halogen atom. Compounds of the formula (I) and their pharmaceutically acceptable salts are useful for inhibition of activity of phosphodiesterase type IV and tumor-specific necrosis factor and ensure to treat patients with asthma, arthritis, bronchitis, chronic obstruction of respiratory ways, psoriasis, allergic rhinitis, dermatitis and other inflammatory diseases caused by phosphodiesterase type IV and also AIDS, sepsis, septic shock and other diseases, for example, cachexia that induce the formation of tumor-specific necrosis factor. Invention describes also method of inhibition of activity of phosphodiesterase type IV and method of inhibition of tumor-specific necrosis factor producing. EFFECT: new compounds indicated above, improved method of inhibition of enzyme and tumor-necrosis factor. 5 cl, 3 dwg, 31 ex