2-ALKYNYL AND 2-ALKENYL-PYRAZOLE-4,3-e-1,2,4-TRIAZOLO-1,5-e-PYRIMIDINE ANTAGONISTS OF ADENOSINE A_2A RECEPTOR

摘要

FIELD: chemistry.;SUBSTANCE: invention relates to new compounds of formula (I) and their pharmaceutically acceptable salts with antagonistic properties towards adenosine A2A receptor, which can be used for treating central nervous system diseases such as Parkinson's disease. In general formula (I) , R is ,, R¹, R², R³, R⁴ and R⁵ is independently selected from a group which consists of hydrogen; R⁶ is hydrogen, (C₁-C₆)alkyl or -CH₂F; R⁷, R⁸ and R⁹ are independently selected from a group which consists of hydrogen, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, haloid and -CF₃; Z is R¹⁰-phenyl, R¹⁰-5-6-member heteroaryl, which contains 1 or 2 hetwroatoms, selected from nitrogen or from nitrogen and oxygen, possibly condensed with a benzene ring, or ; R¹⁰ represents 1 to 3 substitutes, independently selected from a group which consists of hydrogen, (C₁-C₆)-alkyl, hydroxy, (C₁-C₆)-alkoxy, hydroxy-(C₁-C₆)-alkyl, hydroxy-(C₁-C₆)-alkoxy, (C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)-alkoxy-(C₁-C₆)-alkoxy, (C₁-C₆)-alkoxy-(C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (di-(C₁-C₆)-alkoxy)-(C₁-C₆)-alkyl, (hydroxy)-(C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyloxy, (C₃-C₆)-cycloalkyl-O-(C₃-C₆)-alkoxy, (C₁-C₆)-alkyl-SO₂-, (C₁-C₆)-alkyl-SO-, haloid, -CN, cyano-(C₁-C₆)-alkyl, -CHF₂, -CF₃, -C(O)R¹³, -C(O)O-(C₁-C₆)-alkyl, -N(R¹¹)(R¹²), N(R¹¹)(R¹²)- (C₁-C₆)-alkyl, - C(O)N(R¹³)(R¹⁶), R¹¹-5-6-member nitrogen-containing heteroaryl, possibly condensed with a benzene ring, R¹⁵-5-6-member heterocycoalkyl, with 1 or 2 heteroatoms selected from nitrogen and oxygen, R¹⁵-5-6-member heterocycloalkyl-(C₁-C₆)-alkyl, with 1 or 2 heteroatoms selected from nitrogen and oxygen, R¹⁵-5-6-member heterocycloalkyl-(C₁-C₆)-alkoxy, with 1 or 2 heteroatoms selected from nitrogen and oxygen, R¹⁵-5-6-member heterocycloalkyl-oxy, with 1 or 2 heteroatoms in a heterocyclic ring selected from nitrogen and oxygen, CF₃-(C₁-C₄)alkylene-O-(C₁-C₆)alkyl, CF₃-hydroxy(C₁-C₆)alkyl, cyano-(C₁-C₆)-alkoxy, (C₁-C₄)alkylene-C(O)-O-(C₁-C₆)alkyl, -SO₂-N((C₁-C₄)alkyl)₂, ((C₃-C₄)cycloalkyl)hydroxy(C₁-C₆)alkyl, (hydroxy(C₁-C₆)alkyl)-(C₁-C₄)alkoxy, (dihydroxy)-(C₁-C₆)-alkyl, (dihydroxy)(C₁-C₆)alkoxy, -C(=NOR¹⁷)- (C₁-C₆)alkyl and -C(=NOR¹⁷)-CF₃; or two R¹⁰ groups, on neighbouring carbon atoms of the ring, together form -O-CH₂-O-, -O-(CH₂)₂-O-, -CH₂-O(CH₂)₂-O-, -O-(CH₂)₂-, -(CH₂)₃-O-, -O-(CH₂)₃-O, -(CH₂)₃-, where the ring, formed by two R¹⁰ substitutes and ring carbon atoms with which they are bonded, is substituted with R¹⁶; or two R¹⁰ groups on neighbouring ring carbon atoms, together form -O(CH₂)₃CH((OR¹⁸)-, each R¹¹ is independently selected from a group which consists of hydrogen and (C₁-C₆)alkyl; each R¹² is independently selected from a group which consists of (C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl, -C(O)-(C₁-C₆)alkyl, -C(O)O-(C₁-C₆)alkyl, ((C₁-C₆)alkoxy)hydroxy(C₁-C₆)alkyl, (C₁-C₆)alkoxy (C₁-C₆)alkyl-C(O)-, -SO₂(C₁-C₆)alkyl; R¹³ is hydrogen, (C₁-C₆)alkyl or -CF₃; R¹⁴ is (C₁-C₆)alkoxy-C(O)-; R¹⁵ represents 1 to 3 substitutes, independently selected from a group which consists of (C₁-C₆)alkoxy, hydroxy-(C₁-C₆)alkyl; or two R¹5 substitutes, taken together with the carbon atom with which they are bonded, form a -C(=O)- group; R¹⁶ is (C₁-C₆)alkoxy(C₁-C₆)alkyl, hydroxy or hydroxy(C₁-C₆)alkyl; R¹⁷ is hydrogen or (C₁-C₆)alkyl. The invention also relates to a pharmaceutical composition based on said compounds.;EFFECT: increased effectiveness of composition and method of treatment.;17 cl, 23 ex