US 7,067,655 B2 · Adenosine A2a receptor antagonists

Abstract

Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, cycloalkenyl, or heteroaryl; X is alkylene or —C(O)CH2—; Y is —N(R2)CH2CH2N(R3)—, —OCH2CH2N(R2)—, —O—, —S—, —CH2S—, —(CH2)2—NH—, or optionally substituted m and n are 2–3, and Q is nitrogen or optionally substituted carbon; and Z is optionally substituted phenyl, phenylalkyl or heteroaryl, diphenylmethyl, R6—C(O)—, R6—SO2—, R6—OC(O)—, R7—N(R8)—C(O)—, R7—N(R8)—C(S)—, phenyl-CH(OH)—, or phenyl-C(═NOR2)—; or when Q is CH, phenylamino or pyridylamino; or Z and Y together are substituted piperidinyl or substituted phenyl; and R2, R3, R6, R7, and R8 are as defined in the specification are disclosed, their use in the treatment of Parkinson's disease, alone or in combination with other agents for treating Parkinson's disease, and pharmaceutical compositions comprising them; also disclosed are a processes for preparing intermediates useful for preparing compounds of formula I.

Claims3

Dependent claims

A process of preparing a compound of formula II

wherein R is R1-furanyl, R1-thienyl, R1-pyridyl, R1-pyridyl N-oxide, R1-oxazolyl, R10-phenyl, R1-pyrrolyl or C4–C6 cycloalkenyl;
R1 is 1 to 3 substituents independently selected from hydrogen, C1–C6-alkyl, —CF3, halogen, —NO2, NR12R13, C1–C6 alkoxy, C1–C6 alkylthio, C1–C6 alkylsulfinyl, and C1–C6 alkylsulfonyl;
R10 is 1 to 5 substituents independently selected from the group consisting of hydrogen, halogen, C1–C6 alkyl, hydroxy, C1–C6 alkoxy, —CN, —NH2, C1–C6alkylamino, di-((C1–C6)alkyl)amino, —CF3, —OCF3 and —S(O)0-2(C1–C6)alkyl;
R12 is H or C1–C6 alkyl;
and
R13 is (C1–C6)alkyl-C(O)— or (C1–C6)alkyl-SO2—;
comprising
(1) treating 2-amino-4,6-dihydroxypyrimidine
with POCl3 in dimethylformamide to obtain 2-amino-4,6-dichloropyrimidine-5-carboxaldehyde
(2) treating carboxaldehyde VII with a hydrazide of the formula H2N—NH—C(O)—R, wherein R is as defined above, to obtain
(3) treating the intermediate of formula VIII with hydrazine hydrate to form a pyrazolo ring, thus obtaining the intermediate of formula IX
(4) forming the desired compound of formula II by dehydrative rearrangement.

9 more elements

Dependencies are inferred from the claim text.

Adenosine A2a receptor antagonists

Life of this patent

Adenosine A2a receptor antagonists

Life of this patent

Abstract

Claims3