US 2014/0228565 A1 · THIENOPYRIMIDINONE DERIVATIVES AS mGluR1 ANTAGONISTS

Abstract

Disclosed are thienopyrimidinone derivatives as antagonists that act on metabotropic glutamate receptor subtype 1. The thienopyrimidinone derivatives show pharmacological activity against metabotropic glutamate receptor-related diseases, including pain, such as neuropathic pain and migraine, psychiatric diseases, such as anxiety disorder and schizophrenia, urinary incontinence, and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Also disclosed are methods for preparing the thienopyrimidinone derivatives, and pharmaceutical compositions containing the thienopyrimidinone derivatives as active ingredients.

Claims16

Dependent claims

A thienopyrimidinone derivative represented by Formula 1 or 2:

wherein R1 represents an aryl group, R2 represents an alkyl or aryl group, and R3 represents a hydrogen atom, a hydroxyl group, an alkyl group, or an alkylamine group;
wherein R1 and R2 are as defined in Formula 1 and R3′ is oxygen, or a pharmaceutically acceptable salt thereof.

A method for preparing the thienopyrimidinone derivative of Formula 1:

wherein R1 is selected from phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-trimethylstannylphenyl, 3-trimethylstannylphenyl, 4-trimethylstannylphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-benzodioxolyl, 5-benzodioxolyl, 1-naphthalenyl, and 2-naphthalenyl;
R2 is selected from phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, benzonitrile, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-vinylphenyl, 3-vinylphenyl, 4-vinylphenyl, butyl, allyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, cyclopropylmethyl, cyclohexylmethyl, 4-methylcyclohexyl, tetrahydropyran-4-yl, 1,2,3,4-tetrahydronaphthalen-1-yl, tetrahydrofuran-2-ylmethyl, 1-methylpiperidin-4-yl, isobutyl, neopentyl, 2-methylcyclohexyl, 3-methylcyclohexyl, 4-ethylcyclohexyl, and acetyloxy;
and R3 is selected from hydrogen, methyl, and dimethylamino,
the method comprising:
(a) formylating an aryl acetonitrile 2 to afford an aryl hydroxyacrylonitrile 3;
(b) methylating the compound 3 to afford an aryl methoxyacrylonitrile 4;
(c) forming a thiophene ring from the aryl methoxyacrylonitrile to synthesize a thiophene derivative 5;
and
(d) synthesizing the thienopyrimidinone derivative 1 from the thiophene derivative, as depicted in Reaction Scheme 1:

6 more elements

Dependencies are inferred from the claim text.

THIENOPYRIMIDINONE DERIVATIVES AS mGluR1 ANTAGONISTS

Life of this patent

THIENOPYRIMIDINONE DERIVATIVES AS mGluR1 ANTAGONISTS

Life of this patent

Abstract

Claims16