Thienopyrimidinone derivatives as mGluR1 antagonists

Patent metadata

Field	Value
Publication number	US-9260448-B2
Application number	US-201314038324-A
Country	US
Kind code	B2
Filing date	Sep 26, 2013
Priority date	Feb 8, 2013
Publication date	Feb 16, 2016
Grant date	Feb 16, 2016

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.

First claim

What is claimed is:

1. A compound represented by Formula 1:

wherein R1 represents an aryl group, R2 represents an alkyl or aryl group, and R3 represents a hydrogen atom, an alkyl group, or an alkylamine group.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R1 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthalenyl, and substituted or unsubstituted benzodioxolyl; the substituted phenyl is phenyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, substituted or unsubstituted stannyl, and phenyl; the substituted stannyl is alkylstannyl substituted with one to three C 1 -C 7 alkyl groups; the substituted naphthalenyl is naphthalenyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, C 1 -C 7 alkoxy, unsubstituted stannyl, C 1 -C 7 alkylstannyl, C 1 -C 7 dialkylstannyl, C 1 -C 7 trialkylstannyl, and phenyl; and the substituted benzodioxolyl is benzodioxolyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, C 1 -C 7 alkoxy, unsubstituted stannyl, C 1 -C 7 alkylstannyl, C 1 -C 7 dialkylstannyl, C 1 -C 7 trialkylstannyl, and phenyl.

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein (i) R2 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzonitrile, substituted or unsubstituted C 1 -C 7 alkyl, allyl, vinyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted pyranyl, substituted or unsubstituted hydropyranyl, substituted or unsubstituted naphthalenyl, substituted or unsubstituted hydronaphthalenyl, substituted or unsubstituted furanyl, substituted or unsubstituted hydrofuranyl, substituted or unsubstituted piperidinyl, and substituted or unsubstituted C 3 -C 10 heterocycloalkyl; or (ii) R2 has a C 1 -C 7 alkyl group through which a group selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzonitrile, substituted or unsubstituted C 1 -C 7 alkyl, allyl, vinyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted pyranyl, substituted or unsubstituted hydropyranyl, substituted or unsubstituted naphthalenyl, substituted or unsubstituted hydronaphthalenyl, substituted or unsubstituted furanyl, substituted or unsubstituted hydrofuranyl, substituted or unsubstituted piperidinyl, and substituted or unsubstituted C 3 -C 10 heterocycloalkyl is linked to the corresponding nitrogen atom of the thienopyrimidinone ring; the substituted phenyl is phenyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the substituted benzonitrile is benzonitrile in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the substituted C 1 -C 7 alkyl is C 1 -C 7 alkyl in which one to three hydrogen atoms of the alkyl are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, allyl, C 3 -C 10 cycloalkyl, furanyl, and hydrofuranyl; the substituted C 3 -C 10 cycloalkyl is C 3 -C 10 cycloalkyl substituted with substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, allyl, and C 1 -C 7 alkyl; the substituted pyranyl is pyranyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the hydropyranyl is dihydropyranyl or tetrahydropyranyl; the substituted hydropyranyl is hydropyranyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the substituted naphthalenyl is naphthalenyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the hydronaphthalenyl is selected from dihydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, and heptahydronaphthalenyl; the substituted hydronaphthalenyl is hydronaphthalenyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the substituted furanyl is furanyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the hydrofuranyl is dihydrofuranyl or tetrahydrofuranyl; the substituted hydrofuranyl is hydrofuranyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl; the substituted piperidinyl is (i) piperidinyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl, or (ii) piperidinyl in which a substituent selected from C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, vinyl, and allyl is bonded to the nitrogen atom of the piperidine ring; the C 3 -C 10 heterocycloalkyl is heterocycloalkyl in which one or two heteroatoms selected from N, O and S, and three to ten carbon atoms are bonded together to form a ring; and the substituted C 3 -C 10 heterocycloalkyl is heterocycloalkyl in which some or all of the hydrogen atoms are replaced by substituents selected from halogen, C 1 -C 7 alkyl, halogenated C 1 -C 7 alkyl, C 1 -C 7 alkoxy, halogenated C 1 -C 7 alkoxy, hydroxy, nitro, vinyl, and allyl.

4. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R3 is selected from hydrogen, C 1 -C 7 alkyl, and substituted or unsubstituted amino, the substituted amino in R3 being amino substituted with one or two C 1 -C 7 alkyl groups; and R3′ is oxygen.

5. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R1 is selected from phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2bromophenyl, 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-meth

Assignees

• Korea Inst Sci & Tech

Inventors

• Choo Hyunah
• Min Sun Joon
• Seo Seon Hee
• Kim Jee Yeon
• Ki Yoo Ran
• Kim Min Joo
• Kim Sora
• Kim Youngjae

Classifications

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title