Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Substituted cinnoline derivatives as GABAA-receptor modulators and method for their synthesis

A precursor, compound technology, applied in the field of treatment and/or prevention of anxiety disorders, cognitive disorders and/or mood disorders, which can solve problems such as drug incompatibility

Inactive Publication Date: 2009-03-04
ASTRAZENECA AB
View PDF8 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfavorable side effects (including addiction) exhibited by currently available GABA and GABAA receptor modulating drugs make these drugs unsuitable in multitherapy

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Substituted cinnoline derivatives as GABAA-receptor modulators and method for their synthesis
  • Substituted cinnoline derivatives as GABAA-receptor modulators and method for their synthesis
  • Substituted cinnoline derivatives as GABAA-receptor modulators and method for their synthesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0573] Example 1: 4-amino-7-fluoro-8-phenyl-N-propyl-cinnoline-3-carboxamide

[0574] Using Method F, 4-Amino-7-fluoro-8-iodo-N-propyl-cinnoline-3-carboxamide (291 mg, 0.78 mmol) and phenylboronic acid (379 mg, 3.11 mmol) were reacted (refluxed for 4 hours) ) to afford the title compound (65 mg, 26% yield) as a white solid. 1 H NMR (300MHz, CDCl 3 )δ 8.52 (bs, 1H), 7.89 (dd, J = 9.2, 4.6Hz, 1H), 7.42-7.60 (m, 6H), 3.45 (apparent q, J = 6.6Hz, 2H), 1.65 (apparent Sextet, J = 7.2 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H). MS APCI, m / z=325 (M+H). HPLC 1.92min.

Embodiment 2

[0575] Example 2: 4-amino-7-chloro-8-phenyl-N-propyl-cinnoline-3-carboxamide

[0576] Using Method F, 4-Amino-7-chloro-8-iodo-N-propyl-cinnoline-3-carboxamide (184 mg, 0.47 mmol) and phenylboronic acid (229 mg, 1.89 mmol) were reacted (40 hours at reflux ) to afford the title compound (90 mg, 56% yield) as a white solid. 1 H NMR (300MHz, CDCl 3 )δ 8.49 (bs, 1H), 7.82 (d, J = 9.0Hz, 1H), 7.75 (d, J = 9.0Hz, 1H), 7.42-7.55 (m, 5H), 3.43 (obvious q, J = 6.6 Hz, 2H), 1.63 (clear sextet, J = 7.2 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H). MS APCI, m / z=341 (M+H). HPLC 2.04min.

Embodiment 3

[0577] Example 3: 4-amino-7-methoxy-8-phenyl-N-propyl-cinnoline-3-carboxamide

[0578]Using Method F, 4-Amino-7-methoxy-8-iodo-N-propyl-cinnoline-3-carboxamide (311 mg, 0.81 mmol) and phenylboronic acid (394 mg, 3.24 mmol) were reacted (reflux overnight) to afford the title compound (140 mg, 52% yield) as a white solid. 1 H NMR (300MHz, CDCl 3 )δ 8.51(bm, 1H), 7.90(d, J=9.2Hz, 1H), 7.52(d, J=9.2Hz, 1H), 7.36-7.50(m, 5H), 3.92(s, 3H), 3.43 (clear q, J=6.4Hz, 2H), 1.63 (clear sextet, J=7.2Hz, 2H), 0.98 (t, J=7.4Hz, 3H). MS APCI, m / z=337 (M+H). HPLC 1.76min.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

This invention relates to novel Cinnoline -based compounds and their pharmaceutically acceptable salts, tautomers or in vivo- hydrolysable precursors, compositions and methods of use thereof . These novel compounds provide a treatment or prophylaxis of dementia due to Parkinson's disease, dementia due to Alzheimer's disease as well as anxiety disorders, cognitive disorders, and / or mood disorders.

Description

[0001] This application claims the benefit of U.S. Provisional Applications 60 / 752,137 (filed December 20, 2005) and 60 / 823,693 (filed August 28, 2006) under 35 U.S.C. § 119(e), which are hereby incorporated Its contents are incorporated by reference. technical field [0002] The present invention relates to novel cinnoline compounds, their pharmaceutical compositions, methods of use and methods of preparing such compounds. Furthermore, the present invention relates to therapeutic methods for the treatment and / or prevention of anxiety disorders, cognitive disorders and / or mood disorders. Background technique [0003] The present invention includes, inter alia, cinnoline compounds, their use as central nervous system (CNS) depressants (in particular as anxiolytics) and as pharmacological tools, processes for their preparation, pharmaceutical compositions containing said cinnoline compounds and their use in Intermediates for its preparation. [0004] Some cinnoline compounds...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D237/28A61K31/497A61K31/502A61K31/506A61P25/22A61P25/24A61P25/28C07D401/10C07D403/10
Inventor 马克·查普德兰塞勒斯·奥恩马克特克里斯托弗·贝克张蕙芳布鲁斯·德姆博夫斯基
Owner ASTRAZENECA AB
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com