Compound with substituted tetratomic ring structure and medicine use thereof

A technology of four-membered rings and compounds, applied in the field of a class of compounds with substituted four-membered ring structures and their medical applications

Inactive Publication Date: 2008-06-11
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Except for GLP-1 and its peptide analogues, there are no reports on the successful development of non-peptide small molecule GLP-1R agonists

Method used

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  • Compound with substituted tetratomic ring structure and medicine use thereof
  • Compound with substituted tetratomic ring structure and medicine use thereof
  • Compound with substituted tetratomic ring structure and medicine use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0166] Embodiment 1: the preparation of compound S4P

[0167] NMR calibration: δH / C 7.26 / 77.0ppm (CDCl 3 ); δH / C 2.50 / 39.51ppm (DMSO-d 6 ).

[0168]

[0169] The compound Wang516 (1g) was dissolved in an appropriate amount of DMSO, placed under a 150W high-pressure mercury lamp for 3 days, added 1ml of water, and continued to irradiate for 7-10 days, during which the reaction was detected and tracked by HPLC. After the reaction was completed, the solvent was removed by lyophilization, and the residue was separated by column chromatography. Compound S4P was obtained as a light yellow powdery solid.

[0170] 1 HNMR (300MHz, DMSO-d 6 ) 10.053 (2H, br.s), 8.630 (2H, br.s), 8.090 (2H, dd, J 1 = 4.8Hz,J 2 = 1.2Hz), 8.029 (2H, dd, J 1 = 3.6Hz,J 2 =1.2Hz), 7.605(4H, d, J=8.4Hz), 7.395(4H, d, J=8.1Hz), 7.31(2H, m), 7.280(2H, br.s), 7.260(2H, m ), 7.206(2H, br.d, J=8.1Hz), 4.987(2H, br.s), 3.244(6H, s), 2.740(2H, m), 1.815(4H, m), 1.703(4H, m), 1.652 (4H, m), 1.526 (4H, m)...

Embodiment 2

[0172] Embodiment 2: the preparation of compound S4P and its isomer

[0173]

[0174] The compound Wang516 (10 g) was dissolved in an appropriate amount of DMSO, placed under natural light at room temperature for 30-90 days, lyophilized to remove the solvent, and the residue was separated by HPLC to obtain a small amount of light yellow powdery solid compound S4P. conformers and S4P.

[0175] 1 HNMR (300MHz, DMSO-d 6 ) 10.125 (2H, br.s), 8.025 (2H, d, J=4.8Hz), 7.921 (2H, d, J=2.9Hz), 7.667 (4H, br.s), 7.251 (2H, m), 7.220 (2H, br.s), 6.983 (2H, d, J=7.7Hz), 6.908 (2H, d, J=7.7Hz), 5.269 (2H, br.s), 3.335 (6H, s), 2.779 (2H, m), 1.832 (4H, m), 1.715 (4H, m), 1.677 (4H, m), 1.527 (4H, m).

[0176] 13 CNMR (75MHz, DMSO-d 6 ) 174.8, 174.7, 164.7, 159.5, 149.9, 142.1, 136.5, 135.0, 131.7, 129.3, 128.7, 127.6, 121.8, 120.1, 118.4, 112.0, 64.7, 55.1, 51.8, 45.3, 30.1, 25.7.

[0177] The NMR data of S4P are the same as Example 1.

Embodiment 3

[0178] Example 3: Preparation of Compound S4P Using a Catalyst

[0179]

[0180] Dissolve compound Wang516 (20 mg) in an appropriate amount of DMSO, add 25 mg of benzophenone, place it under a 150w high-pressure mercury lamp for 1 day, lyophilize to remove the solvent, and separate the residue by column separation to obtain light yellow powdery solid compound S4P .

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Abstract

The invention provides a compound with a substituted four-membered ring structure represented as formula I or II, relative pharmacy acceptable salt, ester, solvent and metal complex, or prodrug with same pharmacologia function, and ra elative application of being glucagon-like peptide-1 receptor modulator to prevent and/or treat metabolic disorder (as diabetes, insulin resistance and obesity or the like), cardiovascular disease and neurodegenerative disease (as Alzheimer's) or the like.

Description

technical field [0001] The present invention relates to a class of compounds with a substituted four-membered ring structure as glucagon-like peptide-1 receptor (Glucagon like peptide-1 receptor, GLP-1R) regulators in the prevention and / or treatment of metabolic disorders (including but Medical use not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease), etc. Background technique [0002] Glucose metabolism disorder, especially diabetes, has become a major disease that seriously threatens human health and life in modern society. It is predicted that diabetes patients in the world are increasing at an annual rate of 6%, and by the end of 2006 there were 320 million patients (60 million people in my country, ranking second). Diabetes mellitus is a group of clinical syndromes caused by the interaction of genetic and environmental factors. It is mainly divided into type 1 and type 2. The basi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D333/70A61K31/381A61P9/00A61P3/00A61P25/28
CPCC07D333/40A61P3/00A61P3/04A61P3/10A61P9/00A61P25/00A61P25/16A61P25/28
Inventor 王明伟陈德溯李娜刘青廖嘉渝
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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