CN112204018A - 一类丙烯酸类化合物及其制备方法、药物组合物和用途 - Google Patents

一类丙烯酸类化合物及其制备方法、药物组合物和用途 Download PDF

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CN112204018A
CN112204018A CN201980032898.1A CN201980032898A CN112204018A CN 112204018 A CN112204018 A CN 112204018A CN 201980032898 A CN201980032898 A CN 201980032898A CN 112204018 A CN112204018 A CN 112204018A
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acrylic acid
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CN112204018B (zh
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柳红
刘浥
李佳
王江
陈亚琼
蒋昊文
王一冰
夏春梅
傅杨杰
董天成
蒋华良
陈凯先
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Fudan University
Shanghai Institute of Materia Medica of CAS
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Shanghai Institute of Materia Medica of CAS
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Abstract

本发明提供了一类丙烯酸类化合物及其制备方法、药物组合物和用途，具体地，本发明提供了一种如下式I所示的化合物，其中，各基团的定义如说明书中所述。所述的化合物可以作为CREB/CRTC2互作抑制剂，用于制备治疗糖尿病等疾病的药物组合物。

Description

PCT国内申请，说明书已公开。

Claims (11)

  1. PCT国内申请，权利要求书已公开。
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Families Citing this family (1)

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Publication number Priority date Publication date Assignee Title
CN117402123A (zh) * 2022-07-06 2024-01-16 中国科学院上海药物研究所 一类α,β-不饱和酰胺类化合物及其制备方法、药物组合物和用途

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3298917A (en) * 1964-09-15 1967-01-17 Merck & Co Inc Antidiabetic nu-acylaliphaticsulfonamides
WO2004050022A2 (en) * 2002-12-04 2004-06-17 Merck & Co., Inc. Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
CN101111475A (zh) * 2003-06-26 2008-01-23 生物环境有限公司 抗病毒化合物及方法
CN101845025A (zh) * 2010-06-30 2010-09-29 哈尔滨理工大学 3-α,β-不饱和酰基-1,3-噁唑烷-2-酮的制备方法
US20110082109A1 (en) * 2009-10-02 2011-04-07 Ajinomoto Co., Inc. Novel acyl guanidine derivatives
WO2011047432A1 (en) * 2009-10-22 2011-04-28 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
CN103339116A (zh) * 2011-01-31 2013-10-02 中国科学院上海药物研究所 取代正戊酰胺类化合物、其制备方法及用途

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100430386C (zh) * 2002-11-07 2008-11-05 默克公司 苯丙氨酸衍生物作为二肽基肽酶抑制剂用于治疗或预防糖尿病

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3298917A (en) * 1964-09-15 1967-01-17 Merck & Co Inc Antidiabetic nu-acylaliphaticsulfonamides
WO2004050022A2 (en) * 2002-12-04 2004-06-17 Merck & Co., Inc. Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
CN101111475A (zh) * 2003-06-26 2008-01-23 生物环境有限公司 抗病毒化合物及方法
US20110082109A1 (en) * 2009-10-02 2011-04-07 Ajinomoto Co., Inc. Novel acyl guanidine derivatives
WO2011047432A1 (en) * 2009-10-22 2011-04-28 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
CN101845025A (zh) * 2010-06-30 2010-09-29 哈尔滨理工大学 3-α,β-不饱和酰基-1,3-噁唑烷-2-酮的制备方法
CN103339116A (zh) * 2011-01-31 2013-10-02 中国科学院上海药物研究所 取代正戊酰胺类化合物、其制备方法及用途

Non-Patent Citations (23)

* Cited by examiner, † Cited by third party
Title
B. A. SHAINYAN ET AL.: "Reactions of N-Sulfinyltrifluoromethanesulfonamide with Carboxylic Acids" *
CHAOZHONG CAI ET AL.: "Michael Addition Reactions between Chiral Ni(II) Complex of Glycine and 3-(trans-Enoyl)oxazolidin-2-ones. A Case of Electron Donor-Acceptor Attractive Interaction-Controlled Face Diastereoselectivity1", 《J. ORG. CHEM.》 *
DAVID B. BERKOWITZ ET AL.: "Enzyme-Assisted Asymmetric Total Synthesis of (-)-Podophyllotoxin and (-)-Picropodophyllin" *
DEPENG ZHAO ET AL.: "Highly Efficient Asymmetric Michael Addition of Diaryl Phosphine Oxides to a,b-Unsaturated N-Acylated Oxazolidin-2-ones", 《CHEM. ASIAN J.》 *
DEPENG ZHAO ET AL.: "Highly Efficient Asymmetric Michael Addition of Diaryl Phosphine Oxides to α,β-Unsaturated N-Acylated Oxazolidin-2-ones" *
GIULIANA CARDILLO ET AL.: "Lewis Acid-Promoted Synthesis and Reactivity of â-O-Benzylhydroxylamino Imides Derived from D-Glyceraldehyde" *
JASBIR SINGH ET AL.: "Antagonists of the EP3 Receptor for Prostaglandin E2 Are Novel Antiplatelet Agents That Do Not Prolong Bleeding" *
JOSE M. CONCELLON ET AL.: "An Efficient Catalytic Chromium-Mediated Iodocyclopropanation Reaction: Stereoselective Synthesis of Iodocyclopropanecarboxamides", 《ADV. SYNTH. CATAL.》 *
LEI ZHAO ET AL.: "Asymmetric β Boration of α,β-Unsaturated N-Acyloxazolidinones by [2.2]Paracyclophane-Based Bifunctional Catalyst" *
LEI ZHAO ET AL.: "Asymmetric β-Boration of r,β-Unsaturated N-Acyloxazolidinones by [2.2]Paracyclophane-Based Bifunctional Catalyst", 《ORG. LETT.》 *
LIANSUO ZU ET AL.: "Cascade Michael-Aldol Reactions Promoted by Hydrogen Bonding Mediated Catalysis" *
LIANSUO ZU ET AL.: "Cascade Michael-Aldol Reactions Promoted by Hydrogen Bonding Mediated Catalysis", 《J. AM. CHEM. SOC.》 *
LIQIN JIANG ET AL.: "Rh(II)/Brønsted Acid Cocatalyzed Intramolecular Trapping of Ammonium Ylides with Enones: Diastereoselective Synthesis of 2,2,3-Trisubstituted Indolines" *
PHILIP T. CHERIAN ET AL.: "Acyl-sulfamates target the essential glycerol-phosphate acyltransferase (PlsY) in Gram-positive bacteria" *
SHOUJIAO PENG ET AL.: "Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents" *
THI MY UYEN TON ET AL.: "Iron(II)-Catalyzed Amidation of Aldehydes with Iminoiodinanes at Room Temperature and under Microwave-Assisted Conditions" *
VADIM A. SOLOSHONOK ET AL.: "Application of modular nucleophilic glycine equivalents for truly practical asymmetric synthesis of b-substituted pyroglutamic acids", 《TETRAHEDRON LETTERS》 *
VICTORIA MAGRIOTI ET AL.: "New potent and selective polyfluoroalkyl ketone inhibitors of GVIA calcium-independent phospholipase A2", 《BIOORGANIC & MEDICINAL CHEMISTRY》 *
VIDADALA RAMASUBBA RAO ET AL.: "Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)" *
YAN LIU ET AL.: "Catalytic Asymmetric Conjugate Addition of Simple Alkyl Thiols to α,β-Unsaturated N-Acylated Oxazolidin-2-ones with Bifunctional Catalysts" *
YAQIONG CHEN ET AL.: "A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex", 《NATURE COMMUNICATIONS》 *
YIN LUO ET AL.: "Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agent" *
林岱宗 等: "含氟β-氨基酸和β-内酰胺的合成研究进展", 《有机化学》 *

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