ethyl 2-(3-oxopropyl)thiazole-4-carboxylate | 1355026-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-(3-oxopropyl)thiazole-4-carboxylate
• 英文别名: ethyl 2-(3-oxopropyl)-1,3-thiazole-4-carboxylate；Ethyl 2-(3-oxopropyl)-1,3-thiazole-4-carboxylate
• CAS: 1355026-83-3
• 化学式: C₉H₁₁NO₃S
• 分子量: 213.257
• InChiKey: GFZWGBVAXXXKKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  84.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(3-oxopropyl)thiazole-4-carboxylate 、 ethyl (4R,5E,7S)-4-amino-7-hydroxy-8-(3-methylphenyl)-5-octenoate hydrochloride 在 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 ethyl 2-(3-((R)-2-((S,E)-3-hydroxy-4-(m-tolyl)but-1-en-1-yl)-5-oxopyrrolidin-1-yl)propyl)thiazole-4-carboxylate
  参考文献：
  名称：

  Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists

  摘要：

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.018
• 作为产物：
  描述：

  2-溴噻唑-4-甲酸乙酯 在 platinum(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 草酰氯 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， -70.0~80.0 ℃ 、206.85 kPa 条件下， 反应 21.33h， 生成 ethyl 2-(3-oxopropyl)thiazole-4-carboxylate
  参考文献：
  名称：

  [EN] CYCLOPROPYL-AMIDE COMPOUNDS AS DUAL LSD1/HDAC INHIBITORS
  [FR] COMPOSÉS CYCLOPROPYL-AMIDES UTILISÉS COMME INHIBITEURS DOUBLES DE LSD1/HDAC

  摘要：

  公开号：

  WO2017195216A4

文献信息

• Novel dual LSD1/HDAC6 inhibitors for the treatment of multiple myeloma
  作者：M Naveen Sadhu、Dhanalakshmi Sivanandhan、Chandru Gajendran、Subramanyam Tantry、Purushottam Dewang、Kannan Murugan、Srinatha Chickamunivenkatappa、Mohd Zainuddin、Sreekala Nair、Krishnakumar Vaithilingam、Sridharan Rajagopal

  DOI：10.1016/j.bmcl.2020.127763

  日期：2021.2

  HDAC6 selective dual inhibitors to target MM. Our dual inhibitor compound 1 shows superior potency in multiple MM cell lines. In MM.1S xenograft model compound 1 shows superior efficacy compared to single agent LSD1 and HDAC6 inhibitors by oral administration and is well tolerated. Further evaluation of the molecule in other cancers is in progress.

  赖氨酸特异性脱甲基酶1（LSD1）和HDAC6是与多种疾病（包括癌症）相关的表观遗传蛋白，这些蛋白的联合抑制对治疗某些癌症（如AML，MM和实体瘤）可能非常有益。多发性骨髓瘤（MM）是一种具有挑战性的癌症，具有快速复发率，其中需要一小时的治疗方法。我们已经设计和开发了针对MM的新型LSD1和HDAC6选择性双重抑制剂。我们的双重抑制剂化合物1在多种MM细胞系中显示出卓越的功效。在MM.1S异种移植模型化合物1中，口服单药LSD1和HDAC6抑制剂比单药LSD1和HDAC6抑制剂具有更高的疗效，并且耐受性良好。该分子在其他癌症中的进一步评估正在进行中。
• Cyclopropyl-amide compounds as dual LSD1/HDAC inhibitors
  申请人：Jubilant Epicore LLC

  公开号：US11352322B2

  公开（公告）日：2022-06-07

  The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therpeautic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, parkinson's disease and the like.

  本公开描述了通式（I）的新型化合物及其类似物、同分异构体、立体异构体、多晶型、水合物、溶液、药学上可接受的盐、药物组合物、代谢物和原药。这些化合物可同时抑制 LSD 和 HDAC，可用作治疗或改善涉及细胞生长的疾病的药物，如恶性肿瘤、精神分裂症、阿尔茨海默病、帕金森病等。
• Discovery of a novel EP2/EP4 dual agonist with high subtype-selectivity
  作者：Tohru Kambe、Toru Maruyama、Masayuki Nakano、Yoshihiko Nakai、Tadahiro Yoshida、Naoki Matsunaga、Hiroji Oida、Akira Konaka、Takayuki Maruyama、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmcl.2011.10.109

  日期：2012.1

  A series of gamma-lactam prostaglandin E(1) analogs bearing a 16-phenyl moiety in the omega-chain and aryl moiety in the alpha-chain were synthesized and biologically evaluated. Among the tested compounds, gamma-lactam PGE analog 3 designed as a structural hybrid of 1 and 2 was discovered as the most optimized EP2/EP4 dual agonist with excellent subtype-selectivity (K(i) values: mEP2 = 9.3 nM, mEP4 = 0.41 nM). A structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.
• CYCLOPROPYL-AMIDE COMPOUNDS AS DUAL LSD1/HDAC INHIBITORS
  申请人：Jubilant Epicore LLC

  公开号：US20200308110A1

  公开（公告）日：2020-10-01

  The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therpeautic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, parkinson's disease and the like.
• Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hideyuki Yoshida、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.02.018

  日期：2012.4

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.