ethyl 4-chloro-2-methyl-4-oxobutanoate | 137067-89-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 4-chloro-2-methyl-4-oxobutanoate
• 英文别名: 4-Chloro-2-methyl-4-oxobutanoic acid ethyl ester
• CAS: 137067-89-1
• 化学式: C₇H₁₁ClO₃
• 分子量: 178.616
• InChiKey: UXRMQSZFEQZERX-UHFFFAOYSA-N

物化性质

• 沸点：
  220.3±23.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methoxybenzyloxy)-2-hydroxyamidinylpyridine 、 ethyl 4-chloro-2-methyl-4-oxobutanoate 在 吡啶 作用下， 以7.1 g的产率得到Ethyl 3-[3-[5-[(4-methoxyphenyl)methoxy]pyridin-2-yl]-1,2,4-oxadiazol-5-yl]-2-methylpropanoate
  参考文献：
  名称：

  Discovery of a Biaryl Cyclohexene Carboxylic Acid (MK-6892): A Potent and Selective High Affinity Niacin Receptor Full Agonist with Reduced Flushing Profiles in Animals as a Preclinical Candidate

  摘要：

  Biaryl cyclohexene carboxylic acids were discovered as full and potent niacin receptor (GPR109A) agonists. Compound le (MK-6892) displayed excellent receptor activity, good PK across species, remarkably clean off-target profiles, good ancillary pharmacology, and superior therapeutic window over niacin regarding the FFA reduction versus vasodilation in rats and dogs.

  DOI：

  10.1021/jm100022r
• 作为产物：
  描述：

  1-Ethyl 4-hydrogen 2-methylbutanedioate 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl 4-chloro-2-methyl-4-oxobutanoate
  参考文献：
  名称：

  Discovery of a Biaryl Cyclohexene Carboxylic Acid (MK-6892): A Potent and Selective High Affinity Niacin Receptor Full Agonist with Reduced Flushing Profiles in Animals as a Preclinical Candidate

  摘要：

  Biaryl cyclohexene carboxylic acids were discovered as full and potent niacin receptor (GPR109A) agonists. Compound le (MK-6892) displayed excellent receptor activity, good PK across species, remarkably clean off-target profiles, good ancillary pharmacology, and superior therapeutic window over niacin regarding the FFA reduction versus vasodilation in rats and dogs.

  DOI：

  10.1021/jm100022r

文献信息

• Discovery of MK-8318, a Potent and Selective CRTh2 Receptor Antagonist for the Treatment of Asthma
  作者：Xianhai Huang、Jason Brubaker、Wei Zhou、Purakkattle J. Biju、Li Xiao、Ning Shao、Ying Huang、Li Dong、Zhidan Liu、Rema Bitar、Alexei Buevich、Joon Jung、Scott L. Peterson、John W. Butcher、Joshua Close、Michelle Martinez、Rachel N. MacCoss、Hongjun Zhang、Scott Crawford、Kevin D. McCormick、Robert Aslanian、Ravi Nargund、Craig Correll、Francois Gervais、Hongchen Qiu、Xiaoxin Yang、Charles Garlisi、Diane Rindgen、Kevin M. Maloney、Phieng Siliphaivanh、Anandan Palani

  DOI：10.1021/acsmedchemlett.8b00145

  日期：2018.7.12

  A novel series of tricyclic tetrahydroquinolines were identified as potent and selective CRTh2 receptor antagonists. The agonism and antagonism switch was achieved through structure-based drug design (SBDD) using a CRTh2 receptor homologue model. The challenge of very low exposures in pharmacokinetic studies was overcome by exhaustive medicinal chemistry lead optimization through focused SAR studies

  一系列新的三环四氢喹啉被鉴定为有效的和选择性的CRTh2受体拮抗剂。通过使用CRTh2受体同源模型的基于结构的药物设计（SBDD）实现了激动和拮抗作用的转换。通过针对三环核心的SAR研究，通过详尽的药物化学铅优化，克服了药代动力学研究中极低暴露的挑战。进一步的优化导致临床前候选药物4-（环丙基（（3 aS，9 R，9 aR）-7-氟-4-（4-（三氟甲氧基）苯甲酰基）-2,3,3 a，4， 9,9-一个-六氢- 1 H ^环戊二烯并[ b ]喹啉-9-基）氨基）-4-氧代丁酸（15c，MK-8318）具有有效的和选择性的CRTh2拮抗剂活性和有利的PK曲线，适于每天一次口服给药以潜在地治疗哮喘。
• Niacin Receptor Agonists, Compositions Containing Such Compounds and Methods of Treatment
  申请人：Colletti L. Steven

  公开号：US20070281969A1

  公开（公告）日：2007-12-06

  The present invention encompasses compounds of Formula (I); as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating dyslipidemias. Pharmaceutical compositions and methods of use are also included.

  本发明涵盖了式（I）的化合物；以及其药学上可接受的盐和水合物，可用于治疗血脂异常。还包括制药组合物和使用方法。
• WO2006/57922
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/120575
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] NIACIN RECEPTOR AGONISTS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] AGONISTES DU RÉCEPTEUR DE LA NIACINE, COMPOSITIONS CONTENANT DE TELS COMPOSÉS ET MÉTHODES DE TRAITEMENT
  申请人：MERCK & CO INC

  公开号：WO2007120575A2

  公开（公告）日：2007-10-25

  [EN] The present invention encompasses compounds of Formula (I) as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dysliptdemias and the like. Pharmaceutical compositions and methods of use are also included.
  [FR] L'invention a trait à des composés représentés par la formule (I) ainsi qu'à des sels et des hydrates pharmaceutiquement acceptables desdits composés, qui sont utiles pour traiter l'athérosclérose, les dyslipidémies et analogues. L'invention concerne également des compositions pharmaceutiques et des procédés d'utilisation associés.