1-[3-(trifluoromethyl)-phenyl]cyclopropanecarbonyl chloride | 501698-49-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[3-(trifluoromethyl)-phenyl]cyclopropanecarbonyl chloride
• 英文别名: Cyclopropanecarbonyl chloride, 1-[3-(trifluoromethyl)phenyl]-；1-[3-(trifluoromethyl)phenyl]cyclopropane-1-carbonyl chloride
• CAS: 501698-49-3
• 化学式: C₁₁H₈ClF₃O
• 分子量: 248.632
• InChiKey: KCEHQIHQXLMSJO-UHFFFAOYSA-N

物化性质

• 沸点：
  239.7±40.0 °C(Predicted)
• 密度：
  1.416±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  三(三甲基硅氧基)乙烯 、 1-[3-(trifluoromethyl)-phenyl]cyclopropanecarbonyl chloride 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 2-hydroxy-(1-(1-(3-trifluoromethyl)phenyl)cyclopropyl)ethanone
  参考文献：
  名称：

  Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic Acid (PSI-421), a P-Selectin Inhibitor with Improved Pharmacokinetic Properties and Oral Efficacy in Models of Vascular Injury

  摘要：

  Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure activity-studies in this series by branching at the alpha position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.

  DOI：

  10.1021/jm9013696
• 作为产物：
  描述：

  1-[3-(三氟甲基)苯基]环丙烷羧酸 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 15.5h， 生成 1-[3-(trifluoromethyl)-phenyl]cyclopropanecarbonyl chloride
  参考文献：
  名称：

  蛋白质-配体相互作用中卤素键的系统研究

  摘要：

  卤素键触发活性：通过将芳环H原子与Cl，Br和I交换，可以观察到一系列共价的人组织蛋白酶L抑制剂的结合亲和力增加，Cl，Br和I与S3口袋中的Gly61的CO基团进行卤素键合酶。相反，氟强烈避免卤素键（参见方案）。卤素键的强距离和角度依赖性已被证实适用于生物系统。

  DOI：

  10.1002/anie.201006781

文献信息

• [EN] AMINO ARYL ACETAMIDES AND THEIR USE IN THE TREATMENT OF MALARIA<br/>[FR] AMINOARYLACÉTAMIDES ET LEUR UTILISATION DANS LE TRAITEMENT DU PALUDISME
  申请人：GLAXO GROUP LTD

  公开号：WO2011061277A1

  公开（公告）日：2011-05-26

  Amino phenyl acetamide compounds of Formula (I):and pharmaceutically acceptable salts thereof: wherein R1, R2, R3 and Ra are as defined in the description, use of such compounds in the chemotherapy of certain parasitic protozoal infections such as malaria, pharmaceutical compositions including such compounds and processes for the preparation of such compounds, are provided.

  化合物的氨基苯乙酰胺的化合物的分子式（I）及其药学上可接受的盐：其中R1、R2、R3和Ra如描述中所定义，这些化合物在化疗某些寄生原虫感染，如疟疾中的用途，包括这些化合物的制药组合物和制备这些化合物的方法。
• Chemical compounds
  申请人：Adams Leroy Jerry

  公开号：US20050004142A1

  公开（公告）日：2005-01-06

  Furo- and thienopyrimidine derivatives, which are useful as TIE-2 and/or VEGFR-2 inhibitors are described herein. The described invention also includes methods of making such furo- and thienopyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了作为TIE-2和/或VEGFR-2抑制剂有用的呋喃和噻吩嘧啶衍生物。所述发明还包括制备这种呋喃和噻吩嘧啶衍生物的方法，以及使用它们治疗增殖过度性疾病的方法。
• 4-AMINO-2,3-DISUBSTITUTED THIENO [2,3,D]PYRIMIDINES AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Adams Jerry Leroy

  公开号：US20080287466A1

  公开（公告）日：2008-11-20

  Furo- and thienopyrimidine derivatives, which are useful as TIE-2 and/or VEGFR-2 inhibitors are described herein. The described invention also includes methods of making such furo- and thienopyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了作为TIE-2和/或VEGFR-2抑制剂有用的呋喃和噻唑嘧啶衍生物。所述发明还包括制备这种呋喃和噻唑嘧啶衍生物的方法以及使用它们治疗增生性疾病的方法。
• 4-Amino-2,3-disubstituted thieno[2,3-d]pyrimidines and pharmacetical compositions thereof
  申请人：SmithKline Beecham Corporation

  公开号：US07427623B2

  公开（公告）日：2008-09-23

  Furo- and thienopyrimidine derivatives, which are useful as TIE-2 and/or VEGFR-2 inhibitors are described herein. The described invention also includes methods of making such furo- and thienopyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了作为TIE-2和/或VEGFR-2抑制剂有用的呋喃和噻唑嘧啶衍生物。所述发明还包括制备这种呋喃和噻唑嘧啶衍生物的方法，以及在治疗增生性疾病方面使用它们的方法。
• Cyclopropyl Carboxamides: A New Oral Antimalarial Series Derived from the Tres Cantos Anti-Malarial Set (TCAMS)
  作者：Lourdes Rueda、Isabel Castellote、Julia Castro-Pichel、Maria J. Chaparro、Juan Carlos de la Rosa、Adolfo Garcia-Perez、Mariola Gordo、Maria Belen Jimenez-Diaz、Albane Kessler、Simon J.F. Macdonald、Maria Santos Martinez、Laura M. Sanz、Francisco Javier Gamo、Esther Fernandez

  DOI：10.1021/ml2001517

  日期：2011.11.10

  Rapid triaging of three series of related hits selected from the Tres Cantos Anti-Malarial Set (TCAMS) are described. A triazolopyrimidine series was deprioritized due to delayed inhibition of parasite growth. A lactic acid series has derivatives with IC50 < 500 nM in a standard Plasmodium falciparum in vitro whole cell assay (Pf assay) but shows half-lives of < 30 min in both human and murine microsomes. Compound 19, from a series of cyclopropyl carboxamides, is a highly potent in vitro inhibitor of P. falciparum (IC50 = 3 nM) and has an oral bioavailability of 55% in CD-1 mice and an ED90 of 20 mg/kg after oral dosing in a nonmyelo-depleted P.falciparum murine model.