1-(2-氯苯基)环丙烷-1-甲酰氯 | 151154-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(2-氯苯基)环丙烷-1-甲酰氯
• 英文名称: 1-[1-(2-Chlorophenyl)cyclopropyl]carbonyl chloride
• 英文别名: 1-(2-Chlorophenyl)cyclopropane-1-carbonyl chloride
• CAS: 151154-92-6
• 化学式: C₁₀H₈Cl₂O
• 分子量: 215.079
• InChiKey: MVIWGPPSRRVDIU-UHFFFAOYSA-N

物化性质

• 沸点：
  287.4±33.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(2-氯苯基)环丙烷-1-甲酰氯 、 (2S,4R)-4-(2-chlorophenylsulfonyl)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以97 mg的产率得到(4R)-1-{[1-(2-chlorophenyl)cyclopropyl]carbonyl}-4-[(2-chlorophenyl)sulfonyl]-N-(1-cyanocyclopropyl)-L-prolinamide
  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
• 作为产物：
  描述：

  methyl 1-(2-chlorophenyl)cyclopropanecarboxylate 在 氯化亚砜 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 84.75h， 生成 1-(2-氯苯基)环丙烷-1-甲酰氯
  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

• Tetraisoquinoline compounds which have useful pharmaceutical utility
  申请人：The Boots Company PLC

  公开号：US05519034A1

  公开（公告）日：1996-05-21

  Tetrahydroisoquinoline compounds of formula I ##STR1## and pharmaceutically acceptable salts and lipophilic ester thereof have utility as analgesics and in the treatment of psychoses, Parinson's disease, Lesch-Nyan syndrome, attention deficit disorder or cognitive impairment or in the relief of drug dependence or tardive dyskinesia.

  四氢异喹啉化合物的化学式为I ##STR1##，其药用盐和亲脂性酯具有镇痛作用，并可用于治疗精神病、帕金森病、莱施-尼恩综合征、注意力缺陷障碍或认知障碍，以及缓解药物依赖或迟发性运动障碍。
• 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
  作者：Adrian Huang、Alessandro Moretto、Kristin Janz、Michael Lowe、Patricia W. Bedard、Steve Tam、Li Di、Valerie Clerin、Natalia Sushkova、Boris Tchernychev、Desiree H. H. Tsao、James C. Keith、Gray D. Shaw、Robert G. Schaub、Qin Wang、Neelu Kaila

  DOI：10.1021/jm9013696

  日期：2010.8.26

  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.
• 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.
• SUBSTITUTED TETRAHYDROISOQUINOLINES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：The Boots Company PLC

  公开号：EP0618900A1

  公开（公告）日：1994-10-12
• US5519034A
  申请人：——

  公开号：US5519034A

  公开（公告）日：1996-05-21