1-(3-溴-5-氟苯基)-2-甲基-1-丙酮 | 1147871-74-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(3-溴-5-氟苯基)-2-甲基-1-丙酮
• 英文名称: 1-(3-bromo-5-fluorophenyl)-2-methylpropan-1-one
• CAS: 1147871-74-6
• 化学式: C₁₀H₁₀BrFO
• 分子量: 245.091
• InChiKey: PZCAGILAIOQFKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• 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：
  2

安全信息

• 海关编码：
  2914700090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  1-(3-溴-5-氟苯基)-2-甲基-1-丙酮 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 四氯化钛 、 sodium carbonate 作用下， 以 四氢呋喃 、 氯仿 、 水 、 甲苯 为溶剂， 反应 54.1h， 生成 benzyl 3'-(1,1-dicyano-3-methylbut-1-en-2-yl)-5'-fluoro[1,1'-biphenyl]-3-carboxylate
  参考文献：
  名称：

  Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures

  摘要：

  Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development., We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t(1/2) > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 angstrom resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.

  DOI：

  10.1021/acs.jmedchem.7b00008
• 作为产物：
  描述：

  1,3-二溴-5-氟苯 、 异丁酰氯 在 异丙基氯化镁 、 copper(l) chloride 、 zinc(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 2.92h， 生成 1-(3-溴-5-氟苯基)-2-甲基-1-丙酮
  参考文献：
  名称：

  [EN] SYNTHESIS AND CRYSTALLINE FORMS OF CB-1 ANTAGONIST/INVERSE AGONIST
  [FR] SYNTHÈSE ET FORMES CRISTALLINES D'ANTAGONISTE/AGONISTE INVERSÉ DE CB-1

  摘要：

  公开号：

  WO2009054923A3

文献信息

• SYNTHESIS AND CRYSTALLINE FORMS OF CB-1 ANTAGONIST/INVERSE AGONIST
  申请人：Campos Kevin R.

  公开号：US20100292282A1

  公开（公告）日：2010-11-18

  The present invention relates to a process for producing crystalline 3-[(1S)-1-(1-(S)-(4-chlorophenyl)[3-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]methyl}azetidin-3-yl)-2-fluoro-2-methyl-propyl]-5-fluorobenzonitrile, and novel salts, solvates, hydrates and polymorphs thereof.

  本发明涉及一种生产晶体3-[(1S)-1-(1-(S)-(4-氯苯基)[3-(5-氧代-4,5-二氢-1,3,4-噁二唑-2-基)苯基]甲基}氮杂环己烷-3-基)-2-氟-2-甲基-丙基]-5-氟苯甲腈及其新的盐、溶剂化合物、水合物和多晶形式的方法。
• Small molecule Ras inhibitors
  申请人：Briesewitz Roger

  公开号：US10736932B2

  公开（公告）日：2020-08-11

  Disclosed herein are novel compounds that are Ras inhibitors. Also disclosed are compositions comprising the compounds and methods of using the compounds in treating various diseases. In another aspect, provided is an antibody-drug-conjugate comprising an antibody conjugated with a compound described herein. In still another aspect, provided is a pharmaceutical composition comprising a compound or antibody-drug-conjugate described herein. In a further aspect, provided is method of treating a cancer comprising administering a therapeutically effective amount of a compound or antibody-drug-conjugate described herein to a patient in need thereof.

  本文公开了作为 Ras 抑制剂的新型化合物。还公开了包含这些化合物的组合物以及使用这些化合物治疗各种疾病的方法。在另一个方面，提供了一种抗体-药物-结合物，其包含与本文所述化合物共轭的抗体。还有一方面，提供了一种药物组合物，包含本文所述的化合物或抗体-药物-轭合物。在另一个方面，提供了治疗癌症的方法，包括向有需要的患者施用治疗有效量的本文所述化合物或抗体-药物-结合物。
• SMALL MOLECULE RAC OR RHO INHIBITORS
  申请人：Ohio State Innovation Foundation

  公开号：US20170112896A1

  公开（公告）日：2017-04-27

  Disclosed herein are methods of inhibiting Rac or Rho in a cell or tissue or for treating a disease mediated at least in part by Rac or Rho, using a compound of the formula:
• SMALL MOLECULE RAS INHIBITORS
  申请人：Briesewitz Roger

  公开号：US20170304383A1

  公开（公告）日：2017-10-26

  Disclosed herein are novel compounds that are Ras inhibitors. Also disclosed are compositions comprising the compounds and methods of using the compounds in treating various diseases. In another aspect, provided is an antibody-drug-conjugate comprising an antibody conjugated with a compound described herein. In still another aspect, provided is a pharmaceutical composition comprising a compound or antibody-drug-conjugate described herein. In a further aspect, provided is method of treating a cancer comprising administering a therapeutically effective amount of a compound or antibody-drug-conjugate described herein to a patient in need thereof.
• Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures
  作者：Geoffrey Schwertz、Matthias C. Witschel、Matthias Rottmann、Roger Bonnert、Ubolsree Leartsakulpanich、Penchit Chitnumsub、Aritsara Jaruwat、Wanwipa Ittarat、Anja Schäfer、Raphael A. Aponte、Susan A. Charman、Karen L. White、Abhijit Kundu、Surajit Sadhukhan、Mel Lloyd、Gail M. Freiberg、Myron Srikumaran、Marc Siggel、Adrian Zwyssig、Pimchai Chaiyen、François Diederich

  DOI：10.1021/acs.jmedchem.7b00008

  日期：2017.6.22

  Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development., We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t(1/2) > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 angstrom resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.