3,3-二氟-1-甲基环丁烷-1-羧酸乙酯 | 227607-45-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3,3-二氟-1-甲基环丁烷-1-羧酸乙酯
• 英文名称: 3,3-Difluoro-1-methyl-cyclobutanecarboxylic acid ethyl ester
• 英文别名: Ethyl 3,3-difluoro-1-methylcyclobutanecarboxylate；ethyl 3,3-difluoro-1-methylcyclobutane-1-carboxylate
• CAS: 227607-45-6
• 化学式: C₈H₁₂F₂O₂
• 分子量: 178.179
• InChiKey: XPJJHWLCLJNZCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-二氟-1-甲基环丁烷-1-羧酸乙酯 在 sodium hydroxide 、 草酰氯 、 水 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-N-[1-(4-bromophenyl)ethyl]-3,3-difluoro-1-methylcyclobutanecarboxamide
  参考文献：
  名称：

  Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides

  摘要：

  A new fungicide lead has been identified by enzyme screening of a focused combinatorial library. The lead compound 4, a potent inhibitor of scytalone dehydratase (SD), exhibits fungicidal activity upon foliar application but does not show systemic activity. The X-ray crystal structure of the enzyme-inhibitor complex and an appreciation for the relationship between physical properties and systemic activity enabled us to rapidly improve upon this initial lead. The geminal halogen-methyl group combination was found to be optimal for interaction with the bounding serine and asparagine side-chain residues. Replacement of CF3 with methyl was a key discovery, giving inhibitors with slightly diminished enzyme inhibition potency while significantly increasing systemic activity. Amides prepared from amines with 2,4-dichloro substitution on the phenyl ring gave the most potent enzyme inhibitors. Two compounds from this series showed systemic activity comparable to the commercial standard and were selected for outdoor testing in flooded plots which simulate rice paddies. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00034-1
• 作为产物：
  描述：

  1-甲基-3-氧代环丁烷-1-羧酸乙酯 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 为溶剂， 以76%的产率得到3,3-二氟-1-甲基环丁烷-1-羧酸乙酯
  参考文献：
  名称：

  Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides

  摘要：

  A new fungicide lead has been identified by enzyme screening of a focused combinatorial library. The lead compound 4, a potent inhibitor of scytalone dehydratase (SD), exhibits fungicidal activity upon foliar application but does not show systemic activity. The X-ray crystal structure of the enzyme-inhibitor complex and an appreciation for the relationship between physical properties and systemic activity enabled us to rapidly improve upon this initial lead. The geminal halogen-methyl group combination was found to be optimal for interaction with the bounding serine and asparagine side-chain residues. Replacement of CF3 with methyl was a key discovery, giving inhibitors with slightly diminished enzyme inhibition potency while significantly increasing systemic activity. Amides prepared from amines with 2,4-dichloro substitution on the phenyl ring gave the most potent enzyme inhibitors. Two compounds from this series showed systemic activity comparable to the commercial standard and were selected for outdoor testing in flooded plots which simulate rice paddies. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00034-1

文献信息

• NOVEL TRPV3 MODULATORS
  申请人：ABBVIE INC.

  公开号：US20140080803A1

  公开（公告）日：2014-03-20

  Disclosed herein are modulators of TRPV3 of Formula (I) wherein p is 1, 2, 3, or 4, and G 1 , X 1 , X 2 , X 3 , X 4 , X 5 , G 2 , Z 1 , R a , R b , and u are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.

  本文披露了TRPV3的调节剂，其化学式为(I)，其中p为1、2、3或4，G1、X1、X2、X3、X4、X5、G2、Z1、Ra、Rb和u的定义如规范中所述。还提供了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。
• CYSTEINE PROTEASE INHIBITORS
  申请人：Ayesa Susana

  公开号：US20130172232A1

  公开（公告）日：2013-07-04

  Compounds of the formula I wherein R 2a and R 2b are independently H, halo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy, or R 2a and R 2b together with the carbon atom to which they are attached form a C 3 -C 6 cycloalkyl; R 3 is a C 5 -C 10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; or R 3 is a C 2 -C 4 alkyl chain with at least 2 chloro or 3 fluoro substituents; or R 3 is C 3 -C 7 cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; R 4 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino or; R 4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R 4 is Het, carbocyclyl, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

  化合物的公式为I，其中R2a和R2b独立地为H、卤素、C1-C4烷基、C1-C4卤代烷基或C1-C4烷氧基，或者R2a和R2b与它们连接的碳原子一起形成C3-C6环烷基；R3是C5-C10烷基，可选地被1-3个卤素、C1-C4卤代烷基、C1-C4烷氧基或C1-C4卤代烷氧基独立地取代；或者R3是具有至少2个氯或3个氟取代基的C2-C4烷基链；或者R3是C3-C7环烷基甲基，可选地被1-3个C1-C4烷基、卤素、C1-C4卤代烷基、C1-C4烷氧基或C1-C4卤代烷氧基独立地取代；R4是C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6卤代烷氧基、C1-C6烷基氨基、C1-C6二烷基氨基或者R4是Het或Carbocyclyl，它们中的任意一个可选地被1-3个取代基取代，其中R4是Het、carbocyclyl、C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基或C1-C6卤代烷氧基；n为1、2或3；用于预防或治疗由于cathepsin S不适当的表达或激活而表现出的障碍。
• US8772499B2
  申请人：——

  公开号：US8772499B2

  公开（公告）日：2014-07-08
• US8859505B2
  申请人：——

  公开号：US8859505B2

  公开（公告）日：2014-10-14
• Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides
  作者：Lee D. Jennings、Dennis R. Rayner、Douglas B. Jordan、John F. Okonya、Gregory S. Basarab、Denise K. Amorose、Beth M. Anaclerio、John K. Lee、Rand S. Schwartz、Kari Ann Whitmore

  DOI：10.1016/s0968-0896(00)00034-1

  日期：2000.5

  A new fungicide lead has been identified by enzyme screening of a focused combinatorial library. The lead compound 4, a potent inhibitor of scytalone dehydratase (SD), exhibits fungicidal activity upon foliar application but does not show systemic activity. The X-ray crystal structure of the enzyme-inhibitor complex and an appreciation for the relationship between physical properties and systemic activity enabled us to rapidly improve upon this initial lead. The geminal halogen-methyl group combination was found to be optimal for interaction with the bounding serine and asparagine side-chain residues. Replacement of CF3 with methyl was a key discovery, giving inhibitors with slightly diminished enzyme inhibition potency while significantly increasing systemic activity. Amides prepared from amines with 2,4-dichloro substitution on the phenyl ring gave the most potent enzyme inhibitors. Two compounds from this series showed systemic activity comparable to the commercial standard and were selected for outdoor testing in flooded plots which simulate rice paddies. (C) 2000 Elsevier Science Ltd. All rights reserved.