trans-1-benzyl-4-trifluoromethylpyrrolidine-3-carboxylic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: trans-1-benzyl-4-trifluoromethylpyrrolidine-3-carboxylic acid ethyl ester
• 英文别名: ethyl 1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylate；trans-N-benzyl-4-trifluoromethyl-3-pyrrolidinecarboxylic acid ethyl ester；trans-Ethyl 1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylate；ethyl (3R,4R)-1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylate
• 化学式: C₁₅H₁₈F₃NO₂
• 分子量: 301.309
• InChiKey: SJIVVBIUXVKZDK-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  trans-1-benzyl-4-trifluoromethylpyrrolidine-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以91.4%的产率得到((3R,4R)-1-benzyl-4-(trifluoromethyl)pyrrolidin-3-yl)methanol
  参考文献：
  名称：

  Quinolinecarboxylic acid derivatives and salts thereof

  摘要：

  喹啉羧酸衍生物的一般公式（I）如下所示：其中R.sub.1是一个可能被取代的C.sub.1到C.sub.6烷基基团，一个可能被取代的C.sub.2到C.sub.6烯基基团，一个可能被取代的C.sub.3到C.sub.7环烷基基团或一个可能被取代的芳基基团，R.sub.2是氢原子；卤素原子；可能被保护的羟基，氨基或一个可能被保护的C.sub.1到C.sub.6烷基氨基基团；一个C.sub.1到C.sub.6二烷基氨基基团或一个C.sub.1到C.sub.6烷基基团，R.sub.3是氢原子或一个C.sub.1到C.sub.6烷基基团，A是氮原子或##STR2##其中A'是氢原子。卤素原子，一个C.sub.1到C.sub.6烷基基团，一个可能被取代的C.sub.1到C.sub.6烷氧基团，氰基或硝基，A'可以与R.sub.1形成一个环；该环可以包括氧原子、氮原子或硫原子作为构成原子；该环可以被一个C.sub.1到C.sub.6烷基基团取代，X是羟甲基基团；氨甲基基团或氨基每个可能被保护，及其盐，以及以喹啉羧酸衍生物和其盐为活性成分的抗菌剂，以及通过这种方法进行的治疗方法。

  公开号：

  US05668147A1
• 作为产物：
  描述：

  N-(甲氧甲基)-N-(三甲基硅甲基)苄胺 、 ethyl (2E)-5,5,5-trifluoropent-2-enoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到trans-1-benzyl-4-trifluoromethylpyrrolidine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants

  摘要：

  First generation EGFR TKIs (gefitinib, erlotinib) provide significant clinical benefit for NSCLC cancer patients with oncogenic EGFR mutations. Ultimately, these patients' disease progresses, often driven by a second-site mutation in the EGFR kinase domain (T790M). Another liability of the first generation drugs is severe adverse events driven by inhibition of WT EGFR. As such, our goal was to develop a highly potent irreversible inhibitor with the largest selectivity ratio between the drug-resistant double mutants (L858R/T790M, Del/T790M) and WT EGFR A unique approach to develop covalent inhibitors, optimization of reversible binding affinity, served as a cornerstone of this effort. PF-06459988 was discovered as a novel, third generation irreversible inhibitor, which demonstrates (0 high potency and specificity to the T790M-containing double mutant EGFRs, (ii) minimal intrinsic chemical reactivity of the electrophilic warhead, (iii) greatly reduced proteome reactivity relative to earlier irreversible EGFR inhibitors, and (iv) minimal activity against WT EGFR

  DOI：

  10.1021/acs.jmedchem.5b01633

文献信息

• Bicyclic-Fused Heteroaryl or Aryl Compounds
  申请人：Pfizer Inc.

  公开号：US20150284405A1

  公开（公告）日：2015-10-08

  Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物的异构体和药学上可接受的盐已被披露，其中所述化合物具有如规范中定义的Ia式结构。相应的药物组合物、治疗方法、合成方法和中间体也已被披露。
• PYRROLOPYRIMIDINE AND PURINE DERIVATIVES
  申请人：Cheng Hengmiao

  公开号：US20130079324A1

  公开（公告）日：2013-03-28

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R 1 , R 2 , R 3 , R 4 , R 5 , R 5a , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

  本发明涉及式（I）的化合物或其药学上可接受的盐，其中Q、T、V、W、X、Y、Z、环A、R1、R2、R3、R4、R5、R5a、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17和m在此定义。这些新颖的吡咯嘧啶和嘌呤衍生物在哺乳动物中治疗异常细胞生长，如癌症方面具有用处。另外，本发明还涉及含有这些化合物的药物组合物，以及在哺乳动物中治疗异常细胞生长的方法。
• [EN] PYRROLOPYRIMIDINE AND PURINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRROLOPYRIMIDINE ET DE PURINE
  申请人：PFIZER

  公开号：WO2013042006A1

  公开（公告）日：2013-03-28

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

  本发明涉及式(I)的化合物或其药学上可接受的盐，其中Q、T、V、W、X、Y、Z、环A、R1、R2、R3、R4、R5、R5a、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17和m在此定义。这些新型吡咯并嘧啶和嘌呤衍生物在哺乳动物中用于治疗异常细胞增长，例如癌症。其他实施例涉及含有这些化合物的药物组合物以及使用这些化合物和组合物治疗哺乳动物中的异常细胞增长的方法。
• [EN] BICYCLIC-FUSED HETEROARYL OR ARYL COMPOUNDS AND THEIR USE AS IRAK4 INHIBITORS<br/>[FR] COMPOSÉS À BASE D'HÉTÉROARYLE OU D'ARYLE FUSIONNÉ-BICYCLIQUE ET LEUR UTILISATION COMME COMPOSÉS INHIBITEURS DE L'IRAK 4
  申请人：PFIZER

  公开号：WO2015150995A1

  公开（公告）日：2015-10-08

  Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  该专利披露了具有Ia式结构的化合物、互变异构体和药学上可接受的盐，其定义在说明书中。还披露了相应的制药组合物、治疗方法、合成方法和中间体。
• QUINOLINECARBOXYLIC ACID DERIVATIVE AND SALT THEREOF
  申请人：KAKEN PHARMACEUTICAL CO., LTD.

  公开号：EP0726269A1

  公开（公告）日：1996-08-14

  Quinolinecarboxylic acid derivatives which are represented by the general formula (I) wherein R1 is a C1 to C6 alkyl group which may be substituted, a C2 to C6 alkenyl group which may be substituted, a C3 to C7 cycloalkyl group which may be substituted or an aryl group which may be substituted, R2 is hydrogen atom; a halogen atom; hydroxyl group which may be protected, amino group or a C1 to C6 alkylamino group each of which may be protected; a C1 to C6 dialkylamino group or a C1 to C6 alkyl group, R3 is hydrogen atom or a C1 to C6 alkyl group, A is nitrogen atom or wherein A' is hydrogen atom, a halogen atom, a C1 to C6 alkyl group, a C1 to C6 alkoxyl group which may be substituted, cyano group, or nitro group, and A' may form a ring with R1; the ring may include oxygen atom, nitrogen atom, or sulfur atom as a constituent atom; the ring may be substituted with a C1 to C6 alkyl group, X is hydroxymethyl group; aminomethyl group or amino group each of which may be protected, and salts thereof, and antibacterial agents which comprise the quinolinecarboxylic acid derivatives and salts thereof as active ingredients, and therapeutical methods thereby.

  通式(I)表示的喹啉羧酸衍生物 其中 R1 是可被取代的 C1 至 C6 烷基、可被取代的 C2 至 C6 烯基、可被取代的 C3 至 C7 环烷基或可被取代的芳基，R2 是氢原子；卤素原子；可被保护的羟基、氨基或 C1 至 C6 烷基氨基，其中每个都可被保护；C1 至 C6 二烷基氨基或 C1 至 C6 烷基、 R3 是氢原子或 C1 至 C6 烷基、 A 是氮原子或 其中 A'是氢原子、卤素原子、C1 至 C6 烷基、可被取代的 C1 至 C6 烷氧基、氰基或硝基，A'可与 R1 形成环；环的组成原子可包括氧原子、氮原子或硫原子；环可被 C1 至 C6 烷基取代、 X 是羟甲基、氨甲基或氨基，其中每个基团都可以被保护、 及其盐类，以及包含喹啉羧酸衍生物及其盐类作为活性成分的抗菌剂及其治疗方法。