(3S,4S)-tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate | 895245-29-1

• 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: (3S,4S)-tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3S,4S)-3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate；(3S,4S)-3-(tert-butyl-dimethyl-silanyloxymethyl)-4-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (3S,4S)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 895245-29-1
• 化学式: C₁₇H₃₅NO₄Si
• 分子量: 345.555
• InChiKey: NEQWPSWFXDNURG-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S)-tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate 在 palladium 10% on activated carbon sodium azide 、 四丁基氟化铵 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.75h， 生成 (3R,4R)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(2-methyl-2-phenyl-propionylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2006/100036

  摘要：

  公开号：
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 palladium 10% on activated carbon 锂硼氢 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.5h， 生成 (3S,4S)-tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  WO2006/100036

  摘要：

  公开号：

文献信息

• [EN] CELL PROLIFERATION INHIBITORS AND CONJUGATES THEREOF<br/>[FR] INHIBITEURS DE LA PROLIFÉRATION CELLULAIRE ET LEURS CONJUGUÉS
  申请人：NOVARTIS AG

  公开号：WO2014151030A1

  公开（公告）日：2014-09-25

  Disclosed herein are immunoconjugates comprising an inhibitor of Eg5 linked to an antigen binding moiety such as an antibody, useful for treating cell proliferative disorders. Also disclosed are novel inhibitors of Eg5 that can be used either alone or as part of an immunoconjugate to treat cell proliferation disorders. The Eg5 inhibitors include compounds of this formula as described herein: [insert last structure from page 68 here] The invention further provides pharmaceutical compositions comprising these compounds and immunoconjugates, optionally including a therapeutic co-agent, and methods to use these compounds, conjugates and compositions for treating cell proliferation disorders.

  本发明公开了包含Eg5抑制剂的免疫偶联物，该抑制剂与抗原结合部分如抗体相连，用于治疗细胞增殖紊乱。还公开了新颖的Eg5抑制剂，可以单独使用或作为免疫偶联物的一部分来治疗细胞增殖紊乱。Eg5抑制剂包括如本文所述的这种化合物的化合物：[在此插入第68页的最后一个结构]本发明进一步提供了包含这些化合物和免疫偶联物的药物组合物，可选地包括治疗共剂，以及使用这些化合物、偶联物和组合物来治疗细胞增殖紊乱的方法。
• 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均在此定义。这些新型吡咯吡嗪和嘌呤衍生物在哺乳动物中治疗异常细胞生长（如癌症）方面有用。另外，一些实施例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。
• Pyrrolopyrimidine and purine derivatives
  申请人：Cheng Hengmiao

  公开号：US09040547B2

  公开（公告）日：2015-05-26

  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。这些新型吡咯吡嗪和嘌呤衍生物在哺乳动物的异常细胞生长，如癌症治疗中有用。另外，还涉及含有这些化合物的制药组合物以及在哺乳动物的异常细胞生长治疗中使用这些化合物和组合物的方法。
• Discovery of 1-{(3<i>R</i>,4<i>R</i>)-3-[({5-Chloro-2-[(1-methyl-1<i>H</i>-pyrazol-4-yl)amino]-7<i>H</i>-pyrrolo[2,3-<i>d</i>]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
  作者：Hengmiao Cheng、Sajiv K. Nair、Brion W. Murray、Chau Almaden、Simon Bailey、Sangita Baxi、Doug Behenna、Sujin Cho-Schultz、Deepak Dalvie、Dac M. Dinh、Martin P. Edwards、Jun Li Feng、Rose Ann Ferre、Ketan S. Gajiwala、Michelle D. Hemkens、Amy Jackson-Fisher、Mehran Jalaie、Ted O. Johnson、Robert S. Kania、Susan Kephart、Jennifer Lafontaine、Beth Lunney、Kevin K.-C. Liu、Zhengyu Liu、Jean Matthews、Asako Nagata、Sherry Niessen、Martha A. Ornelas、Suvi T. M. Orr、Mason Pairish、Simon Planken、Shijian Ren、Daniel Richter、Kevin Ryan、Neal Sach、Hong Shen、Tod Smeal、Jim Solowiej、Scott Sutton、Khanh Tran、Elaine Tseng、William Vernier、Marlena Walls、Shuiwang Wang、Scott L. Weinrich、Shuibo Xin、Haiwei Xu、Min-Jean Yin、Michael Zientek、Ru Zhou、John C. Kath

  DOI：10.1021/acs.jmedchem.5b01633

  日期：2016.3.10

  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