methyl 2-[(2S)-1-(2-chloro-5-nitropyrimidin-4-yl)pyrrolidin-2-yl]acetate | 1234479-66-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: methyl 2-[(2S)-1-(2-chloro-5-nitropyrimidin-4-yl)pyrrolidin-2-yl]acetate
• CAS: 1234479-66-3
• 化学式: C₁₁H₁₃ClN₄O₄
• 分子量: 300.702
• InChiKey: RJFXBZOFMUWXIW-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-[(2S)-1-(2-chloro-5-nitropyrimidin-4-yl)pyrrolidin-2-yl]acetate 在 铁粉 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 (6S)-13-chloro-9-methyl-2,9,12,14-tetrazatricyclo[8.4.0.02,6]tetradeca-1(14),10,12-trien-8-one
  参考文献：
  名称：

  Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a Potent and Selective Inhibitor of Big MAP Kinase 1

  摘要：

  Kinome-wide selectivity profiling of a collection of 2-amino-pyrido[2,3-d]pyrimidines followed by cellular structure activity relationship-guided optimization resulted in the identification of moderately potent and selective inhibitors of BMK1/ERK5 exemplified by 11, 18, and 21. For example, 11 possesses a dissociation constant (K-d) for BMK1 of 19 nM, a cellular IC50 for inhibiting epidermal growth factor induced BMK1 autophosphorylation of 0.19 +/- 0.04 mu M, and an Ambit KINOMEscan selectivity score (Ss) of 0.035. Inhibitors 18 and I 21 are also potent BMK1 inhibitors and possess favorable pharmacokinetic properties which enable their use as pharmacological probes of BMK1-dependent phenomena as well as starting points for further optimization efforts.

  DOI：

  10.1021/ml100304b
• 作为产物：
  描述：

  (2S)-2-吡咯烷乙酸甲酯盐酸盐 、 2,4-二氯-5 硝基嘧啶 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 以50%的产率得到methyl 2-[(2S)-1-(2-chloro-5-nitropyrimidin-4-yl)pyrrolidin-2-yl]acetate
  参考文献：
  名称：

  [EN] PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS
  [FR] COMPOSÉS PYRIMIDO-DIAZÉPINONE D'ÉCHAFAUDAGE DE KINASE ET PROCÉDÉS DE TRAITEMENT DE TROUBLES

  摘要：

  公开号：

  WO2010080712A3

文献信息

• [EN] PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS<br/>[FR] COMPOSÉS PYRIMIDO-DIAZÉPINONE D'ÉCHAFAUDAGE DE KINASE ET PROCÉDÉS DE TRAITEMENT DE TROUBLES
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2010080712A3

  公开（公告）日：2010-11-11
• PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS
  申请人：Gray Nathanael S.

  公开号：US20120040961A1

  公开（公告）日：2012-02-16

  The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), polo kinase 1, 2, 3, or 4, Ack1, Ack2, AbI, DCAMKL1, ABL1, AbI mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS 1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, AxI, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.
• US9266890B2
  申请人：——

  公开号：US9266890B2

  公开（公告）日：2016-02-23
• US9464091B2
  申请人：——

  公开号：US9464091B2

  公开（公告）日：2016-10-11
• US9701683B2
  申请人：——

  公开号：US9701683B2

  公开（公告）日：2017-07-11