4-[4-氯-5-(2-氯乙基)-6-(3-甲氧基苯基)-嘧啶-2-基]-吗啉 | 1007205-47-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-[4-氯-5-(2-氯乙基)-6-(3-甲氧基苯基)-嘧啶-2-基]-吗啉
• 英文名称: 4-[4-chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)-pyrimidin-2-yl]-morpholine
• 英文别名: 4-Chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)-2-(morpholin-4-yl)-pyrimidine；4-[4-Chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)-pyrimidin-2-yl]morpholine；4-[4-chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)pyrimidin-2-yl]morpholine
• CAS: 1007205-47-1
• 化学式: C₁₇H₁₉Cl₂N₃O₂
• 分子量: 368.263
• InChiKey: AWBSFDFWJCQJIK-UHFFFAOYSA-N

物化性质

• 沸点：
  562.9±60.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  47.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-氯-5-(2-氯乙基)-6-(3-甲氧基苯基)-嘧啶-2-基]-吗啉 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium t-butanolate 、 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene 、 乙硫醇钠 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-phenol
  参考文献：
  名称：

  Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799

  摘要：

  Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase and a promising therapeutic target for cancer. Using structure-based drug design (SBDD), we have identified novel PI3K inhibitors with a dihydropyrrolopyrimidine skeleton. Metabolic stability of the first lead series was drastically improved by replacing phenol with aminopyrimidine moiety. CH5132799, a novel class I PI3K inhibitor, exhibited a strong inhibitory activity especially against PI3K alpha (IC(50) = 0.014 mu M). In human tumor cell lines with PI3K pathway activation, CH5132799 showed potent antiproliferative activity. CH5132799 is orally available and showed significant antitumor activity in PI3K pathway-activated human cancer xenograft models in mice. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.065
• 作为产物：
  描述：

  间甲氧基苯甲酰氯 在 lithium hexamethyldisilazane 、 sodium t-butanolate 、 三氯氧磷 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 反应 26.0h， 生成 4-[4-氯-5-(2-氯乙基)-6-(3-甲氧基苯基)-嘧啶-2-基]-吗啉
  参考文献：
  名称：

  Lead optimization of a dihydropyrrolopyrimidine inhibitor against phosphoinositide 3-kinase (PI3K) to improve the phenol glucuronic acid conjugation

  摘要：

  Our lead compound for a phosphoinositide 3-kinase (PI3K) inhibitor (1) was metabolically unstable because of rapid glucuronidation of the phenol moiety. Based on structure-activity relationship (SAR) information and a FlexSIS docking simulation score, aminopyrimidine was identified as a bioisostere of phenol. An X-ray structure study revealed a hydrogen bonding pattern of aminopyrimidine derivatives. Finally, aminopyrimidine derivatives 33 showed strong tumor growth inhibition against a KPL-4 breast cancer xenograft model in vivo. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.112

文献信息

• PYRIMIDINE DERIVATIVES AS PI3K INHIBITOR AND USE THEREOF
  申请人：Shimma Nobuo

  公开号：US20100069629A1

  公开（公告）日：2010-03-18

  A drug is provided that is useful as a preventive or therapeutic for cancer as a result of having superior PI3K inhibitory effects as well as superior stability in the body and water-solubility. A compound, or pharmaceutically acceptable salt thereof, represented by formula (I): [wherein, X represents a single bond, etc.; Y represents a single bond, etc. (provided that X and Y are not simultaneously single bonds); Z represents a hydrogen atom, etc.; m represents an integer of 1 or 2; and R 1 represents a cyclic substituent].

  提供了一种药物，由于具有优越的PI3K抑制作用以及在体内具有优越的稳定性和水溶性，因此可用作预防或治疗癌症。化合物或其药学上可接受的盐的表示式（I）：[其中，X表示单键等；Y表示单键等（前提是X和Y不同时为单键）；Z表示氢原子等；m表示1或2的整数；R1表示环状取代基]。
• Pyrimidine derivatives as PI3K inhibitor and use thereof
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US08022205B2

  公开（公告）日：2011-09-20

  A drug is provided that is useful as a preventive or therapeutic for cancer as a result of having superior PI3K inhibitory effects as well as superior stability in the body and water-solubility. A compound, or pharmaceutically acceptable salt thereof, represented by formula (I): [wherein, X represents a single bond, etc.; Y represents a single bond, etc. (provided that X and Y are not simultaneously single bonds); Z represents a hydrogen atom, etc.; m represents an integer of 1 or 2; and R1 represents a cyclic substituent].

  提供一种药物，由于具有卓越的PI3K抑制作用以及在体内具有卓越的稳定性和水溶性，因此可用作预防或治疗癌症。该化合物或其药学上可接受的盐的化学式为（I）：[其中，X表示单键等；Y表示单键等（前提是X和Y不同时为单键）；Z表示氢原子等；m表示1或2的整数；R1表示环状取代基]。
• PYRIMIDINE DERIVATIVE AS PI3K INHIBITOR AND USE THEREOF
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP2050749B1

  公开（公告）日：2017-11-22
• US8022205B2
  申请人：——

  公开号：US8022205B2

  公开（公告）日：2011-09-20
• Lead optimization of a dihydropyrrolopyrimidine inhibitor against phosphoinositide 3-kinase (PI3K) to improve the phenol glucuronic acid conjugation
  作者：Hatsuo Kawada、Hirosato Ebiike、Masao Tsukazaki、Mitsuaki Nakamura、Kenji Morikami、Kiyoshi Yoshinari、Miyuki Yoshida、Kotaro Ogawa、Nobuo Shimma、Takuo Tsukuda、Jun Ohwada

  DOI：10.1016/j.bmcl.2012.11.112

  日期：2013.2

  Our lead compound for a phosphoinositide 3-kinase (PI3K) inhibitor (1) was metabolically unstable because of rapid glucuronidation of the phenol moiety. Based on structure-activity relationship (SAR) information and a FlexSIS docking simulation score, aminopyrimidine was identified as a bioisostere of phenol. An X-ray structure study revealed a hydrogen bonding pattern of aminopyrimidine derivatives. Finally, aminopyrimidine derivatives 33 showed strong tumor growth inhibition against a KPL-4 breast cancer xenograft model in vivo. (c) 2012 Elsevier Ltd. All rights reserved.