N-methyl-3-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-benzenesulfonamide | 1007206-00-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-methyl-3-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-benzenesulfonamide
• 英文别名: N-methyl-3-(2-morpholin-4-yl-7-pyridin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamide
• CAS: 1007206-00-9
• 化学式: C₂₂H₂₄N₆O₃S
• 分子量: 452.537
• InChiKey: QJRXICYDDVUZQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-[(甲氨基)磺酰基]苯甲酸 在 2-双环己基膦-2',6'-二甲氧基联苯 、 正丁基锂 、 氯化亚砜 、 sodium methylate 、 palladium diacetate 、 caesium carbonate 、 六甲基二硅氮烷 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 反应 46.25h， 生成 N-methyl-3-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-benzenesulfonamide
  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.