4-(4-chloro-7-(pyridin-3-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)morpholine | 1007206-24-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(4-chloro-7-(pyridin-3-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)morpholine
• 英文别名: 4-Chloro-2-morpholin-4-yl-7-pyridin-3-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine；4-(4-chloro-7-pyridin-3-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-2-yl)morpholine
• CAS: 1007206-24-7
• 化学式: C₁₅H₁₆ClN₅O
• 分子量: 317.778
• InChiKey: XCVLCVFTGBHTDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-chloro-7-(pyridin-3-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)morpholine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 溶剂黄146 、 三氟乙酸 、 三环己基膦 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 6.0h， 生成 4-(4-(1-methylpiperidin-4-yl)-7-(pyridin-3-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)morpholine
  参考文献：
  名称：

  [EN] BICYCLIC HETEROARENES AND METHODS OF THEIR USE
  [FR] HÉTÉROARÈNES BICYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  揭示了在治疗神经系统疾病中有用的化合物。本文描述的这些化合物，单独或与其他药用活性剂结合使用，可用于治疗或预防神经系统疾病。

  公开号：

  WO2021247862A1
• 作为产物：
  描述：

  2-oxotetrahydrofuran-3-carboxylic acid methyl ester 在 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 4-(4-chloro-7-(pyridin-3-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)morpholine
  参考文献：
  名称：

  [EN] BICYCLIC HETEROARENES AND METHODS OF THEIR USE
  [FR] HÉTÉROARÈNES BICYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  揭示了在治疗神经系统疾病中有用的化合物。本文描述的这些化合物，单独或与其他药用活性剂结合使用，可用于治疗或预防神经系统疾病。

  公开号：

  WO2021247862A1

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
• Optimization of the phenylurea moiety in a phosphoinositide 3-kinase (PI3K) inhibitor to improve water solubility and the PK profile by introducing a solubilizing group and ortho substituents
  作者：Hatsuo Kawada、Hirosato Ebiike、Masao Tsukazaki、Shun Yamamoto、Kohei Koyama、Mitsuaki Nakamura、Kenji Morikami、Kiyoshi Yoshinari、Miyuki Yoshida、Kotaro Ogawa、Nobuo Shimma、Takuo Tsukuda、Jun Ohwada

  DOI：10.1016/j.bmc.2016.04.060

  日期：2016.7

  Phosphoinositide 3-kinase (PI3K) is a promising anti-cancer target, because various mutations and amplifications are observed in human tumors isolated from cancer patients. Our dihydropyrrolopyrimidine derivative with a phenylurea moiety showed strong PI3K enzyme inhibitory activity, but its pharmacokinetic property was poor because of lack of solubility. Herein, we report how we improved the solubility of our PI3K inhibitors by introducing a solubilizing group and ortho substituents to break molecular planarity. (C) 2016 Published by Elsevier Ltd.
• Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799
  作者：Jun Ohwada、Hirosato Ebiike、Hatsuo Kawada、Masao Tsukazaki、Mitsuaki Nakamura、Takuya Miyazaki、Kenji Morikami、Kiyoshi Yoshinari、Miyuki Yoshida、Osamu Kondoh、Shino Kuramoto、Kotaro Ogawa、Yuko Aoki、Nobuo Shimma

  DOI：10.1016/j.bmcl.2011.01.065

  日期：2011.3

  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.