3-(3-methoxybenzoyl)-dihydro-furan-2-one | 1007205-44-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(3-methoxybenzoyl)-dihydro-furan-2-one
• 英文别名: 3-(3-Methoxybenzoyl)-dihydrofuran-2-one；3-(3-methoxybenzoyl)oxolan-2-one
• CAS: 1007205-44-8
• 化学式: C₁₂H₁₂O₄
• 分子量: 220.225
• InChiKey: VEZWFPSTKAJKER-UHFFFAOYSA-N

物化性质

• 沸点：
  410.1±35.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-methoxybenzoyl)-dihydro-furan-2-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium t-butanolate 、 三氯氧磷 、 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene 作用下， 以 1,4-二氧六环 、 叔丁醇 为溶剂， 生成 4-(3-methoxy-phenyl)-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine
  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：

  3-[hydroxy(3-methoxyphenyl)methyl]-2-oxotetrahydrofuran 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 生成 3-(3-methoxybenzoyl)-dihydro-furan-2-one
  参考文献：
  名称：

  10.1021/acs.jafc.4c04312

  摘要：

  DOI：

  10.1021/acs.jafc.4c04312

文献信息

• Enantioselective Ketone Hydroacylation Using Noyori’s Transfer Hydrogenation Catalyst
  作者：Stephen K. Murphy、Vy M. Dong

  DOI：10.1021/ja4021974

  日期：2013.4.17

  An enantioselective ketone hydroacylation enables the direct preparation of lactones from keto alcohols. The alcohol is oxidized in situ to an aldehyde, obviating the need to prepare sensitive keto aldehyde substrates. Noyori's asymmetric transfer hydrogenation catalyst was applied to address challenges of reactivity, chemoselectivity, and enantioselectivity.

  对映选择性酮加氢酰化能够从酮醇直接制备内酯。醇被原位氧化成醛，无需制备敏感的酮醛底物。Noyori 的不对称转移氢化催化剂用于解决反应性、化学选择性和对映选择性的挑战。
• 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
• 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.