5-(2-羟基乙基)-2-吗啉嘧啶-4,6-二醇 | 1178564-17-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 5-(2-羟基乙基)-2-吗啉嘧啶-4,6-二醇
• 英文名称: 5-(2-hydroxyethyl)-2-morpholin-4-yl-pyrimidine-4,6-diol
• 英文别名: 5-(2-Hydroxyethyl)-2-morpholinopyrimidine-4,6-diol；4-hydroxy-5-(2-hydroxyethyl)-2-morpholin-4-yl-1H-pyrimidin-6-one
• CAS: 1178564-17-4
• 化学式: C₁₀H₁₅N₃O₄
• 分子量: 241.247
• InChiKey: XJQDWVBTFXSQDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  94.4
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-(2-羟基乙基)-2-吗啉嘧啶-4,6-二醇 在 2-双环己基膦-2',6'-二甲氧基联苯 、 吡啶 、 4-二甲氨基吡啶 、 potassium phosphate 、 硫酸 、 水 、 palladium diacetate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium iodide 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 66.75h， 生成 N,N-bis[(4-methoxyphenyl)methyl]-5-(2-morpholino-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Modification of a dihydropyrrolopyrimidine phosphoinositide 3-kinase (PI3K) inhibitor to improve oral bioavailability

  摘要：

  Phosphoinositide 3-kinase (PI3K) is activated in various human cancer cells and well known as a cancer therapy target. We previously reported a dihydropyrrolopyrimidine derivative as a highly potent PI3K inhibitor that has strong tumor growth inhibition in a xenograft model. In this report, we describe further optimization to improve its bioavailability. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.009
• 作为产物：
  描述：

  2-oxotetrahydrofuran-3-carboxylic acid methyl ester 、 吗啉-4-羧酰胺 在 sodium 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 5-(2-羟基乙基)-2-吗啉嘧啶-4,6-二醇
  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]。
• PYRROLOPYRIMIDINE DERIVATIVE AS P13K INHIBITOR AND USE THEREOF
  申请人：Ebiike Hirosato

  公开号：US20100324284A1

  公开（公告）日：2010-12-23

  A preventive or therapeutic agent of a proliferative disease such as cancer, having superior PI3K inhibitory effects, superior cell proliferation inhibitory action as well as superior stability in a body and water solubility, is provided. A compound represented by formula (I): [wherein, Q represents a linking group represented by —X—Y—; X represents a single bond —CO—, —CONH—, —CON(C 1-4 alkyl)-, —CS—, —CSNH—, —CSN(C 1-4 alkyl)-, or —SO 2 —; Y represents a single bond, arylene or heteroarylene; provided that X and Y are not simultaneously single bonds; and R 1 represents —C 0-6 alkylene-(A) m -C 1-6 alkyl, or C 0-6 alkylene-(A) m -C 0-6 alkylene-(heterocycle)] or a pharmaceutically acceptable salt thereof.

  提供了一种预防或治疗增殖性疾病（如癌症）的药物，具有优越的PI3K抑制作用、优越的细胞增殖抑制作用以及在体内具有优越的稳定性和水溶性。该化合物的式子为（I）：[其中，Q表示由—X—Y—表示的连接基；X表示单键—CO—、—CONH—、—CON（C1-4烷基）-、—CS—、—CSNH—、—CSN（C1-4烷基）-或—SO2—；Y表示单键、芳基或杂芳基；但X和Y不能同时为单键；R1表示—C0-6烷基-(A)m-C1-6烷基，或C0-6烷基-(A)m-C0-6烷基-(杂环)]或其药学上可接受的盐。
• [EN] NOVEL BICYCLIC HETEROARYL COMPOUND AND USE THEREOF<br/>[FR] NOUVEAU COMPOSÉ HÉTÉROARYLE BICYCLIQUE ET SON UTILISATION<br/>[KO] 신규 바이사이클릭 헤테로아릴 화합물 및 이의 용도
  申请人：ILDONG PHARMACEUTICAL CO LTD

  公开号：WO2024014885A1

  公开（公告）日：2024-01-18

  본 발명은 하기 화학식 1로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염을 제공한다. 본 발명은 신규 화합물로써 PIKfyve 억제에 대한 우수한 활성을 가지고 있어 PIKfyve 활성 관련 암 질환, 염증성 질환 또는 리소좀 축적 질환에 대한 치료제로서 유용하다.

  本发明提供了下式 1 所代表的化合物、其光学异构体或其药学上可接受的盐类。作为新型化合物，它们具有优异的抑制 PIKfyve 的活性，因此可用作与 PIKfyve 活性相关的癌症疾病、炎症疾病或溶酶体蓄积疾病的治疗剂。
• PYRROLOPYRIMIDIN DERIVATIVE FOR USE AS PI3K INHIBITOR, AND USE THEREOF
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP2239261A1

  公开（公告）日：2010-10-13

  A preventive or therapeutic agent of a proliferative disease such as cancer, having superior PI3K inhibitory effects, superior cell proliferation inhibitory action as well as superior stability in a body and water solubility, is provided. A compound represented by formula (I): [wherein, Q represents a linking group represented by -X-Y-; X represents a single bond -CO-, -CONH-, -CON(C1-4 alkyl)-, -CS-, -CSNH-, -CSN(C1-4 alkyl)-, or -SO2-; Y represents a single bond, arylene or heteroarylene; provided that X and Y are not simultaneously single bonds; and R1 represents -C0-6 alkylene-(A)m-C1-6 alkyl, or C0-6 alkylene-(A)m-C0-6 alkylene-(heterocycle)] or a pharmaceutically acceptable salt thereof.

  本发明提供了一种癌症等增殖性疾病的预防或治疗剂，它具有优异的 PI3K 抑制作用、优异的细胞增殖抑制作用以及优异的体内稳定性和水溶性。 由式（I）代表的化合物： [其中，Q 代表-X-Y-代表的连接基团；X 代表单键-CO-、-CONH-、-CON(C1-4 烷基)-、-CS-、-CSNH-、-CSN(C1-4 烷基)-或-SO2-；Y 代表单键、芳基或杂芳基；条件是 X 和 Y 不是同时为单键；以及 R1 代表-C0-6 亚烷基-(A)m-C1-6 烷基，或 C0-6 亚烷基-(A)m-C0-6 亚烷基-(杂环)]。 或其药学上可接受的盐。
• EP2239261
  申请人：——

  公开号：——

  公开（公告）日：——