PI3K抑制剂 | 371943-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: PI3K抑制剂
• 中文别名: 复合15e；PI3-激酶抑制剂2B-0304
• 英文名称: 3-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)phenol
• 英文别名: MTPP；3-(4-Morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenol
• CAS: 371943-05-4
• 化学式: C₁₆H₁₅N₃O₂S
• 分子量: 313.38
• InChiKey: XXLAEKOWCYJOKK-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：30 mg/ml； DMF:PBS(pH 7.2)(1:3)：0.25mg/ml； DMSO：25 mg/ml；乙醇：1 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  86.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  PI3K抑制剂 在 lithium hydroxide monohydrate 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 6-[3-(4-morpholin-4-yl-thieno[3,2-d]pyrimidine-2-yl)phenoxy]hexanoic acid
  参考文献：
  名称：

  Synthesis and anticancer activities of thieno[3,2-d]pyrimidines as novel HDAC inhibitors

  摘要：

  A series of thieno[3,2-d]pyrimidines bearing a hydroxamic acid moiety as novel HDAC inhibitors were designed and synthesized. The structures of the new synthesized compounds were confirmed using IR, H-1, C-13 NMR spectrum. Compounds 11-13 showed potent inhibitory activities against HDACs with IC50 values at 0.38, 0.49 and 0.61 mu M. Most of target compounds displayed strong anti-proliferative activity by a MTT assay on three human cancer cell lines including HCT-116, MCF-7 and HeLa. Compound 11, having potent inhibitory activities against HDACs, induced apoptosis and G2/M cell cycle arrest in HCT-116 cell line. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.021
• 作为产物：
  描述：

  间甲氧基苯甲酰氯 在 sodium hydroxide 、 氨 、 氢溴酸 、 sodium acetate 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 氯仿 、 水 、 异丙醇 为溶剂， 反应 82.54h， 生成 PI3K抑制剂
  参考文献：
  名称：

  作为新型PI3激酶p110alpha抑制剂的4-吗啉代-2-苯基喹唑啉及其相关衍生物的合成和生物学评估。

  摘要：

  制备了一系列的4-吗啉代-2-苯基喹唑啉及其相关衍生物，并将其评估为PI3激酶p110alpha的抑制剂。在这个系列中，噻吩并[3,2-d]嘧啶衍生物15e对p110alpha的抑制作用最强，IC（50）值为2.0 nM，并抑制A375黑色素瘤细胞的增殖，IC（50）值为50。 0.58微米 此外，发现15e对p110alpha的选择性高于其他PI3K同工型和蛋白激酶，这使其成为选择性PI3K p110alpha抑制剂的第一个实例。

  DOI：

  10.1016/j.bmc.2006.06.046

文献信息

• TOPICAL PHOSPHOINOSITIDE 3-KINASE INHIBITORS
  申请人：VENTHERA, INC.

  公开号：US20200247816A1

  公开（公告）日：2020-08-06

  The present invention provides compounds and topical formulations including the compounds for the treatment of vascular malformations, wherein the compounds are according to formula (I): wherein subscript m, L 1 , R 1 , and L 1 -R 1 are as described herein.

  本发明提供了用于治疗血管畸形的化合物和含有该化合物的局部制剂，其中该化合物符合以下公式（I）：其中下标m，L1，R1和L1-R1如本文所述。
• Pharmaceutical compounds
  申请人：Shuttleworth Stephen J.

  公开号：US20080207609A1

  公开（公告）日：2008-08-28

  Fused pyrimidines of formula (I): wherein R 1 -R 3 , A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof; have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behavior associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  式(I)的融合嘧啶类化合物： 其中R1-R3、A和n的取值如规范所述；以及其药学上可接受的盐；具有抑制PI3K的活性，因此可用于治疗由与PI3激酶相关的异常细胞生长、功能或行为引起的疾病和障碍，如癌症、免疫障碍、心血管疾病、病毒感染、炎症、代谢/内分泌障碍和神经障碍。还描述了合成这些化合物的过程。
• TRIAZINE, PYRIMIDINE AND PYRIDINE ANALOGS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES
  申请人：Cmiljanovic Vladimir

  公开号：US20110275762A1

  公开（公告）日：2011-11-10

  The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine-, pyrimidine- and pyridine-based compoundŝ Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds; either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders mediated by lipid kinases. •Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. (Formula I)

  本发明涉及新型治疗剂和诊断探针。本发明还涉及磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白酶（mTOR）抑制剂三嗪基、嘧啶基和吡啶基化合物̂公式（I），它们的立体异构体、几何异构体、互变异构体、溶剂化物、代谢物、N-氧化衍生物、药学上可接受的盐以及前药的组合物；新化合物的组合物，可以单独使用或与至少一种额外的治疗剂结合，与药学上可接受的载体；以及使用新化合物的方法，可以单独使用或与至少一种额外的治疗剂结合，用于治疗由脂质激酶介导的疾病。公开了使用公式（I）化合物的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗这种疾病或相关病理条件。(公式I)
• Triazine, pyrimidine and pyridine analogs and their use as therapeutic agents and diagnostic probes
  申请人：Cmiljanovic Vladimir

  公开号：US08921361B2

  公开（公告）日：2014-12-30

  The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine-, pyrimidine- and pyridine-based compounds^ Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds; either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders mediated by lipid kinases. •Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. (Formula I)

  本发明涉及新型治疗剂和诊断探针。本发明还涉及磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂三嗪、嘧啶和吡啶基化合物的式（I），它们的立体异构体、几何异构体、互变异构体、溶剂化物、代谢物、N-氧化衍生物、药学上可接受的盐和其前药化合物的组合物。新化合物的组合物可以单独使用或与至少一种额外的治疗剂联合使用，并与药学上可接受的载体一起使用，用于治疗由脂质激酶介导的疾病。本发明还揭示了使用式（I）化合物的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗这种疾病或相关的病理情况。 （式I）
• CONDENSED HETEROARYL DERIVATIVES
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1277738A1

  公开（公告）日：2003-01-22

  The present invention provides a pharmaceutical composition which is useful as a phosphatidylinositol 3 kinase (PI3K) inhibitor and an antitumor agent, and it provides a novel bicyclic or tricyclic fused heteroaryl derivative or a salt thereof which possesses an excellent PI3K inhibiting activity and cancer cell growth inhibiting activity.

  本发明提供了一种可用作磷脂酰肌醇 3 激酶（PI3K）抑制剂和抗肿瘤剂的药物组合物，并提供了一种新型双环或三环融合杂芳基衍生物或其盐，该衍生物具有优异的 PI3K 抑制活性和癌细胞生长抑制活性。