4-(5-氯噻唑并[5,4-D]嘧啶-7-基)吗啉 | 41975-14-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 1,3-噻唑并[5,4-d]嘧啶
• 中文名称: 4-(5-氯噻唑并[5,4-D]嘧啶-7-基)吗啉
• 英文名称: 5-chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine
• 英文别名: 4-(5-chlorothiazolo[5,4-d]pyrimidin-7-yl)morpholine；4-(5-chloro-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)morpholine
• CAS: 41975-14-8
• 化学式: C₉H₉ClN₄OS
• 分子量: 256.716
• InChiKey: FDVSSSZJPRMYFD-UHFFFAOYSA-N

物化性质

• 沸点：
  399.7±42.0 °C(Predicted)
• 密度：
  1.528±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(5-氯噻唑并[5,4-D]嘧啶-7-基)吗啉 在 sodium tetrahydroborate 、 正丁基锂 、 四甲基乙二胺 、 三溴化磷 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Potent and Highly Selective Benzimidazole Inhibitors of PI3-Kinase Delta

  摘要：

  Inhibition of PI3K delta is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3K delta. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3K delta inhibitors. Instead, the selectivity of the compounds for inhibition of PI3K delta relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3K delta binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.

  DOI：

  10.1021/jm300717c
• 作为产物：
  描述：

  吗啉 、 5,7-二氯噻唑并[5,4-D]嘧啶 以 甲醇 为溶剂， 反应 2.0h， 生成 4-(5-氯噻唑并[5,4-D]嘧啶-7-基)吗啉
  参考文献：
  名称：

  Potent and Highly Selective Benzimidazole Inhibitors of PI3-Kinase Delta

  摘要：

  Inhibition of PI3K delta is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3K delta. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3K delta inhibitors. Instead, the selectivity of the compounds for inhibition of PI3K delta relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3K delta binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.

  DOI：

  10.1021/jm300717c

文献信息

• [EN] BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE<br/>[FR] COMPOSÉS PYRIMIDINES BICYCLIQUES INHIBITEURS DE PI3K SÉLECTIFS POUR P110 DELTA, ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2010138589A1

  公开（公告）日：2010-12-02

  Formula (I) ((Ia) and (Ib)) compounds wherein (i) X1 is N and X2 is S, (ii) X1 is CR7 and X2 is S, (iii) X1 is N and X2 is NR2, or (iv) X1 is CR7 and X2 is O, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. 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.

  公式（I）（（Ia）和（Ib））化合物，其中（i）X1为N且X2为S，（ii）X1为CR7且X2为S，（iii）X1为N且X2为NR2，或（iv）X1为CR7且X2为O，包括其立体异构体，互变异构体，代谢物和药用可接受盐，用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，如炎症，免疫和癌症。公开了使用公式（I）化合物进行体外，体内和体内诊断，预防或治疗哺乳动物细胞中的这类疾病或相关病理状况的方法。
• [EN] THIAZOLOPYRIMIDINE P13K INHIBITOR COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS INHIBITEURS DE LA PI3K À BASE DE THIAZOLOPYRIMIDINE
  申请人：GENENTECH INC

  公开号：WO2009042607A1

  公开（公告）日：2009-04-02

  Compounds of Formulas (Ia and Ib), and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  化合物的公式（Ia和Ib），包括立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和其药用可接受的盐，可用于抑制包括PI3K在内的脂质激酶，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用公式Ia和Ib的化合物进行体外、原位和体内诊断、预防或治疗哺乳动物细胞中的这种疾病或相关病理状况的方法。
• THIAZOLOPYRIMIDINE P13K INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Castanedo Georgette M.

  公开号：US20090118275A1

  公开（公告）日：2009-05-07

  Compounds of Formulas Ia and Ib, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式Ia和Ib的化合物，包括立体异构体，几何异构体，互变异构体，溶剂化物，代谢物和药学上可接受的盐，对于抑制脂质激酶包括PI3K，以及治疗由脂质激酶介导的癌症等疾病是有用的。揭示了使用公式Ia和Ib的化合物在哺乳动物细胞中进行体外，原位和体内诊断，预防或治疗此类疾病或相关病理条件的方法。
• THIAZOLOPYRIMIDINES AND THEIR USE AS INHIBITORS OF PHOSPHATIDYLINOSITOL-3 KINASE
  申请人：Hancox Timothy Colin

  公开号：US20100190769A1

  公开（公告）日：2010-07-29

  Thiazolopyrimidines of formula (I): wherein W represents a thiazole ring; R 1 and R 2 form, together with the N atom to which they are attached, a group of the following formula (IIa): in which A is a ring system; m is 0, 1 or 2; R is H or C 1 -C 6 alkyl; and R is an indole group which is unsubstituted or substituted; and the pharmaceutically acceptable salts thereof are inhibitors of PI3K and are selective for the p110δ isoform, which is a class Ia PD kinase, over both other class Ia and class Ib kinases. The compounds may be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

  式(I)的噻唑嘧啶化合物：其中W代表噻唑环；R1和R2与它们所附着的N原子一起形成下式(IIa)的基团：其中A是一个环系统；m为0、1或2；R为H或C1-C6烷基；R为未取代或取代的吲哚基团；以及其药学上可接受的盐是PI3K的抑制剂，并且选择性地作用于p110δ同工型，这是一种Ia类PD激酶，而不是其他Ia类和Ib类激酶。这些化合物可用于治疗由PI3激酶导致的异常细胞生长、功能或行为引起的疾病和障碍，例如癌症、免疫障碍、心血管疾病、病毒感染、炎症、代谢/内分泌功能障碍和神经系统障碍。
• Thiazolopyrimidine PI3K inhibitor compounds and methods of use
  申请人：F. Hoffmann-La Roche AG

  公开号：US08158626B2

  公开（公告）日：2012-04-17

  Compounds of Formulas Ia and Ib, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式Ia和Ib的化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，可用于抑制脂质激酶，包括PI3K，并用于治疗由脂质激酶介导的癌症等疾病。本文还公开了使用公式Ia和Ib的化合物在哺乳动物细胞中进行体外、原位和体内诊断、预防或治疗此类疾病或相关病理条件的方法。