(5R)-5-methyl-4-(phenylmethyl)-3-morpholinone | 120800-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone
• 英文别名: (R)-4-benzyl-5-methylmorpholine-3-one；(R)-4-Benzyl-5-methylmorpholin-3-one；(5R)-4-benzyl-5-methylmorpholin-3-one
• CAS: 120800-86-4
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: OXRBQBMOPLPNGX-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 红铝 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 生成 (R)-3-甲基吗啉盐酸盐
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

  摘要：

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.

  DOI：

  10.1021/jm101527u
• 作为产物：
  描述：

  (2R)-2-(benzylideneamino)propan-1-ol 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 1.0h， 生成 (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

  摘要：

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.

  DOI：

  10.1021/jm101527u

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010120854A1

  公开（公告）日：2010-10-21

  The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代吲唑衍生物。具体而言，本发明涉及根据公式I的化合物：其中R1-R6和X在此定义。本发明的化合物是PDK1的抑制剂，可用于治疗由组成性激活的ACG激酶（如癌症，特别是白血病、乳腺癌、结肠癌和肺癌）引起的疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。
• Phthalazine, aza- and diaza-phthalazine compounds and methods of use
  申请人：Tasker Andrew

  公开号：US20060199817A1

  公开（公告）日：2006-09-07

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , B, R 1 , R 2 , R 3 and R 4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明包括一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症及相关状况。这些化合物的通用公式为I 其中A 1 ，A 2 ，B，R 1 ，R 2 ，R 3 和R 4 在此定义。该发明还包括包括一个或多个I公式化合物的药物组合物，以及使用这些化合物和组合物治疗激酶介导的疾病，包括类风湿性关节炎，银屑病和其他炎症性疾病，以及用于制备I公式化合物的中间体和工艺。
• 2-AMINOBENZOXAZOLE CARBOXAMIDES AS 5HT3 MODULATORS
  申请人：Yang Zhicai

  公开号：US20080255114A1

  公开（公告）日：2008-10-16

  Compounds of formulae I, II and III: are disclosed as 5-HT3 inhibitors. The compounds are useful in treating CINV, IBS-D and other diseases and conditions.

  化学式I、II和III的化合物被披露为5-HT3受体拮抗剂。这些化合物在治疗化疗诱发恶心呕吐综合征（CINV）、腹泻型肠易激综合征（IBS-D）和其他疾病和症状中很有用。
• 2-aminobenzoxazole carboxamides as 5HT3 modulators
  申请人：Albany Molecular Research, Inc.

  公开号：US07863271B2

  公开（公告）日：2011-01-04

  Compounds of formulae I, II and III: are disclosed as 5-HT3 inhibitors. The compounds are useful in treating CINV, IBS-D and other diseases and conditions.

  公式I、II和III的化合物被披露为5-HT3抑制剂。这些化合物在治疗化疗诱导恶心和呕吐、腹泻型肠易激综合征和其他疾病和病况方面有用。
• Phthalazine compounds and methods of use
  申请人：Amgen Inc.

  公开号：US07759337B2

  公开（公告）日：2010-07-20

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein B, R1, R2, R3, R4 and R5 are d.efined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新类化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关疾病。该化合物具有通式I，其中B，R1，R2，R3，R4和R5在此被定义。本发明还包括药物组合物，包括一个或多个通式I的化合物，使用这些化合物和组合物治疗激酶介导的疾病，包括类风湿性关节炎、牛皮癣和其他炎症性疾病，以及有用于制备通式I化合物的中间体和过程。