Ethyl 2-{4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl}acetate | 1260000-16-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Ethyl 2-{4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl}acetate
• 英文别名: ethyl 2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetate
• CAS: 1260000-16-5
• 化学式: C₁₇H₂₃N₃O₃
• 分子量: 317.388
• InChiKey: AAISZDDCWHLOAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  对环己基苯甲酸 、 Ethyl 2-{4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl}acetate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 ethyl 2-(8-(4-cyclohexylbenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetate
  参考文献：
  名称：

  Spiroimidazolidinone NPC1L1 inhibitors. Part 2: Structure–activity studies and in vivo efficacy

  摘要：

  Ezetimibe (Zetia (R)), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-beta-lactams can be effective CAIs. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.138
• 作为产物：
  描述：

  tert-butyl 3-(2-ethoxy-2-oxo-ethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 以94%的产率得到Ethyl 2-{4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl}acetate
  参考文献：
  名称：

  Spiroimidazolidinone NPC1L1 inhibitors. Part 2: Structure–activity studies and in vivo efficacy

  摘要：

  Ezetimibe (Zetia (R)), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-beta-lactams can be effective CAIs. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.138

文献信息

• Substituted spirocyclic inhibitors of autotaxin
  申请人：X-Rx, Inc.

  公开号：US10011601B2

  公开（公告）日：2018-07-03

  The present invention relates to compounds according to Formula 1 and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancer, lymphocyte homing, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis, and cholestatic pruritus, mediated at least in part by ATX.

  本发明涉及根据式 1 的化合物和药学上可接受的盐、合成、中间体、制剂以及用其治疗疾病的方法，包括至少部分由 ATX 介导的癌症、淋巴细胞归巢、慢性炎症、神经性疼痛、纤维化疾病、血栓形成和胆汁淤积性瘙痒症。
• SUBSTITUTED SPIROCYCLIC INHIBITORS OF AUTOTAXIN
  申请人：X-RX, INC.

  公开号：US20170166568A1

  公开（公告）日：2017-06-15

  The present invention relates to compounds according to Formula 1 and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancer, lymphocyte homing, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis, and cholestatic pruritus, mediated at least in part by ATX.