2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate | 1004536-85-9

• 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: 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate
• 英文别名: 2-trimethylsilylethyl N-[(1R,2S,5R)-5-(tert-butylamino)-2-[(3S)-2-oxo-3-(phenylmethoxycarbonylamino)pyrrolidin-1-yl]cyclohexyl]carbamate
• CAS: 1004536-85-9
• 化学式: C₂₈H₄₆N₄O₅Si
• 分子量: 546.783
• InChiKey: KGDHVEYRYPFWOH-QPXUXIHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate 、 三氟乙酸 在 二氯甲烷 、 碳酸氢钠 、 Sodium sulfate-III 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以to give benzyl (S)-1-((1S,2R,4R)-2-amino-4-(tert-butylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (66 mg, 90%)的产率得到benzyl (S)-1-((1S,2R,4R)-2-amino-4-(tert-butylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate
  参考文献：
  名称：

  N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process

  摘要：

  本发明提供了一种新型的MCP-1受体活性的拮抗剂或部分激动剂/拮抗剂：N-((1R,2S,5R)-5-叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺，或其药学上可接受的盐、溶剂合物或前药，具有意想不到的理想药理特性组合。本发明还提供了该化合物的晶体形式。本发明还旨在提供含有该化合物的制药组合物以及将其用作治疗炎症性疾病、过敏、自身免疫、代谢、癌症和/或心血管疾病的药剂的方法。本公开还提供了一种制备式(I)化合物的方法，包括N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺：其中R1、R8、R9、R10如本文所述。本文还提供了该过程的有用中间体化合物。

  公开号：

  US07629351B2
• 作为产物：
  描述：

  2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(hydroxyamino)cyclohexylcarbamate 、 甲基溴化镁 在 四氢呋喃 、 水 、 乙酸乙酯 、 Brine 、 magnesium sulfate 、 乙腈 、 二硫化碳 、 crude product 、 silica gel 作用下， 以 丙酮 为溶剂， 反应 18.5h， 以to provide the desired 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate (160 mg, 42%)的产率得到2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate
  参考文献：
  名称：

  N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process

  摘要：

  本发明提供了一种新型的MCP-1受体活性的拮抗剂或部分激动剂/拮抗剂：N-((1R,2S,5R)-5-叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺，或其药学上可接受的盐、溶剂合物或前药，具有意想不到的理想药理特性组合。本发明还提供了该化合物的晶体形式。本发明还旨在提供含有该化合物的制药组合物以及将其用作治疗炎症性疾病、过敏、自身免疫、代谢、癌症和/或心血管疾病的药剂的方法。本公开还提供了一种制备式(I)化合物的方法，包括N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺：其中R1、R8、R9、R10如本文所述。本文还提供了该过程的有用中间体化合物。

  公开号：

  US07629351B2

文献信息

• CYCLIC DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Carter Percy H.

  公开号：US20080027080A1

  公开（公告）日：2008-01-31

  This invention relates generally to modulators of chemokine receptor activity having unexpected combination of desirable pharmacological properties. Pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and prevention of inflammatory, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases, particularly diabetes, Crohn's disease, atherosclerosis, and multiple sclerosis, along with methods of preparing compounds and intermediates therefor. Metabolites of active compounds are also provided herein, pharmaceutical compositions and use thereof are also provided.

  这项发明涉及具有意想不到的理想药理特性组合的趋化因子受体活性调节剂。包含这些化合物的药物组合物，以及将其用作治疗和预防炎症、过敏、自身免疫、代谢、癌症和/或心血管疾病的药剂，特别是糖尿病、克罗恩病、动脉粥样硬化和多发性硬化症，以及制备化合物和中间体的方法。此外，还提供了活性化合物的代谢产物，以及药物组合物和其使用方法。
• MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY CRYSTALLINE FORMS AND PROCESS
  申请人：Duncia John V.

  公开号：US20080027084A1

  公开（公告）日：2008-01-31

  The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4 -ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R 1 , R 8 , R 9 , R 10 , and are as described herein. Compounds that are useful intermediates of the process are also provided herein.

  本发明提供了一种新型的MCP-1受体活性的拮抗剂或部分激动剂/拮抗剂：N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺，或其药学上可接受的盐、溶剂化物或前药，具有意想不到的理想药理特性的组合。本发明还提供了该化合物的晶体形式。含有该化合物的制药组合物以及将其作为治疗炎症性疾病、过敏、自身免疫、代谢、癌症和/或心血管疾病的药物的使用方法也是本发明的目标。本公开还提供了制备式(I)化合物的方法，包括N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺：其中R1、R8、R9、R10如本文所述。本文还提供了该过程有用的中间体化合物。
• MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY, CRYSTALLINE FORMS AND PROCESS
  申请人：Duncia John V.

  公开号：US20100113489A1

  公开（公告）日：2010-05-06

  The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin- 4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R 1 , R 8 , R 9 , R 10 , and are as described herein. Compounds that are useful intermediates of the process are also provided herein.

  本发明提供了一种MCP-1受体活性的新型拮抗剂或部分激动剂/拮抗剂：N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺，或其药学上可接受的盐、溶剂化合物或前药，具有意外的理想药理特性组合。本发明还提供了该化合物的晶体形式。本发明还旨在提供含有该化合物的制药组合物，并将其用作治疗炎症性疾病、过敏、自身免疫、代谢、癌症和/或心血管疾病的药物。本公开还提供了一种制备式(I)化合物，包括N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺的方法：其中R1，R8，R9，R10和如本文所述。本文还提供了该过程有用的中间体化合物。
• Substituted pyrrolidine-2-one compounds
  申请人：Bristol-Myers Squibb Company

  公开号：US08049019B2

  公开（公告）日：2011-11-01

  The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and are as described herein. Compounds that are useful intermediates of the process are also provided herein.

  本发明提供了一种新型的MCP-1受体活性拮抗剂或部分激动剂/拮抗剂：N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺，或其药学上可接受的盐、溶剂合物或前药，具有意想不到的理想药理特性的组合。本发明还提供了该化合物的晶体形式。本发明还提供了含有该化合物的药物组合物以及将其用作治疗炎症性疾病、过敏、自身免疫、代谢、癌症和/或心血管疾病的药物的方法。本公开还提供了制备式(I)化合物的方法，包括N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-2-氧代-3-(6-(三氟甲基)喹唑啉-4-基氨基)吡咯烷-1-基)环己基)乙酰胺：其中R1、R8、R9、R10如本文所述。本文还提供了该过程有用的中间体化合物。
• Cyclic derivatives as modulators of chemokine receptor activity
  申请人：Bristol-Myers Squibb Company

  公开号：US07687508B2

  公开（公告）日：2010-03-30

  This invention relates generally to modulators of chemokine receptor activity having unexpected combination of desirable pharmacological properties. Pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and prevention of inflammatory, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases, particularly diabetes, Crohn's disease, atherosclerosis, and multiple sclerosis, along with methods of preparing compounds and intermediates therefor. Metabolites of active compounds are also provided herein, pharmaceutical compositions and use thereof are also provided.

  本发明涉及调节趋化因子受体活性的调节剂，具有意外的理想药理特性的组合。本发明还涉及含有这些调节剂的药物组合物，并将其作为治疗和预防炎症、过敏、自身免疫、代谢、癌症和/或心血管疾病的药剂，特别是糖尿病、克罗恩病、动脉硬化和多发性硬化症的药剂，以及制备化合物和中间体的方法。本发明还提供了活性化合物的代谢产物，提供了药物组合物及其使用方法。