N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide | 1004536-75-7

• 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: N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide
• 英文别名: N-[(1R,2S,5R)-2-[(3S)-3-amino-2-oxopyrrolidin-1-yl]-5-(tert-butylamino)cyclohexyl]acetamide
• CAS: 1004536-75-7
• 化学式: C₁₆H₃₀N₄O₂
• 分子量: 310.44
• InChiKey: ZOUBENYGSIJJKF-RQJABVFESA-N

物化性质

• 沸点：
  534.2±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  87.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 5.0h， 生成 (S)-1-((1S,2R,4R)-2-amino-4-(tert-butylamino)cyclohexyl)-3-((6-(trifluoromethyl)quinazolin-4-yl)amino)pyrrolidin-2-one
  参考文献：
  名称：

  [EN] CYTOTOXICITY TARGETING CHIMERAS FOR CCR2-EXPRESSING CELLS
  [FR] CHIMÈRES CIBLANT LA CYTOTOXICITÉ POUR DES CELLULES EXPRIMANT CCR2

  摘要：

  The present disclosure relates to heterobifunctional molecules, referred to as cytotoxicity targeting chimeras (CyTaCs) or antibody recruiting molecules (ARMs) that are able to simultaneously bind a target cell-surface protein as well as an exogenous antibody protein. The present disclosure also relates to agents capable of binding to a receptor on a surface of a pathogenic cell and inducing the depletion of the pathogenic cell in a subject for use in the treatment of cancer, inflammatory diseases, autoimmune diseases, viral infection, or bacterial infection.

  公开号：

  WO2023017483A1
• 作为产物：
  描述：

  在 氢气 、 palladium(II) hydroxide 作用下， 以 乙酸乙酯 为溶剂， 以95%的产率得到N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide
  参考文献：
  名称：

  Discovery of BMS-753426: A Potent Orally Bioavailable Antagonist of CC Chemokine Receptor 2

  摘要：

  DOI：

  10.1021/acsmedchemlett.1c00082
• 作为试剂：
  描述：

  N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide 、 7-Tert-butyl-4-phenoxy-1,4-dihydropyrazolo[1,5-a][1,3,5]triazine 在 N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide 作用下， 以55的产率得到化合物BMS813160
  参考文献：
  名称：

  N-((1R,2S,5R)-5-(TERT-BUTYLAMINO)-2-((S)-3-(7-TERT-BUTYLPYRAZOLO[1,5-A][1,3,5]TRIAZIN-4-YLAMINO)-2-OXOPYRROLIDIN-1-YL)CYCLOHEXYL)ACETAMIDE, A DUAL MODULATOR OF CHEMOKINE RECEPTOR ACTIVITY, CRYSTALLINE FORMS AND PROCESSES

  摘要：

  本发明提供一种新型拮抗剂：N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-3-(7-叔丁基吡唑并[1,5-a][1,3,5]三嗪-4-基氨基)-2-氧代吡咯烷-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，具有意外的双重CCR-2和CCR-5受体活性。还公开了晶体形式、代谢产物、含有相同物质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。本公开还提供了制备式(I)中所提供的化合物，包括N-((1R,2S,5R)-5-(叔丁基氨基)-2-((S)-3-(7-叔丁基吡唑并[1,5-a][1,3,5]三嗪-4-基氨基)-2-氧代吡咯烷-1-基)环己基)乙酰胺的过程。本文还提供了该过程有用的中间体化合物。

  公开号：

  US20110086857A1

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。
• Scalable Asymmetric Synthesis of the All <i>Cis</i> Triamino Cyclohexane Core of BMS-813160
  作者：Thomas E. La Cruz、Francisco González-Bobes、Martin D. Eastgate、Chris Sfouggatakis、Bin Zheng、Nathaniel Kopp、Yi Xiao、Yu Fan、Kay A. Galindo、Charles Pathirana、Michael A. Galella、Joerg Deerberg

  DOI：10.1021/acs.joc.1c01162

  日期：2022.2.18

  methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich–aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to

  BMS-813160 是 Bristol Myers Squibb 目前正在开发的制药实体。它的定义结构特征是独特的手性全顺式三氨基环己烷核心。BMS 的药物和工艺化学小组之前已经发布了与目标分子相似的化学型的合成策略，但需要一种适合长期供应的简化方法。一种新的合成路线被概念化，实验研究，并确定满足效率标准，解决了以前方法的关键限制。采用/优化 Trost 不对称烯丙基胺化去对称化方法是用于生产具有高光学纯度的合成中间体的关键工具。此外，
• 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。