5-(2-丙烯-1-基)-L-脯氨酸甲酯 | 637355-27-2

• 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
• 中文名称: 5-(2-丙烯-1-基)-L-脯氨酸甲酯
• 英文名称: methyl (2S)-5-allylpyrrolidine-2-carboxylate
• 英文别名: (2S)-Methyl 5-allylpyrrolidine-2-carboxylate；methyl (2S)-5-prop-2-enylpyrrolidine-2-carboxylate
• CAS: 637355-27-2
• 化学式: C₉H₁₅NO₂
• 分子量: 169.224
• InChiKey: FQSPQHRWQMGKNA-MQWKRIRWSA-N

物化性质

• 沸点：
  220℃
• 密度：
  0.986
• 闪点：
  87℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2-丙烯-1-基)-L-脯氨酸甲酯 在 palladium on activated charcoal 、 氢气 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 臭氧 、 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 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 生成 (5S,8S,10AR)-5-((叔丁氧基羰基)氨基)-6-氧代十氢吡咯并[1,2-A][1,5]二氮杂辛-8-羧酸甲酯
  参考文献：
  名称：

  Debio-1143. Inhibitor of apoptosis protein (IAP) antagonist, Cancer therapy

  摘要：

  Inhibitors of apoptosis proteins (IAPs) block caspases, modulate nuclear factor NF-kappa B signaling pathways and are involved in resistance to cancer therapies. Debio-1143, a mimetic of an endogenous IAP inhibitor (second mitochondria-derived activator of caspases [SMAC]), may help to overcome treatment resistance and has demonstrated antitumor activity in various cancer cell lines and xenograft models, alone or in combination with chemotherapy, radiotherapy or immunotherapies. So far, about 150 cancer patients have been enrolled in 5 registered early-phase clinical trials testing Debio-1143. Tolerability was acceptable even when the drug was used in combination therapies. In monotherapy, pharmacokinetics was linear, but varied considerably among patients in combination settings. High tumor penetration and on-target activity were consistently shown in patient surrogate tissues and tumor biopsies. Tumor responses to second-(or higher) line monotherapy in patients with various advanced cancers were rather weak, but currently followed approaches as an adjunct to existing cancer therapies look[GRAPHICS]encouraging. Still, to identify ideal target populations and concomitant regimens remains challenging.

  DOI：

  10.1358/dof.2017.042.12.2702829
• 作为产物：
  描述：

  (2S)-5-烯丙基-1,2-吡咯烷二羧酸 1-叔丁酯 2-甲酯 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-(2-丙烯-1-基)-L-脯氨酸甲酯
  参考文献：
  名称：

  5-oxo-1,2,3,5,8,8a-hexahydroindolizine-3-carboxamide Derivatives Useful As a Factor XIa Inhibitors

  摘要：

  本发明涉及5-氧代-1,2,3,5,8,8a-六氢吲哚啉-3-羧酰胺衍生物、立体异构体、同位素同系物及其药学上可接受的盐，包含该化合物的制药组合物以及在治疗和/或预防血栓栓塞性疾病、炎症性疾病和血浆卡利肌酶活性涉及的疾病或病况中使用该化合物的用途。

  公开号：

  US20230064443A1

文献信息

• Novel interleukin-1beta converting enzyme inhibitors
  申请人：The Procter & Gamble Company

  公开号：US20030236296A1

  公开（公告）日：2003-12-25

  The present invention relates to interleukin-1&bgr; converting enzyme inhibitors having the formula: 1 R is a carbocyclic or heterocyclic ring; R 1 is a cysteine trap; R 2a , R 2a′ , R 2b , and R 2b are each independently hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, and mixtures thereof; or R 2a′ and R 2b′ can taken together to form a double bond; L and L 1 are linking groups having the formula: 2 T is selected from the group consisting of: i) —NR 6 —; ii) —O—; iii) —NR 6 S(O) 2 —; iv) —S(O) 2 NR 6 —; and v) mixtures thereof; R 6 is hydrogen, substituted or unsubstituted C 1 -C 20 linear, branched, or cyclic alkyl, C 6 -C 20 aryl, C 7 -C 20 alkylenearyl, and mixtures thereof; the indices w, w 1 , and w 2 are each independently 0 or 1; i) hydrogen; ii) C 1 -C 4 linear, branched, and cyclic alkyl; iii) R 3a and R 3b or R 4a , and R 4b can be taken together to form a carbonyl unit; iv) two R 3a or two R 3b units from adjacent carbon atoms or two R 4a or two R 4b units from adjacent carbon atoms can be taken together to form a double bond; and v) mixtures thereof; the index m is from 0 to 5; the index n is from 0 to 5.

  本发明涉及具有以下结构的白细胞介素-1β转化酶抑制剂： 1R为碳环或杂环；R1为半胱氨酸陷阱；R2a、R2a′、R2b和R2b各自独立地为氢、C1-C4烷基、C1-C4烷氧基及其混合物；或R2a′和R2b′可以一起形成双键；L和L1为具有以下结构的连接基： 2T从以下组中选择： i) —NR6—； ii) —O—； iii) —NR6S(O)2—； iv) —S(O)2NR6—；和 v) 其混合物； R6为氢、取代或未取代的C1-C20直链、支链或环烷基、C6-C20芳基、C7-C20烷基芳基及其混合物；指数w、w1和w2各自独立地为0或1； i) 氢； ii) C1-C4直链、支链和环烷基； iii) R3a和R3b或R4a和R4b可以一起形成一个羰基单元； iv) 两个相邻碳原子上的R3a或两个相邻碳原子上的R3b单位，或两个相邻碳原子上的R4a或两个相邻碳原子上的R4b单位可以一起形成双键；和 v) 其混合物； 指数m为0至5；指数n为0至5。
• DIAZO BICYCLIC SMAC MIMETICS AND THE USES THEREOF
  申请人：Wang Shaomeng

  公开号：US20100273812A1

  公开（公告）日：2010-10-28

  The invention relates to diazo bicyclic mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

  该发明涉及一种Smac的重氮双环模拟物，其作为细胞凋亡抑制蛋白抑制剂。该发明还涉及利用这些模拟物诱导细胞凋亡死亡以及使细胞对凋亡诱导剂敏感的用途。
• Synthesis and evaluation of novel 8,5-fused bicyclic peptidomimetic compounds as interleukin-1β converting enzyme (ICE) inhibitors
  作者：David L. Soper、Justin X. Sheville、Steven V. O’Neil、Yili Wang、Michael C. Laufersweiler、Kofi A. Oppong、John A. Wos、Christopher D. Ellis、Mark W. Baize、Jack J. Chen、Amy N. Fancher、Wei Lu、Maureen K. Suchanek、Richard L. Wang、William P. Schwecke、Charles A. Cruze、Maria Buchalova、Marina Belkin、Fred Wireko、Amanda Ritter、Biswanath De、Difei Wang、Thomas P. Demuth

  DOI：10.1016/j.bmc.2006.07.056

  日期：2006.12

  An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective ring metathesis reaction was elaborated into potent inhibitors of interleukin-1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase-8. These active analogs generally possessed good activity (IC50 values < 100 nM) in a

  通过立体选择环复分解反应生成的8，5-稠合双环拟肽环系统被精制为有效的白介素1β转化酶（ICE，caspase-1）抑制剂。发现多种化合物的ICE IC50值<10 nM，对caspase-3和caspase-8具有选择性。这些活性类似物在测量IL-1beta产生的全细胞试验中通常具有良好的活性（IC50值<100 nM）。所选活性铅的乙缩醛前药形式的药代动力学分析显示，该化合物具有合理的血浆半衰期（1.1小时）和良好的口服生物利用度（30％）。
• [EN] COMPOUNDS USEFUL AS FACTOR XIA INHIBITORS<br/>[FR] COMPOSÉS UTILES EN TANT QU'INHIBITEURS DU FACTEUR XIA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2022018156A1

  公开（公告）日：2022-01-27

  The present invention is directed to Factor XIa inhibitors, tautomers, stereoisomers, isotopologues, and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions containing said compounds and the use of said compounds in the treatment and / or prophylaxis of thromboembolic disorders, inflammatory disorders, and diseases or conditions in which plasma kallikrein activity is implicated.

  本发明涉及因子XIa抑制剂、互变异构体、立体异构体、同位素拓扑异构体及其药学上可接受的盐和溶剂合物，包含上述化合物的制药组合物以及在治疗和/或预防血栓栓塞性疾病、炎症性疾病以及涉及血浆激肽酶活性的疾病或病况中使用上述化合物的用途。
• Stereoselective Synthesis of 2,5-Di- and 2,2,5-Trisubstituted Pyrrolidines by Allylation Reaction of Acyliminium Ion
  作者：Yasufumi Ohfune、Tetsuro Shinada、Makoto Hamada、Masanori Kawasaki

  DOI：10.3987/com-05-s(k)61

  日期：——