4,5,6,7-四氢-3-羰基-2H-吲唑-5,5-二羧酸 | 138957-98-9

• 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
• 中文名称: 4,5,6,7-四氢-3-羰基-2H-吲唑-5,5-二羧酸
• 英文名称: trans-5-ethynyl-(+/-)-proline
• 英文别名: (2S,5S)-5-ethynylpyrrolidine-2-carboxylic acid
• CAS: 138957-98-9
• 化学式: C₇H₉NO₂
• 分子量: 139.154
• InChiKey: JWOHRHJMTNGZBX-RITPCOANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  trans-N-(tert-butoxycarbonyl)-2-(hydroxymethyl)-5-<2-(trimethylsilyl)ethynyl>pyrrolidine 在 chromium(VI) oxide 、 甲醇 、 硫酸 、 水 、 sodium methylate 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.83h， 生成 4,5,6,7-四氢-3-羰基-2H-吲唑-5,5-二羧酸
  参考文献：
  名称：

  Syntheses of proline analogs as potential mechanism-based inhibitors of proline dehydrogenase: 4-methylene-L-, (E)- and (Z)-4-(fluoromethylene)-L-, cis- and trans-5-ethynyl-(.+-.)-, and cis- and trans-5-vinyl-L-proline

  摘要：

  Proline dehydrogenase is an enzyme involved in the energetic processes required for flight in certain insects including the tse-tse fly. Proline analogues were designed for the inhibition of this enzyme. For this purpose 4-methylene-L-proline and (E)- and (Z)-4-(fluoromethylene)-L-proline were prepared from trans-4-hydroxyl-L-proline through the following sequence: protection at the nitrogen with a tert-butoxycarbonyl and at the caboxylic acid as methyl ester, oxidation of the hydroxyl group to a ketone, Wittig reaction, and removal of the protecting groups. The cis- and trans-5-ethynyl-(+/-)-proline was prepared from N-(tert-butoxycarbonyl)-3-(trimethylsilyl)-2-propynylamine whose dianion reacted with 1,2-epoxy 4-bromobutane. Cyclization in the presence of trifluoroacetic acid, oxidation of the primary alcohol to acid, and removal of the protecting groups gave cis- and trans-5-ethynyl-(+/-)-proline. Stereoselectivity was observed in the reaction of the dianion of 3-(trimethylsilyl)-2-propynylamine with 1,2-epoxy-4-bromobutane. The cis- and trans-5-vinyl-L-prolines were prepared from N-(methoxycarbonyl)-5-methoxy-L-proline ester by reaction with bis(trimethylsilyl)acetylene in the presence of titanium tetrachloride followed by sequential removal of the protecting groups and by reduction. The cis and trans configuration of the 5-vinyl-L-proline obtained was established by comparison of the NMR spectrum of the trans-N-tosyl-5-vinyl-(+/-)-proline methyl ester with the published spectrum of the trans derivative.

  DOI：

  10.1021/jo00033a029

文献信息

• INHIBITION OF PROLINE CATABOLISM FOR THE TREATMENT OF CANCER AND OTHER THERAPEUTIC APPLICATIONS
  申请人：Buck Institute for Research on Aging

  公开号：US20170348266A1

  公开（公告）日：2017-12-07

  In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a “synthetic lethal” and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
• [EN] INHIBITION OF PROLINE CATABOLISM FOR THE TREATMENT OF CANCER AND OTHER THERAPEUTIC APPLICATIONS<br/>[FR] INHIBITION DU CATABOLISME DE LA PROLINE POUR LE TRAITEMENT DU CANCER ET D'AUTRES APPLICATIONS THÉRAPEUTIQUES
  申请人：BUCK INST FOR RES ON AGING

  公开号：WO2016077632A2

  公开（公告）日：2016-05-19

  In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a "synthetic lethal" and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.