4-亚甲基脯氨酸 | 20309-87-9

• 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-亚甲基脯氨酸
• 英文名称: (S)-4-methylene proline
• 英文别名: 4-Methylene-L-proline；(2S)-4-methylidenepyrrolidine-2-carboxylic acid
• CAS: 20309-87-9
• 化学式: C₆H₉NO₂
• 分子量: 127.143
• InChiKey: PEYQZZMUNYLHII-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-亚甲基脯氨酸 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 N-Boc-4-exomethylene-(S)-prolinyl dibenzyl-(S)-aspartate
  参考文献：
  名称：

  A radical route to 2()-4-exomethylene proline

  摘要：

  A new route to 2(S)-4-Exomethylene proline via a favoured 5-Exo-dig radical cyclisation is described.

  DOI：

  10.1016/s0040-4020(01)88243-0
• 作为产物：
  描述：

  N-BOC-4-亚甲基-L-脯氨酸甲酯 在 sodium hydroxide 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 4.5h， 生成 4-亚甲基脯氨酸
  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

• [EN] PYRROLOBENZODIAZEPINES<br/>[FR] PYRROLOBENZODIAZÉPINES
  申请人：SPIROGEN LTD

  公开号：WO2010043877A1

  公开（公告）日：2010-04-22

  The invention relates to certain pyrrolobenzodiazepines (PBDs), and in particular pyrrolobenzodiazepine dimers bearing C2 substitutions, including compounds of formula (T): wherein: R2 is CHR2A, and R2A is independently selected from H, R, CO2R, COR, CHO, CO2H, and halo; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR', NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR', NO2, Me3Sn and halo; R8 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR', NO2, Me3Sn and halo; R is independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; or the compound is a dimer with each monomer being of formula (M), where the R7 groups or R8 groups of each monomer form together a dimer bridge having the formula -X-R"-X- linking the monomers; wherein R" is a C3-I2 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), and/or aromatic rings, e.g. benzene or pyridine; and each X is independently selected from O, S, or N(H); or any pair of adjacent groups from R6 to R9 together form a group -O-(CH2)P-O-, where p is 1 or 2, and salts and solvates thereof, and their use as intermediates for the preparation of other PBD compounds.

  该发明涉及某些吡咯苯并二氮杂环己烷（PBDs），特别是带有C2取代基的吡咯苯并二氮杂环己烷二聚体，包括以下式（T）的化合物：其中：R2为CHR2A，R2A独立选择自H、R、CO2R、COR、CHO、CO2H和卤素；R6和R9独立选择自H、R、OH、OR、SH、SR、NH2、NHR、NRR'、NO2、Me3Sn和卤素；R7独立选择自H、R、OH、OR、SH、SR、NH2、NHR、NRR'、NO2、Me3Sn和卤素；R8独立选择自H、R、OH、OR、SH、SR、NH2、NHR、NRR'、NO2、Me3Sn和卤素；R独立选择自可选择取代的C1-12烷基、C3-20杂环烷基和C5-20芳基；或该化合物是每个单体为式（M）的二聚体，其中每个单体的R7基团或R8基团共同形成具有-X-R"-X-连接单体的二聚体桥，其中R"为C3-I2烷基，该链可以被一个或多个杂原子中断，例如O、S、N（H）和/或芳香环，例如苯或吡啶；每个X独立选择自O、S或N（H）；或从R6到R9的任意相邻基团对共同形成一个基团-O-(CH2)P-O-，其中p为1或2，以及其盐和溶剂化合物，以及它们作为制备其他PBD化合物的中间体的用途。
• [EN] DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS<br/>[FR] COMPOSÉS DIHYDROPYRIMIDINE ET LEUR APPLICATION DANS DES PRODUITS PHARMACEUTIQUES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2015074546A1

  公开（公告）日：2015-05-28

  Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is the use of the compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof for treating and preventing HBV diseases.

  本文提供了二氢嘧啶化合物及其药物应用，特别用于治疗和预防HBV疾病。具体来说，本文提供了具有化学式（I）或（Ia）的化合物，或其对映体、二对映异构体、互变异构体、水合物、溶剂合物或其药学上可接受的盐，其中化学式的变量如规范中所定义。本文还提供了利用具有化学式（I）或（Ia）的化合物，或其对映体、二对映异构体、互变异构体、水合物、溶剂合物或其药学上可接受的盐来治疗和预防HBV疾病。
• Inhibitors of hepatitis C virus NS3 protease
  申请人：——

  公开号：US20020065248A1

  公开（公告）日：2002-05-30

  The present invention relates to compounds of Formula (I): 1 wherein A 1 is methylene, ethylene or propylene group and A 2 is N or CR 5 , or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HCV NS3 protease, and to pharmaceutical compositions and diagnostic kits comprising the same, and methods of using the same for treating viral infection or as an assay standard or reagent.

  本发明涉及化合物的结构公式（I）：其中A1为亚甲基、乙烯基或丙烯基，A2为N或CR5，或其立体异构体形式、立体异构体混合物或药用盐形式，用作HCV NS3蛋白酶的抑制剂，以及包含相同化合物的药物组合物和诊断试剂盒，以及用于治疗病毒感染或作为测定标准或试剂的方法。
• A short and efficient synthesis of (S)-4-methylene proline benzyl ester from (S)-pyroglutamic acid
  作者：Sharad Kumar Panday、Dominique Griffart-Brunet、Nicole Langlois

  DOI：10.1016/s0040-4039(00)73465-4

  日期：1994.9

  (S)-4-methylene proline benzyl ester 2 was synthesized from benzyl N-tert-butoxycarbonyl pyroglutamate through a Mannich and a Cope elimination reactions.

  （S）-4-亚甲基脯氨酸苄基酯2是通过Mannich和Cope消除反应由苄基N-叔丁氧基羰基焦谷氨酸合成的。
• Peptide inhibitors of hepatitis C virus NS3 protein
  申请人：——

  公开号：US20020177725A1

  公开（公告）日：2002-11-28

  This invention relates to a novel class of peptides having the Formula (I): 1 Which are useful as serine protease inhibitors, and more particularly as Hepatitis C virus(HCV) NS3 protease inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same in the treatment of HCV infection.

  本发明涉及一类新型肽的公式(I)：1，其作为丝氨酸蛋白酶抑制剂具有用途，更具体地作为丙型肝炎病毒（HCV）NS3蛋白酶抑制剂。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗HCV感染的方法。