(2S,3R)-2-benzyloxycarbonylamino-3-methyl-4-pentenoic acid | 260270-94-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3R)-2-benzyloxycarbonylamino-3-methyl-4-pentenoic acid
• 英文别名: (2S,3R)-3-methyl-2-(phenylmethoxycarbonylamino)pent-4-enoic acid
• CAS: 260270-94-8
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: BOEOWAAWUCRQHK-PWSUYJOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-benzyloxycarbonylamino-3-methyl-4-pentenoic acid 在 Lindlar's catalyst 吡啶 、 叠氮化锂 、 thexylborane 、 TEA 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 80.0 ℃ 、206.85 kPa 条件下， 反应 37.75h， 生成 tert-butyl (2S,3R)-2-{[(benzyloxy)carbonyl]amino}-5-amino-3-methylpentanoate
  参考文献：
  名称：

  Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor-α Converting Enzyme (TACE)

  摘要：

  A program to improve upon the in vitro, in vivo, and physicochemical properties of N-hydroxyformamide TACE inhibitor GW 3333 (1) is described. Using the primary structure of pro-TNF-alpha, along with a homology model of the catalytic domain of TACE based on the X-ray diffraction coordinates of adamalysin, we synthesized N-hydroxyformamide TACE inhibitors containing a P2' arginine side chain. Introduction of nitro and sulfonyl electron-withdrawing groups covalently bound to the P2' guanidine moiety rendered the inhibitors electronically neutral at cellular pH and led to potent inhibition of TNF-alpha release from stimulated macrophages. Inhibitors containing these arginine mimetics were found to have increased solubility in simulated gastric fluid (SGF) relative to 1, allowing for the incorporation of lipophilic P1' side chains which had the effect of retaining potent TACE inhibition, but reducing potency against matrix metalloproteases (MMPs) thus increasing overall selectivity against MMP1, MMP3, and MMP9. Selected compounds showed good to excellent in vivo TNF inhibition when administered via subcutaneous injection. One inhibitor, 28a, with roughly 10x selectivity over MMPI and MMP3 and high solubility in SGF, was evaluated in the rat zymosan-induced pleuisy model of inflammation and found to inhibit zymosan-stimulated pleural TNF-alpha elevation by 30%.

  DOI：

  10.1021/jm0102654
• 作为产物：
  描述：

  N-苄氧羰基甘氨酸 在 4-二甲氨基吡啶 、 aluminum isopropoxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,3R)-2-benzyloxycarbonylamino-3-methyl-4-pentenoic acid
  参考文献：
  名称：

  评价3-取代的精氨酸类似物作为人一氧化氮合酶同工酶的选择性抑制剂。

  摘要：

  一氧化氮（NO）是多种生理和病理生理过程的介体，由一氧化氮合酶（NOS）的三种同工酶合成。在开发候选临床药物中，不抑制内皮型NOS非常重要，因为它在维持正常的血压和流量中起着重要的作用。在这里，我们描述了基于S-甲基-L-异硫瓜氨酸的3-取代精氨酸类似物的设计，合成和人类NOS抑制活性。具有S-甲基异硫脲部分的3R *-甲基化合物4抑制nNOS和iNOS，但不抑制eNOS（IC（50）> 1 mM）。然而，尽管LN-亚氨基乙基鸟氨酸（L-NIO）有效地抑制了全部三个，但带有5-亚氨基乙基部分的3R *-甲基化合物7没有抑制任何NOS同工酶。

  DOI：

  10.1016/j.bmcl.2005.03.078

文献信息

• Formamide compounds as therapeutic agents
  申请人：Glaxo Wellcome Inc.

  公开号：US06191150B1

  公开（公告）日：2001-02-20

  A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof.

  具有一般结构式的化合物家族，其中W是一个反向羟肟酸基团，而R1、R2、R3、R4、R5和R6如规范中所述，或其药学上可接受的盐、溶剂化合物、生物水解酯、生物水解酰胺、亲和试剂或其前药。
• [EN] BRIDGED TRICYCLIC CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE<br/>[FR] COMPOSÉS DE CARBAMOYLPYRIDONE TRICYCLIQUE PONTÉS ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：GILEAD SCIENCES INC

  公开号：WO2020197991A1

  公开（公告）日：2020-10-01

  Compounds for use in treating or preventing human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2, L, W1, W2, X, Y, and Z are as defined herein. Methods associated with the preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  本发明揭示了用于治疗或预防人类免疫缺陷病毒（HIV）感染的化合物。这些化合物具有以下式（I）：包括立体异构体和其药用可接受的盐，其中R1、R2、L、W1、W2、X、Y和Z如本文所定义。本发明还揭示了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。
• Total synthesis and determination of the stereochemistry of 2-amino-3-cyclopropylbutanoic acid, a novel plant growth regulator isolated from the mushroom Amanita castanopsidis Hongo
  作者：Yoshiki Morimoto、Mamoru Takaishi、Takamasa Kinoshita、Kazuhiko Sakaguchi、Kozo Shibata

  DOI：10.1039/b108752e

  日期：2002.1.14

  The unknown stereostructure of 2-amino-3-cyclopropylbutanoic acid 1, a novel plant growth regulator isolated from the mushroom Amanita castanopsidis Hongo, was determined to be (2S,3S)-2 through its racemic and enantioselective syntheses employing the chelate–enolate Claisen rearrangement as a key step.

  2-amino-3-cyclopropylbutanoic acid 1 是一种从 Amanita castanopsidis Hongo 蘑菇中分离出来的新型植物生长调节剂，其未知的立体结构是 (2S,3S)-2，其外消旋和对映体选择性合成的关键步骤是螯合烯醇克莱森重排。
• [EN] FORMAMIDE COMPOUNDS AS THERAPEUTIC AGENTS<br/>[FR] AGENTS THERAPEUTIQUES A BASE DE COMPOSES DE FORMAMIDES
  申请人：GLAXO GROUP LTD

  公开号：WO2000012466A1

  公开（公告）日：2000-03-09

  A family of compounds having general structural formula (I), where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof. Also described are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine.

  一类化合物的一般结构式（I），其中W为反向羟肟酸基团，R1，R2，R3，R4，R5和R6如规范所述，或其药学上可接受的盐，溶剂化物，生物可水解酯，生物可水解酰胺，亲和试剂或其前药。还描述了它们的制备方法，包括这些化合物的制药组合物以及它们在医学中的使用。
• Bridged tricyclic carbamoylpyridone compounds and their pharmaceutical use
  申请人：Gilead Sciences, Inc.

  公开号：US11084832B2

  公开（公告）日：2021-08-10

  Compounds for use in treating or preventing human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2, L, W1, W2, X, Y, and Z are as defined herein. Methods associated with the preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  本发明公开了用于治疗或预防人类免疫缺陷病毒（HIV）感染的化合物。这些化合物具有下式(I)： 其中 R1、R2、L、W1、W2、X、Y 和 Z 如本文所定义。此外，还公开了与制备和使用此类化合物相关的方法，以及包含此类化合物的药物组合物。