thioacetic acid S-((S)-2-tert-butoxycarbonylamino-4-methyl-pentyl) ester | 112157-31-0

• 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: thioacetic acid S-((S)-2-tert-butoxycarbonylamino-4-methyl-pentyl) ester
• 英文别名: Thioacetic acid S-((S)-2-tert-butoxycarbonylamino-4-methyl-pentyl)ester；S-[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentyl] ethanethioate
• CAS: 112157-31-0
• 化学式: C₁₃H₂₅NO₃S
• 分子量: 275.412
• InChiKey: MONQIJAILIYXNZ-NSHDSACASA-N

物化性质

• 熔点：
  51 °C
• 沸点：
  366.5±25.0 °C(Predicted)
• 密度：
  1.030±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  thioacetic acid S-((S)-2-tert-butoxycarbonylamino-4-methyl-pentyl) ester 在 sodium hydroxide 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 tert-butyl N-[(2S)-4-methyl-1-(pyridin-2-yldisulfanyl)pentan-2-yl]carbamate
  参考文献：
  名称：

  Mixed-inhibitor-prodrug as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes

  摘要：

  In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH(CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.

  DOI：

  10.1021/jm00091a016
• 作为产物：
  描述：

  N-叔丁氧羰基-L-亮氨醇 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 生成 thioacetic acid S-((S)-2-tert-butoxycarbonylamino-4-methyl-pentyl) ester
  参考文献：
  名称：

  C端亮氨酸硫醇作为阿片受体中硫醇基团探针的脑啡肽类似物的合成

  摘要：

  在 C 端具有硫醇基团的脑啡肽类似物 [D-Ala2, Leu(CH2SH)5] 脑啡肽被合成为阿片受体中必需硫醇基团的可能探针。为了保护亮氨酸硫醇的游离 SH 基团，从 L-亮氨酸（2-氨基-4-甲基-1-戊醇）制备氧化的 Boc-L-亮氨酸硫醇二聚体以延长脑啡肽序列。含 SH 的单体脑啡肽类似物是通过在 50% AcOH 中用锌处理从二聚体中获得的，它对 mu 阿片受体具有高亲和力。

  DOI：

  10.1246/cl.1987.997

文献信息

• Synthesis and evaluation of chloromethyl sulfoxides as a new class of selective irreversible cysteine protease inhibitors
  作者：Arwin J. Brouwer、Anton Bunschoten、Rob M.J. Liskamp

  DOI：10.1016/j.bmc.2007.07.045

  日期：2007.11

  The synthesis and biological evaluation of a new class of selective irreversible cysteine protease inhibitors is described. A set of amino acid based chloromethyl sulfoxides was prepared and they were found to inhibit irreversibly the cysteine protease papain. They were selective for cysteine proteases since no inhibition was found for the serine protease chymotrypsin.

  描述了新型的选择性不可逆半胱氨酸蛋白酶抑制剂的合成和生物学评估。制备了一套基于氨基酸的氯甲基亚砜，发现它们不可逆地抑制半胱氨酸蛋白酶木瓜蛋白酶。由于对丝氨酸蛋白酶胰凝乳蛋白酶没有抑制作用，因此它们对半胱氨酸蛋白酶具有选择性。
• [EN] BENZOIMIDAZOLE-CARBOXYLIC ACID AMIDE DERIVATIVES AS APJ RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS D'AMIDE D'ACIDE BENZIMIDAZOLE-CARBOXYLIQUE UTILISÉS COMME MODULATEURS DU RÉCEPTEUR APJ
  申请人：SANOFI SA

  公开号：WO2014044738A1

  公开（公告）日：2014-03-27

  The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, in which R', R", R"', R1, R2, R3, R4, R5, R6 and Z are defined as indicated below. The compounds of the formula I are APJ receptor modulators, and are useful for the treatment of diseases associated with increased blood pressure for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及公式I的苯并咪唑羧酸酰胺化合物，其中R'、R"、R"'、R1、R2、R3、R4、R5、R6和Z如下所示定义。公式I的化合物是APJ受体调节剂，可用于治疗与增高血压相关的疾病。此外，本发明还涉及将公式I的化合物用作药物中的活性成分，以及包含它们的药物组合物。
• BENZOIMIDAZOLE-CARBOXYLIC ACID AMIDE DERIVATIVES AS APJ RECEPTOR MODULATORS
  申请人：HACHTEL Stephanie

  公开号：US20140094450A1

  公开（公告）日：2014-04-03

  The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, in which R′, R″, R′″, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Z are defined as indicated below. The compounds of the formula I are APJ receptor modulators, and are useful for the treatment of diseases associated with increased blood pressure for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及公式I的苯并咪唑羧酰胺化合物，其中R′、R″、R′″、R1、R2、R3、R4、R5、R6和Z的定义如下所示。公式I的化合物是APJ受体调节剂，对治疗与增高血压相关的疾病有用。此外，本发明还涉及将公式I的化合物用作药物中的活性成分，以及包含它们的药物组合物。
• Benzoimidazole-carboxylic acid amide derivatives as APJ receptor modulators
  申请人：SANOFI

  公开号：US09156796B2

  公开（公告）日：2015-10-13

  The present invention relates to benzoimidazole-carboxylic acid amide compounds of the formula I, in which R′, R″, R′″, R1, R2, R3, R4, R5, R6 and Z are defined as indicated below. The compounds of the formula I are APJ receptor modulators, and are useful for the treatment of diseases associated with increased blood pressure for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及式I的苯并咪唑羧酸酰胺化合物，其中R'、R"、R'"、R1、R2、R3、R4、R5、R6和Z如下所示。式I的化合物是APJ受体调节剂，可用于治疗与血压升高相关的疾病。此外，本发明还涉及使用式I的化合物，特别是作为药物的活性成分，以及包含它们的制药组合物。
• Synthesis of sulfur-containing analogs of bestatin. Inhibition of aminopeptidases by .alpha.-thiolbestatin analogs
  作者：Timothy D. Ocain、Daniel H. Rich

  DOI：10.1021/jm00119a022

  日期：1988.11

  Sulfur-containing amino acid and peptide analogues of bestatin [((2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl)-L-leucine] (1) have been synthesized and evaluated as inhibitors of aminopeptidase M (AP-M), leucine aminopeptidase (LAP), and aminopeptidase B (AP-B). The 2-thiolbestatin analogue (6) was found to be a potent inhibitor of all three aminopeptidases (AP-M, Ki = 4.4 microM; LAP, Ki = 0.55 microM; AP-B, Ki = 4.6 nM) but only a slightly better inhibitor of these aminopeptidases than the parent hydroxy-containing compound 1. Synthetic analogues of L-leucinethiol(4), a strong inhibitor of aminopeptidases, were prepared in which the carbon alpha to the thiol groups was substituted with methyl, methyl carboxylate, and carboxamide derivatives and found to be much weaker inhibitors of all aminopeptidases. A thioamide analogue of bestatin (49) is a modest inhibitor of AP-M (Ki = 40 microM), LAP (Ki = 0.33 microM), and AP-B (Ki = 2.4 microM). These results suggest that the sulfur atoms in 2-thiolbestatin and bestatin thioamide do not interact strongly with the active-site zinc atom of these aminopeptidases when the inhibitors are bound to the enzyme. These results are not consistent with proposed models for the inhibition of aminopeptidases by bestatin and related analogues.