S-isobutyl-L-cysteine

• 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: S-isobutyl-L-cysteine
• 英文别名: (2R)-2-amino-3-(2-methylpropylsulfanyl)propanoic acid
• 化学式: C₇H₁₅NO₂S
• 分子量: 177.268
• InChiKey: MTNIUVNRJAVELU-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  S-isobutyl-L-cysteine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 4-二甲氨基吡啶 、 二碳酸二叔丁酯 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 42.75h， 生成 (R,Z)-tert-butyl 2-(9-((2,4-difluorophenyl)ethynyl)-7-oxo-2,5,6,7-tetrahydrobenzo[b][1,5]oxazonine-6-carboxamido)-3-(isobutylthio)-propanoate
  参考文献：
  名称：

  Synthesis of conformationally constrained benzoylureas as BH3-mimetics

  摘要：

  模仿BH3结构域并与Bcl-2蛋白结合的小分子设计已成为发现新型抗癌药物的一种有前途的方法。我们揭示了作为构象探针的构象约束苯甲酰脲骨架的设计和合成。苯甲酰脲中的分子内氢键在螺旋模仿中发挥了关键作用，有助于非环状底物的预组织，以通过环闭合转化实现高效的约束模拟物合成。

  DOI：

  10.1039/c2ob25618e
• 作为产物：
  描述：

  (R)-N-(tert-butyloxycarbonyl)-S-(isobutyl)cysteine 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 S-isobutyl-L-cysteine
  参考文献：
  名称：

  从头设计的苯甲酰脲图书馆BCL-X的抑制剂大号：合成，结构和生化特性

  摘要：

  存活的BCL-2蛋白对于药物化学家而言是有吸引力的但具有挑战性的靶标。它们参与了许多（如果不是全部）肿瘤的发生和发展，使其成为开发新的抗癌疗法的主要靶标。我们介绍了基于从头结构的药物设计方法。利用来自参与BCL-2蛋白质家族相对成员的复合物的已知结构信息，我们使用苯甲酰脲支架设计了拟肽化合物，以再现这些蛋白质之间的关键相互作用。从初始从头词干的文库设计的支架导致与低微摩尔效力（配位体的发现ķ d = 4μM）和选择性BCL-X大号。这些化合物以不同于先前已知的BCL-2抑制剂的结合方式在规范的BH3结合槽中结合。我们的研究结果为针对具有挑战性的蛋白质-蛋白质相互作用类的新型拮抗剂的设计提供了见识。

  DOI：

  10.1021/jm401948b

文献信息

• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF VARIOUS DISEASES<br/>[FR] INHIBITEURS DE LA CATHEPSINE CYSTÉINE PROTÉASE POUR TRAITER DES MALADIES VARIÉES
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010148488A1

  公开（公告）日：2010-12-29

  The present invention relates to compounds capable of inhibiting and/or decreasing the activity of one or more cathepsins, thereby treating and/or preventing various disease states associated with one or more cysteine proteases including, but not limited to, cathepsins and papain-like cysteine proteases. Disease states treated and/or prevented by the compounds of the invention include, but are not limited to, mammalian parasitic diseases in which the parasite utilizes a critical cysteine protease from the papain family. Examples of parasitic diseases to be treated or prevented by the compounds of the invention include, but are not limited to, toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, coccidiosis, giardiosis, cryptosporidiosis or schistosomiasis.

  本发明涉及一种能够抑制和/或减少一种或多种半胱氨酸蛋白酶活性的化合物，从而治疗和/或预防与一种或多种半胱氨酸蛋白酶相关的各种疾病状态，包括但不限于cathepsins和木瓜蛋白酶样半胱氨酸蛋白酶。本发明的化合物治疗和/或预防的疾病状态包括但不限于寄生于哺乳动物的寄生病，其中寄生虫利用木瓜家族的关键半胱氨酸蛋白酶。本发明的化合物可用于治疗或预防的寄生病例包括但不限于弓形虫病、疟疾、非洲锥虫病、查加斯病、利什曼病、球虫病、贾第虫病、隐孢子虫病或血吸虫病。
• CATHEPSIN CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF VARIOUS DISEASES
  申请人：Black Cameron

  公开号：US20120101053A1

  公开（公告）日：2012-04-26

  The present invention relates to compounds capable of inhibiting and/or decreasing the activity of one or more cathepsins, thereby treating and/or preventing various disease states associated with one or more cysteine proteases including, but not limited to, cathepsins and papain-like cysteine proteases. Disease states treated and/or prevented by the compounds of the invention include, but are not limited to, mammalian parasitic diseases in which the parasite utilizes a critical cysteine protease from the papain family. Examples of parasitic diseases to be treated or prevented by the compounds of the invention include, but are not limited to, toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, coccidiosis, giardiosis, cryptosporidiosis or schistosomiasis.

  本发明涉及一种能够抑制和/或减少一种或多种蛋白酶（包括但不限于cathepsins和木瓜样半胱氨酸蛋白酶）活性的化合物，从而治疗和/或预防与一种或多种半胱氨酸蛋白酶相关的各种疾病状态。本发明的化合物治疗和/或预防的疾病状态包括但不限于寄生虫病，其中寄生虫利用来自木瓜家族的关键半胱氨酸蛋白酶。本发明的化合物可用于治疗或预防的寄生虫疾病的例子包括但不限于弓形虫病、疟疾、非洲锥虫病、恙虫病、利什曼病、球虫病、贾第鞭毛虫病、隐孢子虫病或血吸虫病。
• Formation of volatile sulfur compounds and S-methyl-l-cysteine sulfoxide in Brassica oleracea vegetables
  作者：Katharina Friedrich、Nicole S. Wermter、Lars Andernach、Katja Witzel、Franziska S. Hanschen

  DOI：10.1016/j.foodchem.2022.132544

  日期：2022.7

  Besides glucosinolates, vegetables accumulate sulfur-containing (+)--methyl--cysteine sulfoxide (SMCSO, methiin), mainly known from vegetables. Such (+)--alk(en)yl--cysteine sulfoxides can degrade to volatile organosulfur compounds (VOSCs), which have been linked to health beneficial effects. In the present study, the accumulation of SMCSO and the formation of VOSCs was investigated in vegetables.

  除了芥子油苷外，蔬菜还积累主要来自蔬菜的含硫(+)-甲基-半胱氨酸亚砜（SMCSO，蛋氨酸）。这种 (+)--烷(烯)基-半胱氨酸亚砜可以降解为挥发性有机硫化合物 (VOSC)，这与健康有益的作用有关。在本研究中，研究了蔬菜中 SMCSO 的积累和 VOSC 的形成。对市售白甘蓝和红甘蓝的 SMCSO 含量进行了为期三个月的监测，并将其与 VOSC 的形成联系起来。 -甲基硫代亚磺酸甲酯是 SMCSO 释放的主要 VOSC。加热后，它降解为二甲基三硫醚和二甲基二硫醚，这在新鲜匀浆中含量较低。 SMCSO 约占卷心菜干物质的 1%，白卷心菜和红卷心菜的总体含量相似（分别为 3.2–10.2 和 3.9–10.3 µmol/g 鲜重）。使用蛋白质组分析表明，VOSC 的恢复与胱氨酸裂解酶的两种亚型的丰度相关。
• Dipeptide-Derived Alkynes as Potent and Selective Irreversible Inhibitors of Cysteine Cathepsins
  作者：Lydia Behring、Gloria Ruiz-Gómez、Christian Trapp、Maryann Morales、Robert Wodtke、Martin Köckerling、Klaus Kopka、M. Teresa Pisabarro、Jens Pietzsch、Reik Löser

  DOI：10.1021/acs.jmedchem.2c01360

  日期：2023.3.23

  potent peptide nitriles was explored. The synthesis of the dipeptide alkynes was developed with special emphasis on stereochemically homogeneous products obtained in the Gilbert–Seyferth homologation for C≡C bond formation. Twenty-three dipeptide alkynes and 12 analogous nitriles were synthesized and investigated for their inhibition of cathepsins B, L, S, and K. Numerous combinations of residues at positions

  探索了通过等电子置换在可逆作用的强效肽腈中设计不可逆的基于炔烃的半胱氨酸组织蛋白酶抑制剂的潜力。二肽炔烃的合成特别强调在 Gilbert-Seyferth 同系化中获得的 C≡C 键形成的立体化学均质产物。合成了 23 个二肽炔烃和 12 个类似的腈，并研究了它们对组织蛋白酶 B、L、S 和 K 的抑制作用。P1 和 P2 位置的残基以及末端酰基的多种组合允许推导广泛的结构–活动关系，通过选定示例的计算共价对接合理化。炔烃在目标酶上的确定失活常数范围 >–1秒–1 )。值得注意的是，炔烃的选择性分布不一定反映腈类化合物的选择性分布。已证明选定化合物在细胞水平上的抑制活性。
• Acylase I-Catalyzed Deacetylation of <i>N</i>-Acetyl-<scp>l</scp>-cysteine and <i>S</i>-Alkyl-<i>N</i>-acetyl-<scp>l</scp>-cysteines
  作者：Vinita Uttamsingh、D. A. Keller、M. W. Anders

  DOI：10.1021/tx980018b

  日期：1998.7.1

  The aminoacylase that catalyzes the hydrolysis of N-acetyl-L-cysteine (NAC) was identified as acylase I after purification by column chromatography and electrophoretic analysis. Rat kidney cytosol was fractionated by ammonium sulfate precipitation, and the proteins were separated by ion-exchange column chromatography, gel-filtration column chromatography, and hydrophobic interaction column chromatography. Acylase activity with NAC and N-acetyl-L-methionine (NAM), a known substrate for acylase I, as substrates coeluted during all chromatographic steps. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the protein was purified to near homogeneity and had a subunit M-r of 43 000, which is identical with the M-r of acylase I from porcine kidney and bovine liver. n-Butylmalonic acid was a slow-binding inhibitor of acylase I and inhibited the deacetylation of NAC with a K-i of 192 +/- 27 mu M These results show that acylase I catalyzes the deacetylation of NAG. The acylase I-catalyzed deacetylation of a range of S-alkyl-N-acetyl-L-cysteines, their carbon and oxygen analogues, and the selenium analogue of NAM was also studied with porcine kidney acylase I. The specific activity of the acylase I-catalyzed deacetylation of these substrates was related to their calculated molar volumes and lag P values. The S-alkyl-N-acetyl-L-cysteines with short (C-0-C-3) and unbranched S-alkyl substituents were good acylase I substrates, whereas the S-alkyl-N-acetyl-L-cysteines with long (>C-3) and branched S-alkyl substituents were poor acylase I substrates. The carbon and oxygen analogues of S-methyl-N-acetyl-L-cysteine and the carbon analogue of S-ethyl-N-acetyl-L-cysteine were poor acylase I substrates, whereas the selenium analogue of NAM was a good acylase I substrate.