3-ethylthiopropionitrile | 3088-46-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-ethylthiopropionitrile
• 英文别名: Propanenitrile, 3-(ethylthio)-；3-ethylsulfanylpropanenitrile
• CAS: 3088-46-8
• 化学式: C₅H₉NS
• 分子量: 115.199
• InChiKey: IVUFBXHGCATYAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  7
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  49.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-ethylthiopropionitrile 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 以54%的产率得到4-thia-1-hexylamine
  参考文献：
  名称：

  Novel 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamide Transition State Peptidomimetics Are Potent and Orally Active Inhibitors of Human Renin

  摘要：

  The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as I bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of I and extensive P2' modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rhrenin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3(SP)) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.

  DOI：

  10.1021/jm070314y
• 作为产物：
  描述：

  乙硫醇 以82%的产率得到
  参考文献：
  名称：

  MITSUKUCHI, MORIHIRO;IKEMOTO, TOMOYUKI;TAGUCHI, MINORU;HIGUCHI, SHOHEI;AB+, CHEM. AND PHARM. BULL., 38,(1990) N, C. 692-697

  摘要：

  DOI：

文献信息

• Borax as an Efficient Metal-Free Catalyst for Hetero-Michael Reactions in an Aqueous Medium
  作者：Sahid Hussain、Saitanya K. Bharadwaj、Mihir K. Chaudhuri、Harjyoti Kalita

  DOI：10.1002/ejoc.200600691

  日期：2007.1

  Borax, a naturally occurring material, very efficiently catalyzed the conjugate addition of thiols, dithiols and amines to α,β-unsaturated ketones, nitriles, amides, aldehydes and esters in an aqueous medium to afford the corresponding Michael adducts in good yields at room temperature. Recycling of the catalyst and scaling up of the reactions are important attributes of this catalysis. The reactions

  硼砂是一种天然存在的材料，在水性介质中非常有效地催化硫醇、二硫醇和胺与 α,β-不饱和酮、腈、酰胺、醛和酯的共轭加成，在室温下以良好的收率提供相应的迈克尔加合物. 催化剂的再循环和反应的放大是这种催化的重要属性。硫醇和二硫醇的反应比相应的胺更容易。
• Studies on topical antiinflammatory agents. V. 17-(alkylthio)- and methoxyalkanoates of corticosteroids.
  作者：Morihiro MITSUKUCHI、Tomoyuki IKEMOTO、Minoru TAGUCHI、Shohei HIGUCHI、Satoshi ABE、Hajime YASUI、Katsuo HATAYAMA

  DOI：10.1248/cpb.38.692

  日期：——

  As part of our search for new topical antiinflammatory agents, a series of corticosteroid 17-(alkylthio)- and methoxyalkanoate derivatives was prepared and tested for vasoconstrictive activities. Several compounds were proved to have activity superior or comparable to that of 9α-fluoro-11β, 21-dihydroxy-16β-methyl-17α-valeryloxy-1, 4-pregnadiene-3, 20-dione (betamethasone 17-valerate, BV). Among these compounds, 21-chloro-11β-hydroxy-17α-(methylthio)acetoxy-4-pregnene-3, 20-dione (5Aa) was found to have the most potent activity, being more active than BV. The structure-activity relationships of the series revealed that introduction of a (methylthio)acetate function into the 17-position as well as the 21-position of corticosteroids was effective for enhancing the topical antiinflammatory activity.

  作为寻找新型外用抗炎药物的一部分，我们合成并测试了一系列皮质类固醇17-（烷硫基）和甲氧基羧酸酯衍生物的血管收缩活性。多个化合物被证明其活性优于或相当于9α-氟-11β, 21-二羟基-16β-甲基-17α-戊酸酯-1, 4-孕二烯-3, 20-二酮（倍他米松17-戊酸酯，BV）。在这些化合物中，21-氯-11β-羟基-17α-（甲硫基）乙酸酯-4-孕烯-3, 20-二酮（5Aa）显示出最强的活性，其活性超过BV。系列的构效关系揭示，在皮质类固醇的17位和21位引入（甲硫基）乙酸酯功能基团可有效增强其外用抗炎活性。
• Heme-Coordinating Inhibitors of Neuronal Nitric Oxide Synthase. Iron−Thioether Coordination Is Stabilized by Hydrophobic Contacts without Increased Inhibitor Potency
  作者：Jeffrey D. Martell、Huiying Li、Tzanko Doukov、Pavel Martásek、Linda J. Roman、Michael Soltis、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1021/ja908544f

  日期：2010.1.20

  between heme iron and native methionine ligands, but thioether-based heme-coordinating (type II) inhibitors are uncommon due to the difficulty in stabilizing the Fe-S bond. Here, a thioether-based inhibitor (3) of neuronal nitric oxide synthase (nNOS) was designed, and its binding was characterized by spectrophotometry and crystallography. A crystal structure of inhibitor 3 coordinated to heme iron was obtained

  血红素-硫醚配体相互作用通常发生在血红素铁和天然蛋氨酸配体之间，但由于难以稳定 Fe-S 键，基于硫醚的血红素配位（II 型）抑制剂并不常见。在这里，设计了一种基于硫醚的神经元一氧化氮合酶（nNOS）抑制剂（3），并通过分光光度法和晶体学对其结合进行了表征。获得了与血红素铁配位的抑制剂3的晶体结构，据我们所知，这代表了与任何血红素酶复合的硫醚抑制剂的第一个晶体结构。还评估了一系列相关的潜在抑制剂 (4-8)。化合物 4-8 均被发现是铁 nNOS 的 I 型（非血红素配位）抑制剂，但发现 4 和 6-8 在血红素还原为亚铁态时转变为 II 型，反映了硫醚的更高亲和力亚铁血红素比铁血红素。与人们普遍认为的相反，发现硫醚-血红素连接不会增加抑制剂的效力，这说明了硫醚-铁血红素连接的内在弱点。硫醚硫上烷基的细微变化引起了结合构象的剧烈变化，表明疏水接触在稳定硫醚-血红素配位中起着至关重要的作用。
• Thia-Michael Addition Using Cheap and Odorless <i>S</i>-Alkylisothiouronium Salts as Thiol Equivalents in Water
  作者：Ze-Mei Ge、Run-Tao Li、Yan Zhao、Tie-Ming Cheng

  DOI：10.1055/s-2007-982530

  日期：2007.6

  S-Alkylisothiouronium salt has been found to be a nontoxic, odorless and simply operational alternative of thiol for the thia-Michael addition with electron-deficient olefins. The reactions were carried out under alkaline conditions in water at room temperature within 5-20 minutes to afford the expected products in good to excellent yields.

  S-烷基异硫脲盐被发现是一种无毒、无气味且操作简便的硫醇替代品，可用于与电子缺乏烯烃的硫醇-迈克尔加成反应。反应在室温下的水相碱性条件下进行，时间为5至20分钟，能够以良好到优秀的产率得到预期产品。
• Novel atom-economic reaction: comprehensive utilization of S-alkylisothiouronium salt in the synthesis of thioethers and guanidinium salts
  作者：Pengchao Gao、Penglin Leng、Qi Sun、Xin Wang、Zemei Ge、Runtao Li

  DOI：10.1039/c3ra42503g

  日期：——

  A novel atom-economic three-component one-pot reaction of a primary amine, an S-alkylisothiouronium salt and a Michael receptor is reported, which affords a guanidinium salt and thioether simultaneously. The guanidine moiety is involved in catalyzing the conjugated Michael addition of the mercaptan. The reaction proceeds under ambient conditions using a non-toxic EtOH–H2O mixture as the solvent, and the two products can be very easily purified. Complete atom economy is achieved by fully utilizing the S-alkylisothiouronium salt and converting the previously wasted mercaptan by-product into the valuable thioether.

  报道了一种新颖的原子经济性三组分一锅反应，涉及一种初级胺、一种S-烷基异硫脲盐和一个迈克尔受体，能够同时获得盐基盐和硫醚。胍基部分参与催化与巯基的共轭迈克尔加成。该反应在常温下进行，使用无毒的乙醇-水混合物作为溶剂，两个产物可以非常容易地进行纯化。通过充分利用S-烷基异硫脲盐并将之前浪费的巯基副产物转化为有价值的硫醚，实现了完全的原子经济性。