N-(硫代苯甲酰基)甘氨酸乙酯 | 87386-07-0

• 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
• 中文名称: N-(硫代苯甲酰基)甘氨酸乙酯
• 英文名称: N-(thiobenzoyl)glycine ethyl ester
• 英文别名: Ethyl 2-(benzenecarbonothioylamino)acetate
• CAS: 87386-07-0
• 化学式: C₁₁H₁₃NO₂S
• 分子量: 223.296
• InChiKey: UBIFFACMHKFDND-UHFFFAOYSA-N

物化性质

• 沸点：
  324.3±44.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  70.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(硫代苯甲酰基)甘氨酸乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 ethyl 2,5-diphenyloxazole-4-carboxylate
  参考文献：
  名称：

  Synthesis of Oxazoles and Thiazoles Using Thioimidates

  摘要：

  通过在碱的存在下，将N-(甲基硫烷基烯基)甘氨酸乙酯与二乙氧基草酸、酸卤化物和硫醇酯反应，易于合成几种噁唑类和噻唑类化合物。

  DOI：

  10.1055/s-1994-25715
• 作为产物：
  描述：

  马尿酸乙酯 在 2,4-bis(4-phenylthiophenyl)-1,3,2,4-dithiaphosphetane 2,4-disulfide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以97%的产率得到N-(硫代苯甲酰基)甘氨酸乙酯
  参考文献：
  名称：

  用一些新的含p，s的试剂研究有机磷化合物XLVII制备酰胺，内酰胺和酰亚胺的硫醇化合成子

  摘要：

  2,4-双甲硫基-1,3,2,4-二硫代二膦，2,4-二硫，1,2,4-双（4-苯氧基苯基）-1,3,2,4-二硫代磷烷的硫磺化性质为即在室温下（反应时间为5分钟）将2、3和硫氰酸盐中的大部分酰胺和内酰胺溶于THF中，得到相应的亚硫代化合物。酰亚胺很容易在60°C下被2、3和4 In DME硫磺化。1与酰胺，酰亚胺和大多数内酰胺的反应在60°C下进行，以得到相应的亚硫代化合物良好的收率。

  DOI：

  10.1016/s0040-4020(01)88445-3

文献信息

• Inhibitors of P2X3
  申请人：Brotherton-Pleiss E. Christine

  公开号：US20070037974A1

  公开（公告）日：2007-02-15

  Compounds of formula 1 are modulators of P2X3 useful for the treatment of pain and genito-urinary, gastrointestinal, and respiratory disorders: wherein R 1 is —C(═S)CH 3 , pyridyl, pyrimidinyl, pyrazinyl, thiazolyl, furyl, furylcarbonyl, acetyl, or carbamoyl; R 2a and R 2b are independently H, methyl, or ethyl; R 3 is H or methyl; Y is a bond, —(CR 4 R 5 ) n — or —CR 4 ═CR 5 —; wherein R 4 and R 5 are each independently H or methyl and n is 1 or 2; X is N or CH; A is phenyl, 5-membered heterocyclyl, or 6-membered heterocyclyl; R 6 , R 7 and R 8 are each independently H, halo, lower alkyl, cycloalkyl, alkylthio, alkylthio-lower alkyl, alkylsulfonyl-lower alkyl, di(lower alkyl)amino-lower alkyl, morpholinyl-lower alkyl, 4-methyl-piperazinyl-methyl, trifluoromethyl, pyridyl, tetrazolyl, thiophenyl, phenyl, biphenyl, or benzyl (where thiophenyl, phenyl and benzyl are substituted with 0-3 lower alkyl, halo, sulfonamido, trifluoromethyl, lower alkoxy or lower alkylthio) or R 6 and R 7 together form a 5-membered or 6-membered carbocyclic or heterocyclic ring substituted with 0-3 substituents selected from the group consisting of lower alkyl, lower alkoxy, oxo, halo, thiophenyl-lower alkyl, phenyl, benzyl (where phenyl and benzyl are substituted with 0-3 lower alkyl, halo, sulfonamido, trifluoro-methyl, lower alkoxy, lower alkylthio, amino-lower alkyl, lower alkylamino-lower alkyl, or di(lower alkyl)amino-lower alkyl); and pharmaceutically acceptable salts thereof; wherein when R 1 is pyrimidin-2-yl, X is N, Y is a bond and A is oxazol-5-yl the carbon atom at position 4 in said oxazol-5-yl is not substituted by propyl when the carbon atom at position 2 in said oxazol-5-yl is substituted by substituted phenyl and the carbon atom at position 4 in said oxazol-5-yl is not substituted by phenyl when the carbon atom at position 2 is substituted by unsubstituted or substituted phenyl.

  式1的化合物是P2X3的调节剂，用于治疗疼痛和泌尿生殖、胃肠和呼吸系统疾病： 其中 R 1 为—C(═S)CH 3 ，吡啶基，嘧啶基，吡嗪基，噻唑基，呋喃基，呋喃甲酰基，乙酰基或氨基甲酰基；R 2a 和R 2b 独立地为H，甲基或乙基；R 3 为H或甲基；Y为键，—(CR 4 R 5 ) n —或—CR 4 ═CR 5 —；其中R 4 和R 5 各自独立地为H或甲基，n为1或2；X为N或CH；A为苯基，5-成员杂环基或6-成员杂环基；R 6 ，R 7 和R 8 各自独立地为H，卤素，低碳基，环烷基，烷基硫醚，烷基硫醚-低碳基，烷基磺酰基-低碳基，二(低碳基)氨基-低碳基，吗啉基-低碳基，4-甲基哌嗪基-甲基，三氟甲基，吡啶基，四唑基，噻吩基，苯基，联苯基或苄基（其中噻吩基，苯基和苄基被0-3个低碳基，卤素，磺酰胺基，三氟甲基，低烷氧基或低烷硫基取代）或R 6 和R 7 一起形成一个被0-3个取自由低碳基，低烷氧基，氧代基，卤素，噻吩基-低碳基，苯基，苄基（其中苯基和苄基被0-3个低碳基，卤素，磺酰胺基，三氟甲基，低烷氧基，低烷硫基，氨基-低碳基，烷基氨基-低碳基或二(低碳基)氨基-低碳基取代）的5-成员或6-成员碳环或杂环取代环；及其药学上可接受的盐；其中当R 1 为嘧啶-2-基时，X为N，Y为键，A为噁唑-5-基时，所述噁唑-5-基中位置4的碳原子在所述噁唑-5-基中位置2的碳原子被取代的苯基取代时不被丙基取代，且所述噁唑-5-基中位置4的碳原子在位置2被取代的苯基取代时不被苯基取代。
• Transformation of Alkyl<i>N</i>-(Vinyloxy)benzimidates to Alkyloxazoles. Mechanism and Extension
  作者：Masataka Yokoyama、Yasuhiro Menjo、Makoto Ubukata、Masakazu Irie、Mikari Watanabe、Hideo Togo

  DOI：10.1246/bcsj.67.2219

  日期：1994.8

  Transformation of alkyl N-(vinyloxy)benzimidates to alkyloxazoles proceeds through the intermediates: a charge-separated 1,2-oxazetidine derivative and then 1-hydroxy-2-[[methylthio(phenyl)methylene]imino]maleic acid diester, while their photochemical transformation takes place via a concerted [1,3] sigmatropic shift. As the extension of this reaction, the preparation of the precursor proposed for

  N-（乙烯基氧基）苯甲酸烷基酯通过中间体转化为烷基恶唑：电荷分离的 1,2-氧氮杂环丁烷衍生物，然后是 1-羟基-2-[[甲硫基（苯基）亚甲基]亚氨基]马来酸二酯，而它们的光化学转化通过一致的 [1,3] σ 位移发生。作为该反应的延伸，描述了维吉尼亚霉素 M2 合成前体的制备和 N-(乙烯基氧基) 苯甲亚胺酸烷基酯的 N-类似物的反应。
• Studies on amino acids and peptides—IV
  作者：T.P. Andersen、A.-B.A.G. Ghattas、S.-O. Lawesson

  DOI：10.1016/s0040-4020(01)91595-9

  日期：1983.1

  Ethyl esters 2 of N-acyl derivatives of glycine, S-alanine, S-phenylalanine, and S-proline, were thionated by use of 2,4 - bis(4 - methoxyphenyl) - 1,3,2,4 - dithiadiphosphetane 2,4-disulfide (Lawesson's Reagent) 1. The N-thioacyl compounds 3 were reacted with hydrazine hydrate and in most cases a ring-closure reaction took place, giving 1,2,4-triazine derivatives 4. The structural proofs of 4 were

  甘氨酸，S-丙氨酸，S-苯丙氨酸和S-脯氨酸的N-酰基衍生物的乙酯2通过使用2,4-双（4-甲氧基苯基）-1,3,2,4-二硫代二膦烷2进行亚硫酰化，4-二硫键（Lawesson试剂）1。使N-硫酰基化合物3与水合肼反应，并且在大多数情况下发生闭环反应，得到1,2,4-三嗪衍生物4。通过1 H，13 C和15 N NMR光谱获得4的结构证明。
• Association of Quinone-Induced Platelet Anti-Aggregation with Cytotoxicity
  作者：S.-R. Kim、J.-Y. Lee、M.-Y. Lee、S.-M. Chung、O.-N. Bae、J.-H. Chung

  DOI：10.1093/toxsci/62.1.176

  日期：2001.7.1

  Various anti-platelet drugs, including quinones, are being investigated as potential treatments for cardiovascular disease because of their ability to prevent excessive platelet aggregation. In the present investigation 3 naphthoquinones (2,3-dimethoxy-1,4-naphthoquinone [DMNQ], menadione, and 1,4-naphthoquinone [4-NQ]) were compared for their abilities to inhibit platelet aggregation, deplete glutathione (GSH) and protein thiols, and cause cytotoxicity. Platelet-rich plasma, isolated from Sprague-Dawley rats, was used for all experiments. The relative potency of the 3 quinones to inhibit platelet aggregation, deplete intracellular GSH and protein thiols, and cause cytotoxicity was 1,4-NQ > menadione >> DMNQ. Experiments using 2 thiol-modifying agents, dithiothreitol (DTT) and 1-chloro-2,4-dintrobenzene (CDNB), confirmed the key roles for GSH in quinone-induced platelet anti-aggregation and for protein thiols in quinone-induced cytotoxicity. Furthermore, the anti-aggregative effects of a group of 12 additional quinone derivatives were positively correlated with their ability to cause platelet cytotoxicity. Quinones that had a weak anti-aggregative effect did not induce cytotoxicity (measured as LDH leakage), whereas quinones that had a potent anti-aggregative effect resulted in significant LDH leakage (84–96%). In one instance, however, p-chloranil demonstrated a potent anti-aggregative effect, but did not induce significant LDH leakage. This can be explained by the inability of p-chloranil to deplete protein thiols, even though intracellular GSH levels decreased rapidly. These results suggest that quinones that deplete GSH in platelets demonstrate a marked anti-aggregative effect. If this anti-aggregative effect is subsequently followed by depletion of protein thiols, cytotoxicity results.

  多种抗血小板药物，包括醌类，正在被研究作为心血管疾病的潜在治疗方法，因为它们能够防止血小板过度聚集。在本研究中，比较了三种萘醌（2,3-二甲氧基-1,4-萘醌[DMNQ]、甲萘醌和1,4-萘醌[4-NQ]）抑制血小板聚集、耗竭谷胱甘肽（GSH）和蛋白硫醇以及引起细胞毒性的能力。所有实验均使用从Sprague-Dawley大鼠中分离的富含血小板的血浆进行。三种醌抑制血小板聚集、耗竭细胞内GSH和蛋白硫醇以及引起细胞毒性的相对效力为1,4-NQ > 甲萘醌 >> DMNQ。使用两种硫醇修饰剂，二硫苏糖醇（DTT）和对氯间二硝基苯（CDNB）的实验证实了GSH在醌诱导的血小板抗聚集中的关键作用以及蛋白硫醇在醌诱导的细胞毒性中的作用。此外，一组12种额外醌衍生物的抗聚集作用与其引起血小板细胞毒性的能力呈正相关。具有弱抗聚集作用的醌不会诱发细胞毒性（以LDH泄漏衡量），而具有强抗聚集作用的醌则会导致显著的LDH泄漏（84-96%）。然而，在一种情况下，p-氯醌表现出强大的抗聚集作用，但没有诱导显著的LDH泄漏。这可以通过p-氯醌不能耗竭蛋白硫醇来解释，尽管细胞内GSH水平迅速下降。这些结果表明，耗竭血小板中GSH的醌表现出显著的抗聚集作用。如果这种抗聚集作用随后伴随着蛋白硫醇的耗竭，则会导致细胞毒性。
• Effect of Amine Nature on Reaction Mechanism:  Aminolyses of <i>O</i>-4-Nitrophenyl Thionobenzoate with Primary and Secondary Amines
  作者：Ik-Hwan Um、Seung-Eun Lee、Hey-Jin Kwon

  DOI：10.1021/jo0259360

  日期：2002.12.1

  determined for the reactions of 2 with all the primary and secondary amines studied. The k(1) value is larger for the reaction with the primary amine than for the reaction with the isobasic acyclic secondary amines, while the k(-)(1) value is much larger for the latter reaction than for the former reaction. The k(3) value for the reaction with secondary amine is independent of the amine basicity. The small

  已用分光光度法测定了O-4-硝基苯基硫代苯甲酸酯（2）与一系列伯和无环仲胺的反应的伪一级速率常数（k（obs））。对于2与伯胺的反应，k（obs）对胺浓度的曲线是线性的。2与伯胺反应的布朗斯台德型图的斜率随胺碱度的增加而从0.77降低至0.17，表明该反应通过两性离子加成中间体进行，其中速率决定步骤从苯酚的分解而变化胺碱度增加，反应产物的中间体形成中间体。另一方面，对于所研究的所有无环仲胺的反应，k（obs）与胺浓度的关系曲线呈现出向上弯曲，这表明该反应通过两个中间体进行，例如两性离子加成中间体和阴离子中间体。微观速率常数（k（1），k（-）（1），k（2）和k（3）（如果有）已经确定，用于2与所研究的所有伯胺和仲胺的反应。与伯胺的反应的k（1）值比与等重无环仲胺的反应的k（1）值大，而后一个反应的k（-）（1）值比前一个反应大。与仲胺反应的k（3）值与胺的碱性无关。有人认为小k（2）/