(2RS,4R)-2-(3,4-dimethoxyphenyl)-thiazolidine-4-carboxylic acid | 72678-92-3

• 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: (2RS,4R)-2-(3,4-dimethoxyphenyl)-thiazolidine-4-carboxylic acid
• 英文别名: (4R)-2-(3,4-dimethoxyphenyl)thiazolidine-4-carboxylic acid；(R)-2-(3,4-Dimethoxy-phenyl)-thiazolidine-4-carboxylic acid；(4R)-2-(3,4-dimethoxyphenyl)-1,3-thiazolidine-4-carboxylic acid
• CAS: 72678-92-3
• 化学式: C₁₂H₁₅NO₄S
• mdl: MFCD08272841
• 分子量: 269.321
• InChiKey: VVYKDOVBUSRSCZ-YMNIQAILSA-N

物化性质

• 熔点：
  179-180°C
• 沸点：
  476.7±45.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090
• 储存条件：
  | 室温 |

反应信息

• 作为反应物：
  描述：

  (2RS,4R)-2-(3,4-dimethoxyphenyl)-thiazolidine-4-carboxylic acid 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (4R)-N-decyl-2-(3,4-dimethoxyphenyl)thiazolidine-4-carboxamide
  参考文献：
  名称：

  Synthesis and antiproliferative activity of thiazolidine analogs for melanoma

  摘要：

  We have previously described 2-aryl-thiazolidine-4-carboxylic acid amides as a novel class of antiproliferative agents for prostate cancer. Screening these compounds with melanoma cell lines revealed that several of them have potent antiproliferative activity and selectivity against melanoma. To further improve the potency and selectivity, we synthesized a new series of analogs and tested them in two melanoma cell lines and fibroblast cells (negative controls). Comparison of anticancer effects of these compounds with a standard chemotherapeutic agent, sorafenib, showed that they are very effective in killing melanoma cells with low micromolar to nanomolar antiproliferative activity and provide us a new lead for developing potential drugs for melanoma. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.059
• 作为产物：
  描述：

  L-半胱氨酸 、 3,4-二甲氧基苯甲醛 以 乙醇 为溶剂， 反应 10.0h， 以57%的产率得到(2RS,4R)-2-(3,4-dimethoxyphenyl)-thiazolidine-4-carboxylic acid
  参考文献：
  名称：

  设计，合成和生物评价2-（取代苯基）噻唑烷-4-羧酸衍生物作为新型酪氨酸酶抑制剂。

  摘要：

  在这里，我们描述2-（取代的苯基）噻唑烷-4-羧酸衍生物作为新型酪氨酸酶抑制剂的设计，合成和生物学活性。根据N-苯基硫脲，酪氨酸酶抑制剂和酪氨酸的结构特征以及酪氨酸酶的天然底物1-DOPA的结构特征设计和合成目标化合物2a-2j。其中，（2R / S，4R）-2-（2,4-二甲氧基苯基）噻唑烷-4-羧酸（2g）在20μM蘑菇酪氨酸酶的1-DOPA氧化酶活性上产生最大的抑制作用达66.47％。酪氨酸酶抑制的动力学分析表明2g是竞争性抑制剂。我们预测了酪氨酸酶的三级结构，并模拟了蘑菇酪氨酸酶与2g的对接。这些结果表明2g与酪氨酸酶的结合亲和力高。还，2g有效抑制了用α-MSH处理的B16细胞中的酪氨酸酶活性并降低了黑色素水平。这些数据强烈表明2g可通过抑制酪氨酸酶活性来抑制黑色素的产生。

  DOI：

  10.1016/j.biochi.2011.09.002

文献信息

• Synthesis and antihypertensive activity of N-(mercaptoacyl)-thiazolidinecarboxylic acids.
  作者：MASAYUKI OYA、TOSHIO BABA、EISHIN KATO、YOICHI KAWASHIMA、TOSHIO WATANABE

  DOI：10.1248/cpb.30.440

  日期：——

  The synthesis and antihypertensive activity of a new series of N-(mercaptoacyl)-thiazolidinecarboxylic acids (VIIa-d) are described. Antihypertensive activity was evaluated in terms of angiotensin I-converting enzyme (ACE) inhibitory activity. The activities of these compounds were compared with that of (2S)-1-[(2S)-3-mercapto-2-methylpropanoyl] proline, SQ 14225, and many of them were found to be relatively potent inhibitors of ACE. The most potent was (4R)-2-(2-hydroxyphenyl)-3-(3-mercaptopropanoyl)-4-thiazolidinecarboxylic acid (62). Structure-activity relationships among the thiazolidines and some related compounds are discussed.

  报道了一系列新型N-(巯基乙酰基)-噻唑烷羧酸(VIIa-d)的合成及其抗高血压活性。抗高血压活性通过血管紧张素I转化酶(ACE)抑制活性来评估。这些化合物的活性与(2S)-1-[(2S)-3-巯基-2-甲基丙酰基]脯氨酸(SQ 14225)进行了比较，发现其中许多化合物是相对强效的ACE抑制剂。其中最有效的是(4R)-2-(2-羟基苯基)-3-(3-巯基丙酰基)-4-噻唑烷羧酸(62)。讨论了噻唑烷及其相关化合物的结构-活性关系。
• Synthesis, in vitro structure–activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents
  作者：Yan Lu、Zhao Wang、Chien-Ming Li、Jianjun Chen、James T. Dalton、Wei Li、Duane D. Miller

  DOI：10.1016/j.bmc.2009.12.020

  日期：2010.1

  good selectivity and potency against four prostate cancer cell lines (DU 145, PC-3, LNCaP, and PPC-1). The structure–activity relationship (SAR) of the side chain, the thiazolidine ring, and phenyl substituents is discussed. Cell cycle analysis showed that the percentage of cancer cells undergoing apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also strongly inhibited melanoma

  合成了一系列(2RS , 4R ) -2-芳基噻唑烷-4-甲酰胺(ATCAA)。与对照细胞（分别为成纤维细胞和 RH7777）相比，评估了针对黑色素瘤和前列腺癌细胞的抗增殖活性。化合物3id对三种黑色素瘤细胞系（B16-F1、A375 和 WM-164）表现出最佳的选择性和生长抑制活性。化合物15b和3ac对四种前列腺癌细胞系（DU 145、PC-3、LNCaP 和 PPC-1）具有良好的选择性和效力。讨论了侧链、噻唑烷环和苯基取代基的构效关系（SAR）。细胞周期分析表明，用1b和3ad处理后，发生凋亡（亚 G1 期）的癌细胞百分比增加，这也强烈抑制了黑色素瘤集落的形成。对带有 A375 黑色素瘤肿瘤的裸鼠的体内研究表明，化合物1b以剂量依赖性方式抑制肿瘤生长。在 10 mg/kg 的剂量下，1b显着抑制黑色素瘤肿瘤的生长，并且比 60 mg/kg 的达卡巴嗪显示出更高的疗效。
• Discovery of 2-Arylthiazolidine-4-carboxylic Acid Amides as a New Class of Cytotoxic Agents for Prostate Cancer
  作者：Veeresa Gududuru、Eunju Hurh、James T. Dalton、Duane D. Miller

  DOI：10.1021/jm049208b

  日期：2005.4.1

  To improve the selectivity and antiproliferative activity of previously reported serine amide phosphates (SAPs), we designed a new series of 4-thiazolidinone amides, in which the 4-thiazolidinone moiety was introduced as a phosphate mimic. However, these 4-thiazolidinone derivatives demonstrated less cytotoxicity in prostate cancer cells despite improved selectivity over RH7777 cells. To further optimize the thiazolidinone analogues in terms of cytotoxicity and selectivity, we made closely related structural modifications, which led us to the discovery of a new class of 2-arylthiazolidine-4-carboxylic acid amides. These compounds were potent cytotoxic agents with IC50 values in the low micromolar concentration range and demonstrated enhanced selectivity in receptor-negative cells compared to SAPs and 4-thiazolidinone amides.
• [EN] N-CYCLIC SULFONAMIDO INHIBITORS OF GAMMA SECRETASE<br/>[FR] INHIBITEURS SULFONAMIDO N-CYCLIQUES DE GAMMA-SECRETASE
  申请人：ELAN PHARM INC

  公开号：WO2005113542A3

  公开（公告）日：2006-03-02
• OYA, MASAYUKI;BABA, TOSHIO;KATO, EISHIN;KAWASHIMA, YOICHI;WATANABE, TOSHI+, CHEM. AND PHARM. BULL., 1982, 30, N 2, 440-461
  作者：OYA, MASAYUKI、BABA, TOSHIO、KATO, EISHIN、KAWASHIMA, YOICHI、WATANABE, TOSHI+

  DOI：——

  日期：——