Gly-Meth methyl ester hydrochloride

• 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: Gly-Meth methyl ester hydrochloride
• 英文别名: methyl (2S)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate;hydrochloride
• 化学式: C₈H₁₆N₂O₃S*ClH
• 分子量: 256.754
• InChiKey: OYURLLAFXTXLJP-RGMNGODLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.22
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(5s)-2,4-二氧代噻唑烷-5-基]乙酸酯 、 Gly-Meth methyl ester hydrochloride 在 sodium hydroxide 、 氯化亚砜 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.83h， 以66%的产率得到SSDMA15
  参考文献：
  名称：

  Novel thiazolidinedione-5-acetic-acid-peptide hybrid derivatives as potent antidiabetic and cardioprotective agents

  摘要：

  Thiazolidinediones (TZDs) are one of the important clinically established antidiabetic agents. Aminoacid and peptides have an advantage of better target selectivity and specificity. As hybrids, they also improved absorption and showed better bioavailability, which in turn makes them safer. Hence, here an effort has been made to synthesize hybrids of thiazolidinedione with amino-acids and peptides and evaluate their antidiabetic and cardioprotective effect in streptozotocin-nicotinamide (STZ-NA) induced Type 2 diabetes mellitus (T2DM) rat models.A series of 14 thiazolidinedione-5-acetic acid hybrids with of different amino-acids and peptide combinations were synthesized, characterized and further screened for antidiabetic and cardioprotective activity.Among all, six compounds T1 (SSDMA1), T4 (SSDMA4), T5 (SSDMA5), T7 (SDMA13), T9 (SSDMA15) and T13 (SSDMA49) showed better antioxidant activity and comparable % glucose uptake by yeast cells.Hence, the in vivo antidiabetic screening was done for these six compounds. Among all six T1, T7, T13 showed significant blood glucose level decrease compared to standard pioglitazone HCl. Also T1, T7 and T13 showed better antioxidant activity with lower IC50 value than standard ascorbic acid, and hence in vivo cardioprotective studies were done for these. The ECG studies showed that T1 (SSDMA1) and T7 (SSDMA13) were better effective than SDMA49 (T13) in restoring the normal functioning of the heart, thus may help in preventing the development of diabetic cardiomyopathy (DCM) and controlling T2DM. (C) C 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biopha.2017.01.160
• 作为产物：
  描述：

  L-蛋氨酸甲酯盐酸盐 在 乙醇 、 五氯化磷 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 Gly-Meth methyl ester hydrochloride
  参考文献：
  名称：

  Novel thiazolidinedione-5-acetic-acid-peptide hybrid derivatives as potent antidiabetic and cardioprotective agents

  摘要：

  Thiazolidinediones (TZDs) are one of the important clinically established antidiabetic agents. Aminoacid and peptides have an advantage of better target selectivity and specificity. As hybrids, they also improved absorption and showed better bioavailability, which in turn makes them safer. Hence, here an effort has been made to synthesize hybrids of thiazolidinedione with amino-acids and peptides and evaluate their antidiabetic and cardioprotective effect in streptozotocin-nicotinamide (STZ-NA) induced Type 2 diabetes mellitus (T2DM) rat models.A series of 14 thiazolidinedione-5-acetic acid hybrids with of different amino-acids and peptide combinations were synthesized, characterized and further screened for antidiabetic and cardioprotective activity.Among all, six compounds T1 (SSDMA1), T4 (SSDMA4), T5 (SSDMA5), T7 (SDMA13), T9 (SSDMA15) and T13 (SSDMA49) showed better antioxidant activity and comparable % glucose uptake by yeast cells.Hence, the in vivo antidiabetic screening was done for these six compounds. Among all six T1, T7, T13 showed significant blood glucose level decrease compared to standard pioglitazone HCl. Also T1, T7 and T13 showed better antioxidant activity with lower IC50 value than standard ascorbic acid, and hence in vivo cardioprotective studies were done for these. The ECG studies showed that T1 (SSDMA1) and T7 (SSDMA13) were better effective than SDMA49 (T13) in restoring the normal functioning of the heart, thus may help in preventing the development of diabetic cardiomyopathy (DCM) and controlling T2DM. (C) C 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biopha.2017.01.160

文献信息

• EP0725650A4
  申请人：——

  公开号：EP0725650A4

  公开（公告）日：1999-02-03
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO. INC.

  公开号：EP0725650A1

  公开（公告）日：1996-08-14
• [EN] INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE FARNESYL-PROTEINE TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：WO1995009001A1

  公开（公告）日：1995-04-06

  (EN) The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation $i(in vivo). These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogs differ from those previously described as inhibitors of Ras farnesyl transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.(FR) L'invention concerne des analogues de la séquence CAAX de la protéine Ras modifiée par farnésylation $i(in vivo). Ces analogues de CAAX inhibent la farnésylation de Ras et se distinguent, par ailleurs, de celles décrites précédemment en tant qu'inhibiteurs de la Ras farnésyl-transférase par le fait qu'ils ne comprennent pas de fraction thiol. L'absence de thiol présente des avantages uniques en termes de comportement pharmacocinétique amélioré chez l'animal, de prévention des réactions chimiques dues au thiol telles que l'autoxydation et la formation de bisulfure avec des thiols endogènes, et de toxicité systémique réduite. L'invention concerne également des compositions chimiothérapeutiques contenant ces inihibiteurs de la farnésyl-transférase et leurs procédés de production.