3-甲基-1,2,4-噻二唑-5-羧酸甲酯 | 352356-71-9

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-甲基-1,2,4-噻二唑-5-羧酸甲酯
• 中文别名: 1,2,4-噻二唑-5-羧酸-1,3-甲基-,甲酯
• 英文名称: methyl 3-methyl-1,2,4-thiadiazole-5-carboxylate
• CAS: 352356-71-9
• 化学式: C₅H₆N₂O₂S
• 分子量: 158.181
• InChiKey: SWQYWYUMRAIOJA-UHFFFAOYSA-N

物化性质

• 沸点：
  254.4±23.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 储存条件：
  室温

制备方法与用途

3-甲基-1,2,4-噻二唑-5-羧酸甲酯可用作有机合成中间体和医药中间体，主要应用于实验室研发及化工生产的各个过程。

反应信息

• 作为反应物：
  描述：

  3-甲基-1,2,4-噻二唑-5-羧酸甲酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 14.0h， 以100%的产率得到3-methyl-1,2,4-thiadiazole-5-carbohydrazide
  参考文献：
  名称：

  Discovery and Optimization of Novel Antagonists to the Human Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part I)

  摘要：

  Neurokinin-3 receptor (NK3R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. We therefore decided to explore NK3R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma luteinizing hormone (LH) and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK3R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described. A concomitant improvement in the antagonist bioactivity and ligand lipophilic efficiency (LLE) parameter were the principal guidelines in the lead optimization efforts. Examples of advanced lead analogues to demonstrate the amenability of this chemotype to achieving a suitable pharmacokinetic (PK) profile are provided as well as pharmacokinetic-pharmacodynamic (PKPD) correlations to analyze the trends observed for LH inhibition in castrated rats and monkeys that served as preliminary in vivo efficacy models.

  DOI：

  10.1021/jm5017413
• 作为产物：
  描述：

  乙酰胺 、 氰基甲酸甲酯 、 氯羰基亚磺酰氯 以 甲苯 为溶剂， 反应 6.0h， 以11%的产率得到3-甲基-1,2,4-噻二唑-5-羧酸甲酯
  参考文献：
  名称：

  [EN] NOVEL CHIRAL N-ACYL-5,6,7,(8-SUBSTITUTED)-TETRAHYDRO-[1,2,4]TRIAZOLO[4,3-a]PYRAZINES AS SELECTIVE NK-3 RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITION, METHODS FOR USE IN NK-3 RECEPTOR MEDIATED DISORDERS AND CHIRAL SYNTHESIS THEREOF
  [FR] NOUVELLES N-ACYL-5,6,7,8-TÉTRAHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZINES 8-SUBSTITUÉES CHIRALES UTILISÉES COMME ANTAGONISTES SÉLECTIFS DES RÉCEPTEURS NK-3, COMPOSITION PHARMACEUTIQUE, PROCÉDÉS DESTINÉS À ÊTRE UTILISÉS DANS DES TROUBLES À MÉDIATION PAR LE RÉCEPTEUR NK-3 ET LEUR SYNTHÈSE CHIRALE

  摘要：

  本发明涉及公式I的新化合物及其在治疗治疗中的应用。该发明还涉及使用N-sp3保护基对5,6,7,(8-取代)-四氢-[1,2,4]三唑并[4,3-a]吡嗪进行新的手性合成。该发明还提供了用于合成公式I化合物的中间体。

  公开号：

  WO2013050424A1

文献信息

• [EN] NOVEL CHIRAL N-ACYL-5,6,7,(8-SUBSTITUTED)-TETRAHYDRO-[1,2,4]TRIAZOLO[4,3-a]PYRAZINES AS SELECTIVE NK-3 RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITION, METHODS FOR USE IN NK-3 RECEPTOR MEDIATED DISORDERS AND CHIRAL SYNTHESIS THEREOF<br/>[FR] NOUVELLES N-ACYL-5,6,7,8-TÉTRAHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZINES 8-SUBSTITUÉES CHIRALES UTILISÉES COMME ANTAGONISTES SÉLECTIFS DES RÉCEPTEURS NK-3, COMPOSITION PHARMACEUTIQUE, PROCÉDÉS DESTINÉS À ÊTRE UTILISÉS DANS DES TROUBLES À MÉDIATION PAR LE RÉCEPTEUR NK-3 ET LEUR SYNTHÈSE CHIRALE
  申请人：EUROSCREEN SA

  公开号：WO2013050424A1

  公开（公告）日：2013-04-11

  The present invention relates to novel compounds of Formula I and their use in therapeutic treatments. The invention further relates to a novel chiral synthesis of 5,6,7,(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines using N-sp3 protective groups. The invention also provides intermediates for use in the synthesis of compounds of Formula I.

  本发明涉及公式I的新化合物及其在治疗治疗中的应用。该发明还涉及使用N-sp3保护基对5,6,7,(8-取代)-四氢-[1,2,4]三唑并[4,3-a]吡嗪进行新的手性合成。该发明还提供了用于合成公式I化合物的中间体。
• Discovery and Optimization of Novel Antagonists to the Human Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part I)
  作者：Hamid R. Hoveyda、Graeme L. Fraser、Marie-Odile Roy、Guillaume Dutheuil、Frédéric Batt、Mohamed El Bousmaqui、Julien Korac、François Lenoir、Alexey Lapin、Sophie Noël、Sébastien Blanc

  DOI：10.1021/jm5017413

  日期：2015.4.9

  Neurokinin-3 receptor (NK3R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. We therefore decided to explore NK3R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma luteinizing hormone (LH) and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK3R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described. A concomitant improvement in the antagonist bioactivity and ligand lipophilic efficiency (LLE) parameter were the principal guidelines in the lead optimization efforts. Examples of advanced lead analogues to demonstrate the amenability of this chemotype to achieving a suitable pharmacokinetic (PK) profile are provided as well as pharmacokinetic-pharmacodynamic (PKPD) correlations to analyze the trends observed for LH inhibition in castrated rats and monkeys that served as preliminary in vivo efficacy models.