10S-methylthio-DDACTHF | 1050370-09-6

• 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: 10S-methylthio-DDACTHF
• 英文别名: (S)-2-(4-((S)-4-(2,4-diamino-6-oxo-1,6-dihydropyrmidin-5-yl)-1-(methylthio)butyl)benzamido)pentanedioic acid；N-({4-[(1s)-4-(2,4-Diamino-6-Oxo-1,6-Dihydropyrimidin-5-Yl)-1-(Methylsulfanyl)butyl]phenyl}carbonyl)-L-Glutamic Acid；(2S)-2-[[4-[(1S)-4-(2,4-diamino-6-oxo-1H-pyrimidin-5-yl)-1-methylsulfanylbutyl]benzoyl]amino]pentanedioic acid
• CAS: 1050370-09-6
• 化学式: C₂₁H₂₇N₅O₆S
• 分子量: 477.541
• InChiKey: GEZLAVXTPLTVRU-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  223
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  di-tert-butyl (S)-2-(4-((S)-4-(2,4-diamino-6-oxo-1,6-dihydropyrmidin-5-yl)-1-(methylthio)butyl)benzamido)pentanedioate 在 三氟乙酸 作用下， 以 氯仿 为溶剂， 生成 10S-methylthio-DDACTHF
  参考文献：
  名称：

  Asymmetric Synthesis of Inhibitors of Glycinamide Ribonucleotide Transformylase

  摘要：

  Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors and has emerged as a productive target for antineoplastic therapeutic intervention. The asymmetric synthesis and evaluation of the two diastereomers of 10-methylthio-DDACTHF (10R-3 and 10S-3) and related analogues as potential inhibitors of GAR Tfase are reported. This work, which defines the importance of the C10 stereochemistry for this class of inhibitors of GAR Tfase, revealed that both diastereomers are potent inhibitors of rhGAR Tfase (10R-3 K-i = 210 nM, 10S-3 K-i = 180 nM) that exhibit effective cell growth inhibition (CCRF-CEM IC50 80 and 50 nM, respectively), which is dependent on intracellular polyglutamation by folylpolyglutamate synthetase (FPGS) but not intracellular transport by the reduced folate carrier.

  DOI：

  10.1021/jm800555h

文献信息

• Monocyclic thieno, pyrido, and pyrrolo pyrimidine compounds and methods of use and manufacture of same
  申请人：Duquesne University of the Holy Spirit

  公开号：US11078214B2

  公开（公告）日：2021-08-03

  The present invention provides a compound of Formula XXVII: wherein X is CH2 or O, and R1 is H or CH3; or a salt or a hydrate of the compound, and further provides a pharmaceutical composition comprising the compound of Formula XXVII and one or more acceptable pharmaceutical carriers. A method of treating a patient having cancer comprising administering a therapeutically effective amount of a compound of Formula XXVII, or a pharmaceutical composition comprising a compound of Formula XXVII and one or more acceptable pharmaceutical carriers to the patient is disclosed.

  本发明提供了一种式 XXVII 的化合物： 其中X为CH2或O，R1为H或CH3；或该化合物的盐或水合物，并进一步提供了一种药物组合物，该组合物包含式XXVII化合物和一种或多种可接受的药物载体。本发明公开了一种治疗癌症患者的方法，包括向患者施用治疗有效量的式XXVII化合物或包含式XXVII化合物和一种或多种可接受的药物载体的药物组合物。
• MONOCYCLIC THIENO, PYRIDO, AND PYRROLO PYRIMIDINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE OF SAME
  申请人：Duquesne University of the Holy Spirit

  公开号：US20200079788A1

  公开（公告）日：2020-03-12

  The present invention provides a compound of Formula XXVII: wherein X is CH 2 or O, and R 1 is H or CH 3 ; or a salt or a hydrate of the compound, and further provides a pharmaceutical composition comprising the compound of Formula XXVII and one or more acceptable pharmaceutical carriers. A method of treating a patient having cancer comprising administering a therapeutically effective amount of a compound of Formula XXVII, or a pharmaceutical composition comprising a compound of Formula XXVII and one or more acceptable pharmaceutical carriers to the patient is disclosed.
• Asymmetric Synthesis of Inhibitors of Glycinamide Ribonucleotide Transformylase
  作者：Jessica K. DeMartino、Inkyu Hwang、Stephen Connelly、Ian A. Wilson、Dale L. Boger

  DOI：10.1021/jm800555h

  日期：2008.9.11

  Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors and has emerged as a productive target for antineoplastic therapeutic intervention. The asymmetric synthesis and evaluation of the two diastereomers of 10-methylthio-DDACTHF (10R-3 and 10S-3) and related analogues as potential inhibitors of GAR Tfase are reported. This work, which defines the importance of the C10 stereochemistry for this class of inhibitors of GAR Tfase, revealed that both diastereomers are potent inhibitors of rhGAR Tfase (10R-3 K-i = 210 nM, 10S-3 K-i = 180 nM) that exhibit effective cell growth inhibition (CCRF-CEM IC50 80 and 50 nM, respectively), which is dependent on intracellular polyglutamation by folylpolyglutamate synthetase (FPGS) but not intracellular transport by the reduced folate carrier.