[3-(5-cyano-6-oxo-4-thiophen-2-yl-1,6-dihydropyrimidin-2-ylsulfanylmethyl)phenyl]acetic acid | 1883602-21-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: [3-(5-cyano-6-oxo-4-thiophen-2-yl-1,6-dihydropyrimidin-2-ylsulfanylmethyl)phenyl]acetic acid
• 英文别名: 2-[3-[(5-Cyano-6-oxo-4-thiophen-2-yl-1H-pyrimidin-2-yl)sulfanylmethyl]phenyl]acetic acid；2-[3-[(5-cyano-6-oxo-4-thiophen-2-yl-1H-pyrimidin-2-yl)sulfanylmethyl]phenyl]acetic acid
• CAS: 1883602-21-8
• 化学式: C₁₈H₁₃N₃O₃S₂
• 分子量: 383.452
• InChiKey: RJQYGCGMQYVVIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [3-(5-cyano-6-oxo-4-thiophen-2-yl-1,6-dihydropyrimidin-2-ylsulfanylmethyl)phenyl]acetic acid 在 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 [3-(5-cyano-4-morpholin-4-yl-6-thiophen-2-ylpyrimidin-2-ylsulfanylmethyl)phenyl]acetic acid
  参考文献：
  名称：

  WO2020104456A5

  摘要：

  公开号：

  WO2020104456A5
• 作为产物：
  描述：

  3-甲基苯乙酸 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 N,N-二异丙基乙胺 作用下， 以 四氯化碳 、 二甲基亚砜 为溶剂， 生成 [3-(5-cyano-6-oxo-4-thiophen-2-yl-1,6-dihydropyrimidin-2-ylsulfanylmethyl)phenyl]acetic acid
  参考文献：
  名称：

  [EN] INHIBITORS OF α-AMINO-β-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE
  [FR] INHIBITEURS DE LA SEMIALDÉHYDE DÉCARBOXYLASE DE L'ACIDE ALPHA-AMINO-BÊTA-CARBOXYMUCONIQUE

  摘要：

  本公开揭示了能够调节α-氨基-β-羧基黄酮酸半醛脱羧酶（ACMSD）活性的化合物，这些化合物对于预防和/或治疗与NAD+生物合成缺陷相关的疾病和紊乱非常有用，例如代谢紊乱、神经退行性疾病、慢性炎症性疾病、肾脏疾病以及与衰老相关的疾病。本申请还揭示了包含所述化合物的药物组合物以及将这些化合物用作药物的用途。

  公开号：

  WO2016030534A1

文献信息

• Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase
  申请人：TES Pharma S.r.l.

  公开号：US11254644B2

  公开（公告）日：2022-02-22

  The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.

  本申请公开了能够调节α-氨基-β-羧基琥珀酸半醛脱羧酶（ACMSD）活性的化合物，这些化合物可用于预防和/或治疗与NAD+生物合成缺陷有关的疾病和紊乱，例如代谢紊乱、神经退行性疾病、慢性炎症性疾病、肾脏疾病以及与衰老有关的疾病。本申请还公开了包含所述化合物的药物组合物以及将此类化合物用作药物的方法。
• α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD⁺) Biosynthesis
  作者：Roberto Pellicciari、Paride Liscio、Nicola Giacchè、Francesca De Franco、Andrea Carotti、Janet Robertson、Lucia Cialabrini、Elena Katsyuba、Nadia Raffaelli、Johan Auwerx

  DOI：10.1021/acs.jmedchem.7b01254

  日期：2018.2.8

  NAD(+) has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD(+) homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD(+) on mitochondrial fitness, metabolism, and lifespan are well established, to date, no therapeutic enhancers of 4 novo NAD(+) biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thieny1)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and selective inhibitor of human ACMSD (IC50 = 0.013 mu M) that increases NAD(+) levels in cellular systems. The results of physicochemical-property, ADME, and safety profiling, coupled with in vivo target-engagement studies, support the hypothesis that ACMSD inhibition increases de novo NAD(+) biosynthesis and position 22 as a first-class molecule for the evaluation of the therapeutic potential of ACMSD inhibition in treating disorders with perturbed NAV-supply or homeostasis.
• INHIBITORS OF ALPHA-AMINO-BETA-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE
  申请人：Tes Pharma S.r.l.

  公开号：EP3186242B1

  公开（公告）日：2021-10-06
• US9708272B2
  申请人：——

  公开号：US9708272B2

  公开（公告）日：2017-07-18