6-(Hydroxymethyl)-2-(methylthio)nicotinonitrile | 474823-68-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-(Hydroxymethyl)-2-(methylthio)nicotinonitrile
• 英文别名: 6-(hydroxymethyl)-2-methylsulfanylpyridine-3-carbonitrile
• CAS: 474823-68-2
• 化学式: C₈H₈N₂OS
• 分子量: 180.23
• InChiKey: SGDUHBMABASLJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(Hydroxymethyl)-2-(methylthio)nicotinonitrile 在 咪唑 、 sodium chlorite 、 potassium dihydrogenphosphate 、 2-甲基-2-丁烯 、 乙基溴化镁 、 二异丁基氢化铝 、 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 、 间氯过氧苯甲酸 作用下， 以 乙醚 、 乙醇 、 氯仿 、 甲苯 为溶剂， 生成 2-ethyl-N-(2-(4-isopropoxy-3-methylphenyl)-2-oxoethyl)-6-(((triisopropylsilyl)oxy)methyl)nicotinamide
  参考文献：
  名称：

  Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists

  摘要：

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.067
• 作为产物：
  描述：

  6-(二甲氧基甲基)-2-硫代-1,2-二氢-3-吡啶甲腈 在 sodium tetrahydroborate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 水 、 乙腈 为溶剂， 生成 6-(Hydroxymethyl)-2-(methylthio)nicotinonitrile
  参考文献：
  名称：

  Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists

  摘要：

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.067

文献信息

• Novel arylheteroalkylamine derivatives
  申请人：——

  公开号：US20040242871A1

  公开（公告）日：2004-12-02

  There are provided novel compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, T, U, X, Y, V and W are as defined in the specification, and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.

  本发明提供了式 (I) 的新型化合物（其中 R1、R2、R3、R4、R5、R6、T、U、X、Y、V 和 W 如说明书中所定义）及其药学上可接受的盐，以及其对映体和外消旋体；同时还提供了制备它们的工艺、含有它们的组合物以及它们在治疗中的用途。这些化合物是一氧化氮合酶的抑制剂，因此特别适用于治疗或预防炎症性疾病和疼痛。
• 3-AZETIDINECARBOXYLIC ACID DERIVATIVES FOR USE AS IMMUNOSUPPRESSANTS
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1873153B1

  公开（公告）日：2010-07-07
• NOVEL ARYLHETEROALKYLAMINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1572655A2

  公开（公告）日：2005-09-14
• [EN] NOVEL ARYLHETEROALKYLAMINE DERIVATIVES<br/>[FR] NOUVEAUX DERIVES D'ARYL HETEROALKYL AMINES
  申请人：ASTRAZENECA AB

  公开号：WO2002090332A2

  公开（公告）日：2002-11-14

  There are provided novel compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, T, U, X, Y, V and W are as defined in the specification, and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.