2-碘-3-甲基吡嗪 | 58139-08-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-碘-3-甲基吡嗪
• 英文名称: 2-iodo-3-methyl-pyrazine
• 英文别名: methyl-iodopyrazine；2-Iodo-3-methylpyrazine
• CAS: 58139-08-5
• 化学式: C₅H₅IN₂
• 分子量: 220.013
• InChiKey: YHDKNCREPBBGDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-碘-3-甲基吡嗪 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 叔丁基锂 、 sodium methylate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 25.0~120.0 ℃ 、344.73 kPa 条件下， 反应 28.75h， 生成 (3S,4S)-3-(3-Methyl-pyrazin-2-yl)-1-aza-bicyclo[2.2.1]heptane
  参考文献：
  名称：

  奎宁环烷基和（1-氮杂降冰片基）吡嗪衍生物的合成和毒蕈碱活性。

  摘要：

  描述了基于吡嗪的新型激动剂的合成和皮质毒蕈碱活性。通过锂化吡嗪与氮杂双环酮的反应，然后氯化和还原，或通过氮杂双环酯的烯醇锂与2-氯吡嗪的反应，然后酯水解和脱羧，来制备喹喔啶和金刚烷硼烷衍生物。已经研究了杂芳环的所有三个位置上的取代。对于金刚烷烷系列中未取代的吡嗪，观察到最佳的毒蕈碱激动剂活性。exo-1-azanorbornaneane 18a是已知的最有效和最有效的中枢活性毒蕈碱激动剂之一。对3-取代衍生物的研究提供了这些配体对于最佳毒蕈碱活性的优选构象的证据。在C6处取代使配体具有增加的亲和力和降低的功效。移动二嗪环氮的位置以得到嘧啶和哒嗪衍生物导致毒蕈碱活性的显着损失。

  DOI：

  10.1021/jm00080a014
• 作为产物：
  描述：

  2-羟基-3-甲基吡嗪 生成 2-碘-3-甲基吡嗪
  参考文献：
  名称：

  Pyrazines, pyrimidines and pyridazines useful in the treatment of senile

  摘要：

  本发明提供了吡啶、吡啶嗪或嘧啶，或其盐或前药，其中其中一个环碳原子上取代为非芳香性氮杂环或氮杂双环系统；并且独立地，在其他每个环碳原子上取代为低亲脂性取代基或烃取代基；这些化合物刺激中枢胆碱能受体，因此在治疗神经和精神疾病中是有用的。

  公开号：

  US05260293A1

文献信息

• First metallation of iodo diazines. Iodo and nitrogen directed metallations. Diazines XXII
  作者：Nelly Plé、Alain Turck、Arnault Heynderickx、Guy Quéguiner

  DOI：10.1016/s0040-4020(98)00526-2

  日期：1998.8

  Lithiation of iodopyrazine and 4-iodo-2-methylthiopyrimidine followed by reaction with various electrophiles was successfully achieved and was used to synthesize new pyrazine and pyrimidine derivatives. Iodo and nitrogen directed metallations were observed.

  成功实现了碘吡嗪和4-碘-2-甲基硫代嘧啶的锂化，然后与各种亲电试剂反应，并将其用于合成新的吡嗪和嘧啶衍生物。观察到碘和氮定向的金属化。
• [EN] 3, 3 -DISUBSTITUTED- ( 8 - AZA - BICYCLO [3.2.1] OCT- 8 - YL) -[5- (1H - PYRAZOL - 4 -YL) -THIOPHEN-3 -YL] METHANONES AS INHIBITORS OF 11 (BETA) -HSD1<br/>[FR] (8-AZA-BICYCLO[3.2.1]OCT-8-YL)-[5-(1H-PYRAZOL-4-YL]-MÉTHANONES 3,3-DISUBSTITUÉES EN TANT QU'INHIBITEURS DE 11-(BÊTA)-HSD1
  申请人：UNIV EDINBURGH

  公开号：WO2011135276A1

  公开（公告）日：2011-11-03

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza- bicyclo [3.2.1]oct-8-yl)[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted- (6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4, 4-disubstituted piperidin-1 -yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula (I) that, inter alia, inhibit 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1 ). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11 β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11 β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明通常涉及治疗化合物领域。更具体地，本发明涉及某些3,3-二取代-(8-aza-双环[3.2.1]辛-8-基)[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮，3,3-二取代-(6-aza-双环[3.1.1]庚-6-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮和4,4-二取代哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮的化合物，其具有以下式（I）的结构，其在某种程度上抑制11β-羟基甾醇脱氢酶1（11β-HSD1）。本发明还涉及包含这些化合物的药物组合物，以及在体内外使用这些化合物和组合物抑制11β-羟基甾醇脱氢酶1；治疗通过抑制11β-羟基甾醇脱氢酶1而改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质紊乱和心血管疾病，如缺血性（冠状）心脏病；治疗中枢神经系统疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等。
• 3,3-DISUBSTITUTED-(8-AZA-BICYCLO[3.2.1]OCT-8-YL)-[5-(1H-PYRAZOL-4-YL)-THIOPHEN-3-YL]-METHANONES AS INHIBITORS OF 11 (BETA)-HSD1
  申请人：Webster Scott Peter

  公开号：US20130123268A1

  公开（公告）日：2013-05-16

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明涉及治疗化合物领域。更具体地，本发明涉及以下化合物的某些3,3-二取代-(8-氮杂双环[3.2.1]辛-8-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮，3,3-二取代-(6-氮杂双环[3.1.1]庚-6-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮和4,4-二取代哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮化合物，其中包括抑制11β-羟化甾酮脱氢酶1型(11β-HSD1)的作用。本发明还涉及包含这些化合物的制药组合物，以及使用这些化合物和组合物在体内外抑制11β-羟化甾酮脱氢酶1型；治疗通过抑制11β-羟化甾酮脱氢酶1型而改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖症等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质代谢紊乱和缺血(冠状动脉)性心脏病；治疗CNS疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等。
• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05854264A1

  公开（公告）日：1998-12-29

  The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

  本发明涉及抑制法尼酰-蛋白质转移酶(FTase)和致癌蛋白Ras的法尼酰化的化合物。本发明进一步涉及包含本发明化合物的化疗组合物和抑制法尼酰-蛋白质转移酶和致癌蛋白Ras的法尼酰化的方法。
• 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanones as inhibitors of 11 (β)-HSD1
  申请人：Webster Scott Peter

  公开号：US09365564B2

  公开（公告）日：2016-06-14

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及某些3,3-二取代-(8-氮杂双环[3.2.1]辛-8-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮、3,3-二取代-(6-氮杂双环[3.1.1]庚-6-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮和4,4-二取代哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮化合物，其化学式如下，可抑制11β-羟基类固醇脱氢酶1型（11β-HSD1）等。本发明还涉及包括这些化合物的制药组合物以及使用这些化合物和组合物在体外和体内抑制11β-羟基类固醇脱氢酶1型；治疗由抑制11β-羟基类固醇脱氢酶1型改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖症等疾病，并伴随有胰岛素抵抗、高血压、脂质紊乱和缺血性（冠状动脉）心脏病等相关疾病；治疗中枢神经系统疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等等。