1-(3-chloro-1,2,5-thiadiazol-4-yl)-4-azatricyclo<2.2.1.0^2,6>heptane | 198143-09-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(3-chloro-1,2,5-thiadiazol-4-yl)-4-azatricyclo<2.2.1.0^2,6>heptane
• 英文别名: 1-(3-chloro-1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.02,6]heptane；3-(4-azatricyclo[2.2.1.02,6]heptan-1-yl)-4-chloro-1,2,5-thiadiazole
• CAS: 198143-09-8
• 化学式: C₈H₈ClN₃S
• 分子量: 213.691
• InChiKey: HSNHQGXOTNQZAD-UHFFFAOYSA-N

物化性质

• 沸点：
  297.5±30.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-1,2,5-thiadiazol-4-yl)-4-azatricyclo<2.2.1.0^2,6>heptane 在 盐酸 、 Oxone 、 sodium hydrogensulfide 、 potassium carbonate 作用下， 反应 4.0h， 生成 1-(3-propylsulfonyl-1,2,5-thiadiazol-4-yl)-4-azatricyclo<2.2.1.0^2,6>heptane
  参考文献：
  名称：

  1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0^2,6]heptanes as New Potent Muscarinic M₁ Agonists:  Structure−Activity Relationship for 3-Aryl-2-propyn-1-yloxy and 3-Aryl-2-propyn-1-ylthio Derivatives

  摘要：

  Two new series of 1-(1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes were synthesized and evaluated for their in vitro activity in cell lines transfected with either the human M-1 or M-2 receptor. 3-Phenyl-2-propyn-1-yloxy and -1-ylthio analogues substituted with halogen in the meta position showed high functional potency, efficacy, and selectivity toward the M-1 receptor subtype. A quite unique functional M-1 receptor selectivity was observed for compounds 8b, 8d, 8f, 9b, 9d, and 9f. Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite.

  DOI：

  10.1021/jm9910019
• 作为产物：
  描述：

  4-氮杂三环[2.2.1.02,6]庚烷-1-甲醛 在 ammonium hydroxide 、 sulfur monochloride 、 ammonium chloride 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 1-(3-chloro-1,2,5-thiadiazol-4-yl)-4-azatricyclo<2.2.1.0^2,6>heptane
  参考文献：
  名称：

  1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0^2,6]heptanes as New Potent Muscarinic M₁ Agonists:  Structure−Activity Relationship for 3-Aryl-2-propyn-1-yloxy and 3-Aryl-2-propyn-1-ylthio Derivatives

  摘要：

  Two new series of 1-(1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes were synthesized and evaluated for their in vitro activity in cell lines transfected with either the human M-1 or M-2 receptor. 3-Phenyl-2-propyn-1-yloxy and -1-ylthio analogues substituted with halogen in the meta position showed high functional potency, efficacy, and selectivity toward the M-1 receptor subtype. A quite unique functional M-1 receptor selectivity was observed for compounds 8b, 8d, 8f, 9b, 9d, and 9f. Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite.

  DOI：

  10.1021/jm9910019

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND THEIR PREPARATION AND USE<br/>[FR] COMPOSES HETEROCYCLIQUES, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NOVO NORDISK A/S

  公开号：WO1997036906A1

  公开（公告）日：1997-10-09

  (EN) The present invention relates to therapeutically active azatricyclic compounds of formula (I), a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating a disease in the central nervous system caused by malfunctioning of the muscarinic cholinergic system.(FR) Composés azatricycliques à activité thérapeutique de la formule (I), procédé de préparation de ces composés et compositions pharmaceutiques les contenant. Ces nouveaux composés conviennent au traitement d'une affection du système nerveux central causé par le dysfonctionnement du système cholinergique muscarinique.

  本发明涉及公式(I)的治疗活性的氮杂环化合物，其制备方法以及包含这些化合物的药物组合物。这些新型化合物可用于治疗由肌肉型胆碱能系统功能异常引起的中枢神经系统疾病。
• Heterocyclic compounds and their preparation and use
  申请人：Novo Nordisk

  公开号：US05914338A1

  公开（公告）日：1999-06-22

  The present invention relates to therapeutically active azatricyclic compounds of formula I ##STR1## a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating a disease in the central nervous system caused by malfunctioning of the muscarinic cholinergic system.

  本发明涉及公式I的治疗活性氮杂环化合物，其制备方法以及包含该化合物的制药组合物。这些新型化合物可用于治疗由胆碱能肌肉型受体系统功能失调引起的中枢神经系统疾病。
• HETEROCYCLIC COMPOUNDS AND THEIR PREPARATION AND USE
  申请人：NOVO NORDISK A/S

  公开号：EP0891363A1

  公开（公告）日：1999-01-20
• 1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0^2,6]heptanes as New Potent Muscarinic M₁ Agonists:  Structure−Activity Relationship for 3-Aryl-2-propyn-1-yloxy and 3-Aryl-2-propyn-1-ylthio Derivatives
  作者：Lone Jeppesen、Preben H. Olesen、Lena Hansen、Malcolm J. Sheardown、Christian Thomsen、Thøger Rasmussen、Anders Fink Jensen、Michael S. Christensen、Karin Rimvall、John S. Ward、Celia Whitesitt、David O. Calligaro、Frank P. Bymaster、Neil W. Delapp、Christian C. Felder、Harlan E. Shannon、Per Sauerberg

  DOI：10.1021/jm9910019

  日期：1999.6.1

  Two new series of 1-(1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes were synthesized and evaluated for their in vitro activity in cell lines transfected with either the human M-1 or M-2 receptor. 3-Phenyl-2-propyn-1-yloxy and -1-ylthio analogues substituted with halogen in the meta position showed high functional potency, efficacy, and selectivity toward the M-1 receptor subtype. A quite unique functional M-1 receptor selectivity was observed for compounds 8b, 8d, 8f, 9b, 9d, and 9f. Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite.