1-Methyl-5-(4-(2-(2-(2-(2-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-yloxy)ethoxy)ethoxy)ethoxy)ethoxy)-1,2,5-thiadiazol-3-yl)-1,2,3,6-tetrahydropyridine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-Methyl-5-(4-(2-(2-(2-(2-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-yloxy)ethoxy)ethoxy)ethoxy)ethoxy)-1,2,5-thiadiazol-3-yl)-1,2,3,6-tetrahydropyridine
• 英文别名: 3-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-4-[2-[2-[2-[2-[[4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazol-3-yl]oxy]ethoxy]ethoxy]ethoxy]ethoxy]-1,2,5-thiadiazole
• 化学式: C₂₄H₃₆N₆O₅S₂
• 分子量: 552.719
• InChiKey: NHUURXLCGOCXHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  161
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  3-氯-4-(吡啶-3-基)-1,2,5-噻二唑 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 氯仿 、 丙酮 为溶剂， 反应 27.0h， 生成 1-Methyl-5-(4-(2-(2-(2-(2-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-yloxy)ethoxy)ethoxy)ethoxy)ethoxy)-1,2,5-thiadiazol-3-yl)-1,2,3,6-tetrahydropyridine
  参考文献：
  名称：

  Design, Synthesis, and Biological Characterization of Bivalent 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Selective Muscarinic Agonists

  摘要：

  Selective muscarinic agonists could be useful in the treatment of neurological disorders such as Alzheimer's disease, schizophrenia, and chronic pain. Many muscarinic agonists have been developed, yet most exhibit at best limited functional selectivity for a given receptor subtype perhaps because of the high degree of sequence homology within the putative binding site, which appears to be buried within the transmembrane domains. Bivalent compounds containing essentially two agonist pharmacophores within the same molecule were synthesized and tested for receptor binding affinity and muscarinic agonist activity. A series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine linked by an alkyloxy moiety exhibited very high affinity (K-i < 1 nM) and strong agonist activity. The degree of activity depended on the length of the linking alkyl group, which could be replaced by a poly(ethylene glycol) moiety, resulting in improved water solubility, binding affinity, and agonist potency.

  DOI：

  10.1021/jm0102405

文献信息

• Muscarinic receptor agonists
  申请人：——

  公开号：US20010036953A1

  公开（公告）日：2001-11-01

  A compound of Formula (III): 1 wherein X is a linkage independently selected from (CH 2 ) 12 or (CH 2 CH 2 ) 4 O 3 and wherein R 3 is independently selected from H, CH 2 CH 3 , COCH 3 or 2 and acid addition salts, solvates and hydrates thereof. The compounds have unusually high affinity for muscarinic receptors, and exhibit agonist activity useful in the treatment of neurological and other disorders, in which stimulating cholinergic activity is desirable.

  化合物公式(III):1，其中X是独立选择自(CH2)12或(CH2CH2)4O3的连接基，R3是独立选择自H、CH2CH3、COCH3或2的基团，以及它们的酸加合物、溶剂合物和水合物。这些化合物对于肌动蛋白受体有异常高的亲和力，并表现出激动剂活性，可用于治疗神经和其他疾病，其中刺激胆碱能活性是可取的。
• MUSCARINIC RECEPTOR AGONISTS
  申请人：UNIVERSITY OF TOLEDO

  公开号：EP1355646A1

  公开（公告）日：2003-10-29
• EP1355646A4
  申请人：——

  公开号：EP1355646A4

  公开（公告）日：2004-06-16
• US6096767A
  申请人：——

  公开号：US6096767A

  公开（公告）日：2000-08-01
• US6211204B1
  申请人：——

  公开号：US6211204B1

  公开（公告）日：2001-04-03