3-(3-Pentyloxy-1,2,5-thiadiazol-4-yl)-1-methylpyridinium iodide | 131988-16-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(3-Pentyloxy-1,2,5-thiadiazol-4-yl)-1-methylpyridinium iodide
• 英文别名: 1-methyl-3-(4-(pentyloxy)-1,2,5-thiadiazol-3-yl)pyridin-1-ium iodide；3-(4-pentyloxy-1,2,5-thiadiazol-3-yl)-1-methylpyridinium iodide；3-(1-methylpyridin-1-ium-3-yl)-4-pentoxy-1,2,5-thiadiazole;iodide
• CAS: 131988-16-4
• 化学式: C₁₃H₁₈N₃OS*I
• 分子量: 391.276
• InChiKey: CZIAAGBLEUVHOD-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  67.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3-Pentyloxy-1,2,5-thiadiazol-4-yl)-1-methylpyridinium iodide 在 甲醇 、 sodium tetrahydroborate 作用下， 以75%的产率得到占诺美林
  参考文献：
  名称：

  Tacrine-xanomeline and tacrine-iperoxo hybrid ligands: Synthesis and biological evaluation at acetylcholinesterase and M1 muscarinic acetylcholine receptors

  摘要：

  We synthesized a set of new hybrid derivatives (7-C8, 7-C10, 7-C12 and 8-C8, 8-C10, 8-C12), in which a polymethylene spacer chain of variable length connected the pharmacophoric moiety of xanomeline, an M-1/M-4 preferring orthosteric muscarinic agonist, with that of tacrine, a well-known acetylcholinesterase (AChE) inhibitor able to allosterically modulate muscarinic acetylcholine receptors (mAChRs). When tested in vitro in a colorimetric assay for their ability to inhibit AChE, the new compounds showed higher or similar potency compared to that of tacrine. Docking analyses were performed on the most potent inhibitors in the series (8-C8, 8-C10, 8-C12) to rationalize their experimental inhibitory power against AChE. Next, we evaluated the signaling cascade at M-1 mAChRs by exploring the interaction of G alpha(q)-PLC-beta 3 proteins through split luciferase assays and the myo-Inositol 1 phosphate (IP1) accumulation in cells. The results were compared with those obtained on the known derivatives 6-C7 and 6-C10, two quite potent AChE inhibitors in which tacrine is linked to iperoxo, an exceptionally potent muscarinic orthosteric activator. Interestingly, we found that 6-C7 and 6-C10 behaved as partial agonists of the M-1 mAChR, at variance with hybrids 7-Cn and 8-Cn containing xanomeline as the orthosteric molecular fragment, which were all unable to activate the receptor subtype response.

  DOI：

  10.1016/j.bioorg.2020.103633
• 作为产物：
  描述：

  alpha-氨基-(9ci)-3-吡啶乙腈 在 二氯化二硫 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 5.5h， 生成 3-(3-Pentyloxy-1,2,5-thiadiazol-4-yl)-1-methylpyridinium iodide
  参考文献：
  名称：

  Tacrine-xanomeline and tacrine-iperoxo hybrid ligands: Synthesis and biological evaluation at acetylcholinesterase and M1 muscarinic acetylcholine receptors

  摘要：

  We synthesized a set of new hybrid derivatives (7-C8, 7-C10, 7-C12 and 8-C8, 8-C10, 8-C12), in which a polymethylene spacer chain of variable length connected the pharmacophoric moiety of xanomeline, an M-1/M-4 preferring orthosteric muscarinic agonist, with that of tacrine, a well-known acetylcholinesterase (AChE) inhibitor able to allosterically modulate muscarinic acetylcholine receptors (mAChRs). When tested in vitro in a colorimetric assay for their ability to inhibit AChE, the new compounds showed higher or similar potency compared to that of tacrine. Docking analyses were performed on the most potent inhibitors in the series (8-C8, 8-C10, 8-C12) to rationalize their experimental inhibitory power against AChE. Next, we evaluated the signaling cascade at M-1 mAChRs by exploring the interaction of G alpha(q)-PLC-beta 3 proteins through split luciferase assays and the myo-Inositol 1 phosphate (IP1) accumulation in cells. The results were compared with those obtained on the known derivatives 6-C7 and 6-C10, two quite potent AChE inhibitors in which tacrine is linked to iperoxo, an exceptionally potent muscarinic orthosteric activator. Interestingly, we found that 6-C7 and 6-C10 behaved as partial agonists of the M-1 mAChR, at variance with hybrids 7-Cn and 8-Cn containing xanomeline as the orthosteric molecular fragment, which were all unable to activate the receptor subtype response.

  DOI：

  10.1016/j.bioorg.2020.103633

文献信息

• Piperidine compounds and their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US05041455A1

  公开（公告）日：1991-08-20

  The present invention relates to therapeutically active piperidine compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful as stimulants of the cognitive function of the forebrain and hippocampus of mammals and especially in the treatment of Alzheimer's disease, severe painful conditions and glaucoma.

  本发明涉及治疗活性哌啶化合物，一种制备该化合物的方法以及包含该化合物的药物组合物。这些新颖化合物可用作哺乳动物前脑和海马体认知功能的刺激剂，特别适用于治疗阿尔茨海默病、严重疼痛症状和青光眼。
• Novel functional M1 selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines
  作者：Per Sauerberg、Preben H. Olesen、Susanne Nielsen、Svend Treppendahl、Malcolm J. Sheardown、Tage Honore、Charles H. Mitch、John S. Ward、Andrew J. Pike

  DOI：10.1021/jm00090a019

  日期：1992.6

  novel 3-(3-substituted-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro- 1-methylpyridines (substituted-TZTP; 5a-l, 7a-h, 8, 9c-n, 11, 13j) were synthesized and tested for central muscarinic cholinergic receptor affinity by using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. The potency and efficacy of the compounds for the pharmacological defined M1 and M2 muscarinic receptors were determined

  一系列新颖的3-（3-取代-1,2,5-噻二唑-4-基）-1,2,5,6-四氢-1-甲基吡啶（取代的TZTP; 5a-1，7a-h，合成了8、9c-n，11、13j），并通过使用[3H]-氧代remorine-M（Oxo-M）和[3H]-哌仑西平（Pz）作为配体测试了中央毒蕈碱胆碱能受体亲和力。在分离的电刺激兔输精管和自发跳动的豚鼠心房上分别测定化合物对药理定义的M1和M2毒蕈碱受体的效力和功效。还测试了所选化合物在分离的豚鼠回肠中的M3活性。C1-8烷氧基-TZTP 5a-1类似物均以低纳摩尔亲和力取代了[3H] -Oxo-M和[3H] -Pz。描述针对Oxo-M结合和针对Pz结合的链长，直链C1-8烷氧基-TZTP（5a-h）衍生物产生U形曲线，其中丁氧基（5d）和（戊氧基）-TZTP（5e）为最佳链长度。在化合物5a-h抑制输精管制剂中的抽搐高度的能力中也看到了该U形曲线。（戊氧基）
• Method of treating urinary bladder dysfunctions with
  申请人：——

  公开号：US05565475A1

  公开（公告）日：1996-10-15

  The present invention relates to a novel method for treating a mammal suffering from urinary bladder dysfunctions.

  本发明涉及一种治疗患有尿道膀胱功能障碍的哺乳动物的新方法。
• Method of treating schizophrenia
  申请人：Novo Nordisk A/S

  公开号：US05750541A1

  公开（公告）日：1998-05-12

  The present invention relates to a novel method for treating a mammal suffering from or susceptible to schizophrenia and schizophreniform diseases by administering thiadiazole or oxadiazole compounds.

  本发明涉及一种通过给予噻二唑或氧二唑化合物治疗患有或易患精神分裂症和分裂形障碍的哺乳动物的新方法。
• Method of treating gastrointestinal motility disorders
  申请人：Novo Nordisk A/S

  公开号：US05545638A1

  公开（公告）日：1996-08-13

  The present invention relates to a novel method for treating a mammal suffering from gastrointestinal motility disorders.

  本发明涉及一种治疗患有胃肠蠕动障碍的哺乳动物的新方法。