methyl 3-hydroxy-4,5,6,7-tetrahydroisothiazolo<4,5-c>pyridine-5-carboxylate | 85250-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 3-hydroxy-4,5,6,7-tetrahydroisothiazolo<4,5-c>pyridine-5-carboxylate
• 英文别名: methyl 3-hydroxy-4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridine-5-carboxylate；methyl 3-oxo-6,7-dihydro-4H-[1,2]thiazolo[4,5-c]pyridine-5-carboxylate
• CAS: 85250-64-2
• 化学式: C₈H₁₀N₂O₃S
• 分子量: 214.245
• InChiKey: HGQDVEAJENBUQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-hydroxy-4,5,6,7-tetrahydroisothiazolo<4,5-c>pyridine-5-carboxylate 在 氢氧化钾 作用下， 以 甲醇 、 乙醚 、 乙醇 为溶剂， 反应 21.0h， 生成 3-methoxy-4,5,6,7-tetrahydroisothiazolo<4,5-c>pyridine
  参考文献：
  名称：

  一系列槟榔碱的4,5,6,7-四氢异噻唑并[4,5-c]吡啶生物等位基因的合成及毒蕈碱受体药理作用。

  摘要：

  通过处理适当取代的4-苄基氨基-1,2,5,6，合成了4,5,6,7-四氢异噻唑并[4,5-c]吡啶-3-醇的一系列O-和环烷基化衍生物-四氢吡啶-3-甲酰胺与硫化氢，然后通过用溴氧化来闭环。使用大鼠脑膜和许多ti化的毒蕈碱受体配体测定了该系列双环槟榔碱生物等排物的毒蕈碱受体亲和力以及估计的相对功效和亚型选择性。使用受体选择和扩增技术（R-SAT）研究了已建立的绝对立体化学对选定系列手性类似物的五个克隆的人毒蕈碱受体亚型的影响。效力，相对功效，

  DOI：

  10.1016/s0968-0896(99)00033-4
• 作为产物：
  描述：

  1-(methoxycarbonyl)-4-(benzylamino)-1,2,5,6-tetrahydropyridine-3-carboxamide 在 硫化氢 、 溴 作用下， 生成 methyl 3-hydroxy-4,5,6,7-tetrahydroisothiazolo<4,5-c>pyridine-5-carboxylate
  参考文献：
  名称：

  4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogs of THIP. Synthesis and biological activity

  摘要：

  The thio analogues of the GABA (gamma-aminobutyric acid) agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), the GABA uptake inhibitor THPO (4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol), and the glycine antagonist THAZ (5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol) have been synthesized and tested biologically on single neurons in the cat spinal cord and in vitro by using synaptic membrane preparations obtained from rat brains. In contrast to THIP, thio-THIP (4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridin-3-ol, 5) was only a weak GABA agonist. Thio-THPO (4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol, 10) was slightly weaker than THPO as an inhibitor of GABA uptake in vitro, and these two compounds were approximately equipotent in enhancing the inhibition of the firing of cat spinal neurons by GABA. Like THAZ and structurally related bicyclic isoxazole zwitterions, thio-THAZ (5,6,7,8-tetrahydro-4H-isothiazolo[4,5-d]azepin-3-ol, 15) was an antagonist at glycine receptors on cat spinal neurons. The I/U ratios, which reflect the ability of neutral amino acids to penetrate the blood-brain barrier (BBB), were calculated for 5 (I/U = 16), 10 (63), and 15 (200). These low I/U ratios, compared with the findings that THIP (I/U = 500 or 1500) and THPO (I/U = 2500) enter the brain after systemic administration, suggest that the thio analogues may penetrate the BBB very easily.

  DOI：

  10.1021/jm00360a020

文献信息

• 4,5,6,7-Tetrahydroisothiazolo (4,5-c) pyridine derivatives
  申请人：H. Lundbeck A/S

  公开号：US04923880A1

  公开（公告）日：1990-05-08

  The present invention relates to novel compounds of the following formula: ##STR1## individual isomers and pharmaceutically acceptable acid addition salts thereof, wherein R.sup.1 is hydrogen, alkyl or phenyl-lower alkyl, in which the phenyl group may be substituted with halogen, lower alkyl or lower alkoxy; R.sup.2 is alkyl, alkenyl, alkynyl, branched or unbranched, with 1-6 carbon atoms inclusive, which group may be optionally substituted with fluoro, hydroxy or phenyl optionally substituted with halogen, trifluoromethyl, lower alkyl, hydroxy or lower alkoxy; R.sup.3 and R.sup.4 are the same or different, and each represents hydrogen, alkyl(1-6 C-atoms), cycloalkyl (3-6 C-atoms), phenyl optionally substituted with halogen trifluoromethyl, lower alkyl, hydroxy or lower alkoxy, or phenyl-lower alkyl, in which the phenyl group may be substituted with halogen, trifluoromethyl, lower alkyl, hydroxy or lower alkoxy. The invention moreover relates to methods for the preparation of the compounds of formula I, to novel intermediates, to pharmaceutical compositions containing same and to methods for the treatment of disorders, caused by malfunction of the acetylcholine (AcCh) or muscarinic system, by administering a non-toxic effective amount of a compound of formula I.

  本发明涉及以下式的新化合物：##STR1## 其中R.sup.1是氢、烷基或苯基-低烷基，其中苯基可以被卤素、低烷基或低烷氧基取代；R.sup.2是烷基、烯基、炔基、支链或直链，含1-6个碳原子，该基团可以选择性地被氟、羟基或苯基取代，该苯基可以被卤素、三氟甲基、低烷基、羟基或低烷氧基取代；R.sup.3和R.sup.4相同或不同，分别表示氢、烷基（1-6个C原子）、环烷基（3-6个C原子）、苯基，该苯基可以被卤素三氟甲基、低烷基、羟基或低烷氧基取代，或苯基-低烷基，其中苯基可以被卤素、三氟甲基、低烷基、羟基或低烷氧基取代。此外，本发明还涉及制备式I化合物的方法、新的中间体、含有该化合物的制药组合物以及通过给予式I化合物的非毒性有效量治疗由乙酰胆碱（AcCh）或肌动系统失调引起的疾病的方法。
• 4,5,6,7-Tetrahydroisothiazolo (4,5-c)pyridine derivatives and isomers
  申请人：H. LUNDBECK A/S

  公开号：EP0336555A1

  公开（公告）日：1989-10-11

  Novel compounds of the formula: wherein R¹, R², R³ and R⁴ are as defined in Claim 1, as well as individual isomers and pharmaceutically acceptable acid addition salts are described as having acetylcholine agonistic activity making them useful in the treatment of diseases of the brain, e.g. Alzheimer's disease. Methods for the preparation of the novel compounds are also described, as well as pharmaceutical compositions containing same.

  式的新型化合物： 其中 R¹、R²、R³ 和 R⁴ 如权利要求 1 所定义、 以及单个异构体和药学上可接受的酸加成盐具有乙酰胆碱激动活性，可用于治疗脑部疾病，如阿尔茨海默病。 此外，还介绍了新型化合物的制备方法以及含有这些化合物的药物组合物。
• US4923880A
  申请人：——

  公开号：US4923880A

  公开（公告）日：1990-05-08