3-hydroxy-4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridine-6-carboxylic acid methyl ester | 85250-60-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-hydroxy-4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridine-6-carboxylic acid methyl ester
• 英文别名: methyl 3-hydroxy-4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridine-6-carboxylate；methyl 3-oxo-5,7-dihydro-4H-[1,2]thiazolo[5,4-c]pyridine-6-carboxylate
• CAS: 85250-60-8
• 化学式: C₈H₁₀N₂O₃S
• 分子量: 214.245
• InChiKey: DQEDVNMVZBWWSB-UHFFFAOYSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)

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：

  3-hydroxy-4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridine-6-carboxylic acid methyl ester 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 48.0h， 以85%的产率得到4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridin-3-ol hydrobromide
  参考文献：
  名称：

  Aza-THIP and related analogues of THIP as GABA C antagonists

  摘要：

  The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K-i = 25 muM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xenopus oocytes. Protolytic properties (pK(a) values for the acidic bioisosteric groups) and the presence of steric bulk in the molecules appear to be structural parameters of importance for blockade of the GABA(C) rho(1) receptor. Within this series of moderately potent GABA(C) antagonists, only 4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact delectably with GABA(A) receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.016
• 作为产物：
  描述：

  4-吡啶甲酰胺 在 sodium hydroxide 、 sodium tetrahydroborate 、 磺酰氯 、 双氧水 作用下， 以 甲醇 、 乙醇 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 151.5h， 生成 3-hydroxy-4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridine-6-carboxylic acid methyl ester
  参考文献：
  名称：

  Aza-THIP and related analogues of THIP as GABA C antagonists

  摘要：

  The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K-i = 25 muM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xenopus oocytes. Protolytic properties (pK(a) values for the acidic bioisosteric groups) and the presence of steric bulk in the molecules appear to be structural parameters of importance for blockade of the GABA(C) rho(1) receptor. Within this series of moderately potent GABA(C) antagonists, only 4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact delectably with GABA(A) receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.016

文献信息

• 4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogs of THIP. Synthesis and biological activity
  作者：Povl Krogsgaard-Larsen、Hans Mikkelsen、Poul Jacobsen、Erik Falch、David R. Curtis、Martin J. Peet、John D. Leah

  DOI：10.1021/jm00360a020

  日期：1983.6

  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.
• Aza-THIP and related analogues of THIP as GABA C antagonists
  作者：Dorte Krehan、Bente Frølund、Bjarke Ebert、Birgitte Nielsen、Povl Krogsgaard-Larsen、Graham A.R Johnston、Mary Chebib

  DOI：10.1016/j.bmc.2003.09.016

  日期：2003.11

  The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K-i = 25 muM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xenopus oocytes. Protolytic properties (pK(a) values for the acidic bioisosteric groups) and the presence of steric bulk in the molecules appear to be structural parameters of importance for blockade of the GABA(C) rho(1) receptor. Within this series of moderately potent GABA(C) antagonists, only 4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact delectably with GABA(A) receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies. (C) 2003 Elsevier Ltd. All rights reserved.