7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine | 848579-85-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine
• 英文别名: 7-Methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine；7-methoxy-4-morpholin-4-yl-[1,3]thiazolo[5,4-c]pyridin-2-amine
• CAS: 848579-85-1
• 化学式: C₁₁H₁₄N₄O₂S
• 分子量: 266.324
• InChiKey: MGWYMAVULHUALE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine 、 氯贝酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以21%的产率得到2-(4-chlorophenoxy)-N-(7-methoxy-4-morpholinothiazolo[5,4-c]pyridin-2-yl)-2-methylpropanamide
  参考文献：
  名称：

  新型，有效，选择性，口服生物利用腺苷A 2A受体拮抗剂的设计，合成及其生物学评价

  摘要：

  我们对7位-甲氧基-4-吗啉代-苯并噻唑衍生物在2位上具有特征性的芳氧基-2-甲基丙酰胺部分的初步构效关系研究导致将化合物25鉴定为有效且选择性的A 2A腺苷受体（A 2A AdoR ）具有合理ADME和药代动力学特性的拮抗剂。但是，固有溶解性差和口服生物利用度低至中等，使得该系列不适合进一步开发。使用基于结构的药物设计方法进行的进一步优化导致发现了有效和选择性的腺苷A 2A受体拮抗剂在苯并噻唑支架的2位带有取代的1-甲基环己基甲酰胺基，具有更好的溶解度和口服生物利用度。化合物41和49在体外ADME特性方面表现出许多积极的特性。两种化合物在大鼠中均表现出良好的药代动力学性质，口服生物利用度分别为63％和61％。此外，化合物49在帕金森氏病的6-OHDA损伤的大鼠模型中显示出口服功效。

  DOI：

  10.1021/acs.jmedchem.6b01584
• 作为产物：
  描述：

  (5-methoxy-2-morpholin-4-yl-pyridin-4-yl)-thiourea 在 氢溴酸 、 二甲基亚砜 作用下， 以 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 0.83h， 以64%的产率得到7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine
  参考文献：
  名称：

  Thiazolopyridine

  摘要：

  本发明涉及式I的化合物，其中R1和R2如下所述。这些化合物对A2A受体具有高亲和力，并对A1和A3受体具有良好的选择性。这些化合物在治疗阿尔茨海默病、抑郁症、帕金森病和注意力缺陷多动障碍等方面具有用途。

  公开号：

  US20050065151A1

文献信息

• THIAZOLOPYRIDINE DERIVATIVES AS ADENOSINE RECEPTOR LIGANDS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1670805A1

  公开（公告）日：2006-06-21
• US7273865B2
  申请人：——

  公开号：US7273865B2

  公开（公告）日：2007-09-25
• [EN] THIAZOLOPYRIDINE DERIVATIVES AS ADENOSINE RECEPTOR LIGANDS<br/>[FR] DERIVES DE THIAZOLOPYRIDINE EN TANT QUE LIGANDS DU RECEPTEUR D'ADENOSINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005028484A1

  公开（公告）日：2005-03-31

  The present invention relates to compounds of the general formula (I) wherein R1 is morpholin-4-yl, phenyl or tetrahydropyran-4-yl; R2 is -(CH2)n-aryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of halogen, lower alkoxy, lower alkyl, -(CH2)n NR’R', -0 (CH2)n-O -lower alkyl, or -(CH2)n-heterocyclyl, or is heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, -(CH2)n NR'R', -(CH2)n-heterocyclyl, which is optionally substituted by hydroxy or lower alkoxy, or is -(CH2)n-heterocyclyl, optionally substituted by one or more substituents selected from the group consisting of -(CH2)n,-OH, -(CH2)n-O-lower alkyl or lower alkyl, or is -(CH2)n-cycloalkyl, or is - (CH2)n,-O -lower alkyl, or is NR'R’’, or is benzo[1,3]dioxole, 2-methyl-l-oxo-2,8-diaza-spiro[4,5] decane, 2-oxa-5-aza­bicyclo [2.2.1]heptane or I-oxa-8-aza-spiro[4.5]decane; R',R' are independently from each other lower alkyl, - (CH2)n ,-O -lower alkyl or cycloalkyl, optionally substituted by hydroxy; n is 0, 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. These compounds may be used in the control or prevention of illnesses based on the modulation of the adenosine system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, drug addiction, such as amphetamine, cocaine, opioids, ethanol, nicotine, cannabinoids, or against asthma, allergic responses, hypoxia, ischaernia, seizure and substance abuse. Furthermore, compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardiaprotective agents for disorders such as coronary artery disease and heart failure. The most preferred indications in accordance with the present invention are those which include disorders of the central nervous system, for example the treatment or prevention of Alzheimer's disease, certain depressive disorders, drug addiction, neuroprotection and Parkinson's disease as well as ADHD.
• Design, Synthesis of Novel, Potent, Selective, Orally Bioavailable Adenosine A_2AReceptor Antagonists and Their Biological Evaluation
  作者：Sujay Basu、Dinesh A. Barawkar、Sachin Thorat、Yogesh D. Shejul、Meena Patel、Minakshi Naykodi、Vaibhav Jain、Yogesh Salve、Vandna Prasad、Sumit Chaudhary、Indraneel Ghosh、Ganesh Bhat、Azfar Quraishi、Harish Patil、Shariq Ansari、Suraj Menon、Vishal Unadkat、Rhishikesh Thakare、Madhav S. Seervi、Ashwinkumar V. Meru、Siddhartha De、Ravi K. Bhamidipati、Sreekanth R. Rouduri、Venkata P. Palle、Anita Chug、Kasim A. Mookhtiar

  DOI：10.1021/acs.jmedchem.6b01584

  日期：2017.1.26

  identification of compound 25 as a potent and selective A2A adenosine receptor (A2AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A2A receptor

  我们对7位-甲氧基-4-吗啉代-苯并噻唑衍生物在2位上具有特征性的芳氧基-2-甲基丙酰胺部分的初步构效关系研究导致将化合物25鉴定为有效且选择性的A 2A腺苷受体（A 2A AdoR ）具有合理ADME和药代动力学特性的拮抗剂。但是，固有溶解性差和口服生物利用度低至中等，使得该系列不适合进一步开发。使用基于结构的药物设计方法进行的进一步优化导致发现了有效和选择性的腺苷A 2A受体拮抗剂在苯并噻唑支架的2位带有取代的1-甲基环己基甲酰胺基，具有更好的溶解度和口服生物利用度。化合物41和49在体外ADME特性方面表现出许多积极的特性。两种化合物在大鼠中均表现出良好的药代动力学性质，口服生物利用度分别为63％和61％。此外，化合物49在帕金森氏病的6-OHDA损伤的大鼠模型中显示出口服功效。
• Thiazolopyridine
  申请人：Norcross David Roger

  公开号：US20050065151A1

  公开（公告）日：2005-03-24

  The present invention relates to compounds of formula I wherein R 1 and R 2 are described hereinbelow. These compounds have high affinity to A 2A receptors and good selectivity to A 1 and A 3 receptors. These compounds are useful, inter alia, in the treatment of Alzheimer's disease, depression, Parkinson's disease and ADHD.

  本发明涉及式I的化合物，其中R1和R2如下所述。这些化合物对A2A受体具有高亲和力，并对A1和A3受体具有良好的选择性。这些化合物在治疗阿尔茨海默病、抑郁症、帕金森病和注意力缺陷多动障碍等方面具有用途。