1-[2-(3-氯苯基)-1,3-噻唑-4-基]甲胺 | 775579-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-[2-(3-氯苯基)-1,3-噻唑-4-基]甲胺
• 中文别名: (2-(3-氯苯基)噻唑-4-基)甲胺
• 英文名称: [2-(3-chlorophenyl)-1,3-thiazol-4-yl]methanamine
• 英文别名: (2-(3-Chlorophenyl)thiazol-4-yl)methanamine
• CAS: 775579-08-3
• 化学式: C₁₀H₉ClN₂S
• 分子量: 224.714
• InChiKey: YTIMHDSIFDCEDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  390.4±52.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  1-[2-(3-氯苯基)-1,3-噻唑-4-基]甲胺 、 7-(2-bromoethyl)-8-(bromomethyl)-1,3-dimethylpurine-2,4-dione 在 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 为溶剂， 以80%的产率得到8-((2-(3-chlorophenyl)thiazol-4-yl)methyl)-1,3-dimethyl-6,7,8,9-tetrahydro-pyrazino[2,1-f]purine-2,4(1H,3H)-dione
  参考文献：
  名称：

  8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors

  摘要：

  Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A(2A) adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A(1) ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A(1) and A(2A)ARs at similar concentrations representing dual A(1)/A(2A) antagonists with high selectivity versus the other AR subtypes. Among the best dual A(1)/A(2A)AR antagonists were 8-(3-(4-chlorophenyl)propy1)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-flpurine-2,4(1H,3H)-dione (41,K-i human A(1): 65.5 nM, A(2A): 230 nM; K-1 rat A(1): 352 nM, A(2A): 316 nM) and 1,3-dimethy1-84(2(thiophen-2-yl)thiazol-4-y1)methyl)-6,7,8,9-tetrahydropyrazino[2,1-fjpurine-2,4(1H,3H)-dione (57, K-i human A(1): 642 nM, A(2A): 203 nM; K-i rat A(1): 166 nM, A(2A): 121 nM). Compound 57 was found to be well water-soluble (0.7 mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple -target inhibition: (R)-1,3-dimethy1-8-(2,1,3,4-tetrahydronaphthalen-1-y1)-6,7,8,9-tetrahydropyrazino[2,1-Apurine-2,4(1H,3H)-dione (49) was about equipotent at A(1) and A(2A)ARs and at MAO-B (K-i human A(1): 393 nM, human A(2A): 595 nM, IC50 human MAO-B: 210 nM) thus allowing future in vivo explorations of the intended multi-target approach. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.003

文献信息

• Discovery of a potent and selective small molecule hGPR91 antagonist
  作者：Debnath Bhuniya、Dhananjay Umrani、Bhavesh Dave、Deepak Salunke、Gagan Kukreja、Jayasagar Gundu、Minakshi Naykodi、Nadim S. Shaikh、Prasad Shitole、Santosh Kurhade、Siddhartha De、Sreemita Majumdar、Srinivasa B. Reddy、Suhas Tambe、Yogesh Shejul、Anita Chugh、Venkata P. Palle、Kasim A. Mookhtiar、Doris Cully、Joseph Vacca、Prasun K. Chakravarty、Ravi P. Nargund、Samuel D. Wright、Michael P. Graziano、Sheo B. Singh、Sophie Roy、Tian-Quan Cai

  DOI：10.1016/j.bmcl.2011.04.091

  日期：2011.6

  GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand. Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis. Starting from a small molecule high-throughput screening hit 1 (hGPR91 IC(50): 0.8 mu M)-originally synthesized in Merck for Bradykinin B(1) Receptor (BK(1)R) program, systematic structure-activity relationship study led us to discover potent and selective hGPR91 antagonists e.g. 2c, 4c, and 5g (IC(50): 7-35 nM; >1000 fold selective against hGPR99, a closest related GPCR; > 100 fold selective in Drug Matrix screening). This initial work also led to identification of two structurally distinct and orally bio-available lead compounds: 5g (%F: 26) and 7e (IC(50): 180 nM; > 100 fold selective against hGPR99; %F: 87). A rat pharmacodynamic assay was developed to characterize the antagonists in vivo using succinate induced increase in blood pressure. Using two representative antagonists, 2c and 4c, the GPR91 target engagement was subsequently demonstrated using the designed pharmacodynamic assay. (C) 2011 Elsevier Ltd. All rights reserved.