2-(aminomethyl)-4,5-bis(4-methoxyphenyl)thiazole | 156500-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(aminomethyl)-4,5-bis(4-methoxyphenyl)thiazole
• 英文别名: 2-aminomethyl-4,5-bis(4-methoxyphenyl)thiazole；[4,5-bis(4-methoxyphenyl)-1,3-thiazol-2-yl]methanamine
• CAS: 156500-89-9
• 化学式: C₁₈H₁₈N₂O₂S
• 分子量: 326.419
• InChiKey: GXXSGUOWMXMVBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  85.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (甲硫基)乙酸 、 2-(aminomethyl)-4,5-bis(4-methoxyphenyl)thiazole 在 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 3.0h， 生成 N-[[4,5-bis(4-methoxyphenyl)-1,3-thiazol-2-yl]methyl]-2-methylsulfanylacetamide
  参考文献：
  名称：

  Antiplatelet Agents Based on Cyclooxygenase Inhibition without Ulcerogenesis. Evaluation and Synthesis of 4,5-Bis(4-methoxyphenyl)-2-substituted-thiazoles

  摘要：

  The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis-( 4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl) thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 mu M) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED(50) 2.0 mu M). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-[(1-methylpiperazin-4-yl)carbonyl] thiazole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 mu M) and platelet aggregation in guinea pigs ex vivo (100% inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED(50) = 6.2 mu M). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 mu M(14)), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect.(8) Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.

  DOI：

  10.1021/jm00034a017

文献信息

• Thiazole compounds and pharmaceutical composition comprising the same
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05145860A1

  公开（公告）日：1992-09-08

  The invention relates to new thiazole compounds, of antithrombotic, vasodilating, antiallergic, antiinflammatory and 5-lipoxygenase inhibitory activity, of the formula: ##STR1## wherein A is lower alkylene or carbonyl; R.sup.1 and R.sup.2 are each halogen, lower alkyloxy, lower alkylthio or lower alkylsulfinyl; R.sup.3 is acyl derived from an aliphatic carboxylic or carbamic acid; and R.sup.4 is hydrogen, lower alkyl, amidino or acyl derived from an aliphatic carboxylic or carbamic acid, or the pharmaceutically acceptable salt thereof.

  本发明涉及一种新的噻唑化合物，具有抗血栓、扩血管、抗过敏、抗炎和5-脂氧合酶抑制活性，其化学式为：##STR1## 其中A为低级烷基或羰基；R1和R2分别为卤素、低级烷氧基、低级烷硫基或低级烷基磺酰基；R3为由脂肪族羧酸或氨基甲酸衍生的酰基；R4为氢、低级烷基、氨基甲酰基或由脂肪族羧酸或氨基甲酸衍生的酰基，或其药学上可接受的盐。
• Thiazole compounds, processes for the preparation thereof and
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05229386A1

  公开（公告）日：1993-07-20

  The invention relates to new thiazole compounds, of antithrombotic, vasodilating, antiallergic, antiinflammatory and 5-lipoxygenase inhibitory activity, of the formula: ##STR1##

  本发明涉及一种新的噻唑化合物，具有抗血栓、扩张血管、抗过敏、抗炎和5-脂氧合酶抑制活性，其化学式为：##STR1##
• Thiazole compounds, processes for the preparation thereof and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0388909A2

  公开（公告）日：1990-09-26

  A compound of the formula : wherein A is iower alkylene or carbonyl, R¹ and R² are each halogen, lower alkyloxy, lower alkylthio or lower alkylsulfinyl, R³ is amino-protective group, and R⁴ is hydrogen, lower alkyl which may have heterocyclic group, piperidyl which may have suitable substituent(s), amidino or amino-protective group, and pharmaceutically acceptable salt thereof, processes for their preparation and pharmaceutical compositions comprising them as an active ingredient.

  式中的化合物 其中 A 是烯烃或羰基、 R¹ 和 R² 分别为卤素、低级烷氧基、低级烷硫基或低级烷基亚磺酰基、 R³ 是氨基保护基团，以及 R⁴ 是氢、可带有杂环基的低级烷基、可带有适当取代基的哌啶基、脒基或氨基保护基、 及其药学上可接受的盐、 它们的制备工艺和含有它们作为活性成分的药物组合物。
• US5145860A
  申请人：——

  公开号：US5145860A

  公开（公告）日：1992-09-08
• US5229386A
  申请人：——

  公开号：US5229386A

  公开（公告）日：1993-07-20