2-硫代嘧啶衍生物的合成与生物学评价
Synthesis and biological evaluation of 2-thiopyrimidine derivatives.
作者信息
Sondhi Sham M, Goyal Rajendra N, Lahoti Anand M, Singh Nirupma, Shukla Rakesh, Raghubir Ram
机构信息
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India.
出版信息
Bioorg Med Chem. 2005 May 2;13(9):3185-95. doi: 10.1016/j.bmc.2005.02.047.
Various 2-thiopyrimidine derivatives have been synthesized by an efficient, one-pot reaction of functionalized amines with either 4-isothiocyanato-4-methyl-2-pentanone or 3-isothiocyanatobutanal. All the synthesized compounds were fully characterized by elemental analysis (CHN), FT-IR, (1)H NMR, and mass spectral data. One of the compounds, 7,7,8a-trimethyl-hexahydro-thiazolo[3,2-c]pyrimidine-5-thione (17) showed good anti-inflammatory (37.4% at 100 mg/kg p.o.) and analgesic activity (75% at 100 mg/kg p.o.). 7-(1-Mercapto-3,3,4a-trimethyl-4,4a,5,9b-tetrahydro-3H-pyrido[4,3-b]indol-7-yl)-3,3,4a-trimethyl-3,4,4a,5-tetrahydro-benzo[4,5]imidazo[1,2-c]pyrimidine-1-thiol (3) showed moderate activity against CDK-1 (IC(50)=5 microM). The other compounds showed moderate anti-inflammatory (5-20%), analgesic (25-75%) and protein kinase (CDK-5, GSK-3) inhibitory activities (IC(50)> 10 microM).
通过官能化胺与4-异硫氰酸根合-4-甲基-2-戊酮或3-异硫氰酸根合丁醛的高效一锅反应，合成了各种2-硫代嘧啶衍生物。所有合成的化合物均通过元素分析（CHN）、傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（¹H NMR）和质谱数据进行了全面表征。其中一种化合物，7,7,8a-三甲基-六氢-噻唑并[3,2-c]嘧啶-5-硫酮（17）表现出良好的抗炎活性（口服100 mg/kg时为37.4%）和镇痛活性（口服100 mg/kg时为75%）。7-(1-巯基-3,3,4a-三甲基-4,4a,5,9b-四氢-3H-吡啶并[4,3-b]吲哚-7-基)-3,3,4a-三甲基-3,4,4a,5-四氢-苯并[4,5]咪唑并[1,2-c]嘧啶-1-硫醇（3）对细胞周期蛋白依赖性激酶-1（CDK-1）表现出中等活性（半数抑制浓度（IC₅₀）=5 μM）。其他化合物表现出中等的抗炎活性（5-20%）、镇痛活性（25-75%）和蛋白激酶（CDK-5、糖原合成酶激酶-3（GSK-3））抑制活性（IC₅₀>10 μM）。
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