Crystal Structure of 2-(4-Fluorophenylamino)-2-thiomethyl acetophenone

The title compound 2-(4-fluorophenylamino)-2-thiomethyl acetophe-none (C15H14FNOS, M. = 275. 34 ) was synthesized by the reaction of 2-hydroxy-2-thiomethyl acetohenone (abenzoylhemithioacetal ) with 4-fluoroaniline. The crystal ismonoclinic, space group P21/n. with unit cell constants a = 12. 434 (4 ), b = 6. 00l2(6), c=l8. 49l(2) A, β=100. 87(l)° Z = 4, V = 1355. O(5) A, D'= 1. 350g/cm3, μ(MoKa) = 2. 41 cm-l, F(000) = 576, R=0. 029, Rw.= 0. 041 for 14l2 ob-served reflections (I> 3σ(I) ). X-ray analysis reveals that the dihedral angle betweenplane l (C(l)~C(6), F, N ) and plane 2 (C(8)~C(14), O ) is 4. l8° and theC(7) -S bond is longer than normal single C-S bond.

N-甲基-N-(2-噻吩甲基)-N′-(4-甲基-2-噻唑)甘氨酰胺的合成、降血糖活性及药动学研究

目的在前期发现的DPP-IV抑制剂N-(2-噻吩甲基)-N′-(4-甲基-2-噻唑)甘氨酰胺(1)基础上,设计并合成N-甲基-N-(2-噻吩甲基)-N′-(4-甲基-2-噻唑)甘氨酰胺(2),以延长半衰期,并保证其降血糖活性。方法尝试了两种方法合成化合物2,一是对化合物1用氨化-还原法甲基化,二是用N-甲基-2-噻吩甲胺(3)与2-氯-N-(4-甲基-2-噻唑)乙酰胺(4)反应制得化合物2。葡萄糖耐量实验降血糖模型研究化合物2的降血糖活性,并研究其药动学。结果两种方法合成了化合物2,其中方法二收率较高。化合物2的降血糖活性与化合物1相当,但是半衰期延长。结论获得了合成化合物2的较优方法 ,保证化合物2降血糖活性前提下,延长了半衰期。