College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bioorg Med Chem Lett. 2010 Aug 15;20(16):4771-3. doi: 10.1016/j.bmcl.2010.06.123. Epub 2010 Jul 1.
In order to define the structural requirements of quinazoline-2(1H)-thiones 1 for their inhibitory activity on melanogenesis, a novel series of 3,4-dihydroquinazoline-2(1H)-thiones (3a-h) were prepared and screened for their melanogenesis inhibition on melanoma B16 cell line under the stimulant of alpha-MSH. The anti-melanogenesis activity of 3 is mainly mediated by the hydrogen bonding ability of thioamide unit in addition to complexation ability of thione and the hydrophobic binding power of side chain substitutions at 3-position. Thus, the pharmacophore of 3,4-dihydroquinazoline-2(1H)-thiones for their anti-melanogenesis activity could be refined as 3-hydrophobic substituted quinazolinethione.
为了确定喹唑啉-2(1H)-硫酮 1 对黑色素生成抑制活性的结构要求，我们合成了一系列新型的 3,4-二氢喹唑啉-2(1H)-硫酮（3a-h），并在 α-MSH 的刺激下对黑色素瘤 B16 细胞系进行了黑色素生成抑制筛选。3 的抗黑色素生成活性主要是通过硫代酰胺单元的氢键能力介导的，除了硫酮的络合能力和 3 位取代基的疏水性结合能力。因此，3,4-二氢喹唑啉-2(1H)-硫酮类化合物的抗黑色素生成活性的药效团可以被精修为 3-位取代的疏水性喹唑啉硫酮。
