Ando Naoki, Terashima Shiro
Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
Bioorg Med Chem Lett. 2009 Sep 15;19(18):5461-3. doi: 10.1016/j.bmcl.2009.07.099. Epub 2009 Jul 23.
By employing a previously established synthetic scheme, the synthesis described in the title was carried out in order to explore the substituent effects in the pyrrole ring of ageladine A on MMP-12 inhibitory activity. It became evident that a halogen atom (Br or Cl) at the 2-position and an additional bromine atom at the 4-position are highly effective for improving the inhibitory activity. These studies led us to discover three novel ageladine A analogs (4a, c, o) showing more potent MMP-12 inhibitory activity than the natural product.
通过采用先前建立的合成方案，进行了标题中所述的合成，以探究阿格拉定A吡咯环上的取代基对基质金属蛋白酶-12（MMP-12）抑制活性的影响。结果表明，2-位的卤原子（Br或Cl）和4-位的额外溴原子对提高抑制活性非常有效。这些研究使我们发现了三种新型阿格拉定A类似物（4a、c、o），它们对MMP-12的抑制活性比天然产物更强。
