Cravotto Giancarlo, Balliano Gianni, Tagliapietra Silvia, Palmisano Giovanni, Penoni Andrea
Dip. to di Scienza e Tecnologia del Farmaco, Università di Torino, via Giuria 9, 10125 Turin, Italy.
Eur J Med Chem. 2004 Nov;39(11):917-24. doi: 10.1016/j.ejmech.2004.06.010.
The synthesis is described of several aminoalkyl derivatives of coumarin, obtained in good yields under microwave or high-intensity ultrasound irradiation. These compounds proved uniformly active as inhibitors of squalene-hopene cyclase (SHC) from Alicyclobacillus acidocaldarius. Their design stemmed from our recent finding that the umbelliferone nucleus acquires inhibitory properties towards SHC when functionalized with a suitable chain such as the omega-epoxyfarnesyl group. Under our experimental conditions the most active ones, such as 7-(4'-allylmethylamino-but-2-ynyloxy)chromen-2-one (IC(50) 0.75 mM), approached the potency of anticholesteremic drug Ro 48-8071 (IC(50) 0.35 mM), an effective inhibitor of both squalene- and oxidosqualene-cyclases (OSC). Tests are in progress to determine their efficacy on different eukaryotic OSCs.
本文描述了几种香豆素的氨基烷基衍生物的合成方法，这些衍生物在微波或高强度超声辐射下能以较高产率获得。已证实这些化合物作为嗜酸热脂环酸芽孢杆菌鲨烯-藿烯环化酶（SHC）的抑制剂具有一致的活性。它们的设计源于我们最近的发现，即伞形酮核在用合适的链（如ω-环氧法呢基）官能化时对SHC具有抑制特性。在我们的实验条件下，最具活性的化合物，如7-(4'-烯丙基甲基氨基-2-丁炔氧基)色原酮-2-酮（IC(50) 0.75 mM），接近抗胆固醇药物Ro 48-8071（IC(50) 0.35 mM）的效力，Ro 48-8071是鲨烯环化酶和氧化鲨烯环化酶（OSC）的有效抑制剂。目前正在进行测试以确定它们对不同真核OSC的功效。
