Tamura Y, Watanabe F, Nakatani T, Yasui K, Fuji M, Komurasaki T, Tsuzuki H, Maekawa R, Yoshioka T, Kawada K, Sugita K, Ohtani M
Shionogi Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
J Med Chem. 1998 Feb 12;41(4):640-9. doi: 10.1021/jm9707582.
Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2. In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.
合成了多种N-磺酰基氨基酸衍生物，并对其抑制IV型胶原酶（MMP-9和MMP-2）的体外和体内活性进行了评估。当氨基酸残基和磺酰胺部分被修饰时，它们的抑制活性受到磺酰胺部分结构的极大影响。发现一系列含有联芳基、四唑、酰胺和三键的芳基磺酰胺衍生物是MMP-9和MMP-2的强效且高度选择性抑制剂。此外，这些化合物在肿瘤生长和转移的动物模型中具有口服活性。这些结果揭示了N-磺酰基氨基酸衍生物作为一种新型抗癌候选药物的潜力。
