C4'-氨基修饰的 pradimicin 衍生物的抗真菌活性。

Antifungal activities of pradimicin derivatives modified at C4'-amino group.

作者信息

Kamachi H, Okuyama S, Hirano M, Masuyoshi S, Konishi M, Oki T

机构信息

Bristol-Myers Squibb Research Institute, Bristol-Myers Squibb K.K., Tokyo, Japan.

出版信息

J Antibiot (Tokyo). 1993 Aug;46(8):1246-51. doi: 10.7164/antibiotics.46.1246.

DOI:10.7164/antibiotics.46.1246

PMID:8407587

Abstract

In order to explore potent derivatives of pradimicins (PRMs), modification of their C4'-amino group was carried out. 4'-N-Cyano (1,2), 4'-deamino-4'-nitroguanidino (4), 4'-deamino-4'-ureido (7-9) and 4'-deamino-4'-thioureido (10) derivatives were synthesized by trimethylsilylation of PRMs A and C, followed by condensation with appropriate reagents. 4'-Deamino-4'-guanidino (5) and 4'-deamino-4'-amidino (6) derivatives were synthesized by catalytic hydrogenation of 4 and 2, respectively. 4'-N-Nitroso derivative 3 was prepared by treatment of PRM A with nitrous acid. Among these compounds, the 4'-N-cyano derivative of PRM C (2) exhibited in vitro and in vivo antifungal activities comparable to the parent compounds together with good water-solubility.

摘要

为了探索制霉菌素（PRMs）的有效衍生物，对其C4'-氨基进行了修饰。通过制霉菌素A和C的三甲基硅烷化反应，然后与适当的试剂缩合，合成了4'-N-氰基（1,2）、4'-脱氨基-4'-硝基胍基（4）、4'-脱氨基-4'-脲基（7-9）和4'-脱氨基-4'-硫脲基（10）衍生物。4'-脱氨基-4'-胍基（5）和4'-脱氨基-4'-脒基（6）衍生物分别通过4和2的催化氢化反应合成。4'-N-亚硝基衍生物3是通过用亚硝酸处理制霉菌素A制备的。在这些化合物中，制霉菌素C的4'-N-氰基衍生物（2）在体外和体内均表现出与母体化合物相当的抗真菌活性，同时具有良好的水溶性。