Kanda Y, Kawanishi Y, Oda K, Sakata T, Mihara S I, Asakura K, Kanemasa T, Ninomiya M, Fujimoto M, Konoike T
Shionogi Research Laboratories, Shionogi & Co, Ltd, Osaka, Japan.
Bioorg Med Chem. 2001 Apr;9(4):897-907. doi: 10.1016/s0968-0896(00)00305-9.
The synthesis and structure activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a, previously reported, (1) was selected as a lead compound, and isosteric replacement of the isoxazole ring of 1a with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation.
描述了一系列作为ETB选择性拮抗剂的N-嘧啶基苯磺酰胺的合成及其构效关系。先前报道的N-异恶唑基苯磺酰胺1a（1）被选为先导化合物，用嘧啶环对1a的异恶唑环进行等排取代，导致发现了具有口服生物利用度的高效ETB选择性拮抗剂6e。研究了嘧啶环6位末端醛基的修饰，发现丙二酸酯15b和酰腙16f与醛6e具有同等效力。化合物6e在体内评价中显示出ETB拮抗活性。
