Synthesis and Diuretic Activities of Tolvaptan Analogues

7-Chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine(2) was prepared by a five-step reaction from methyl 2-amino-5-chlorobenzoate.Two key intermediates,4a and 4b,was prepared by N-acetylation of 2 with 5-nitrylpyridine-2-carbamoyl chloride or p-nitrylbenzoyl chlorid,then reduction in the presence of SnCl2.Fifteen novel potential inhibition of the AVP-V2 receptors,tolvaptan derivatives(5a～5k,6b,6i,7b and 8d) were synthesized by introducing substituted-benzoyl or substituted-phenyl-sulfonyl at amino of 4.The structures were characterized by 1H NMR,IR and MS.The SD rats diuretic test showed that some of them exhibited better diuretic activities.