Tetrandrine derivatives with substituted 5-carbon, preparation method and use thereof

摘要

The present invention belongs to the field of natural medicine and pharmaceutical chemistry and specifically relates to novel 5-substituted tetrandrine derivatives of formula (I) and a pharmaceutically acceptable adduct, complex and salt thereof, to a process for the preparation of these compounds, pharmaceutical compositions containing such compounds and their use in preparing antineoplastic medicaments.;

主权项

1. A compound of formula (I), wherein X is selected from oxygen, sulfur, nitrogen and carbonyloxy; n is 1 or 2, wherein n=1 when X is oxygen or sulfur, and n=2 when X is nitrogen; R is independently selected from H, C1-C6 alkyl, C3-C7 cycloalkyl or cycloalkenyl, aryl or C3-C10 heteroaryl, aryl-C1-C3 alkyl, C3-C10 heteroaryl-C1-C3 alkyl, aryloxy-C1-C3 alkyl and C3-C10 heteroaryloxy-C1-C3 alkyl; when X is carbonyloxy, R can also be C1-C6 alkoxy or C1-C6 alkyl-SH; when X is nitrogen, the two R groups together with the nitrogen atom to which they are connected can form non-aromatic nitrogen-containing C3-C10 heterocyclyl or nitrogen-containing C3-C10 heteroaryl; wherein the R groups, except for H, are optionally substituted with a substituent selected from the group consisting of halogen, amino, C1-C6 alkyl amino, nitro, cyano, hydroxyl, C1-C6 alkoxy, —SH and C1-C6 alkyl-SH; said cycloalkyl, cycloalkenyl, aryl, C3-C10 heteroaryl, nitrogen-containing C3-C10 heterocyclyl or nitrogen-containing C3-C10 heteroaryl are optionally substituted with a substituent selected from C1-C6 alkyl, hydroxyl C1-C6 alkyl, C1-C6 alkyl-SH and phenyl; wherein said C3-C10 heteroaryl, C3-C10 heteroaryloxy, and C3-C10 heterocyclyl rings are monocyclic or bicyclic, and contain 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur; or a pharmaceutically acceptable salt thereof.