Creation of Readily Accessible and Orally Active Analogue of Cortistatin A

Syntheses of structurally simplified analogues of cortistatin A (<b>1</b>), a novel antiangiogenic steroidal alkaloid from Indonesian marine sponge, and their biological activities were investigated. The analogues were designed by considering the 3-D structure of <b>1</b>. Compound <b>30</b>, in which the isoquinoline moiety was appended to the planar tetracyclic core structure, showed potent antiproliferative activity against human umbilical vein endothelial cells (HUVECs) together with high selectivity and also showed <i>in vivo</i> antiangiogenic activity and significant antitumor effect by oral administration