Synthesis and biological evaluation of novel 1,5-benzothiazepin-4(5H)-ones as potent antiangiogenic and antioxidant agents

Abstract

Novel 1,5-benzothiazepin-4-(5H)-one derivatives (8a-8g) have been synthesized by intramolecular cyclization of 6 using propyl phosphonic anhydride (T3P) as a cyclodehydrating agent. The anti-angiogenic and anti-oxidant properties of the new derivatives were then evaluated. Compounds 8b, 8d, 8e, 8f and 8g exhibited very good inhibition of capillary proliferation, thus proving their anti-angiogenic properties. In addition, the in vitro antioxidant activities of these compounds were evaluated using diphenyl picryl hydrazine (DPPH), OH-, metal ion-chelating and NO (nitric oxide) assays, and the results compared with butylated hydroxytoluene (BHT), a well known anti-oxidant. Compounds 8a-8g showed excellent free-radical scavenging activities in the metal ion-chelating assay, and compounds 8f and 8g showed nitric oxide radical scavenging properties at a concentration of 20-100 µg/mL, and are thus more potent than BHT.

Synthesis and crystal structure of 7-bromo-3,3-dibutyl-8-methoxy-5-phenyl-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one

“…However, there are only a few studies reported that discuss the synthesis of the title compound in the literature. 9,10 Herein, we report an efficient route to prepare the title compound. Compared with the original research patent, we have shortened the reaction time of the last step (from 17 h to 30 min) and reduced the reaction temperature (from 190 °C to 130 °C).…”