Design, synthesis, and biological activities of novel hexahydropyrazino [1, 2-a] indole derivatives as potent inhibitors of apoptosis (IAP) proteins antagonists with …

…, M Yoshimatsu, Y Kosugi, Y Debori, N Morishita…

Index: Shiokawa, Zenyu; Hashimoto, Kentaro; Saito, Bunnai; Oguro, Yuya; Sumi, Hiroyuki; Yabuki, Masato; Yoshimatsu, Mie; Kosugi, Yohei; Debori, Yasuyuki; Morishita, Nao; Dougan, Douglas R.; Snell, Gyorgy P.; Yoshida, Sei; Ishikawa, Tomoyasu Bioorganic and Medicinal Chemistry, 2013 , vol. 21, # 24 p. 7938 - 7954

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Citation Number: 9

Abstract

Abstract We previously reported octahydropyrrolo [1, 2-a] pyrazine derivative 2 (T-3256336) as a potent antagonist for inhibitors of apoptosis (IAP) proteins. Because compound 2 was susceptible to MDR1 mediated efflux, we developed another scaffold, hexahydropyrazino [1, 2-a] indole, using structure-based drug design. The fused benzene ring of this scaffold was aimed at increasing the lipophilicity and decreasing the basicity of the scaffold to improve ...