TY - JOUR
T1 - Synthesis of heptaoxazole macrocyclic analogues of telomestatin and evaluation of their telomerase inhibitory activities
AU - Shibata, Kazuaki
AU - Yoshida, Masahito
AU - Takahashi, Takashi
AU - Takagi, Motoki
AU - Shin-Ya, Kazuo
AU - Doi, Takayuki
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - We have demonstrated various synthetic routes to heptaoxazole macrocyclic analogues of telomestatin and evaluated their inhibitory activities against telomerase. We synthesized three heptaoxazole macrocycles consisting of different numbers of methyloxazole moieties and another heptaoxazole analogue with a bromooxazole moiety instead of one of the two methyloxazole moieties found in the structure of telomestatin. The bromooxazole analogue underwent SuzukiMiyaura coupling leading to six analogues having aromatic substituents on the oxazole moiety. The substituents on the oxazole moiety in the heptaoxazole macrocycles, which include a methyl group, a bromine atom, and aromatic substituents, did not affect the inhibitory activity of the overall molecule. In addition, three amine-linked analogues were synthesized by modification of the S-tert-butyl group in the bromooxazole analogue with amine-linked a-bromoacetamides. Notably, one of the amine-linked heptaoxazole analogues exhibited almost the same inhibitory activity as telomestatin.
AB - We have demonstrated various synthetic routes to heptaoxazole macrocyclic analogues of telomestatin and evaluated their inhibitory activities against telomerase. We synthesized three heptaoxazole macrocycles consisting of different numbers of methyloxazole moieties and another heptaoxazole analogue with a bromooxazole moiety instead of one of the two methyloxazole moieties found in the structure of telomestatin. The bromooxazole analogue underwent SuzukiMiyaura coupling leading to six analogues having aromatic substituents on the oxazole moiety. The substituents on the oxazole moiety in the heptaoxazole macrocycles, which include a methyl group, a bromine atom, and aromatic substituents, did not affect the inhibitory activity of the overall molecule. In addition, three amine-linked analogues were synthesized by modification of the S-tert-butyl group in the bromooxazole analogue with amine-linked a-bromoacetamides. Notably, one of the amine-linked heptaoxazole analogues exhibited almost the same inhibitory activity as telomestatin.
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U2 - 10.1246/bcsj.20130198
DO - 10.1246/bcsj.20130198
M3 - Article
AN - SCOPUS:84890583563
VL - 86
SP - 1453
EP - 1465
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
SN - 0009-2673
IS - 12
ER -