TY - JOUR
T1 - Small-molecular inhibitors of Ca2+-induced mitochondrial permeability transition (MPT) derived from muscle relaxant dantrolene
AU - Murasawa, Shinpei
AU - Iuchi, Katsuya
AU - Sato, Shinichi
AU - Noguchi-Yachide, Tomomi
AU - Sodeoka, Mikiko
AU - Yokomatsu, Tsutomu
AU - Dodo, Kosuke
AU - Hashimoto, Yuichi
AU - Aoyama, Hiroshi
N1 - Funding Information:
The work described in this paper was partially supported by a Grant-in-Aid for Young Scientists (B) 24790119 from the Ministry of Education, Culture, Sports, Science and Technology.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - A structure consisting of substituted hydantoin linked to a 5-(halophenyl)furan-2-yl group via an amide bond was identified as a promising scaffold for development of low-molecular-weight therapeutic agents to treat vascular dysfunction, including ischemia/reperfusion injury. Among the compounds synthesized, 5-(3,5-dichlorophenyl)-N-{2,4-dioxo-3-[(pyridin-3-yl)methyl] imidazolidin-1-yl}-2-furamide (17) possessed the most potent inhibitory activity against Ca2+-induced mitochondrial swelling. The structural development, synthesis and structure-activity relationship of these compounds are described.
AB - A structure consisting of substituted hydantoin linked to a 5-(halophenyl)furan-2-yl group via an amide bond was identified as a promising scaffold for development of low-molecular-weight therapeutic agents to treat vascular dysfunction, including ischemia/reperfusion injury. Among the compounds synthesized, 5-(3,5-dichlorophenyl)-N-{2,4-dioxo-3-[(pyridin-3-yl)methyl] imidazolidin-1-yl}-2-furamide (17) possessed the most potent inhibitory activity against Ca2+-induced mitochondrial swelling. The structural development, synthesis and structure-activity relationship of these compounds are described.
KW - Cyclophilin A
KW - Cyclophilin D
KW - Dantrolene
KW - Ischemia/reperfusion
KW - Mitochondrial permeability transition (MPT)
KW - Mitochondrial swelling
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U2 - 10.1016/j.bmc.2012.08.062
DO - 10.1016/j.bmc.2012.08.062
M3 - Article
C2 - 23026083
AN - SCOPUS:84867571036
SN - 0968-0896
VL - 20
SP - 6384
EP - 6393
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 21
ER -