Optimization of (2, 3-dihydro-1-benzofuran-3-yl) acetic acids: discovery of a non-free fatty acid-like, highly bioavailable G protein-coupled receptor 40/free fatty acid …

…, J Miyazaki, T Santou, T Odani, N Kanzaki…

Index: Negoro, Nobuyuki; Sasaki, Shinobu; Mikami, Satoshi; Ito, Masahiro; Tsujihata, Yoshiyuki; Ito, Ryo; Suzuki, Masami; Takeuchi, Koji; Suzuki, Nobuhiro; Miyazaki, Junichi; Santou, Takashi; Odani, Tomoyuki; Kanzaki, Naoyuki; Funami, Miyuki; Morohashi, Akio; Nonaka, Masami; Matsunaga, Shinichiro; Yasuma, Tsuneo; Momose, Yu Journal of Medicinal Chemistry, 2012 , vol. 55, # 8 p. 3960 - 3974

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Citation Number: 44

Abstract

G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic β-cells. We previously identified (2, 3-dihydro-1-benzofuran-3-yl) acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase- ...