60100-18-7Relevant academic research and scientific papers
Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that Act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists
Negoro, Nobuyuki,Sasaki, Shinobu,Ito, Masahiro,Kitamura, Shuji,Tsujihata, Yoshiyuki,Ito, Ryo,Suzuki, Masami,Takeuchi, Koji,Suzuki, Nobuhiro,Miyazaki, Junichi,Santou, Takashi,Odani, Tomoyuki,Kanzaki, Naoyuki,Funami, Miyuki,Tanaka, Toshimasa,Yasuma, Tsuneo,Momose, Yu
supporting information; experimental part, p. 1538 - 1552 (2012/04/10)
The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2′,6′-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl} propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to β-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methoxy} -2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.
Total synthesis of cortistatins A and J
Yamashita, Shuji,Iso, Kentaro,Kitajima, Kazuki,Himuro, Masafumi,Hirama, Masahiro
, p. 2408 - 2425 (2011/06/20)
This paper describes the details of our synthetic studies on the marine steroidal alkaloids cortistatins A and J. The key features of our strategy include (i) an efficient Knoevenagel/electrocyclic strategy to couple the diketone and the CD-ring fragment, (ii) a chemoselective radical cyclization to construct the oxabicyclo[3.2.1]octene B-ring system, (iii) a highly stereocontrolled installation of the isoquinoline unit, and (iv) a late-stage functionalization of the A-ring.
HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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, (2011/04/14)
Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
A highly stereoselective synthesis of des-A B-aromatic azasteroids
Trehan, I. R.,Singh, N. P.,Jain, Vinay K.
, p. 484 - 486 (2007/10/02)
An efficient stereoselective synthesis of des-A B-aromatic azasteroid (5) has been achieved by intramolecular Diels-Alder reaction (IMDAR) of the orthoquinodimethane obtained by thermolysis of N--2-methylpropenamide (3).
