242473-46-7Relevant articles and documents
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
, 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.
1,2,4,5-Tetrahydro-3H-benzazepine compounds, a process for their preparation and pharmaceutical compositions containing them
-
Page/Page column 7, (2009/04/24)
Compounds of formula (I): wherein: R1 represents a hydrogen atom or a group selected from cycloalkyl, benzyl and optionally substituted alkyl,R2, R3, R4 and R5 each represent a hydrogen atom or a hydroxy, methyl, —OSO2R10, —OCOR10 or optionally substituted alkoxy group, or R2 and R3, or R3 and R4, or R4 and R5 together form a group —O—(CH2)q—O—, —O—CH═CH—O— or —O—CH═CH—,R6, R7, R8 and R9 each represent a hydrogen atom or an alkoxy group, or R6 and R7, or R7 and R8, or R8 and R9 together form a group —O—(CH2)q—O—-,R10 represents a group selected from linear or branched C1-C6alkoxy, NR11R′11 and optionally substituted alkyl,R11 and R′11 each represent a hydrogen atom or an alkyl group, or R11 and R′1 together with the nitrogen atom carrying them form an optionally substituted, monocyclic or bicyclic, nitrogen-containing heterocycle,X represents O, NH or CH2,m and p each represent 0 or 1,n and q each represent 1 or 2, in racemic form or in the form of optical isomers,and also addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating various pathologies.
A practical asymmetric synthesis of trans-4,5-benzhydrindan-1-ones as a precursor of A-nor B-aromatic steroidal compounds
Matsuya, Yuji,Masuda, Seiji,Itoh, Takakatsu,Murai, Taiki,Nemoto, Hideo
, p. 6898 - 6903 (2007/10/03)
The enantio-controlled synthesis of trans-4,5-benzhydrindan-1-ones was achieved by means of a stereoselective [4+2] cycloaddition of o-quinodimethanes generated by a thermal cleavage of benzocyclobutene derivatives as a key step. The chiral substrates of
Synthesis of new potentially antiviral furan-fused compounds by thermolysis of benzocyclobutene derivatives
Matsuya, Yuji,Qin, Hongbo,Nagaoka, Mamiko,Nemoto, Hideo
, p. 207 - 211 (2007/10/03)
New potentially antiviral furan-fused tetracyclic compounds were prepared using intramolecular cycloaddition of o-quinodimethane generated by thermolysis of benzocyclobutene derivatives. It was found that the reaction course was changed depending on the length of alkyl chain connecting quinodimethane and furan ring.
Synthesis of a new class of furan-fused tetracyclic compounds using o-quinodimethane chemistry and investigation of their antiviral activity
Matsuya, Yuji,Sasaki, Kazushige,Nagaoka, Mamiko,Kakuda, Hiroko,Toyooka, Naoki,Imanishi, Nobuko,Ochiai, Hiroshi,Nemoto, Hideo
, p. 7989 - 7993 (2007/10/03)
The synthesis and evaluation of antiviral activity of new furan-fused tetracyclic compounds are described. The syntheses were satisfactorily achieved on the basis of o-quinodimethane chemistry, using furan-containing benzocyclobutene derivatives as a substrate, in high generality and stereoselectivity. The various derivatives thus synthesized were examined on their inhibitory activity on virus growth using a hemagglutinin (HA) method, leading to a discovery of promising candidates for new antiviral drugs having high activity and good therapeutic index.
