4112-62-3Relevant academic research and scientific papers
Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats
Dhanya, Raveendra-Panickar,Sidique, Shyama,Sheffler, Douglas J.,Nickols, Hilary Highfield,Herath, Ananda,Yang, Li,Dahl, Russell,Ardecky, Robert,Semenova, Svetlana,Markou, Athina,Conn, P. Jeffrey,Cosford, Nicholas D. P.
experimental part, p. 342 - 353 (2011/03/18)
The modification of 3′-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3- dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties. These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes. They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration. The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence.
Development of tryptase inhibitors derived from thalidomide
Tetsuhashi, Masashi,Ishikawa, Minoru,Hashimoto, Mariko,Hashimoto, Yuichi,Aoyama, Hiroshi
experimental part, p. 5323 - 5338 (2010/09/15)
A novel series of tryptase inhibitors with a N-phenylphthalimide skeleton structurally derived from thalidomide (1) has been developed. Structure-activity relationship studies led to a potent and selective tryptase inhibitor, 2-(4-cyanophenyl)isoindole-1,3-dione-5-yl 3-(2-aminopyridin-5-yl)propanoate (7), with the IC50 value of 78 nM.
