Details

Autor(en) / Beteiligte

• Zhong, Min
• Shen, Wang
• Barr, Kenneth J.
• Arbitrario, Jennifer P.
• Arkin, Michelle R.
• Bui, Minna
• Chen, Teresa
• Cunningham, Brian C.
• Evanchik, Marc J.
• Hanan, Emily J.
• Hoch, Ute
• Huen, Karen
• Hyde, Jennifer
• Kumer, Jeffery L.
• Lac, Teresa
• Lawrence, Chris E.
• Martell, Jose R.
• Oslob, Johan D.
• Paulvannan, Kumar
• Prabhu, Saileta
• Silverman, Jeffrey A.
• Wright, Jasmin
• Yu, Chul H.
• Zhu, Jiang
• Flanagan, W. Mike

Titel

Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2010-09, Vol.20 (17), p.5269-5273

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• The discovery of a novel series of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists is described. This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester ( 6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester ( 6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model.