76597-77-8Relevant academic research and scientific papers
New anti-viral drugs for the treatment of the common cold
Maugeri, Caterina,Alisi, Maria A.,Apicella, Claudia,Cellai, Luciano,Dragone, Patrizia,Fioravanzo, Elena,Florio, Saverio,Furlotti, Guido,Mangano, Giorgina,Ombrato, Rosella,Luisi, Renzo,Pompei, Raffaello,Rincicotti, Vito,Russo, Vincenzo,Vitiello, Marco,Cazzolla, Nicola
, p. 3091 - 3107 (2008/09/20)
Human Rhinovirus (HRV) is the most important aetiologic agent of common cold in adults and children. HRV is a single-stranded, positive sense RNA virus and, despite the high level of conservation among different serotypes, sequence alignment of viral protease 3C with mammalian protease reveals no homology. Thus, protease 3C is an optimal target for the development of anti-HRV agents. In the present work we investigated the design, the synthesis and the development of new potential reversible inhibitors against HRV protease 3C. Docking studies on the crystallized structure of HRV2 protease 3C led us to the design and the synthesis of a series of 3,5 disubstituted benzamides able to act as analogues of the substrate. We also developed 1,3,5 trisubstituted benzamides where aromatic substitutions on the aryl ring led us to investigate the importance of π-π interaction on the stabilization of protease 3C-inhibitor complex. All structures were tested for enzymatic inhibition on HRV14 protease 3C. Results highlighted the inhibitory activity of compounds 13, 14, and 20 (91%, 81%, and 85% at 10 μM, respectively), with the latter exhibiting an ID50 (dose that inhibits 50% of the viral cytopathic effect) on HRV-14 = 25 μg/ml.
Potential Thyroliberin Affinity Labels. 1. Chloroacetyl-Substituted Phenylalanylpyrrolidines
Goebel, Richard J.,Currie, Bruce L.,Bowers, Cyril Y.
, p. 366 - 370 (2007/10/02)
Six analogues of thyroliberin (THR) that have a chloroacetyl substituent at the amino terminus have been prepared as potential affinity labels for the TRH receptor.These compounds are N-(chloroacetyl)-L-alanyl-L-phenylalanylpyrrolidine (ClAc-Ala-Phe-Pyrr; 14), N--L-phenylalanyl>pyrrolidine (m-ClAcBz-Phe-Pyrr; 11a), N--L-alanyl-L-phenylalanylpyrrolidine (m-ClAcBz-Ala-Phe-Pyrr; 15a), N--L-phenylalanylpyrrolidine (p-ClAcBz-Phe-Pyrr; 11b), and N--L-alanyl-L-phenylalanylpyrrolidine (p-ClAcBz-Ala-Phe-Pyrr; 15b).Pyroglutamyl-L-phenylalanylpyrrolidine was also synthesized as a model agonist.Weak agonist activity was observed for 11a, 11b, and 15b.These three analogues do not contain the amide group of the pyroglutamyl moiety that was previously thought to be essential for intrinsic activity.No significant antagonist activity was observed for these compounds at the doses tested.
