tetano
Editor, Senior Moderator
Eur J Med Chem. 2012 Jun 29. [Epub ahead of print]
Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities.
Ye D, Shin WJ, Li N, Tang W, Feng E, Li J, He PL, Zuo JP, Kim H, Nam KY, Zhu W, Seong BL, Tai No K, Jiang H, Liu H.
Source
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu chong zhi Road, Shanghai 201203, China.
Abstract
With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound D26 exerts the most potency, with IC(50) values of 0.58 and 2.72 μM against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts ∼58% protective against AIV infection, which was comparable to zanamivir (∼67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t(1/2)) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents.
Copyright ? 2012 Elsevier Masson SAS. All rights reserved.
PMID:
22795831
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22795831
Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities.
Ye D, Shin WJ, Li N, Tang W, Feng E, Li J, He PL, Zuo JP, Kim H, Nam KY, Zhu W, Seong BL, Tai No K, Jiang H, Liu H.
Source
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu chong zhi Road, Shanghai 201203, China.
Abstract
With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound D26 exerts the most potency, with IC(50) values of 0.58 and 2.72 μM against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts ∼58% protective against AIV infection, which was comparable to zanamivir (∼67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t(1/2)) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents.
Copyright ? 2012 Elsevier Masson SAS. All rights reserved.
PMID:
22795831
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22795831