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Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir.
Bioorg Med Chem. 2011 Aug 15; 19(16):4796-802.BM

Abstract

Zanamivir (ZA) is a potent anti-influenza drug, but it cannot be administrated orally because of the hydrophilic carboxylate and guanidinium groups. Guanidino-oseltamivir (GO) is another effective neuraminidase inhibitor with polar guanidinium group under physiological conditions. The ester prodrugs ZA-HNAP (5) and GO-HNAP (6) were prepared to incorporate a 1-hydroxy-2-naphthoic (HNAP) moiety to attain good lipophilicity in the intramolecular ion-pairing forms. ZA-HNAP resumed high anti-influenza activity (EC(50)=48 nM), in cell-based anti-influenza assays, by releasing zanamivir along with nontoxic HNAP. Under similar conditions, the hydrolysis of the GO-HNAP ester was too sluggish to show the desired anti-influenza activity.

Authors+Show Affiliations

Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21778065

Citation

Liu, Kung-Cheng, et al. "Intramolecular Ion-pair Prodrugs of Zanamivir and Guanidino-oseltamivir." Bioorganic & Medicinal Chemistry, vol. 19, no. 16, 2011, pp. 4796-802.
Liu KC, Lee PS, Wang SY, et al. Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir. Bioorg Med Chem. 2011;19(16):4796-802.
Liu, K. C., Lee, P. S., Wang, S. Y., Cheng, Y. S., Fang, J. M., & Wong, C. H. (2011). Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir. Bioorganic & Medicinal Chemistry, 19(16), 4796-802. https://doi.org/10.1016/j.bmc.2011.06.080
Liu KC, et al. Intramolecular Ion-pair Prodrugs of Zanamivir and Guanidino-oseltamivir. Bioorg Med Chem. 2011 Aug 15;19(16):4796-802. PubMed PMID: 21778065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir. AU - Liu,Kung-Cheng, AU - Lee,Pei-Shan, AU - Wang,Shi-Yun, AU - Cheng,Yih-Shyun E, AU - Fang,Jim-Min, AU - Wong,Chi-Huey, Y1 - 2011/07/01/ PY - 2011/04/27/received PY - 2011/06/26/revised PY - 2011/06/27/accepted PY - 2011/7/23/entrez PY - 2011/7/23/pubmed PY - 2012/2/9/medline SP - 4796 EP - 802 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 19 IS - 16 N2 - Zanamivir (ZA) is a potent anti-influenza drug, but it cannot be administrated orally because of the hydrophilic carboxylate and guanidinium groups. Guanidino-oseltamivir (GO) is another effective neuraminidase inhibitor with polar guanidinium group under physiological conditions. The ester prodrugs ZA-HNAP (5) and GO-HNAP (6) were prepared to incorporate a 1-hydroxy-2-naphthoic (HNAP) moiety to attain good lipophilicity in the intramolecular ion-pairing forms. ZA-HNAP resumed high anti-influenza activity (EC(50)=48 nM), in cell-based anti-influenza assays, by releasing zanamivir along with nontoxic HNAP. Under similar conditions, the hydrolysis of the GO-HNAP ester was too sluggish to show the desired anti-influenza activity. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/21778065/Intramolecular_ion_pair_prodrugs_of_zanamivir_and_guanidino_oseltamivir_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(11)00530-X DB - PRIME DP - Unbound Medicine ER -