合成胍基克流感與胍基零流感衍生物以改善親脂性

李佩珊

3.239.51.78，Hello！

Close
Search Quick Search Advanced Search Publication Search	Personal Service Member Login Searching History Use Bonus Card SYMSKAN
Browse Browse by University of Graduate Thesis Browse by Pinyin of Graduate Thesis Browse by Conference Proceedings Topic Browse by Conference Proceedings Publisher Browse by Pinyin of Conference Proceedings Browse by eBook Category Browse by eBook Topic Browse by eBook Publisher
Customer Services Authorize Airiti Recommend a Journal

Search Symbol (Half-width)	Description of Search Symbols
Space	"AND" indicates the intertwining of key terms used in a search
Double Quotation Marks ("") ( " " )	Double quotation marks indicate the beginning and end of a phrase, and the search will only include terms that appear in the same order of those within the quotations. Example: "image process" ： " image process "
?	Indicates a variable letter. Entering two ? will indicate two variable letters, and so on. Example: "Appl?", search results will yield apple, apply… e , appl y … ( (often used to English word searches) )
*	Indicates an unlimited number of variable letters to follow, from 1~n. Example: Enter "appl*", search results will yield apple, apples, apply, applied, application…(often used in English word searches) e , appl es , appl y , appl ied , appl ication … ( (often used to English word searches) )
AND、OR、NOT	Boolean logic combinations of key words is a skill used to expand or refine search parameters. (1) AND (1) AND: Refines search parameters (2) OR (2) OR: Expands search parameters (3) NOT: Excludes irrelevant parameters

DOI stands for Digital Object Identifier （ D igital O bject I dentifier ） ,
and is the unique identifier for objects on the internet. It can be used to create persistent link and to cite articles.

Using DOI as a persistent link

To create a persistent link, add「http://dx.doi.org/」「 http://dx.doi.org/ 」 before a DOI.
For instance, if the DOI of an article is 10.5297/ser.1201.002 , you can link persistently to the article by entering the following link in your browser: http://dx.doi.org/ 10.5297/ser.1201.002 。
The DOI link will always direct you to the most updated article page no matter how the publisher changes the document's position, avoiding errors when engaging in important research.

Cite a document with DOI

When citing references, you should also cite the DOI if the article has one. If your citation guideline does not include DOIs, you may cite the DOI link.

DOIs allow accurate citations, improve academic contents connections, and allow users to gain better experience across different platforms. Currently, there are more than 70 million DOIs registered for academic contents. If you want to understand more about DOI, please visit airiti DOI Registration （ doi.airiti.com ）。

Data Source

Basic & Applied Sciences > Chemistry
College of Science > Graduate Institute of Chemistry

Bibliography Management Tool

Related Links

Report an Issue

Purchase Single Articles

Download PDF

合成胍基克流感與胍基零流感衍生物以改善親脂性

Synthesis of Guanidino-Oseltamivir and Guanidino-Tamiphosphor Derivatives with Improved Lipophilicity

李佩珊 , Masters　　Advisor：方俊民　　

繁體中文

克流感；零流感；前驅藥物；胍基； tamiphosphor ； oseltamivir ； guanidine ； prodrug ； 150-cavity

Abstract │ Reference (73) │ Altmetrics

Abstract 〈TOP〉

Parallel Abstract 〈TOP〉

Influenza is a respiratory infection. It caused high mortality of annual epidemics and occasional pandemics in the past. Recently, the new type of mutated influenza viruses occurred. The outbreak of H5N1 avian flu and the new type H1N1 human flu in 2009 have increased public awareness of the potential for global influenza pandemics. Zanamivir and oseltamivir are main anti-influenza drugs targeting neuraminidase (NA). Another NA inhibitor tamiphosphor was developed by our group in 2007. Most importantly, guanidino-oseltamivir carboxylic acid (14, GOA) and gaunidino-tamiphosphor (51, TPG) are better inhibitors than oseltamivir against wild-type human H1N1 and avian H5N1 viruses. However, GOA (14) and TPG (51) have low oral bioavailability due to the high polarity of guanidine group. Therefore, my research focused on the synthesis of GOA (14) and TPG (51) derivatives with improved bioavailability.
In the first approach, GOA (14) was modified with 1-hydroxy-2-naphthoic acid (HNAP) as a possible ester prodrug GO-HNAP (27), which formed intramolecular ion-pair to increase lipophilicity. Besides, our preliminary study showed that GO-HNAP conjugate could release the active anti-influenza drug, GOA (14), by esterase catalyzed hydrolysis in rat plasma.
In the second approach, the guanidine group of TPG (51) or TPGEt (52) was modified as alkylguanidine, hydroxyguanidine and acylguanidine. Comparing the log D of compound 45 with compound 63, the modification at the terminal position of guanidine in compound 45 seemed to have better lipophilicity. In addition, these derivatives were subjected to inhibitory assays against influenza NA and viruses. The NA inhibitory activity of compounds 62 and 63 decreased, and compound 71 had no inhibition against NA. Although compound 46 showed better inhibition against NA (IC50 = 6.1 nM), it only slightly improved the lipophilicity. Therefore, modification of the N-hydroxyguanidino proup may lead to better lipophilicity.

Reference ( 73 ) 〈TOP〉

1. Lowen, A. C.; Palese, P. Infect. Disord. Drug Targets 2007, 7, 318–328. Influenza virus transmission: basic science and implications for the use of antiviral drugs during a pandemic.
2. Suzuki, Y. Biol. Pharm. Bull. 2005, 28, 399–408. Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses.
3. Preziosi, P. Expert Opin. Pharmacother. 2011, 12, 1523–1549. Influenza pharmacotherapy: present situation, strategies and hopes.
4. von Itzstein, M. Nat. Rev. Drug Discov. 2007, 6, 967–974. The war against influenza: discovery and development of sialidase inhibitors.
5. Wilson, I. A.; Skehel, J. J.; Wiley, D. C. Nature 1981, 289, 366–373. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 [Å] resolution.

Altmetrics

〈TOP〉

E-mail ：

When an article is available to download, a notice will be sent to your mailbox address.

E-mail ：