C3-thia and C3-carba isosteres of a carbocyclic influenza neuraminidase inhibitor, (3R,4R,5S).4-acetamido-5-amino-3-propoxy-1-cyclohexene-1-carboxylic acid

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 14, 1997, Pages 1843-1846

  Lew, Willard ^a   Williams, Matthew A ^a   Mendel, Dirk B ^a   Escarpe, Paul A ^a   Kim, Choung U ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 ACETAMIDO 5 AMINO 1 CYCLOHEXENE 1 CARBOXYLIC ACID DERIVATIVE; 4 ACETAMIDO 5 AMINO 3 ISOPENTYLOXY 1 CYCLOHEXENE 1 CARBOXYLIC ACID ETHYL ESTER; OSELTAMIVIR; SIALIDASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; IN VITRO STUDY; INFLUENZA VIRUS A; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

INFLUENZA VIRUS; INFLUENZAVIRUS A; THIA;

EID: 0030739707     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00332-6     Document Type: Article

References (10)

1. Kim, C. U.; Lew, W.; Williams, M. A.; Liu, H.; Zhang, L.; Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Tai, C. Y.; Laver, W. G.; Stevens, R. C. J. Am. Chem. Soc. 1997, 119, 681.
2. Williams, M. A.; Kim, C. U.; Lew, W.; Mendel, D. B.; Tai, C. Y.; Escarpe, P.; Laver, W. G.; Stevens, R. C. manuscript submitted.
3. Kim, C. U.; Lew, W.; Williams, M. A.; Zhang, L.; Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Li, W.; Tai, L.; Escarpe, P.; Cundy, K. C.; Eisenberg, E. J.; Lacy, S.; Sidwell, R. W.; Stevens, R. C.; Laver, W. G. 1996. New Potent, Orally Active Neuraminidase Inhibitors as Anti-Influenza Agents: In Vitro and In Vivo Activity of GS4071 and Analogs, abstr. H44, P171. In Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Washington, D.C.
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5. (b) Chong, A. K. J.; Pegg, M.S.; von Itzstein, M. Biochem. Int. 1991, 24, 165.
6. (c) Janakiraman, M. N.; White, C. L.; Laver, W. G.; Air, G. M.; Luo, M. Biochemistry, 1994, 33, 8172.
7. Compound 9 was incubated in rat plasma for 30 min at 37°C to convert the methyl ester to the parent amino acid 4. This was then used directly in the enzymatic assay.
8. Montchamp, J-L.; Tian, F.; Hart, M. E.; Frost, J. W. J. Org. Chem. 1996, 61, 3897.
9. The steric bulk of the triethylsilyl group is essential for the stereochemical outcome of the hydrogenation since direct hydrogenation of 11 under the same conditions yields a 2:1 mixture of α:β n-butyl derivatives.
10. Potier, M.; Mameli, L.; Belisle, M.; Dallaire, L.; Melancon, S. B. Anal. Biochem. 1979, 94, 287. Also see ref 1.