Pyrazole NNRTIs 1: Design and initial optimisation of a novel template

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 19, 2009, Pages 5599-5602

  Mowbray, Charles E ^a   Burt, Catherine ^a   Corbau, Romuald ^a   Perros, Manos ^a   Tran, Isabelle ^a   Stupple, Paul A ^a   Webster, Rob ^a   Wood, Anthony ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

HIV; NNRTI; Reverse transcriptase

Indexed keywords

CAPRAVIRINE; EFAVIRENZ; PYRAZOLE; RNA DIRECTED DNA POLYMERASE;

ARTICLE; GLUCURONIDATION; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; VIRUS MUTANT; WILD TYPE;

ANTI-HIV AGENTS; DRUG DESIGN; HIV REVERSE TRANSCRIPTASE; HUMANS; MICROSOMES, LIVER; PYRAZOLES; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 69949092805     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.08.039     Document Type: Article

References (17)

1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. November 3, 2008; 1-139. Available at http://www.aidsinfo.nih.gov.
2. Antiretroviral Treatment of Adult HIV Infection: 2008 Recommendations of the International AIDS Society-USA Panel:. Hammer S.M., Eron Jr. J.J., Reiss P., Schooley R.T., Thompson M.A., Walmsley S., Cahn P., Fischl M.A., Gatell J.M., Hirsch M.S., Jacobsen D.M., Montaner J.S.G., Richman D.D., Yeni P.G., and Volberding P.A. J. Am. Med. Assoc. 300 (2008) 555. http://www.who.int/hiv/en/ For further information see also: www.who.int/hiv/en/
3. Abdel-Malak M., Gallati C., and Mousa S.A. Drugs Future 33 (2008) 691
4. Bachelor L.T. Drug Resist. Updat. 2 (1999) 56
5. Fujiwara T., Sato A., El-Farrash M., Miki S., Abe K., Isaka Y., Kodama M., Wu Y., Chen L.B., Harada H., Sugimoto H., Hatanaka M., and Hinuma Y. Antimicrob. Agents Chemother. 42 (1998) 1340
6. Brown W.M. Curr. Opin. Anti-infect. invest. Drugs 2 (2000) 286
7. Subsequent to this analysis capravirine failed to meet its primary outcome in two Phase 2 clinical trials, and no further development of CPV is planned. This vindicated our decision to look for compounds with improved properties compared to capravirine. Sato A., Hammond J., Alexander T.N., Graham J.P., Binford S., Sugita K., Sugimoto H., Fujiwara T., and Patick A.K. Antiviral Res. 70 (2006) 66
8. Pesano, R.; Piraino, S.; Hawley, P.; Hammond, J.; Tressler, R.L.; Ryan, R.J.; Nickens, D.; Ruiz, R. 2005, Abstracts of Papers, 555, Proceedings of the Twelfth Conference on Retroviruses and Opportunistic Infections, Boston.
9. Hawley, P.; Hammond, J.; Ryan, R.J.; Tressler, R.L.; Raber, S.R.; Hodges, M. 2006, Abstracts of Papers, J-130, Proceedings of the 13th Conference on Retroviruses and Opportunistic Infections, Colorado.
10. Ren J., Nichols C., Bird L.E., Fujiwara T., Sugimoto H., Stuart D.I., and Stammers D.K. J. Biol. Chem. 275 (2000) 14316
11. Van de Waterbeemd H., Smith D.A., Beaumont K., and Walker D. J. Med. Chem. 44 (2001) 1313
12. Lipinski C.A., Lombardo F., Dominy B.W., and Feeney P.J. Adv. Drug Delivery Rev. 46 (2001) 3
13. Ohkawa T., Goto S., Miki S., Sato A., Kuroda T., Iwatani K., Takeuchi M., and Nakano M. Xenobiotica 28 (1998) 877
14. Sugimoto, H.; Fujiwara, T. European Patent Application EP 0786455A1.
15. 50s in these two assays is due to the different experimental conditions used. The rank order of potencies within the series is the same in both assay formats.
16. Corbau, R., et al. Poster Presentation, 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 17-20, 2007, Chicago.
17. Corbau, R.; Mori, J.; Phillips, C.; Fishburn, L.; Martin, A.; Mowbray, C.; Panton, W.; Smith-Burchnell, C.; Thornberry, A.; Ringrose, H.; Knöechel, T.; Irving, S.; Westby, M.; Wood, A.; Perros, M. Antimicrob. Agents Chemother. 2009, in press.