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of the enzyme.
Following extensive preclinical testing, GW0385 suc-
cessfully entered clinical trials for the treatment of
HIV infection. The drug was generally safe and well tol-
erated. Pharmacoenhancement with ritonavir improved
exposures 33- to 85-fold in humans, depending on dose,
providing drug levels anticipated to be well above those
estimated to effectively inhibit resistant viruses.17
GW0385 (brecanavir18) has received fast track designa-
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in HIV-infected patients.
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In summary, we have disclosed the synthesis and SAR
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to proceed into Phase III clinical development for the
treatment of HIV in 2006.
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Acknowledgments
We acknowledge Wayne Schairer of Vertex Pharmaceu-
ticals for his contributions to our research program. We
would also like to acknowledge Ashley Jarvis, Stephen
Price, and David Wilkes of Oxford Asymmetry Interna-
tional for the preparation of a P1 compound set that
was employed in preliminary screening.
12. Daylight V.4.81, Daylight Chemical Information Systems,
Mission Viejo, CA.
References and notes
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˚
15. 2.80 A, RCSB Protein Data Bank ID 2FDE.
˚
16. 1.58 A, RCSB Protein Data Bank ID 2FDD.
17. Ford, S.; Reddy, S.; Anderson, M.; Murray, S.; Ng-
Cashin, J.; Johnson, M.; Abstract 563, 12th Conference on
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18. USAN approved only.