Orally bioavailable highly potent HIV protease inhibitors against PI-resistant virus

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 23, 2005, Pages 5311-5314

  Lu, Zhijian ^a   Bohn, Joann ^a   Rano, Tom ^a   Rutkowski, Carrie A ^a   Simcoe, Amy L ^a   Olsen, David B ^a   Schleif, William A ^a   Carella, Anthony ^a   Gabryelski, Lori ^a   Jin, Lixia ^a   Lin, Jiunn H ^a   Emini, Emilio ^a   Chapman, Kevin ^a   Tata, James R ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

HIV; Inhibitors; Protease

Indexed keywords

PROTEINASE INHIBITOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; ARTICLE; BIOCHEMISTRY; BIOLOGICAL ACTIVITY; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERANCE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INHIBITION KINETICS; STRUCTURE ACTIVITY RELATION; VIRUS ISOLATION; VIRUS RESISTANCE; VIRUS STRAIN; WILD TYPE;

ADMINISTRATION, ORAL; BIOLOGICAL AVAILABILITY; DRUG RESISTANCE, VIRAL; HIV; HIV PROTEASE; HIV PROTEASE INHIBITORS; INDINAVIR; MOLECULAR STRUCTURE;

EID: 26844577922     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.08.072     Document Type: Article

References (15)

1. J.P. Vacca, and J.H. Condra Drug Discov. Today 2 1997 261
2. D.J. Kempf, and J.L. Sham Curr. Pharm. Design 2 1996 225
3. J.P. Vacca, B.D. Dorsey, W.A. Schlief, R.B. Levin, S.L. MeDaniel, P.L. Derke, J. Zugay, J.C. Quintero, O.M. Blanhy, E. Roth, V.V. Sardana, A.J. Schlabach, P.I. Graham, J.H. Condra, L. Gotlib, M.K. Holloway, J. Lin, I.-W. Chen, K. Vastag, D. Ostovic, P.S. Anderson, E.A. Emini, and J.R. Huff Proc. Natl. Acad. Sci. U.S.A. 91 1994 4096
4. J.H. Condra Drug Resist. Updates 1 1998 1
5. D. Boden, and M. Markowits Antimicrob. Agents Chemother. 42 1998 2775
6. J.L. Duffy, N.J. Kevin, B.A. Kirk, K.T. Chapman, W.A. Schleif, D.B. Olsen, M. Stahlhut, C.A. Rutkowski, L.C. Kuo, L. Jin, J.H. Lin, E.A. Emini, and J.R. Tata Bioorg. Med. Chem. Lett. 12 2002 2423
7. Y. Cheng, F. Zhang, T.A. Rano, Z. Lu, K.T. Chapman, W.A. Schleif, D.B. Olsen, M. Stahlhut, C.A. Rutkowski, L.C. Kuo, L. Jin, J.H. Lin, E.A. Emini, and J.R. Tata Bioorg. Med. Chem. Lett. 12 2002 2419
8. For other synthesis of aminochromanol, see: A.K. Ghosh, S.P. Mckee, and W.M. Sanders Tetrahedron Lett. 32 1991 711
9. I.W. Davies, M. Taylor, J.-F. Marcoux, L. Matty, J. Wu, D. Hughes, and P.J. Reider Tetrahedron Lett. 41 2000 8021
10. F. Zhang, K.T. Chapman, W.A. Schleif, D.B. Olsen, M. Stahlhut, C.A. Rutkowski, L.C. Kuo, L. Jin, J.H. Lin, E.A. Emini, and J.R. Tata Bioorg. Med. Chem. Lett. 13 2003 2573
11. J.P. Vacca, B.D. Dorsey, W.A. Schleif, R.B. Levin, S.L. McDaniel, P.L. Darke, J. Zugay, J.C. Quintero, O.M. Blahy, E. Roth, V.V. Sardana, A.J. Schlabach, P.I. Graham, J.H. Condra, L. Gotlib, M.K. Holloway, J. Lin, I.-W. Chen, K. Vastag, D. Ostovic, P.S. Anderson, E.A. Emini, and J.R. Huff Proc. Natl. Acad. Sci. U.S.A. 91 1994 4096
12. For the genotype of these isolates and their susceptibility to protease inhibitors, see J.H. Condra, D.J. Holder, W.A. Schleif, O.M. Blahy, R.M. Danovich, L.J. Gabyelski, D.J. Graham, D. Laird, J.C. Quintero, A. Rhodes, H.L. Robbins, E. Roth, M. Shivaprakash, T. Yang, J.A. Chodakewitz, P.J. Deutsch, R.Y. Leavitt, F.E. Massari, J.W. Mellors, K.E. Squires, R.T. Steigbigel, H. Teppler, and E.A. Emini J. Virol. 70 1996 8270
13. D.B. Olsen, M.W. Stahlhut, C.A. Rutkowski, H.B. Schock, A.L. vanOlden, and L.C. Kuo J. Biol. Chem. 274 1999 23699
14. R.M. Kim, E.A. Rouse, K.T. Chapman, W.A. Schleif, D.B. Olsen, M. Stahlhut, C.A. Rutkowski, L.C. Kuo, L. Jin, J.H. Lin, E.A. Emini, and J.R. Tata Bioorg. Med. Chem. Lett. 14 2004 4651
15. Manuscripts in preparation.