P1′ oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 18, 2004, Pages 4651-4654

  Kim, Ronald M ^a   Rouse, Elizabeth A ^a   Chapman, Kevin T ^a   Schleif, William A ^a   Olsen, David B ^a   Stahlhut, Mark ^a   Rutkowski, Carrie A ^a   Emini, Emilio A ^a   Tata, James R ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

HIV; Protease inhibitor

Indexed keywords

CARBOXYLIC ACID; OXADIAZOLE DERIVATIVE; PROTEINASE INHIBITOR; DRUG DERIVATIVE; INDINAVIR; PYRIDINE DERIVATIVE;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG STRUCTURE; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; STEREOCHEMISTRY; VIRUS STRAIN; CHEMISTRY; COMPARATIVE STUDY; DRUG EFFECT; ENZYMOLOGY; HUMAN; ISOLATION AND PURIFICATION; MULTIDRUG RESISTANCE; STEREOISOMERISM; SYNTHESIS; TUMOR CELL LINE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

CELL LINE, TUMOR; DRUG RESISTANCE, MULTIPLE, VIRAL; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; INDINAVIR; OXADIAZOLES; PYRIDINES; STEREOISOMERISM;

EID: 8544239373     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.06.092     Document Type: Article

References (18)

1. D.J. Kempf, A. Molla, and A. Hsu E. De Clercq Antiretroviral Therapy 2001 ASM Washington, DC 147
2. S. Rusconi, and S. Catamancio Expert Opin. Inv. Drugs 11 2002 387
3. Y. Cheng, T.A. Rano, T.T. Huening, F. Zhang, Z. Lu, W.A. Schleif, L. Gabryelski, D.B. Olsen, M. Stahlhut, L.C. Kuo, J.H. Lin, X. Xu, L. Jin, T.V. Olah, D.A. McLoughlin, R.C. King, K.T. Chapman, and J.R. Tata Bioorg. Med. Chem. Lett. 12 2002 529
4. S. Raghavan, Z. Yang, R.T. Mosley, W.A. Schleif, L. Gabryelski, D.B. Olsen, M. Stahlhut, L.C. Kuo, E.A. Emini, K.T. Chapman, and J.R. Tata Bioorg. Med. Chem. Lett. 12 2002 2855
5. 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
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. J.L. Duffy, T.A. Rano, N.J. Kevin, K.T. Chapman, W.A. Schleif, D.B. Olsen, M. Stahlhut, C.A. Rutkowski, L.C. Kuo, L. Jin, J. Lin, E.A. Emini, and J.R. Tata Bioorg. Med. Chem. Lett. 13 2003 2569
8. J.L. Duffy, B.A. Kirk, N.J. Kevin, 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 3323
9. N.J. Kevin, J.L. Duffy, 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. 13 2003 4027
10. For the genotypes of the viral isolates and their susceptibility to protease inhibitors, see: 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
11. 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
12. 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. Bluhy, 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. 91 1994 4096
13. P.E. Maligres, V. Upadhyay, K. Rossen, S.J. Cianciosi, R.M. Purick, K.K. Eng, R.A. Reamer, D. Askin, R.P. Volante, and P.J. Reider Tetrahedron Lett. 36 1995 2195
14. P.E. Maligres, S.A. Weissman, V. Upadhyay, S.J. Cianciosi, R.A. Reamer, R.M. Purick, J. Sager, K. Rossen, K.K. Eng, D. Askin, R.P. Volante, and P.J. Reider Tetrahedron 52 1996 3327
15. C.J. Ainsworth Am. Chem. Soc. 77 1955 1148
16. 3): δ 9.33 (t, J = 6.4 Hz, 1H); 7.55 (m, 2H); 7.42 (m, 2H); 7.28 (s, 1H); 7.13 (d, J = 8.0 Hz, 1H); 7.10 (t, J = 7.8 Hz, 1H); 6.83 (d, J = 8.2 Hz, 1H); 6.77 (m, 1H); 5.25 (dd, J = 8.2, 4.1 Hz, 1H); 4.26 (dd, J = 7.7, 4.6 Hz, 1H); 4.20 (m, 1H); 4.14 (d, J = 11.7 Hz); 3.82 (m, 1H); 3.72 (m, 1H); 3.35 (s, 1H); 3.16-3.23 (m, 2H); 3.05 (d, J = 11.7 Hz, 1H); 2.92 (m, 1H); 2.81 (d, J = 4.1 Hz, 1H); 2.62-2.74 (m, 4H); 2.46 (d, J = 3.2 Hz, 1H); 2.42 (s, 3H); 1.87 (t, J = 11.3 Hz, 1H); 1.73 (m, 1H); 1.62 (s, 3H); 1.61 (s, 3H); 1.47 (m, 1H). MS (ESI) 812.5 (M + 23); 790.5 (M + 1)
17. H.B. Schock, V.M. Garsky, and L.C. Kuo J. Biol. Chem. 271 1996 31957
18. B.D. Dorsey, S.L. McDaniel, R.B. Levin, J.P. Vacca, P.L. Darke, J.A. Zugay, E.A. Emini, W.A. Schleif, J.H. Lin, I.-W. Chen, M.K. Holloway, P.S. Anderson, and J.R. Huff Bioorg. Med. Chem. Lett. 4 1994 2769