Identification of MK-944a: A second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors

Journal of Medicinal Chemistry

Volumn 43, Issue 18, 2000, Pages 3386-3399

  Dorsey, B D ^a   McDonough, C ^a   McDaniel, S L ^a   Levin, R B ^a   Newton, C L ^a   Hoffman, J M ^a   Darke, P L ^a   Zugay Murphy, J A ^a   Emini, E A ^a   Schleif, W A ^a   Olsen, D B ^a   Stahlhut, M W ^a   Rutkowski, C A ^a   Kuo, L C ^a   Lin, J H ^a   Chen, I W ^a   Michelson, S R ^a   Holloway, M K ^a   Huff, J R ^a   Vacca, J P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HUMAN SERUM ALBUMIN; HYDROXYLAMINEPENTANAMIDE; INDINAVIR; L 756423; MK 944A; N (2 HYDROXY 1 INDANYL) 2 PHENYLMETHYL 4 HYDROXY 5 [1 [4 (2 BENZO[B]FURANYLMETHYL) 2 N' (TERT BUTYLCARBOXAMIDO)PIPERAZINYL]]PENTANAMIDE; NELFINAVIR; OROSOMUCOID; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL ACTIVITY; ARTICLE; CELL SPREADING; CLINICAL TRIAL; COMPETITIVE INHIBITION; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG INDUCED DISEASE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; LYMPHOID CELL; NONHUMAN; RAT; VIRUS RESISTANCE;

ANIMALS; ANTIVIRAL AGENTS; CATTLE; CELL CULTURE TECHNIQUES; DOGS; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, MICROBIAL; HAPLORHINI; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; INDANS; MALE; PIPERAZINES; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; URINARY CALCULI;

EID: 0034618547     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9903848     Document Type: Article

References (56)

1. Isolation of a T-lymphotropic retrovirus from a patient at risk for Acquired Immunodeficiency Syndrome (AIDS)
2. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and Pre-AIDS
3. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS
4. Complete nucleotide sequence of the AIDS virus, HTLV-III
5. Active HIV protease is required for viral infectivity
6. Active site mutagenesis of the AIDS virus protease and its alleviation by trans complementation
7. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less
8. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy
9. Simultaneous vs sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infection (100-Week Follow-up)
10. L-735,524: An orally bioavailable human immunodeficiency virus type 1 protease inhibitor
11. Antiretroviral therapy for HIV infection in 1998 (Updated Recommendations of the International AIDS Society-USA Panel)
12. Antiretroviral therapy for HIV infection in 1998 (Updated Recommendations of the International AIDS Society-USA Panel)
13. Rational design of peptide-based HIV proteinase inhibitors
14. Discovery of ritonavir, a potent inhibitor of HIV protease with high oral biavailability and clinical efficacy
15. Iterative protein structure-based drug design and synthesis of HIV protease inhibitors
16. Viracept (nelfinavir mesylate, AG 1343): A potent, oraly bioavailable inhibitor of HIV-1 protease
17. Amprenavir
18. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors
19. L-735,524: The design of a potent and orally bioavailable hiv protease inhibitor
20. Synthesis and evaluation of pyridyl analogues of L-735,524: Potent HIV-1 protease inhibitors
21. Disposition of indinavir, a potent HIV-1 protease inhibiter, after an oral dose in humans
22. Design and selection of DMP 850 and DMP 851: The next generation of cyclic urea HIV protease inhibitors
23. 1-acid glycoprotein on the anti-human immunodeficiency virus (HIV) activity of the protease inhibitor CGP 61755: A comparative study with other relevant HIV protease inhibitors
24. Highly diasteroeselective reaction of a chiral, nonracemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibiter L-735,524
25. A practical synthesis of 5-(Chloromethyl)furo[2,3-b]pyridine, a key intermediate for the HIV protease inhibiter, L-754, 394
26. A facile synthesis of polyfunctionally substituted pyridines from ethoxycarbonylmalonaldehyde
27. Time and dose dependent pharmacokinetics of L-754,394, an HIV protease inhibiter, in rats, dogs, and monkeys
28. Role of cytechrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor
29. Resistance to human immunodefiiciency virus tpye 1 protease inhibitors
30. News and views: Protease uninhibited
31. Characterization of human immunodeficiency virsu type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959
32. Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor
33. In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease
34. Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor
35. Cross-resistance analysis of human immunodeficiency virus type 1 variants individually selected for resistance to five different protease inhibitors
36. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor
37. In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: Mutations, kinetics, and frequencies
38. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir
39. HIV protease genotype and viral senesitivity to HIV protease inhibitors following saquinavir therapy
40. Human immunodefiency virus type 1 protease genotypes and in vitro protease inhibitor susceptibilities of isolates from individuals who were switched to other protease inhibitors after long-term saquinavir treatment
41. Nonactive site changes elicit broad-based cross-resistance of the HIV-1 protease to inhibitors
42. Furopyridines. VI. Preparation and reactions of substituted furo[2,3-b]pyridines
43. Furopyridines. VII. Preparation and hydrolysis of 2-cyano and 3-cyano derivatives of furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine
44. Furopyridines. I. Synthesis of furo[2,3-c]pyridine
45. 13C NMR spectra of 2- or 3-substituted furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]-, and furo[3,2-c]pryridine
46. Chemistry of thienopyridines. XVIII. Lithiation as a route to 2- and 3- substituted thieno[2,3-b]pyridines