HIV protease inhibitors

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C514S231500, C514S252010, C514S254100, C514S256000, C514S326000, C514S336000, C514S367000, C514S365000, C514S372000, C514S378000, C514S381000, C514S383000, C514S393000, C514S406000, C514S444000, C514S451000, C544S060000, C544S149000, C544S238000, C544S333000, C544S374000, C544S405000, C546S284400, C546S192000, C548S152000, C548S215000, C548S240000, C548S255000, C548S267200, C548S254000, C548S364100, C549S060000, C549S292000

Reexamination Certificate

active

06927217

ABSTRACT:
The present invention relates to novel dihydropyrones of Formula Iwherein X is NH or NR8, which inhibit the HIV aspartyl protease blocking HIV infectivity. The dihydropyrones are useful in the development of therapies for the treatment of viral infections and diseases, including AIDS.

REFERENCES:
patent: 5789440 (1998-08-01), Ellsworth et al.
patent: 5834506 (1998-11-01), Boyer, Jr. et al.
patent: 0015625 (2000-03-01), None
Navia and McKeever, “A Role for the Aspartyl Protease from the Human Immunodeficiency Virus Type I (HIV-1) in the Orchestration of Virus Assembly”,New York Acad. Sci., 1990; 616:73-85.
von der Helm, “Retroviral Proteases: Structure, Function and Inhibition From a Non-Anticipated Viral Enzyme to the Target of a Most Promising HIV Therapy”,Biol. Chem., 1996;377:765-774.
Deeks et al., “HIV-1 Protease Inhibitors”,JAMA, 1997;277:145-153.
Barry et al., “Protease Inhibitors in Patients with HIV Disease”,Clin. Pharmacokinet., 1997; 32:194-209.
Schock et al., “Mutational Anatomy of an HIV-1 Protease Variant Conferring Cross-resistance to Protease Inhibitors in Clinical Trials”,J. Biol. Chem., 1996; 271:31957-31963.
Fätkenheuer et al., “Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients”,AIDS, 1997; 11:F113-F116.
Wallace, “New HIV protease inhibitors”,DDT, 1997; 2:83-84.
Tummino et al., “Discovery and Optimization of Nonpeptide HIV-1 Protease Inhibitors”,Bioorganic&Med. Chem., 1996; 4:1401-1410.
Tait et al., “4-Hydroxy-5,6-dihydropyrones. 2. Potent Non-Peptide Inhibitors of HIV Protease”,J. Med. Chem., 1997; 40:3781-3792.
Hagen et al., “Synthesis of 5,6-Dihydro-4-hydroxy-2-pyrones as HIV-1 Protease Inhibitors: The Profound Effect of Polarity on Antiviral Activity”,J. Med. Chem., 1997; 40:3707-3711.
Vander Roest et al., “Pharmacokinetic evaluation for a series of dihydropyrone HIV protease inhibitors in mice”,37thInterscience Conference on Antimicrobial Agents and Chemotherapy, Sep. 8-Oct. 1, 1997, Toronto, Canada. Abstract 1-84.
Domagala et al., “PD 178390: A Novel Potent Non Peptide HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy-2-pyrone Class”,5thConference on Retroviruses and Opportunistic Infections, Feb. 1-5, 1998, Chicago, Illinois. Abstract 638.
Thaisrivongs et al., “Structure-Based Design of HIV Protease Inhibitors: Sulfonamide-Containing 5,6-Dihydro-4-hydroxy-2-pyrones as Non-Peptide Inhibitors”,J. Med. Chem., 1996; 39:4349-4353.
Copending U.S. Appl. No. 09/674,381, filed Oct. 31, 2000.

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