Inhibitors of aspartyl protease

Details Inhibitors of aspartyl protease Inhibitors of aspartyl protease

2005-04-12

2005-04-12

Rotman, Alan L. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S233800, C514S367000, C514S378000, C514S470000, C544S148000, C546S270100, C546S270700, C548S159000, C548S247000, C549S464000

Reexamination Certificate

active

06878728

ABSTRACT:
The invention provides novel compounds of formula (I)wherein all variables are as defined in the specification, that are useful as inhibitors of aspartyl proteases.

REFERENCES:
patent: 3743722 (1973-07-01), Mohrs et al.
patent: 4330542 (1982-05-01), Descamps et al.
patent: 4629724 (1986-12-01), Ryono et al.
patent: 5196438 (1993-03-01), Martin et al.
patent: 5354866 (1994-10-01), Kempf et al.
patent: 5622949 (1997-04-01), Talley et al.
patent: 5723490 (1998-03-01), Tung
patent: 5744481 (1998-04-01), Vazquez et al.
patent: 5808056 (1998-09-01), Amato et al.
patent: 5843946 (1998-12-01), Vazquez et al.
patent: 3542567 (1986-06-01), None
patent: 0 022 118 (1981-01-01), None
patent: 0 181 071 (1986-03-01), None
patent: 0 264 795 (1988-04-01), None
patent: 0 346 847 (1989-12-01), None
patent: 0 364 804 (1990-04-01), None
patent: 0 434 365 (1991-06-01), None
patent: 0 468 641 (1992-01-01), None
patent: 0 486 948 (1992-05-01), None
patent: 0 541 168 (1993-05-01), None
patent: 0 594 540 (1994-04-01), None
patent: 2167759 (1986-06-01), None
patent: 2200115 (1988-07-01), None
patent: 59046252 (1984-03-01), None
patent: 59048449 (1984-03-01), None
patent: 61071830 (1986-04-01), None
patent: WO9007329 (1990-07-01), None
patent: WO9100725 (1991-01-01), None
patent: WO9118866 (1991-12-01), None
patent: WO9208688 (1992-05-01), None
patent: WO9208698 (1992-05-01), None
patent: WO9208699 (1992-05-01), None
patent: WO9208700 (1992-05-01), None
patent: WO9208701 (1992-05-01), None
patent: WO9217176 (1992-10-01), None
patent: WO9323368 (1993-11-01), None
patent: WO9323379 (1993-11-01), None
patent: WO9323388 (1993-11-01), None
patent: WO9404491 (1994-03-01), None
patent: WO9404492 (1994-03-01), None
patent: WO9404493 (1994-03-01), None
patent: WO9405639 (1994-03-01), None
patent: WO9410134 (1994-05-01), None
patent: WO9410136 (1994-05-01), None
patent: WO9418192 (1994-08-01), None
patent: WO9419322 (1994-09-01), None
patent: WO9506030 (1995-03-01), None
patent: WO9507269 (1995-03-01), None
patent: WO9509843 (1995-04-01), None
patent: WO9514016 (1995-05-01), None
patent: WO9532185 (1995-11-01), None
STN CAPLUS Database Search RN 132:49885 (1999).*
Banker et al.,Modern Pharmaceutics, pp. 627-629 (1996).
R. Bone et al., “X-ray Crystal Structure of the HIV Protease Complex with L-700,417, an Inhibitor with Pseudo C2Symmetry”,J. Am. Chem. Soc., 113, pp. 9382-9384 (1991).
J.C. Craig et al., “Antiviral Synergy Between Inhibitors of HIV Proteinase and Reverse Transcriptase”,Antiviral Chem. and Chemotherapy, 4(3), pp. 161-166 (1990).
S. Crawford et al., “A Deletion Mutation in the 5′ Part of the pol Gene of Moloney Murine Leukemia Virus Blocks Proteolytic Processing of the gag and pol Polyproteins”,J. Virol., 53, pp. 899-907 (1985).
M. Cushman et al., “Development of Methodology for the Synthesis of Stereochemically Pure Pheψ[CH2N]Pro Linkages in HIV Protease Inhibitors”,J. Org. Chem., 56, pp. 4161-4167 (1991).
D.S. Dhanoa et al., “The Synthesis of Potent Macrocyclic Renin Inhibitors”,Tetrahedron Lett., 33, pp. 1725-1728 (1992).
G.B. Dreyer et al., “Hydroxyethylene Isostere Inhibitors of Human Immunodeficiency Virus-1 Protease: Structure-Activity Analysis Using Enzyme Kinetics, X-ray Crystallography, and Infected T-Cell Assays”,Biochemistry, 31, pp. 6646-6659 (1992).
G.A. Flynn et al., “An Acyl-Iminium Ion Cyclization Route to a Novel Conformationally Restricted Dipeptide Mimic: Applications to Angiotensin-Converting Enzyme Inhibition”,J. Am. Chem. Soc., 109, pp, 7914-15 (1989).
G. Fontenot et al., “PCR Amplification of HIV-1 Proteinase Sequences Directly from Lab Isolates Allows Determination of Five Conserved Domains”,Virology, 190, pp. 1-10 (1992).
J. Freskos et al., “(Hydroxyethyl)sulfonamide HIV-1 Protease Inhibitors: Identification of the 2-Methylbenzoyl Moiety at P-2”,Bio. &Med. Chem. Lett., 6, pp. 445-450 (1996).
A. Ghosh et al., “Potent HIV Protease Inhibitors Incorporating High-Affinty P2-Ligands and (R)-(Hydroxyethylamino)sulfonamide Isostere”,Bio. &Med. Chem. Lett., 8, pp. 687-690 (1998).
E.E. Gilbert, “Recent Developments in Preparative Sulfonation and Sulfation”,Synthesis, 1969, pp. 3-10 (1996).
A. Goldblum, “Modulation of the Affinity of Aspartic Proteases by the Mutated Residues in Active Site Models”,FEBS, 261, pp. 241-244 (1990).
D. Grobelny et al., “Selective Phosphinate Transition-State Analogue Inhibitors of the Protease of Human Immunodeficiency Virus”,Biochem. Biophys. Res. Commun., 169, pp. 1111-1116 (1990).
G.D. Hartman et al., “4-Substituted Thiophene- and Furan-2-sulfonamides as Topical Carbonic Anhydrase Inhibitors”,J. Med. Chem., 35, pp. 3822-3331 (1992).
S. J. Hays et al., “Synthesis of cis-4-(Phosphonooxy)-2-piperidinecarboxylic Acid, an N-Methyl-D-aspartate Antagonist”, J. Org. Chem., 56, pp. 4984-4086 (1991).
J.R. Huff, “HIV Protease: A Novel Chemotherapeutic Target for AIDS”,Journal of Medicinal Chemistry, 34(8), pp. 2305-2314 (1991).
K.Y. Hui et al., “A Rational Approach in the Search for Potent Inhibitors Against HIV Proteinase”,FASEB, 5, pp. 2606-2610 (1991).
Y. Kiso et al., “‘O→N Intramolecular Acyl Migration’-type Prodrugs of Tripeptide Inhibitors of HIV Protease”,Peptides: Chemistry, Structure and Biology, 61, pp. 157-159 (1996).
N.E. Kohl et al., “Active HIV Protease Is Required for Viral Infectivity”,Proc. Natl. Acad. Sci. USA, 85, pp. 4686-4690 (1988).
X. Lin et al., “Enzymic Activities of Two-Chain Pepsinogen, Two-Chain Pepsin, and the Amino-Terminal Lobe of Pepsinogen”,J. Biol. Chem., 267(24), pp. 17257-17263 (1992).
K.P. Manfredi et al., “Examination of HIV-1 Protease Secondary Structure Specificity Using Conformationally Constrained Inhibitors”,J. Med. Chem., 34, pp. 3395-3399 (1991).
F.R. Marshall, “Computer-Aided Drug Design”,Ann. Ref. Pharmacol. Toxicol., 27, pp. 193-213 (1987).
J.A. Martin, “Recent Advances in the Design of HIV Proteinase Inhibitors”,Antiviral Research, 17, pp. 265-278 (1992).
T.D. Meek et al., “Inhibition of HIV-1 Protease in Infected T-Lymphocytes by Synthetic Peptide Analogues”,Nature, 343, pp. 90-92 (1990).
M. Miller et al., “Structure of Complex of Synthetic HIV-1 Protease with a Substrate-Based Inhibitor at 2.3 Å Resolution”,Science, 246, pp. 1149-1152 (1989).
M. Miller et al., “Crystal Structure of a Retroviral Protease Proves Relationship to Aspartic Protease Family”,Nature, 337, pp. 576-579 (1989).
K.H.M. Murthy et al., “Crystal Structures at 2.2-Å Resolution of Hydroxyethylene-Based Inhibitors Bound to Human Immunodeficiency Virus Type 1 Protease Show That the Inhibitors Are Present in Two Distinct Orientations”,J. Biol. Chem., 267, pp. 22770-22778 (1992).
J.B. Nichols et al., “A Molecular Mechanics Valence Force Field for Sulfonamides Derived by ab initio Methods”,J. Phys. Chem., 95, pp. 9803-9811 (1991).
J. Palca, “Shooting at a New HIV Target”,Science, 247, p. 410 (1990).
L.H. Pearl et al., “A Structural Model for the Retroviral Proteases”,Nature, 329, pp. 329-351 (1987).
J.W. Perich et al., “The Synthesis of Multiple O-Phosphoseryl-Containing Peptides via Phenyl Phosphate Protection”,J. Org. Chem., 53, pp. 4103-4105 (1988).
M.S. Plummer et al., “Design of Peptidomimetic Ligands for the pp60srcSH2 Domain”,Bioorganic&Medicinal Chemistry, 5, pp. 41-47 (1997).
M. Popvic et al., “Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS”,Science, 224, pp. 497-500 (1984).
M.D. Power et al., “Nucleotide Sequence of SRV-1, a Type D Simian Acquired Immune Deficiency Syndrome Retrovirus”,Science, 231, pp. 1567-1573 (1986).
N.A. Roberts, 

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