Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1994-04-14
1995-09-26
Prescott, Arthur C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
560145, 560147, 560155, 560156, 560179, 560184, 560205, C07C 6900, C07C 6962, A01N 3728, A01N 4102
Patent
active
054535336
ABSTRACT:
An influenza virus neuraminidase inhibitor, its analogs, its pharmaceutically acceptable salts, derivatives, and mixtures thereof having the following formula: ##STR1## where A is CO.sub.2 H, CO.sub.2 H.sub.3, NO.sub.2, SO.sub.3 H or PO.sub.3 H.sub.2, B is CH, N, O or S, R.sub.1 and R.sub.2 are H, NO.sub.2 or (CH.sub.m).sub.n X.sub.1 where m=1 or 2, n is an integer from 0 to 4 and X.sub.1 is guanidino, OH, NH.sub.2, SH, NO.sub.2, F, Cl, Br, I, CN, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2, R.sub.3 and R.sub.4 are H, (CH.sub.o).sub.p X.sub.2, (CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2, NH(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2, NHCO(CH.sub.o).sub.p CH.sub.2 X.sub.2 or NHCO(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2 where o=1 or 2, p is an integer from 0 to 4 and X.sub.2 is H, guanidino, OH, NH.sub.2, SH, NO.sub.2, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2 , R.sub.5 =H, OH, NH.sub.2, (CH.sub.k).sub.1 X.sub.3, CO(CH.sub.k).sub.1 X.sub.3, SO(CH.sub.k).sub.1 X.sub.3 or SO.sub.2 (CH.sub.k).sub.1 X.sub.3 where k=1 or 2, 1 is an integer from 0 to 4 and X.sub.3 is guanidino, OH, NH.sub.2, SH, NO.sub.2, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2, R.sub.6 is H, CH(OH)X.sub.4, CH(NH.sub.2)X.sub.4, COX.sub.4, SOX.sub.4, or SO.sub.2 X.sub.4, where X.sub.4 is H, CH.sub.3, CH.sub.3 CH.sub.2, CH.sub.3 CHCH.sub.3, CH.sub.3 CH.sub.2 CH.sub.2 or halogen substituted analogs of X.sub.4. The inhibitor in a composition with a pharmaceutically acceptable carrier. A method of inhibiting influenza virus neuraminidase where the inhibitor is administered to a subject in a pharmaceutically acceptable amount along with effective amounts of a pharmaceutically acceptable carrier. Methods of marking a pharmaceutical composition of an acceptable carrier and the inhibitor. Methods of treating and preventing a subject infected with influenza virus (type A or B) using the inhibitor.
REFERENCES:
patent: 4478823 (1984-10-01), Sanderson
patent: 4537769 (1985-08-01), Cerini
patent: 5360817 (1994-11-01), Von Izstein et al.
G. M. Air and W. G. Laver, "The Neuraminidase of Influenza Virus", Proteins: Structure, Function, and Genetics, 6, 341-356 (1989).
P. Bossart-Whitaker, et al., "Three-Dimensional Structure of Influenza A N9 Neuraminidase and its Complex with the Inhibitor 2-Deoxy-2,3-dehydro-N-acetyl Neuraminic Acid", J. Mol. Biol., 232, 1069-1089 (1993).
K. W. Brammer, et al., Antiviral Properties of 1-Phenoxymethyl-3,4-dihydro- and 1,2,3,4-Tetrahydroisoquinolines, Nature, 219, 515-517 (1968).
R. Brossmer, et al., "Inhibition Studies on Vibrio cholerae Neuraminidase", Hoppe-Seyler's Z. Physiol. Chem., 358, 391-396 (1977).
G. Bruno and L. Randaccio, "A Refinement of the Benzoic Acid Structure at Room Temperature", Acta Cryst., B36, 1711-1712 (1980).
R. F. Bryan, et al., "3-(p-Bromobenzoyl)-1,3-thiazolidine-2-thione", Acta Cryst., B36, 1709-1710 (1980).
W. P. Burmeister, et al., "The 2.2 .ANG. Resolution Crystal Structure of Influenza B Neuraminidase and its Complex with Sialic Acid", EMBO J., 11, 49-56 (1992).
P. A. Carpy and J. L. Goursolle, "Acide [Dichloro-2,3(Thenoyl-2)-4 Phenoxy] Acetique (Acide Tienilique)", Acta Cryst., B36, 1706-1708 (1980).
G. P. Ellis and R. T. Jones, "One-Step Synthesis and Spectral Study of Some 1-Methylbenzimidazoles, Including Use of a Lanthanide Shift Reagent", J. Chem. Soc. Perk. Trans. I, 8, 903-909 (1974).
P. H. Gozlan and C. Riche, "Analogues de la Noraderenaline. Structure Cristalline de la (Methylene Dioxy-3',4')-phenyl-2 Hydroxy-2 Acetamideoxime", Acta Cryst., B32, 1662-1665 (1976).
T. H. Haskell, et al., "Neuraminidase Inhibition and Chemotherapy", J. Med. Chem., 13, 697-704 (1970).
M. N. Janakiraman, et al., "Structural Evidence for Hydrolysis Catalyzed by Influenza Virus Neuraminidase Driven by Stabilization of the Oxocarbonium Ion Intermediate", Biochemistry, 33, 8172-8179 (1994).
Y. Kageyama, et al., "Structure of the Phosphate Form of p-Nitrocinnamic acid", Acta Cryst., C49, 833-834 (1993).
F. Kasuya, et al., "Metabolism of Benoxinate in Humans", J. Pharm. Sci., 76, 303-305 (1987).
T. Kudo, et al., "Synthesis of the Potent Inhibitors of Neuramindase. N-(1,2-Dihydroxypropyl) Derivatives of Siastatin B and its 4-Deoxy Analogs", J. Antibiot., 46, 300-309 (1993).
V. Kumar, et al., "Methyl 5-Acetamido-2,6-anhydro-3,5-dideoxy-D-manno-non-2-en-4-ulosonate", Carbohyd. Res., 103, 281-285 (1982).
P. Meindl, et al., "Inhibition of Neuraminidase Activity by Derivatives of 2-Deoxy-2,3-dehydro-N-acetylneuraminic Acid", Virology, 58, 457-463 (1974).
R. M. Metzger, et al., "Crystal Structure of DMAP-C-HMTCAQ, C3.sub.30 H.sub.20 N.sub.6 O.sub.2 N.sub.1 N,N-dimethylaminophenylcarbamate-2'-hydroxymethyl-11,11,12,12-tetracyano-a nthraquinodimethan", J. Cryst. Spect. Research., 19(3), 475-482 (1989).
R. M. Metzger, et al., "Structure of MAP:MNA, the 1:1 Adduct Between (R)Methyl2-(2,4-Dinitroanilino)propanoate (MAP) and 2-Methyl-4-nitroaniline (MNA), a New Nonlinear Optical Crystal", Acta Cryst., C49, 738-741 (1993).
T. Nagai, et al., "In Viro Anti-Influenza Virus Activity of Plant Flavonoids Possessing Inhibitory Activity for Influenza Virus Sialidase", Antiviral Res., 19, 207-217 (1992).
G. O'Neill, "Have Aussies Found a Cure for the Flu?", J. NIH Res., 5, 40-42 (1993).
B. B. Nielsen and I. K. Larsen, "3,4,5-Trihydroxybenzohydroxamic Acid Monohydrate, A Ribonucleotide Reductase Inhibitor", Acta Cryst., C49, 810-813 (1993).
P. Palese and R. W. Compans, "Inhibition of Influenza Virus Replication in Tissue Culture by 2-Deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA): Mechanism of Action", J. Gen. Virology, 33, 159-164 (1976).
E. Schreiner, et al., "Synthesis of Some 2,3-Didehydro-2-deoxysialic Acids Structurally Varied at C-4 and their Behavior Towards Sialidase from Vibrio cholerae", Liebigs Ann. Chem., 129-134 (1991).
S. Soundarajan, et al., "Structure 4-Carboxy-2-nitrobenzeneboronic Acid", Acta Cryst., C49, 690-693 (1993).
N. R. Taylor, et al., "Molecular Modeling Studies on Ligand Binding to Sialiase from Influenza Virus and the Mechanism of Catalysis", J. Med. Chem., 37, 616-624 (1994).
W. R. Tulip, et al., "Refined Atomic Structures of N9 Subtype Influenza Virus Neuraminidase and Escape Mutants", J. Mol. Biol., 221, 487-497 (1991).
W. R. Tulip, et al., "Refined Crystal Structure of the Influenza Virus N9 Neuraminidase-NC41 Fab Complex", J. Mol. Biol., 227, 122-148 (1992).
J. N. Varghese, et al., "The Structure of the Complex Between Influenza Virus Neuraminidase and Sialic Acid, the Viral Receptor", Proteins: Structure, Function and Genetics, 14, 327-332 (1992).
A. Vasella and R. Wyler, "Sythesis of a Phosphonic Acid Analogue of N-Acetyl-2,3-didehydro-2-deoxyneuraminic Acid, and Inhibitor of Vibrio cholerae Sialidase", Helv. Chim. Acta, 74, 451-463 (1991).
R. Varma and I. Kahn, "Synthesis of Indophenazines and 6-Piperidino/morpholinomethyl-indophenazines As Possible Excystment and Cysticidal Agents", J. Ind. Chem. Soc., 55, 1043-1045 (1978).
L. M. Von Itzstein, et al., "Derivatives and Analogues of 2-Deoxy-2,3-didehydro-N-acetylneuraminic Acid and their Use as Antiviral Agents", Intern. Patent WO 91/16320 (Oct. 31, 1994).
A. Okuyama, et al., "Preparation of quanidinobenzoic acid amides as antiviral agents (182869p)", 25-Benzenes, 115, 879 (1991).
Air Gillian
Brouillette Wayne J.
Luo Ming
Prescott Arthur C.
The University of Alabama at Birmingham
LandOfFree
Inhibitors of influenza virus neuraminidase and methods of makin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Inhibitors of influenza virus neuraminidase and methods of makin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibitors of influenza virus neuraminidase and methods of makin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1552696