4-aryl quinols and analogs thereof as therapeutic agents

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C514S312000, C514S367000, C514S365000, C514S374000, C514S375000, C514S412000, C514S394000, C514S396000, C546S144000, C546S173000, C546S344000, C548S178000, C548S224000, C548S302700, C549S078000, C549S469000

Reexamination Certificate

active

07144893

ABSTRACT:
The present invention pertains to compounds of the formula (1) which are, inter alia, antiproliferative agents, anticancer agents, antimycobacterial agents, antituberculosis agents, and/or thioredoxin/thioredoxin reductase inhibitor: wherein: Q is ═O or ═N—S(═O)2—RQ;RQis —II or optionally substituted C1-7alkyl, C3-20heterocyclyl, or C5-20aryl; Ar is optionally substituted C5-20aryl; ROis an oxy substituent; the bond marked α is a single bond or a double bond; the bond marked β is a single bond or a double bond; R3and R5are each independently ring substituents; R2and R6are each independently ring substituents; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for example, in the treatment of proliferative conditions, (e.g., cancer), mycobacterial infections (e.g., tuberculosis), and/or conditions mediated by thioredoxin/thioredoxin reductase

REFERENCES:
patent: 4357345 (1982-11-01), Moore
patent: 4535165 (1985-08-01), Moore
patent: 5391570 (1995-02-01), Catt et al.
patent: 6153611 (2000-11-01), Mattson et al.
patent: 0 469 984 (1992-02-01), None
patent: 0 546 583 (1993-06-01), None
patent: 0 546 583 (1993-06-01), None
patent: 83/01775 (1983-05-01), None
patent: 01/92239 (2001-12-01), None
patent: WO 01/92239 (2001-12-01), None
patent: WO 03/004479 (2003-01-01), None
DeCosta, Chemical Abstracts 117:191642, 1992, abstract of J of the Chem Soc, Perkin Trans 1: Organic and Bio-org Chem, (1972-1999), vol. 13, pp. 1671-1680, 1992.
Wada, Chemical Abstracts 109:3771, abstract of Chem & Pharm Bull, vol. 35(12), p. 4757-4762, 1987.
Fukushima, Chemical Abstract 72:21599, abstract of Yakugaku Zasshi, vol. 89(9), pp. 1272-1275, 1969.
Noro, Chemical Abstracts 71:81092, abstract of Yakugaku Zasshi, vol. 89(6), pp. 851-856, 1969.
NL 6513784, Chemical Abstracts 65:82177, abstract only, 1966.
Minz, CA 93:222093, abstract of Kemia=Kemi, 7(9), 477-480, 1980.
Ershov, CA 59:3192, abstract of Izvestiya akademii nauk sssr, Seriya Khimicheskaya, pp. 157-161, 1963.
Alcaraz, L., et al., 1998, “Manumycin A: synthesis of the (+)-enantiomer and revision of stereochemical assignment,”J. Org. Chem., vol. 63, pp. 3526-3527.
Alley et al., 1988, “Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay,”Cancer Research, vol. 48, pp. 589-601.
Boyd, M.R., Paull, K.D., 1995, “Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery system,”Drug Dev. Res., vol. 34, pp. 91-104.
Callinan et al., 1990, “Spiro-annulated 2,5-cyclohexadienones via oxidation 2'-alkenyl-p-phenyl phenols with iodobenzene diacetate,”Tetraderon Letters, vol. 31, No. 32, pp. 4551-4552.
Capparelli et al., 1987, “Structural and solvent/electrolyte effects on the selectivity and efficiency of the anodic oxidation of para-substituted aromatic ethers. An efficient route to quinol ether ketals and quinol ethers,”J. Org. Chem., vol. 52, pp. 4953-4961.
Collins, L.; Franzblau, S.G.; 1997, “Microplate Alamar Blue Assay versus BACTEC 460 System for High-throughput Screening of Compounds againstMycobacterium tuberculosisandMycobacterium avium,”Antimicrob. Agents Chemother., vol. 41, pp. 1004-1009.
Dengler et al., 1995, “Development of a propidium iodide fluorescence assay for proliferation and cytotoxicity assays,”Anti-cancer drugs, vol. 6, pp. 522-532.
Faaland et al., 1991, “Rapid uptake to tyrphostin into A431 human epidermoid cells is followed by delayed inhibition of epidermal growth factor (EGF) stimulated EFG receptor tyrosine kinase activity,”Mol. Cell Biol., vol. 11, pp. 2697-2703.
Gasdaska et al., 1994, “The predicted amino acid sequence of human thioredoxin is identical to that of the autocrine growth factor human adult T-cell derived cofactor (ADF): thioredoxin mRNA is elevated in some human tumors,”Biochimica et Biophysica Acta, vol. 1218, pp. 292-296.
Geran et al., 1972, “Protocols for screening chemical agents and natural products against tumor and other biological systems,”Cancer Chemother. Rep., vol. 3, No. 2, pp. 1-103.
Hutchinson et al., 2001, Antitumour benzothiazoles. 14. Synthesis and in vitro biological properties of fluroinated 2-(4-aminophenyl)benzothiazoles,J. Med. Chem., vol. 44, pp. 1446-1455.
Kirkpatrick et al., 1999, “Parallel synthesis of disulfide inhibitors of the thioredoxin redox system as potential antitumor agents,”Anti-Cancer Drug Design, vol. 14, pp. 421-432.
Kunkel et al., 1997, “Cell-line-directed screening assay for inhibitors of thioredoxin reductase signaling as potential anti-cancer drugs,”Anti-Cancer Drug Design, vol. 12, pp. 659-670.
McKillop et al., 1993, “A concise synthesis of the novel antibiotic aranorosin,”Tetrahedron Lett., vol. 34, pp. 5519-5522.
Milić, D. R., et al., “X-Ray crystal structure of 10β-hydroxy-4β, 5β-epoxyestr-1-en-3,17-dione and antitumor activity of its congeners,”Molecules, vol. 4, pp. 338-352.
Oblong et al., 1993, “Purification of human thioreductase; properties and characterization by absorption and circular dichroism spectroscopy,”Biochemistry, vol. 32, pp. 7271-7277.
Pelter, A., Elgendy, S.M.A., 1993, “Phenolic oxidations with phenyliodonium diacetate,”J. Chem. Soc., Perkin Trans. 1, pp. 1891-1896.
Powis, G., Mustacich, D, Coon, A., 2000, “The role of the redox protein thioredoxin in cell growth and cancer,” Free Radical Biology & Medicine, vol. 29, Nos. 3/4, pp. 312-322.
Rambas et al., 1994, “The degree of inhibition of protein tyrosine kinase activity by activity by Tyrphostin 23 and 25 is related to their instability,”Cancer Research, vol. 54, pp. 867-869.
Reddy et al., 1992, “Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor,”Cancer Research, vol. 52, pp. 3631-3641.
Sonnenwirth, A.C., and Jarett, L. (eds.), Gradwohl's Clinical Laboratory Methods and Diagnosis, 8th edition, vol. 2, pp. 1707-1708.
Umezawa et al., 1991, “Use of erbstatin as protein tyrosine kinase inhibitor,”Methods Enzymol., vol. 201, pp. 379-385.
Wada, H., et al., 1987, “Chemical and chemotaxonomical studies of ferns. LXXIII. New flavonoids with modified B-ring from the genus Pseudophegopteris (Thelypteridacae),”Chem. Pharm. Bull., vol. 35, pp. 4757-4762.
Weinstein, J. N., et al., 1997, “An information-intensive approach to the molecular pharmacology of cancer,”Science, vol. 275, pp. 343-349.
Wells et al., Mar. 6, 2000, “Antitumour benzothiazoles. Part 10: The synthesis and antitumour activity of benzothiazole substituted quinol derivatives,”Bioorganic&Medicinal Chemistry Letters, vol. 10, No. 5, pp. 513-515.
Wessely et al., 1952, “Uber die Elnwirkung von metallorganischen Verbingungen auf Chinole I,”Monatsch. Chem., vol. 83, pp. 1253-1261.
Wipf, P., et al., “Synthesis of the antitumor antibiotic LL-C10037α,”J. Org. Chem., vol. 59, pp. 3518-3519.
Takeya et al; “Total Synthesis of (+/−)-Plumbazeylanone, A Naphthoquinone Trimer from Plubago Zeylanica”; Chemical and Pharmaceutical Bulletin, vol. 47, No. 2, 1999, pp. 209-219, XP002215315.
Dodge et al; “Competitive Dienone-Phenol Type Rearrangements for the Regioselective Preparation of 2,4-Disubstituted-NAPHT-1-OLS”; Tetrahedron Letters, Elsevier Science, vol. 29, No. 38, 1988, pp. 4827-4830, XP002201194.
Well et al; Antitumor Benzothiazoles. Part 10: The Synthesis and Antitumor Activity of Benzothiazole Quinol Derivatives; Bioorganic & Medicinal Chemistry Letters, vol. 10, 2000, pp. 513-515, XP002215316.
Hutchinson, et al; “

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

4-aryl quinols and analogs thereof as therapeutic agents does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 4-aryl quinols and analogs thereof as therapeutic agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 4-aryl quinols and analogs thereof as therapeutic agents will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3687279

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.