17B-hydroxysteroid dehydrogenase inhibitors

Details 17B-hydroxysteroid dehydrogenase inhibitors 17B-hydroxysteroid dehydrogenase inhibitors

2011-08-23

2011-08-23

Badio, Barbara P. (Department: 1613)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C514S176000

Reexamination Certificate

active

08003783

ABSTRACT:
There is provided a compound of Formula (III)whereinR1is a selected from an alkyloxyalkyl group, a nitrile group, alkylaryl group, alkenylaryl group, alkylheteroaryl group, alkenylheteroaryl group, ═N—O—alkyl or ═N—O—H group, branched alkenyl, alkyl-alcohol group, amide or alkylamide or —CHO so that R1together with R3provide the enol tautomer or R1together with R3form a pyrazole, wherein (a) R4is ═N—O-alkyl or ═N—O—H group, (b) the pyrazole is substituted with one of alkyl-OH group, alkyl ester group, alkyloxyalkyl group, branched alkyl group, and an amide and/or (c) the 2-position is substituted with a group selected from —OH and —O-hydrocarbyl or a heteroaryl ring;R2is selected from —OH and a sulphamate group; andR3is selected from —OH or ═O; wherein the ring system may be further substituted with one or more hydroxyl, alkyl, alkoxy, alkinyl or halo substituents.

REFERENCES:
patent: 3047568 (1962-07-01), Kissman et al.
patent: 3163641 (1964-12-01), Christiansen et al.
patent: 3398140 (1968-08-01), Clinton
patent: 5585405 (1996-12-01), Labrie et al.
patent: 5880115 (1999-03-01), Li et al.
patent: 6046186 (2000-04-01), Tanabe et al.
patent: 1 176 131 (1961-07-01), None
patent: 1033520 (1966-06-01), None
patent: 1096732 (1967-12-01), None
patent: 2331987 (1999-06-01), None
patent: WO 02/16392 (2002-02-01), None
patent: 02/32409 (2002-04-01), None
patent: WO 02/058634 (2002-08-01), None
Martin R. Tremblay, et al “Overview of a Rational Approach to Design Type I 17 β-Hydroxysteroid Dehydrogenase Inhibitors Without Estrogenic Activity: Chemical Synthesis and Biological Evaluation” 66(4) J. Steroid Biochem (1998): 179-191.
Maninder Minu, et al. “Synthesis and Biological Activity of 16-arylidene derivatives of Estrone and Estrone Methyl Ether” 42 (1) Indian Journal of Chemistry Section B (2003): 166-172.
Donald Poirier, et al. “A Multidetachable Sulfamate Linker Successfully Used in a Solid-Phase Strategy to Generate Libraries of Sulfamate and Phenol Derivatives” 12 Bioorganic & Medicinal Chemistry Letters (2002) 2833-2838.
Tremblay et al., “Synthesis of 16-(Bromoalkyl)-Estradiols having Inhibitory Effect on Human Placental Estradiol 17β-Hydroxysteroid Dehydrogenase (17β-HSD Type 1)”, Bioorganic and Medicinal Chemistry, vol. 3, No. 5, pp. 505-523 (1995).
Liviu Constantin Ciobanu et al., “Nonsteroidal compounds designed to mimic potent steroid sulfatase inhibitors”, Journal of Steroid Biochemistry & Molecular Biology, vol. 80, pp. 339-353, (2002).
Adamski, et al., Molecular cloning of a novel widely expressed human 80 kDa 17β-hydroxysteroid dehydrogenase IV, Biochem. J., 1995, vol. 311, p. 437-443.
Agnusdei D., et la. B. Ann. Endocrinol, 1999, vol. 60, No. 3, p. 242-246.
Appel et al., Uber das hydrazidosulpfamid, Chem. Ber., 1958, vol. 91, p. 1339-1341.
Breton, et al., The structure of a complex of human 17 β-hydroxysteroid dehydrogenase with oestradiol and NADP8 identifies two principal targets for the design of inhibitors, Structure (Lond.), 1996, vol. 4, p. 905-915.
Castiglione-Gertsch J. New aromatase inhibitors: more selectivity, less toxicity, unfortunately, the same activity, Eur. J. Cancer, 1996, vol. 32A, p. 393-395.
Claussner A. et al., J. Steroid. Biochem, 1992, vol. 41, p. 609-614.
Coldham et al., A possible mechanism for increased breast cell proliferation by progestins through increased reductive 17 β-hydroxysteroid dehydrogenase activity, Int. J. Cancer, 1990, vol. 45, p. 174-178.
Collins et al., The estrogenic and anti-oestrogenic activities of phytochemicals with the human estrogen receptor expressed in yeast, Steroids, 1997, vol. 62, p. 365-372.
Coulson C.J., Steroid biosynthesis and action, 2ndedition, Molecular Mechanism of Drug Action, 1994, p. 95-122.
Deyashiki, et al., Molecular cloning and characterization of mouse oestradiol 17 β-dehydrogenase (A-specific), a member of the aldoketoreductase family, J. Biol. chem., 1995, vol. 270, p. 10461-10467.
Duncan, et al. Inhibition of oestrone sulphatase activity by estrone-3-methyl-thiophosphonate: a potential therapeutic agent in breast cancer, Cancer Res., 1993, vol. 53, p. 298-303.
Early Breast Cancer Trialists' Collaborative Group. Effects of adjuvant Tamoxifen and of cytotoxic therapy on mortality in early breast cancer, N. Eng. J. Med., 1988, vol. 319, p. 1681-1692.
Geissler et al., Male pseudohermaphroditism caused by mutation of testicular 17 β-hydroxysteroid dehydrogenase 3, Nat. Genet., 1994, vol. 7, p. 34-39.
Ghosh, et al., Structure of the human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20A resolution, Structure, 1995, vol. 3, p. 503-513.
Gorski J., et al., Current models of steroid hormone action; a critique, Ann. Rev. Physiol., 1976, vol. 36, p. 425-450.
Gorski J., et al., Hormones receptors: studies on the interaction of estrogens with uterus, Recent Prog. Horm., Res., 1968, vol. 24, p. 45-80.
Gupta, et al., Synthesis and biological activity of some D-ring modified oestrone derivative, Ind. J. Chem. 1999, vol. 38B, p. 563-571.
Heer, et al., Uber Steroide, Marrianol-und Doisynoisaure, Uber oestrogene carbonsauren II. Heiv. Chim. Acta. 1945, vol. 28, p. 156-165.
Horiuchi, et al., Regioselective 2-Iodination of Estradiol, Estriol & Oestrone, J. Chem. Soc. Chem. Commun., 1982, p. 671-672.
Holli K., et al. Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: results of a randomized study, Br. J. Cancer, 2001, vol. 84, No. 2, p. 164-169.
Horwitz K. B., et al., Nuclear mechanism of estrogen action: effects of oestradiol and anti-estrogens on estrogens receptors and nuclear receptor processing, J. Biol., Chem., 1978, vol. 253, p. 8185-8192.
Horwitz K.B. et al. Oestrogen control of progesterone receptor in human breast cancer; role of oestradiol and antiestrogen, Endocrinology, 1978, vol. 103, p. 1742-1751.
Jin J.-Z. et al., Human estrogenic 17 β-hydroxysteroid dehydrogenase : predominance of oestrone reduction and its induction by NADPH, Biochem, Biophys. Res., 1999, 259, p. 489-493.
Jordan V.C., The Strategic use of antiestrogens to control the development and growth of breast cancer, Cancer, 1992, vol. 70, p. 977-982.
Kaae S., et al., Does simple mastectomy followed by irradiation offer the survival comparable to radical procedures:, International Journal of Radiation Oncology, Biology, Physics, 1977, vol. 2, p. 1163-1166.
Labrie F, At the cutting edge, Intracrinology, Mol. Cell. Endocrinolo., 1991, 78, C113-118.
Lebail et al., Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavinoids, Cancer Lett., 1998, vol. 133, p. 101-106.
Li P.-K. et al., Development of potent non-estrogenic oestrone sulphatase inhibitors, Steroids, 1998, 63, p. 425-432.
Lin et al., 3D structure of human estrogenic 17 β-HSD: binding with various steroids, J. Steroid. Biochem. Mol. Biol., 1999, vol. 69, p. 425-429.
Loev et al., Alkylphenols related to the poison ivy principle, An improved method of synthesis involving the Na-Butanol cleavage of benzyl ethers, J. Am. Chem. Soc., 1956, vol. 78 p. 6095-6101.
Makela, et al., Inhibition of 17 beta-hydroxysteroid oxidoreductase by flavonids in breast and prostate cancer cells, Proc. Soc. Exp, Biol. Med. 1998, vol. 217, p. 310-316.
Malini B., et al., Inhibition of steroid sulphatase activity by tricyclic coumarin sulfamates, J. Steroid Biochem. Molecular Biol., 2000, vol. 75, p. 253-258.
Matkovics, et al., Rearrangement of steroids, VII, Schmidt reaction and Beckmann rearrangement of oestrone and its derivatives, Acta Chim. Acad. Scien. Hung., 1974, vol. 80, p. 79-87.
Miller B.A., et al. (eds), Racial/Ethnic patterns of Cancer in the United States, 1988-1992, National Cancer Institute, 1996.
Miller W.R., Aromatase Inhibitors—where are we now?, Br. J. Cancer, 1996, vol. 73, p. 415-417.
Nicholls P.J., Breast Cancer Management: Science and Care To

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