Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1994-01-24
1996-02-13
Brust, Joseph Paul
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
564324, A61K 31135, C07C21726, C07C21748
Patent
active
054911737
ABSTRACT:
The invention provides novel compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2, which can be the same or different are H or OH, R.sub.3 is ##STR2## wherein R.sub.4 and R.sub.5, which can be the same or different are H or an alkyl group of 1 to 4 carbon atoms, and their non-toxic pharmaceutically acceptable salts and esters and mixtures thereof, which compounds include metabolites of toremifene and exhibit valuable pharmacological properties as oestrogenic, anti-oestrogenic, and progestanic agents.
REFERENCES:
patent: 2914563 (1959-11-01), Allen et al.
patent: 3010965 (1961-11-01), Elpern
patent: 3168565 (1965-02-01), Palopoli et al.
patent: 3288806 (1966-11-01), DeWald
patent: 3634517 (1972-01-01), Palopoli et al.
patent: 4307111 (1981-12-01), Crawley
patent: 4696949 (1987-09-01), Toivola et al.
patent: 4990538 (1991-02-01), Harris et al.
patent: 5192525 (1993-03-01), Yang et al.
patent: 5219548 (1993-06-01), Yang et al.
Anttila et al., "Pharmacokinetics of Toremifene", J. Steroid Biochem 36, 1990, pp. 249-252.
Bergmann et al., "Phenyl-styryl-methyl-natrium", Ber. 66 B;, 1933; pp. 54-58.
Binart et al., "Monohydroxytamoxifen: An Antioestrogen with High Affinity for the Chick Oviduct Oestrogen Receptor", Biochem. Biophys. Res. Commun. 91, No. 3, (1979), pp. 812-818.
Black et al., "Uterine Bioassay of Tamoxifen, Trioxifene and a New Estrogen Antagonist (LY117018) in Rats and Mice", Life Sciences 26, 1980, pp. 1453-1458.
Bonner et al., "The Dehydroxylation of 1,2,2-Triphenylethanol-1-C.sup.14 . . . " J. Amer. Chem. Soc. 81, 1954, pp. 1181-1183.
Borgna et al., "High-Affinity Binding to the Estrogen Receptor . . . ", Mol. Cell. Endocrinol., 20, No. 1, (1980) pp. 71-85.
Cattaneo et al., "Sintesi di Nuovi Composti ad Attivita Estrogena" Farmaco, 15, 1960, pp. 632-641.
Coradini et al., "Effects of Toremifene and its Main Metabolites . . . " Anticancer Res., 11, 1991, pp. 2191-2197.
Curtin et al., "Stereoisomeric Vinyllithium Compounds. III. Reactions . . . " J. Amer. Chem. Soc., 77, 1955, pp. 4566-4570.
Dix et al., "Modulation of Rat Uterine Steroid Hormone Receptors by . . . " Endocrinology, 1980, pp. 2011-2020.
Dornow et al., "Umsetzungen des Komplexes aus Zimtaldehyd und . . . ", Berg. Jahrg., 87, 5, 1954, pp. 629-633.
Fromson et al., "The Metabolism of Tamoxifen* (I.C.I. 46, 47-4) Part I:" Xenobiotica, (1973), 3, No. 11, pp. 693-709.
Hasan et al., "Quantitative Analysis of Toremifene Metabolites . . . " Anal. Lett., 23, 1990, pp. 327-334.
Hassner et al., "Phenyl Migration in Psuedohalogen Additions . . . " J. Org. Chem. 35, (10), 1970; pp. 3397-3401.
Hassner et al., "Ionic vs. Free-Radical Additions with Opportunity . . . " J. Org. Chem., 36, (15), 1971; pp. 2176-2180.
Hauptmann et al., "Die Einwirkung von Thionylchlorid auf Pinakole" J. Prakt. Chem, 19, 1963; pp. 175-179.
Holleran et al., "Quantitation of Toremifene and its Major Metabolites . . . " Anal. Lett., 20, 1987, pp. 871-879.
Jordan et al., "Effect of Oestradiol Benzoate Tamoxifen and . . . " J. Steroid Biochem., 1979, pp. 285-291.
Kangas, L., "Biochemical and Pharmacological effects of toremifene . . . " Cancer Chemother. Pharmacol., 27, 1990, pp. 8-12.
Koelsch, C. F., "Triphenylvinylmagnesium Bromide" J.A.C.S., 54, 1932; pp. 2045-2048.
Kole et al., CA 88 152153g (1978).
Markaverich et al., "Progesterone and Dexamethasone Antagonism of Uterine . . . " J. Steroid Biochem, 14, 1980, pp. 125-132.
Mihailovic et al., "Vicinal Phenyl Group Shift in the Lead Tetraacetate . . . " Tetrahedron 1978, 34, (16), pp. 2587-2589.
Namer et al., "Increase of Progesterone Receptor by Tamoxifen . . . " Cancer Res., 40, 1980, pp. 1750-1752.
Norman et al., "Carbonium-ion Rearrangements in the Readdition of Bromine . . . " J. Che. Soc. B., 1967, (6), pp. 598-604.
Norman et al., "Reaction of Lead Tetra-acetate. Part X. Mechanism . . . " J. Chem. Soc. B., 1967, (6), pp. 604-611.
Pollard et al., "The Oestrogenic and Anti-Oestrogenic Activity of . . . " Steroids, 11, 1968, pp. 897-907.
Polman et a., "Photoaddition of Aromatic Ketones to Some Arylacetylenes . . . " Recl. Trav. Chim. Pays., Bas, 92, 1973; pp. 845-854.
Robinson et al., "Antitumor Actions of Toremifence in the 7,12-Dimethylbenzanthracene . . . " Eur. J. Cancer Clin. Oncol., 24, 1988, pp. 1817-1821.
Simamura et al. "Some Observations on the Reactions of a,d-Dimethylstilbene . . . " Bull. Chem. Soc., Japan, 27, 1954; pp. 231-235.
Simberg et al., "In Vitro and In Vivo Binding of Toremifene and . . . " J. Steroid Biochem., 36, 1990, pp. 197-202.
Sipila et al., "Metabolism of Toremifene in the Rat" J. Steroid Biochem., 36, 1990, pp. 211-215.
Sutherland et al., "Mechanisms of Oestrogen Antagonsi by Nonsteroidal . . . " Moecular+Cell. Endoc., 25, (1982), pp. 5-23.
Valavaara et al., "Toremifene, a New Antiestrogenic Compound for Treatment . . . " J. Cancer Clin. Oncol., 24, (1988), pp. 785-790.
Van den Koedijk et al. "Comparative Affinity of Steroidal and Nonsteroidal . . . " Biochem. Pharmacol., 43, 1992, pp. 2511-2518.
Vaulx et al., "Metalations of Certain .beta.-Phenylethyl- and .gamma.-Phenylpropyl . . . " J. Org. Chem., 30, (1), 1965, pp. 58-60.
Webster et al., "High-performance liquid chromatographic method for the . . . " J. Chromatogr. 565 1991, pp. 482-487.
Wiebe et al., "Toremifene and its metabolites enhance doxorubicin . . . " Invest. New Drugs, 10, 1992, pp. 63-71.
Wurz et al., "Targeting chemosensitizing doses of toremifene based on . . . " Cancer Chemother. Pharmacol., 31, pp. 412-414. (1986).
Xu et al., Acta Pharmaceutica Sinica, 15 (11), 1980, pp. 648-655.
Morrison & Boyd, "Organic Chemistry", 3rd Ed. 210 Allen & Bacon Inc., p. 210. (1980).
Roberts & Casero, "Basic Principles of Organic Chemistry", pp. 320-322, (1980) W. A. Benjamin Inc.
"Tamoxifen"; cited in the Merck Index, pp. 1171 and 1772 9th Edition, (1980).
Toremifene--A New Antitumor Antioestrogen--Farmos Report vol. 2, Ser. A. No. 3 1986 of Round Table Conference and Poster Discussion, Budapest Aug. 25, 1986, Farmos Groups Ltd., Finland.
Blanco Guillermo L.
Kalapudas Arja
Kangas Lauri V. M.
Karjalainen Arto J.
Kurkela Kauko O. A.
Brust Joseph Paul
Kubovcik Ronald J.
Orion-yhtyma Oy
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