Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-05-15
2000-08-08
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514460, 549416, 552653, A61K 3135, C07C40100, C07D30904
Patent
active
061002941
ABSTRACT:
Novel cyclic ether vitamin D3 compounds having a cyclic ether side chain are disclosed. These compounds were first identified as metabolites of 3-epi vitamin D3 produced via a tissue-specific metabolic pathway which catalyzes the formation of a cyclic ether structure. Also disclosed are 1.alpha.(OH) 3-epi vitamin D3 compounds, which are produced via the epimerization of a 3-.beta.-hydroxyl group of 1.alpha.(OH) vitamin D3 precursor in vivo. The vitamin D3 compounds of the present invention can be used as substitutes for natural and synthetic vitamin D3 compounds.
REFERENCES:
patent: 4021423 (1977-05-01), Baggiolini et al.
patent: 4038272 (1977-07-01), Partridge, Jr. et al.
patent: 4188345 (1980-02-01), Deluca et al.
patent: 4206131 (1980-06-01), Salmond
patent: 4595776 (1986-06-01), Baggiolini et al.
patent: 4711881 (1987-12-01), Ikekawa
patent: 4804502 (1989-02-01), Baggiolini et al.
patent: 5145846 (1992-09-01), Baggiolini et al.
patent: 5206229 (1993-04-01), Calverley et al.
patent: 5206230 (1993-04-01), Ikekawa et al.
patent: 5389622 (1995-02-01), Posner et al.
patent: 5401733 (1995-03-01), McLane et al.
patent: 5428029 (1995-06-01), Doran et al.
patent: 5547947 (1996-08-01), Dore et al.
patent: 5789607 (1998-08-01), Okabe
patent: 5824811 (1998-10-01), Kubodera et al.
patent: 5830885 (1998-11-01), Posner
Muralidharan, K.R., "Studies on the A-Ring Diastereomers of 1Alfa, 25-Dihydroxyvitamin D.sub.3.sup.1a," Journal of Organic Chemistry, No. 7, 58:1895-1899 Easton, U.S. (1993).
Okamura, W.H. et al., "Studies on vitamin D (Calciferol) and Its Analogues 13," Journal of Organic Chemistry, No. 4, 43:574-580, Easton, U.S. (1978).
Scheddin, D. et al., "Synthesis and Biological Activities of 26-Hydroxy-27-Nor-Derivatives of 1-Alfa, 25-Dihydroxyvitamin D.sub.3," Steroids, No. 10, 61:598-608 (1996).
Muralidharam et al., Studies on the A-Ring Diastereomers of 1.alpha.,25-Dihydroxyvitamin D.sub.3. J. Org. Chem. 58(7) p. 1895-1899, 1993.
Baggiolini, E. et al., "Stereocontrolled Total Synthesis of 1.alpha.25-Dihydroxycholecalciferol and 1.alpha.,25-Dihydroxyergocalciferol," J. Org. Chem., vol. 51, 3098-3108 (1986).
Bishop, J. et al., "Profile of Ligand Specificity of the Vitamin D Binding Protein for 1.alpha.,25-Dihydroxyvitamin D.sub.3 and its Analogs," Journal of Bone and Mineral Research, vol. 9, No. 8, 1277-88 (1994).
Bouillon, R. et al., "Biologic Activity of Dihydroxylated 19-Nor-(Pre) Vitamin D.sub.3," Journal of Bone and Mineral Research, vol. 8, No. 8, 1009-15 (1993).
Bouillon, R. et al., "Structure-Function Relationships in the Vitamin D Endocrine System," Endocrine Reviews, vol. 16, No. 2, 200-57 (1995).
Campbell, M. et al., "Vitamin D.sub.3 Analogs and Their 24-Oxo Metabolites Equally Inhibit Clonal Proliferation of a Variety of Cancer Cells but Have Differing Molecular Effects," Journal of Cellular Biochemistry, vol. 66, 413-25 (1997).
Cross, H. et al., "Vitamin D Metabolism in Human Colon Adenocarcinoma-derived Caco-2 Cells: Expression of 25-Hydroxyvitamin D.sub.3 -1.alpha.-hydroxylase Activity and Regulation of Side-chain Metabolism," J. Steroid Biochem. Molec. Biol., vol. 62, No. 1, 21-8 (1997).
de Vos, S. et al., "Effects of Potent Vitamin D.sub.3 Analogs on Clonal Proliferation of Human Prostate Cancer Cell Lines," The Prostate, vol. 31, No. 2, 77-83 (1997).
Dusso, A.S. et al., "On the Mechanisms for the Selective Action of Vitamin D Analogs," Endocrinology, vol. 128, No. 4, 1687-92 (1991).
Fioravanti, L. et al., "Synthetic Analogs of Vitamin D.sub.3 Have Inhibitory Effects on Breast Cancer Cell Lines," Anticancer Research, vol. 18, 1703-8 (1998).
Fleet, J. et al., "1.alpha.,25-(OH).sub.2 -Vitamin D.sub.3 Analogs with Minimal in Vivo Calcemic Activity Can Stimulate Significant Transepithelial Calcium Transport and mRNA Expression in Vitro," Archives of Biochemistry and Biophysics, vol. 329, No. 2, 228-34 (1996).
Fleet, J.C. et al., "Effect of A-Ring Diastereomers of 1.alpha.,25-Dihydroxy Vitamin D.sub.3 on Calcium Transport in Caco-2 Cells," FASEB J., vol. 9, No. 3, 168 (1995); (Abstract).
Gardner, J. et al., "Vitamin D Analog 25-(OH)-16,23E-Diene-26,27-Hexafluoro-Vitamin D.sub.3 Induces Differentiation of HL60 Cells with Minimal Effects on Cellular Calcium Homeostasis," Journal of Cellular Biochemistry, vol. 63, 500-12 (1996).
Jung, S. et al., "1,25(OH).sub.2 -16ENE-Vitamin D.sub.3 is a Potent Antileukemic Agent with Low Potential to Cause Hypercalcemia," Leukemia Research, vol. 18, No. 6, 453-63 (1994).
Kim, H. et al., "1,25-Dihydroxy-Vitamin-D.sub.3 Enhances Antiproliferative Effect and Transcription of TGF-.beta.1 on Human Keratinocytes in Culture," Journal of Cellular Physiology, vol. 151, 579-87 (1992).
Lemire, J. et al., "1,25-Dihydroxy-24-OXO-16ene-Vitamin D3, a Renal Metabolite of the Vitamin D Analog 1,25-Dihydroxy-16ene-vitamin D3, Exerts Immunosuppressive Activity Equal to its Parent Without Causing Hypercalcemia in vivo," Endocrinology, vol. 135, No. 6, 2818-21 (1994).
Mayer, E. et al., "23,25-Dihydroxy-24-oxovitamin D.sub.3 : A Metabolite of Vitamin D.sub.3 Made in the Kidney," Biochemistry, vol. 22, No. 8, 1798-1805 (1983).
Norman, A. et al., "Demonstration That 1.beta.,25-Dihydroxyvitamin D.sub.3 is an Antagonist of the Nongenomic but not Genomic Biological Responses and Biological Profile of the Three A-ring Diastereomers of 1.alpha.,25-Dihydroxyvitamin D.sub.3," The Journal of Biological Chemistry, vol. 268, No. 27, 20022-30 (1993).
Reddy, G.S. and Tserng, KY, "Calcitroic Acid, End Product of Renal Metabolism of 1,25-Dihydroxyvitamin D.sub.3 Through C-24 Oxidation Pathway," Biochemistry, vol. 28, 1763-9 (1989).
Reddy, G.S. et al., "Metabolism of 1a,25-Dihydroxyvitamin D.sub.3 and One of its A-Ring Diastereomer 1a,25-Dihydroxy-3-Epivitamin D.sub.3 in Neonatal Human Keratinocytes," Vitamin D: A Pluripotent Steroid Hormone: Structural Studies, Molecular Endocrinology and Clinical Applications, Prodeedings of the Ninth Workshop on Vitamin D, Orlando, Fl., 172-3 (May 28-Jun. 2, 1994).
Reddy, G.S. et al., "Stimulation of 24R,25-dihydroxyvitamin D.sub.3 Synthesis by Metabolites of Vitamin D.sub.3," Am. J. Physiol., vol. 245, No. 4, E359-64 (1983).
Reddy, G.S. et al., "Study of 1,25-Dihydroxyvitamin D.sub.3 Induced Alterations in the Metabolism of [.sup.3 H]25-Hydroxyvitamin D.sub.3 Using Isolated Perfused Kidneys From D-Sufficient Rats," Biochemical and Biophysical Research Communications, vol. 107, No. 3, 922-8 (1982).
Reichel, H. and Norman, A., "Systemic Effects of Vitamin D," Ann. Rev. Med., vol. 40, 71-8 (1989).
Schwartz, G. et al., "1,25-Dihydroxy-16-ENE-23-YNE-Vitamin D.sub.3 and Prostate Cancer Cell Proliferation in Vivo," Urology, vol. 46, No. 3, 365-9 (1995).
Siu-Caldera, ML et al., "The Enhanced Biological Activities Ascribed to its Parent Analog, 1.alpha.,25-(OH).sub.2 -16-ene-D.sub.3," J. Steroid Biochem. Molec. Biol., vol. 59, No. 5/6, 405-12 (1996).
Veyron, P. et al., "New 20-Epi-Vitamin D3 Analogs: Immunosuppressive Effects on Skin Allograft Survival," Transplantation Proceedings, vol. 27, No. 1, 450 (1995).
Richter Johann
Solola Taofiq A.
Women and Infants Hospital
LandOfFree
Cyclic ether vitamin D3 compounds, 1.alpha.(OH) 3-epi-vitamin D3 does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cyclic ether vitamin D3 compounds, 1.alpha.(OH) 3-epi-vitamin D3, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cyclic ether vitamin D3 compounds, 1.alpha.(OH) 3-epi-vitamin D3 will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1150630