Low-calcemic oxime analogs of 1α,25-dihydroxy vitamin D3

Details Low-calcemic oxime analogs of 1α,25-dihydroxy vitamin D3 Low-calcemic oxime analogs of 1α,25-dihydroxy vitamin D3

2006-01-03

2006-01-03

Qazi, Sabiha (Department: 1616)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

9,10-seco- cyclopentanohydrophenanthrene ring system doai

C552S653000

Reexamination Certificate

active

06982258

ABSTRACT:
The present invention provides novel 16-ene-C25-oxime and 16-ene-C-25-oxime ether analogs of 1α,25-dihydroxy vitamin D3, compositions comprising these compounds and methods of using these compounds as inhibitors of CYP24. In particular, the compound of Formula I are useful for treating diseases which benefit from a modulation of the levels of 1α,25-dihydroxy vitamin D3, for example, cell-proliferative disorders.

REFERENCES:
patent: 4481198 (1984-11-01), DeLuca et al.
patent: 98/21580 (1998-05-01), None
Boyan, B. D. et al., “1,25-(OH)2D3Modulates Growth Plate Chondrocytes via Membrane Receptor-Mediated Protein Kinase C by a Mechanism That Involves Changes in Phospholipid Metabolism and the Action of Arachidonic Acid and PGE2”, Steroids, 1999, vol. 64, pp. 129-136.
Crawford, K. R., “Design, Synthesis, and Preliminary Biological Evaluation of Analogs of 1α,25-Dihydroxyvitamin D3: Modifications to the A-Ring and C,D-Ring Side Chain”, Ph.D. Thesis, Johns Hopkins University, 2001, pp. 13-16, 51-55.
Dai, H. et al., “Synthetic Approahces to Vitiman D”, Synthesis, Dec. 1994, pp. 1383-1398.
Greising, D. M. et al., “A-Ring Analogues of 1,25-(OH)2D3With Low Affinity for the Vitamin D Receptor Modulate Chondrocytes via Membrane Effects That Are Dependent on Cell Maturation”, Journal of Cellular Physiology, 1997, vol. 171, pp. 357-367.
Guyton, K. Z. et al., “Cancer Chemoprevention Using Natural Vitamin D and Synthetic Analogs”, Annu. Rev. Pharmacol. Toxicol., 2001, vol. 41, pp. 421-442.
Guyton, K. Z. et al., “Vitamin D and Vitamin D Analogs as Cancer Chemopreventive Agents”, Nutrition Reviews, 2003, vol. 61, No. 7, pp. 1-12.
Haidar, S. et al., Synthesis and Evaluation of Steroidal Hydroxamic Acids as Inhibitors of P450 17(17α-Hydroxylase/C17-20-Lyase), Arch. Pharm. Pharm. Med. Chem. 2001, vol. 334, pp. 138-140.
Hartmann, R. W. et al., “Synthesis and Evaluation of Novel Steroidal Oxime Inhibitors of P450 17(17α-Hydroxylase/C17-20-Lyase) and 5-α-Reductase Types 1 and 2”, J. Med. Chem., 2000, vol. 43, pp. 4266-4277.
Hatcher, M. A. et al., “[3,3]-Sigmatropic Rearrangements: Short, Stereocontrolled Syntheses of Functionalized Vitamin D3Side-chain Units”, Tetrahedron Letters, 2002, vol. 43, pp. 5009-5012.
Hilpert, H. et al., “Novel Versatile Approach to an Enantiopure 19-nor,des-C,D Vitamin D3Derivative”, Tetrahedron, 2001, vol. 57, pp. 681-694.
Hofer, H. et al., “Biological Effects of 1α-Hydroxy- and 1β-(Hydroxymethyl)-Vitamin D Compounds Relevant for Potential Colorectal Cancer Therapy”, The Journal of Pharmacology and Experimental Theraputics, 1999, vol. 291, No. 2, pp. 450-455.
Kensler, T. W. et al., “Conceptually New Deltanoids (Vitamin D Analogs) Inhibit Multistage Skin Tumorigenesis”, Carcinogenesis, 2000, vol. 21, No. 7, pp. 1341-1345, XP-001121614.
Peleg, S. et al., “Vitamin D Analogs as Modulators of Vitamin D Receptor Action”, Current Topics in Medicinal Chemistry, 2003, vol. 3, No. 8, pp. 1-20.
Peleg, S. et al., “A 20-Epi Side Chain Restores Growth-Regulatory and Transcriptional Activities of an A Ring-Modified Hybrid Analog of 1α,25-Dihydroxyvitamin D3Without Increasing Its Affinity to the Vitamin D Receptor”, Journal of Cellular Biochemistry, 1996, vol. 63, pp. 149-161.
Peleg, S. et al., “Differential Use of Transcription Activation Function 2 Domain of the Vitamin D Receptor by 1,25-Dihydroxyvitamin D3and Its A Ring-Modified Analogs”, Molecular Endocrinology, 1998, vol. 12, No. 4, pp. 525-535.
Posner, G. H. et al., “1α,25-Dihydroxyvitamin D3Analogs Featuring Aromatic and Heteroaromatic Rings: Design, Synthesis, and Preliminary Biological Testing”, J. Med. Chem., 1995, vol. 38, pp. 4529-4537.
Posner, G. H. et al., “1α,25-Dihydroxyvitamin D3Hybrid Analogs with Structural Changes at Both the A-Ring and the C,D-Ring Side-chain”, Bioorganic & Medicinal Chemistry Letters, 1994, vol. 4, No. 24, pp. 2919-2924.
Posner, G. H. et al., “1α,25-Dihydroxyvitamin D3Hybrid Analogs with Structural Changes at Both the A-Ring and the C,D-Ring Side-chain. II”, Bioorganic & Medicinal Chemistry Letters, 1995, vol. 5, No. 18, pp. 2163-2168.
Posner, G. H. et al., “2,2-Disubstituted Analogues of the Natural Hormone 1α,25-Dihydroxyvitamin D3: Chemistry and Biology”, Bioorganic & Medicinal Chemistry, 2002, vol. 10, pp. 2353-2365.
Posner, G. H. et al., “2-Fluoroalkyl A-Ring Analogs of 1α,25-Dihydroxyvitamin D3. Stereocontrolled Total Synthesis via Intramolecular and Intermolecular Diels-Alder Cycloadditions. Preliminary Biological Testing”, J. Org. Chem., 1995, vol. 60, No. 14, pp. 4617-4628.
Posner, G. H. et al., “A Non-Calcemic Sulfone Version of the Vitamin D3Analogue Seocalcitol (EB 1089): Chemical Synthesis, Biological Evaluation and Potency Enhancement of the Anticancer Drug Adriamycin”, Bioorganic & Medicinal Chemistry, 2001, vol. 9, pp. 2365-2371.
Posner, G. H., et al., “Antiproliferative Hybrid Analogs of the Hormone 1α,25-Dihydroxyvitamin D3: Design, Synthesis, and Preliminary Biological Evaluation”, J. Org. Chem., 1997, vol. 62, pp. 3299-3314.
Posner, G. H. et al., “Conceptually New Low-Calcemic Oxime Analogues of the Hormone 1α,25-Dihydroxyvitamin D3: Synthesis and Biological Testing”, J. Med. Chem., 2002, vol. 45, pp. 1723-1730.
Posner, G. H. et al., “Conceptually New Low-Calcemic Oxime Analogues of the Hormone 1α,25-Dihydroxyvitamin D3: Synthesis and Biological Testing”, J. Med. Chem., 2002, vol. 45, No. 8, pp. 1723-1730, XP-002229473.
Posner, G. H. et al., “Conceptually New 20-epi-22-Oxa Sulfone Analogues of the Hormone 1α,25-Dihydroxyvitamin D3: Synthesis and Biological Evaluation”, Journal of Medicinal Chemistry, 2000, vol. 43, No. 19, pp. 3581-3586.
Posner, G. H. et al., “Conceptually New Sulfone Analogues of the Hormone 1α,25-Dihydroxyvitamin D3: Synthesis and Biological Evaluation”, Journal of Medicinal Chemistry, 1999, vol. 42, No. 18, pp. 3425-3435.
Posner, G. H., “New Vitamin D Analogues”, Nephrol Dial Transplant, 1996, vol. 11, Suppl. 3, pp. 32-36.
Posner, G. H. et al., “New Vitamin D3Derivatives with Unexpected Antiproliferative Activity: 1-(Hydroxymethyl)-25-hydroxyvitamin D3Homologs”, J. Med. Chem., 1992, vol. 35, No. 17, pp. 3280-3287.
Posner, G. H. et al., “Noncalcemic Antiproliferative, Transcriptionally Active, 24-Fluorinated Hybrid Analogues of the Hormone 1α,25-Dihydroxyvitamin D3. Synthesis and Preliminary Biological Evaluation” Journal of Medicinal Chemistry, 1998, vol. 41, No. 16, pp. 3008-3014.
Posner, G. H. et al., “Stereocontrolled Synthesis of a Trihydroxylated A Ring as an Immediate Precursor to 1α,2α,25-Trihydroxyvitamin D3”, J. Org. Chem., 1991, vol. 56, No. 14, pp. 4339-4341.
Posner, G. H. et al., “Stereocontrolled Total Synthesis of Calcitriol Derivatives; 1-25-Dihydroxy-2-(4′-hydroxybutyl) Vitamin D3Analogs of an Osteoporosis Drug”, J. Org. Chem., 1994, vol. 59, No. 25, pp. 7855-7861.
Posner, G. H. et al., “Vitamin D Endocrine System—Structural, Biological, Genetic and Clinical Aspects”, Proceedings of the Eleventh Workshop on Vitamin D, Nashville, Tennessee, USA, May 27-Jun. 1, 2000, pp. 3-10.
Schuster, I. et al., “Selective Inhibition of Vitamin D Hydroxylases in Human Keratinocytes”, Steroids, 2001, vol. 66, pp. 409-422, XP-002229474.
Wang, Q., “Noncalcemic, Antiproliferative, Transcriptionally Active Hybrid Analogs of the Hormone 1α,25-Dihydroxyvitamin D3: Design, Synthesis, and Preliminary Biological Evaluation”, Ph.D. Thesis, Johns Hopkins University, 2000, pp. 39-57.

Affiliated with

Also associated with

Rating

Low-calcemic oxime analogs of 1α,25-dihydroxy 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 Low-calcemic oxime analogs of 1α,25-dihydroxy vitamin D3, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Low-calcemic oxime analogs of 1α,25-dihydroxy vitamin D3 will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3568063