Abstract
The structure-activity relationships of 1α,25-dihydroxyvitamin D3 on simultaneous modification at both C2α and CD-ring side chain, including 20-epimerization, double side chain (gemini), and vitamin D receptor (VDR) antagonists TEI-9647 and TEI-9648 lactone rings, and also on simultaneous modifications at both C2 and C10 positions, i.e., C2 modified active 19-norvitamin D3, have been studied in our laboratory to find new seeds of B-seco-steroidal medicine for treating bone diseases, psoriasis, secondary hyperparathyroidism, and certain kinds of cancers. We developed an efficient and systematic route to the 2α-substituted 1α,25-dihydroxyvitamin D3 analogs, i.e., VDR-agonists (20-epi-2-4, double side chain 13a-c, 19-nor 15a-c) and antagonists (36a-c, 37a-c). The A-ring precursors (11a-o) for these analogs were synthesized from D-glucose as a chiral template. In the 19-nor series, we used radical coupling reaction for preparing the A-ring parts from (-)-quinic acid, and the resulting 2-substituted A-ring moiety was coupled with 25-hydroxy Grundmanns ketone utilizing Julia olefination to connect between the C5 and C6 positions. We also synthesized the highly potent VDR-antagonists by introducing the 2α-functional group to the TEI-9647 and TEI-9648 skeletons.
Keywords: palladium coupling, B-seco steroidal, HL-60 Cell Differentiation, Docking, CD-ring lactones
Current Topics in Medicinal Chemistry
Title: Recent Results on A-Ring Modification of 1α,25-Dihydroxyvitamin D3: Design and Synthesis of VDR-Agonists and Antagonists with High Biological Activity
Volume: 6 Issue: 12
Author(s): Nozomi Saito, Shinobu Honzawa and Atsushi Kittaka
Affiliation:
Keywords: palladium coupling, B-seco steroidal, HL-60 Cell Differentiation, Docking, CD-ring lactones
Abstract: The structure-activity relationships of 1α,25-dihydroxyvitamin D3 on simultaneous modification at both C2α and CD-ring side chain, including 20-epimerization, double side chain (gemini), and vitamin D receptor (VDR) antagonists TEI-9647 and TEI-9648 lactone rings, and also on simultaneous modifications at both C2 and C10 positions, i.e., C2 modified active 19-norvitamin D3, have been studied in our laboratory to find new seeds of B-seco-steroidal medicine for treating bone diseases, psoriasis, secondary hyperparathyroidism, and certain kinds of cancers. We developed an efficient and systematic route to the 2α-substituted 1α,25-dihydroxyvitamin D3 analogs, i.e., VDR-agonists (20-epi-2-4, double side chain 13a-c, 19-nor 15a-c) and antagonists (36a-c, 37a-c). The A-ring precursors (11a-o) for these analogs were synthesized from D-glucose as a chiral template. In the 19-nor series, we used radical coupling reaction for preparing the A-ring parts from (-)-quinic acid, and the resulting 2-substituted A-ring moiety was coupled with 25-hydroxy Grundmanns ketone utilizing Julia olefination to connect between the C5 and C6 positions. We also synthesized the highly potent VDR-antagonists by introducing the 2α-functional group to the TEI-9647 and TEI-9648 skeletons.
Export Options
About this article
Cite this article as:
Saito Nozomi, Honzawa Shinobu and Kittaka Atsushi, Recent Results on A-Ring Modification of 1α,25-Dihydroxyvitamin D3: Design and Synthesis of VDR-Agonists and Antagonists with High Biological Activity, Current Topics in Medicinal Chemistry 2006; 6 (12) . https://dx.doi.org/10.2174/156802606777864953
DOI https://dx.doi.org/10.2174/156802606777864953 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Xeno-Cannibalism as an Exacerbation of Self-Cannibalism: A Possible Fruitful Survival Strategy for Cancer Cells
Current Pharmaceutical Design The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition
Combinatorial Chemistry & High Throughput Screening The Indolylcoumarin COUFIN Exhibits Potent Activity Against Renal Carcinoma Cells without Affecting Hematopoietic System
Anti-Cancer Agents in Medicinal Chemistry Anti-inflammatory Phytochemicals for Chemoprevention of Colon Cancer
Current Cancer Drug Targets Cardiac Tumors: Clinical Perspective and Therapeutic Considerations
Current Drug Targets Cancer and Aids: New Trends in Drug Design and Chemotherapy
Current Computer-Aided Drug Design Advances in Transient Receptor Potential Vanilloid-2 Channel Expression and Function in Tumor Growth and Progression
Current Protein & Peptide Science Nano Hydroxyapatite (nano-HAp): A Potential Bioceramic for Biomedical Applications
Current Nanomaterials Approaches for Administering Chemotherapy in the Intensive Care Unit
Current Drug Safety Piper Sarmentosum: A New Hope for the Treatment of Osteoporosis
Current Drug Targets Update on Statins: Hope for Osteoporotic Fracture Healing Treatment
Current Drug Targets Gene Delivery for Periodontal Tissue Engineering: Current Knowledge – Future Possibilities
Current Gene Therapy Methods for Identifying Cardiovascular Agents: A Review
Recent Patents on Cardiovascular Drug Discovery Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery Exploiting Microwave-Assisted Organic Synthesis (MAOS) for Accessing Bioactive Scaffolds
Current Organic Chemistry Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Current Drug Targets Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival in Patients Diagnosed with Hepatocellular Carcinoma (HCC)
Current Cancer Drug Targets Stimuli Responsive Nanoparticles for Controlled Anti-cancer Drug Release
Current Medicinal Chemistry Liposomal Muramyl Tripeptide Phosphatidylethanolamine: Targeting and Activating Macrophages for Adjuvant Treatment of Osteosarcoma
Current Cancer Drug Targets Vitamin D and Physical Performance in Athletes
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)