Abstract
Certain 4,5-diarylisoxazole derivatives have been found to possess broad biological effects, including antiinflammatory and anticancer activities. Recently, we have reported preparation of certain isoflavone derivatives and investigated for their anti-osteoporotic and antiproliferative activities in a detailed SAR study. The present report describes the conversion of isoflavones into novel 4,5-diphenylisoxazole derivatives by the treatment with NH2OH. Alkylation followed by amination of these 4,5-diphenylisoxazoles gave the desired aminoalkoxy substituted 4,5-diphenylisoxazole derivatives. These compounds were evaluated in vitro for the osteogenic differentiation and quantification of mineralization. Although 5-isopropoxy-2-[4-(4-methoxyphenyl)isoxazol-5-yl]phenol (3) exhibited approximately 2.8-fold more activity than the positive Ipriflavone in the promotion of osteoblast activity (277% mineralization), the low cell viability (6%) and high cytotoxicity (68%) prompted us to further pursue more suitable candidates. A series of aminoalkyl side chains were introduced with aims to decrease cytotoxicity. Among them, 5-{4-isopropoxy-2-[4-(pyrrolidin-1-yl)butoxy]phenyl}-4-(4- methoxyphenyl)isoxazole (7a) exhibited approximately 2-fold more activity than the positive Ipriflavone in the promotion of osteoblast activity (194% mineralization) with comparable cell viability (71% v.s. 77%). Compound 7a was non cytotoxic against hADSCs and therefore, was selected as a lead for further structural optimization.
Keywords: 4, 5-Diphenylisoxazole, Cytotoxicity, Anti-osteoporotic Agents.
Medicinal Chemistry
Title:Synthesis of Aminoalkoxy Substituted 4,5-Diphenylisoxazole Derivatives as Potential Anti-osteoporotic Agents
Volume: 9 Issue: 5
Author(s): Yeh-Long Chen, Chih-Hua Tseng, You-Chih Lo, Ru-Wei Lin, Chain-Fu Chen, Gwo-Jaw Wang, Mei-Ling Ho and Cherng-Chyi Tzeng
Affiliation:
Keywords: 4, 5-Diphenylisoxazole, Cytotoxicity, Anti-osteoporotic Agents.
Abstract: Certain 4,5-diarylisoxazole derivatives have been found to possess broad biological effects, including antiinflammatory and anticancer activities. Recently, we have reported preparation of certain isoflavone derivatives and investigated for their anti-osteoporotic and antiproliferative activities in a detailed SAR study. The present report describes the conversion of isoflavones into novel 4,5-diphenylisoxazole derivatives by the treatment with NH2OH. Alkylation followed by amination of these 4,5-diphenylisoxazoles gave the desired aminoalkoxy substituted 4,5-diphenylisoxazole derivatives. These compounds were evaluated in vitro for the osteogenic differentiation and quantification of mineralization. Although 5-isopropoxy-2-[4-(4-methoxyphenyl)isoxazol-5-yl]phenol (3) exhibited approximately 2.8-fold more activity than the positive Ipriflavone in the promotion of osteoblast activity (277% mineralization), the low cell viability (6%) and high cytotoxicity (68%) prompted us to further pursue more suitable candidates. A series of aminoalkyl side chains were introduced with aims to decrease cytotoxicity. Among them, 5-{4-isopropoxy-2-[4-(pyrrolidin-1-yl)butoxy]phenyl}-4-(4- methoxyphenyl)isoxazole (7a) exhibited approximately 2-fold more activity than the positive Ipriflavone in the promotion of osteoblast activity (194% mineralization) with comparable cell viability (71% v.s. 77%). Compound 7a was non cytotoxic against hADSCs and therefore, was selected as a lead for further structural optimization.
Export Options
About this article
Cite this article as:
Chen Yeh-Long, Tseng Chih-Hua, Lo You-Chih, Lin Ru-Wei, Chen Chain-Fu, Wang Gwo-Jaw, Ho Mei-Ling and Tzeng Cherng-Chyi, Synthesis of Aminoalkoxy Substituted 4,5-Diphenylisoxazole Derivatives as Potential Anti-osteoporotic Agents, Medicinal Chemistry 2013; 9 (5) . https://dx.doi.org/10.2174/1573406411309050015
DOI https://dx.doi.org/10.2174/1573406411309050015 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
Related Articles
-
New Targets of Therapy in T-Cell Lymphomas
Current Drug Targets New Biomarkers for Colon Cancer Diagnosis: A Review of Recent Patents
Recent Patents on Biomarkers Potential of DNMT and its Epigenetic Regulation for Lung Cancer Therapy
Current Genomics Intracellular Redox State as Target for Anti-Influenza Therapy: Are Antioxidants Always Effective?
Current Topics in Medicinal Chemistry Stem Cell Genetic Therapy for Fanconi Anemia – A New Hope
Current Gene Therapy Therapeutic Strategies to Correct Proteostasis-Imbalance in Chronic Obstructive Lung Diseases
Current Molecular Medicine Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis
Current Drug Metabolism Toxicogenomics to Improve Comprehension of the Mechanisms Underlying Responses of In Vitro and In Vivo Systems to Nanomaterials: A Review
Current Genomics Detecting Growing Mammary Tumors with Monoclonal Antibodies Against Vascular Endothelial Growth Factor Receptor – 3
Current Radiopharmaceuticals State of the Art of the Therapeutic Perspective of Sorafenib Against Hematological Malignancies
Current Medicinal Chemistry Resveratrol and Its Analogues: Promising Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Role of Transmembrane Domain/Transmembrane Domain Interfaces of PGlycoprotein (ABCB1) in Solute Transport. Convergent Information from Photoaffinity Labeling, Site Directed Mutagenesis and in Silico Importance Prediction
Current Medicinal Chemistry Overview of Ribonucleotide Reductase Inhibitors: An Appealing Target in Anti-Tumour Therapy
Current Medicinal Chemistry Applications of Umbilical Cord Derived Mesenchymal Stem Cells in Autoimmune and Immunological Disorders: From Literature to Clinical Practice
Current Stem Cell Research & Therapy Cancer Chemoprevention by Targeting the Epigenome
Current Drug Targets Monitoring Therapy with Gene Expression Profiling Reveals Physiological Differences in Drug Action
Current Pharmaceutical Design Signaling Mechanism(S) of Reactive Oxygen Species in Epithelial-Mesenchymal Transition Reminiscent of Cancer Stem Cells in Tumor Progression
Current Stem Cell Research & Therapy Adjuvant Zoledronic Acid Reduces Disease Recurrence in Breast Cancer: Antitumor Effects on the Seed and the Soil
Current Cancer Therapy Reviews Immunomodulatory Lactoferrin in the Regulation of Apoptosis Modulatory Proteins in Cancer
Protein & Peptide Letters Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors
Anti-Cancer Agents in Medicinal Chemistry