Abstract
1,3-dioxane carboxylic acid derivatives were prepared based on our previous studies directed towards identifying novel pharmacophore for the development of PPAR α/γ dual agonists. Based on the typical topology of PPAR agonists we focused our design approach on modifying lipophilic tail and prepared a series of compounds by replacing the oxazole moiety of our previously reported compound with optimized lipophilic groups. Compound 8a was found to be a weak PPAR activator but exhibited potent hypolipidemic and anti-hyperglycemic activities in vivo due to superior bioavailability, whereas 8f exhibited potent in vitro and invivo effects. The activity of 8f is further supported by molecular docking study.
Keywords: PPAR agonist, PPAR α/γ dual agonists, Type 2 diabetes, 1,3-dioxane carboxylic acid
Letters in Drug Design & Discovery
Title: Design and Synthesis of Novel 1,3-Dioxane-2-carboxylic Acid Derivatives as PPARα/γ Dual Agonists
Volume: 7 Issue: 6
Author(s): Harikishore Pingali, Mukul Jain, Shailesh Shah, Pankaj Makadia, Pandurang Zaware, Jeevankumar Jamili, Kalapatapu V.V.M. Sairam, Pravin Patil, Dinesh Suthar, Suresh Giri, Harilal Patel and Pankaj Patel
Affiliation:
Keywords: PPAR agonist, PPAR α/γ dual agonists, Type 2 diabetes, 1,3-dioxane carboxylic acid
Abstract: 1,3-dioxane carboxylic acid derivatives were prepared based on our previous studies directed towards identifying novel pharmacophore for the development of PPAR α/γ dual agonists. Based on the typical topology of PPAR agonists we focused our design approach on modifying lipophilic tail and prepared a series of compounds by replacing the oxazole moiety of our previously reported compound with optimized lipophilic groups. Compound 8a was found to be a weak PPAR activator but exhibited potent hypolipidemic and anti-hyperglycemic activities in vivo due to superior bioavailability, whereas 8f exhibited potent in vitro and invivo effects. The activity of 8f is further supported by molecular docking study.
Export Options
About this article
Cite this article as:
Pingali Harikishore, Jain Mukul, Shah Shailesh, Makadia Pankaj, Zaware Pandurang, Jamili Jeevankumar, V.V.M. Sairam Kalapatapu, Patil Pravin, Suthar Dinesh, Giri Suresh, Patel Harilal and Patel Pankaj, Design and Synthesis of Novel 1,3-Dioxane-2-carboxylic Acid Derivatives as PPARα/γ Dual Agonists, Letters in Drug Design & Discovery 2010; 7 (6) . https://dx.doi.org/10.2174/157018010791306533
DOI https://dx.doi.org/10.2174/157018010791306533 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
![](/images/wayfinder.jpg)
- 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
Related Articles
-
Acute Kidney Injury in Pediatric Heart Failure
Current Cardiology Reviews Vitamin D, Sunlight and Cancer Connection
Anti-Cancer Agents in Medicinal Chemistry From fungus to pharmaceuticals – the chemistry of statins
Mini-Reviews in Medicinal Chemistry Gene Therapy in the Transplantation of Allogeneic Organs and Stem Cells
Current Gene Therapy Subject Index To Volume 4
Cardiovascular & Hematological Agents in Medicinal Chemistry Blockade of Ser16-Hsp20 Phosphorylation Attenuates Neuroprotection Dependent Upon Bcl-2 and Bax
Current Neurovascular Research Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets Clinical Analysis of Resemblance and Dissimilarities of Glucagon-like Peptide-1 Receptor Agonists: Therapeutic Approach Towards the Management of Diabetes Mellitus
Current Drug Therapy Evaluation of Echocardiographic Abnormalities in HIV Positive Patients Treated with Antiretroviral Medications
Infectious Disorders - Drug Targets Bivalirudin or Heparin Treatment During Transcatheter Valve Interventions: Where are we Now?
Current Pharmaceutical Design Endothelial (Dys)Function in Lone Atrial Fibrillation
Current Pharmaceutical Design Amiodarone - A ‘Broad Spectrum’ Antiarrhythmic Drug
Cardiovascular & Hematological Disorders-Drug Targets DNA Damage and Epigenetic Changes in Kidney Diseases - Focused on Transcription Factors in Podocytes
Current Hypertension Reviews Patent Selections
Recent Patents on Biomarkers Anticancer Properties of Flavonoids: Roles in Various Stages of Carcinogenesis
Cardiovascular & Hematological Agents in Medicinal Chemistry Immunomodulatory Effects of <i>Allium sativum</i> L. and its Constituents against Viral Infections and Metabolic Diseases
Current Topics in Medicinal Chemistry Dietary Potassium in Cardiovascular Prevention: Nutritional and Clinical Implications
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Overview of Pediatric Epilepsy
Current Pediatric Reviews Structural Chromosome Abnormalities Associated with Obesity: Report of Four New Subjects and Review of Literature
Current Genomics Preface [Hot topic: Anti-Hypertensive Agents in Relation to Modifying Coronary Risk Factors (Executive Editor : Aurelio Leone)]
Current Pharmaceutical Design