Abstract
Digitalis compounds are used in the treatment of congestive heart failure as positive inotropic agents; their action is mainly due to the inhibition of the Na+,K+-ATPase. A well-known drawback is their arrhythmogenic potential together with a low therapeutic index. Digitalis compounds are characterized by a cis/trans/cis steroidal skeleton with an α, β-unsaturated lactone ( γ-butyrolactone) in the 17 β-position, a 14 β- hydroxy group and a 3 β-hydroxy group, the latter usually linked to one or more sugar rings. The first three moieties are considered essential for inotropic activity, while the glycosides are responsible for the pharmacokinetics of the compounds. This review briefly reports on some of the replacements for the unsaturated γ-butyrolactone moiety and then summarizes the work at Prassis that led to the discovery of the O-aminoalkyloxime group as a very powerful substitute. We also report on the development of new steroidal compounds which act as digitalis-like inhibitors of the Na+,K+-ATPase, without any of the chemical features that are peculiar to naturally occurring digitalis glycosides.
Keywords: digitalis-like compounds, k atpase, unsaturated -butyrolactone, o-aminoalkyloxime, congestive heart failure, inotropic
Current Medicinal Chemistry
Title: Digitalis-like Compounds: the Discovery of the O-aminoalkyloxime Group as a Very Powerful Substitute for the Unsaturated γ-Butyrolactone Moiety
Volume: 12 Issue: 20
Author(s): Mauro Gobbini and Alberto Cerri
Affiliation:
Keywords: digitalis-like compounds, k atpase, unsaturated -butyrolactone, o-aminoalkyloxime, congestive heart failure, inotropic
Abstract: Digitalis compounds are used in the treatment of congestive heart failure as positive inotropic agents; their action is mainly due to the inhibition of the Na+,K+-ATPase. A well-known drawback is their arrhythmogenic potential together with a low therapeutic index. Digitalis compounds are characterized by a cis/trans/cis steroidal skeleton with an α, β-unsaturated lactone ( γ-butyrolactone) in the 17 β-position, a 14 β- hydroxy group and a 3 β-hydroxy group, the latter usually linked to one or more sugar rings. The first three moieties are considered essential for inotropic activity, while the glycosides are responsible for the pharmacokinetics of the compounds. This review briefly reports on some of the replacements for the unsaturated γ-butyrolactone moiety and then summarizes the work at Prassis that led to the discovery of the O-aminoalkyloxime group as a very powerful substitute. We also report on the development of new steroidal compounds which act as digitalis-like inhibitors of the Na+,K+-ATPase, without any of the chemical features that are peculiar to naturally occurring digitalis glycosides.
Export Options
About this article
Cite this article as:
Gobbini Mauro and Cerri Alberto, Digitalis-like Compounds: the Discovery of the O-aminoalkyloxime Group as a Very Powerful Substitute for the Unsaturated γ-Butyrolactone Moiety, Current Medicinal Chemistry 2005; 12 (20) . https://dx.doi.org/10.2174/0929867054864787
DOI https://dx.doi.org/10.2174/0929867054864787 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Medicinal Plants with Multiple Effects on Cardiovascular Diseases: A Systematic Review
Current Pharmaceutical Design In Vivo Roles of CDC25 Phosphatases: Biological Insight into the Anti-Cancer Therapeutic Targets
Anti-Cancer Agents in Medicinal Chemistry Combination Secondary Prevention Therapies in Vascular Diseases
Vascular Disease Prevention (Discontinued) Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy
Current Drug Targets Circulating Biomarkers for the Diagnosis and Prognosis of Heart Failure
Current Medicinal Chemistry Pharmacological Inhibition of Poly(ADP-ribose) Polymerase in Cardiovascular Disorders: Future Directions
Current Vascular Pharmacology Medicolegal Aspects of Disclosure of Side Effects of Biologic Drugs in Rheumatology: A Pilot Study
New Emirates Medical Journal From Nature to Drug Discovery: The Indole Scaffold as a ‘Privileged Structure’
Mini-Reviews in Medicinal Chemistry The Impact of Uncontrolled Hypertension on the Longitudinal Systolic Function of the Left Ventricle
Current Hypertension Reviews Molecular Mechanisms Regulating Matrix Metalloproteinases
Current Topics in Medicinal Chemistry PPAR-γ Agonists in Polycystic Kidney Disease with Frequent Development of Cardiovascular Disorders
Current Molecular Pharmacology Strategies to Avoid TAVI-related Acute Kidney Injury
Current Pharmaceutical Design The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments
Current Neuropharmacology Small Heat Shock Proteins and Protein-Misfolding Diseases
Current Pharmaceutical Biotechnology Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I
Inflammation & Allergy - Drug Targets (Discontinued) Post Cardiovascular Surgery Atrial Fibrillation. Biomarkers Determining Prognosis
Current Medicinal Chemistry Pathophysiology of Arterial Hypertension: Insights from Pediatric Studies
Current Pediatric Reviews Medical Management of the Diabetic Patient with Coronary Artery Disease
Current Pharmaceutical Design Neuroprotective Properties of Erythropoietin in Cerebral Ischemia
Central Nervous System Agents in Medicinal Chemistry Current Therapeutic Approaches for Targeting Inflammation in Depression and Cardiovascular Disease
Current Drug Metabolism