Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disorder and demands approaches for prevention and delayed onset. The development of therapeutics for AD is based on the amyloid cascade hypothesis (vaccines, β- and γ-Secretase inhibitors), or targeting tau and neurofibrillary tangle formation, neuroinflammation, etc. Cholinesterase, BACE-1, amyloid-β 1-42, γ and β-Secretase, and Phosphodiesterase type IV (PDE4) inhibitors are the reported treatment options. Among these, the γ- and β-Secretase inhibitors can be clustered in several heterocyclic classes (imidazoles, thiazoles, indoles, benzaldehydes, pyrimidine, etc), with subsequent description of the structure-activity relationships, and extended to the pharmacological profile in order to evaluate their drug-likeness, with special attention to toxicity and bioavailability. This article discusses the approaches proposed by several research groups working on the synthesis of enzyme inhibitors, based on modelling studies and the way these findings were used to obtain new drugs for the treatment of AD.
Keywords: Alzheimer's disease, heterocyclic compounds, secretase inhibitors, SAR studies, molecular modeling.
Graphical Abstract
Central Nervous System Agents in Medicinal Chemistry
Title:Heterocyclic Secretase Inhibitors for the Treatment of Alzheimer’s Disease: An Overview
Volume: 17 Issue: 1
Author(s): Neeraj Masand, Satya P. Gupta, Ratan Lal Khosa and Vaishali M. Patil
Affiliation:
Keywords: Alzheimer's disease, heterocyclic compounds, secretase inhibitors, SAR studies, molecular modeling.
Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder and demands approaches for prevention and delayed onset. The development of therapeutics for AD is based on the amyloid cascade hypothesis (vaccines, β- and γ-Secretase inhibitors), or targeting tau and neurofibrillary tangle formation, neuroinflammation, etc. Cholinesterase, BACE-1, amyloid-β 1-42, γ and β-Secretase, and Phosphodiesterase type IV (PDE4) inhibitors are the reported treatment options. Among these, the γ- and β-Secretase inhibitors can be clustered in several heterocyclic classes (imidazoles, thiazoles, indoles, benzaldehydes, pyrimidine, etc), with subsequent description of the structure-activity relationships, and extended to the pharmacological profile in order to evaluate their drug-likeness, with special attention to toxicity and bioavailability. This article discusses the approaches proposed by several research groups working on the synthesis of enzyme inhibitors, based on modelling studies and the way these findings were used to obtain new drugs for the treatment of AD.
Export Options
About this article
Cite this article as:
Masand Neeraj, Gupta P. Satya, Khosa Lal Ratan and Patil M. Vaishali, Heterocyclic Secretase Inhibitors for the Treatment of Alzheimer’s Disease: An Overview, Central Nervous System Agents in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1570159X13666151029105752
DOI https://dx.doi.org/10.2174/1570159X13666151029105752 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
![](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
Targeting Histone Deacetylases for the Treatment of Immune, Endocrine & Metabolic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Asymmetric Dimethylarginine: A Possible Link between Vascular Disease and Dementia
Current Alzheimer Research Efficacy of Ropinirole-Loaded PLGA Microspheres for the Reversion of Rotenone- Induced Parkinsonism
Current Pharmaceutical Design Peripheral Kynurenine Metabolism in Focal Dystonia
Medicinal Chemistry Novel Indications for Benzodiazepine Antagonist Flumazenil in GABA Mediated Pathological Conditions of the Central Nervous System
Current Pharmaceutical Design Application of the Phage Display Technology for the Development of Peptide- mediated Drug Delivery Systems through the Blood-Brain Barrier
Current Pharmaceutical Biotechnology NMDA Receptors are not Alone: Dynamic Regulation of NMDA Receptor Structure and Function by Neuregulins and Transient Cholesterol-Rich Membrane Domains Leads to Disease-Specific Nuances of Glutamate- Signalling
Current Topics in Medicinal Chemistry Therapeutic Potential of Vasoactive Intestinal Peptide and its Receptors in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review
Current Neuropharmacology A Review of Agents Patented for their Neuroprotective Properties
Recent Patents on CNS Drug Discovery (Discontinued) Selective Modulator of Cannabinoid Receptor Type 2 Reduces Memory Impairment and Infarct Size During Cerebral Hypoperfusion and Vascular Dementia
Current Neurovascular Research Late Onset Alzheimer’s Disease: Novel Clinical Prospects for the Future
Current Neurovascular Research Molecular Pharmacology of the Glycine Receptor Chloride Channel
Current Pharmaceutical Design Neurodegenerative Pathways in Alzheimer’s Disease: A Review
Current Neuropharmacology Conformational Changes and Aggregation of Expanded Polyglutamine Proteins as Therapeutic Targets of the Polyglutamine Diseases: Exposed β-Sheet Hypothesis
Current Pharmaceutical Design Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration
Current Neuropharmacology Potential Application of Dietary Polyphenols from Red Wine to Attaining Healthy Ageing
Current Topics in Medicinal Chemistry Neuroinflammation and its Modulation by Flavonoids
Endocrine, Metabolic & Immune Disorders - Drug Targets The ASK1-MAP Kinase Signaling in ER Stress and Neurodegenerative Diseases
Current Molecular Medicine The Metabotropic Glutamate Receptor System: G-Protein Mediated Pathways that Modulate Neuronal and Vascular Cellular Injury
Current Medicinal Chemistry - Central Nervous System Agents