Abstract
The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH2. Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N’-2- or N’-(4-chlorophenyl)piperazine moiety (IC50 values range from 0.55 to 8.5 nM), with N’-(2-pyrimidyl)piperizine (IC50 values range from 0.5 to 21.6 nM), with NN’- L-piperazinocolinamide (IC50 values range from 0.001 – 0.25 nM), or N-N’-L-piperazinocolin-N-methylamide (IC50 values range from 0.015 – 7.3 nM) .
Keywords: Aspartyl protease, Cathepsin D, Inhibitors, Hydroxyethylamine, Piperazine, Pipecolinate, Piperazinocolinate
Medicinal Chemistry
Title:New Cathepsin D Inhibitor Library Utilizing Hydroxyethyl Isosteres with Cyclic Tertiary Amines
Volume: 8 Issue: 6
Author(s): Rose M. McConnell, Kalyani Inapudi, Naveen Kadasala, Karthika Yarlagadda, Priya Velusamy, Matthew S. McConnell, Adam Green, Carol Trana, Kelley Sayyar and James S. McConnell
Affiliation:
Keywords: Aspartyl protease, Cathepsin D, Inhibitors, Hydroxyethylamine, Piperazine, Pipecolinate, Piperazinocolinate
Abstract: The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH2. Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N’-2- or N’-(4-chlorophenyl)piperazine moiety (IC50 values range from 0.55 to 8.5 nM), with N’-(2-pyrimidyl)piperizine (IC50 values range from 0.5 to 21.6 nM), with NN’- L-piperazinocolinamide (IC50 values range from 0.001 – 0.25 nM), or N-N’-L-piperazinocolin-N-methylamide (IC50 values range from 0.015 – 7.3 nM) .
Export Options
About this article
Cite this article as:
M. McConnell Rose, Inapudi Kalyani, Kadasala Naveen, Yarlagadda Karthika, Velusamy Priya, S. McConnell Matthew, Green Adam, Trana Carol, Sayyar Kelley and S. McConnell James, New Cathepsin D Inhibitor Library Utilizing Hydroxyethyl Isosteres with Cyclic Tertiary Amines, Medicinal Chemistry 2012; 8 (6) . https://dx.doi.org/10.2174/1573406411208061146
DOI https://dx.doi.org/10.2174/1573406411208061146 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
Related Articles
-
Inhibitors of Nitrogen Oxide Species Production in Animal Models of Inflammation and Future Directions for Therapy in Inflammatory Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Neuroprotective Effects of Citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer's and Parkinson's Disease
CNS & Neurological Disorders - Drug Targets A Novel Marine Drug, SZ–685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR–200c
Current Medicinal Chemistry Safety and Complications Reporting Update on the Re-Implantation of Culture-Expanded Mesenchymal Stem Cells Using Autologous Platelet Lysate Technique
Current Stem Cell Research & Therapy CircRNA 001418 Promoted Cell Growth and Metastasis of Bladder Carcinoma via EphA2 by miR-1297
Current Molecular Pharmacology Non-histone Methylation of SET7/9 and its Biological Functions
Recent Patents on Anti-Cancer Drug Discovery Natural Small Molecules as Stabilizers and Activators of Cancer-Associated NQO1 Polymorphisms
Current Drug Targets Analysis of Carcinogenic Polycyclic Aromatic Hydrocarbons (PAHS): An Overview of Modern Electroanalytical Techniques and their Applications
Current Drug Delivery Challenges in the Correct Assessment of a Case of Aggressive Thyroid Carcinoma with Synchronous Breast Cancer: A Case Report and Review of the Literature of Essential Role of Radiopharmaceuticals
Current Radiopharmaceuticals Statins and Type 2 Diabetes Mellitus: An Update After 1 Year
Current Pharmaceutical Design Current Evaluation of the Millennium Phytomedicine- Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine
Current Medicinal Chemistry Endothelin Receptors in Gastrointestinal Smooth Muscle
Current Protein & Peptide Science Gold and Silver Nanoparticles for Applications in Theranostics
Current Topics in Medicinal Chemistry Mucoadhesive Formulation Designs for Oral Controlled Drug Release at the Colon
Current Pharmaceutical Design Flavonoid-Based Cancer Therapy: An Updated Review
Anti-Cancer Agents in Medicinal Chemistry Liquid-Crystalline Nanodispersions Containing Monoolein for Photodynamic Therapy of Skin Diseases: A Mini-Review
Current Nanoscience Chemoresistance in Non-Small Cell Lung Cancer
Current Medicinal Chemistry - Anti-Cancer Agents Polymeric Carriers for Gene Delivery: Chitosan and Poly(amidoamine) Dendrimers
Current Pharmaceutical Design Liposomes: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design Molecular Targets of Gemcitabine Action: Rationale for Development of Novel Drugs and Drug Combinations
Current Pharmaceutical Design