Succinyl hydroxamates as potent and selective non-peptidic inhibitors of procollagen C-proteinase: Design, synthesis, and evaluation as topically applied, dermal anti-scarring agents
| Autor: | Jon Bordner, Simon Bailey, Charlotte Reed, Doris Greiling, Paul V. Fish, Rob Webster, Andrew B. McElroy, Stephane Billotte, Kim James, James Edward John Mills |
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| Rok vydání: | 2008 |
| Předmět: |
Cicatrix
Hypertrophic medicine.drug_class Chemistry Pharmaceutical Clinical Biochemistry Molecular Conformation Pharmaceutical Science Carboxamide Matrix metalloproteinase Administration Cutaneous Hydroxamic Acids Biochemistry Bone Morphogenetic Protein 1 Cicatrix Inhibitory Concentration 50 chemistry.chemical_compound In vivo Cell Line Tumor Drug Discovery medicine Humans Oxazoles Molecular Biology Hydroxamic acid integumentary system Organic Chemistry Biological activity Fibrosis In vitro Procollagen peptidase Models Chemical chemistry Drug Design Molecular Medicine Epidermis Wound healing |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 18:6562-6567 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2008.10.036 |
| Popis: | Succinyl hydroxamates 1 and 2 are disclosed as novel series of potent and selective inhibitors of procollagen C-proteinase (PCP) which may have potential as anti-fibrotic agents. Carboxamide 7 demonstrated good PCP inhibition and had excellent selectivity over MMPs involved in wound healing. In addition, 7 was effective in a cell-based model of collagen deposition (fibroplasia model) and was very effective at penetrating human skin in vitro. Compound 7 (UK-383,367) was selected as a candidate for evaluation in clinical studies as a topically applied, dermal anti-scarring agent. |
| Databáze: | OpenAIRE |
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