1. Design and synthesis of orally active inhibitors of TNF synthesis as anti-rheumatoid arthritis drugs
- Author
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Xiaohong Lin, Nolan James Dewdney, Harold E. Van Wart, Jane Huang, Humberto Bartolome Arzeno, Elsie M. Eugui, Keshab Sarma, Jian Jeffrey Chen, Frances Chu, Yong Kim, Robert L. Martin, Anna Mirkovich, and Keith A. M. Walker
- Subjects
medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Arthritis ,Pharmacology ,Matrix metalloproteinase ,Biochemistry ,Chemical synthesis ,Arthritis, Rheumatoid ,Mice ,Structure-Activity Relationship ,Pharmacokinetics ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Molecular Biology ,Chemistry ,Tumor Necrosis Factor-alpha ,Organic Chemistry ,medicine.disease ,Disease Models, Animal ,Cytokine ,Rheumatoid arthritis ,Antirheumatic Agents ,Drug Design ,Molecular Medicine ,Tumor necrosis factor alpha - Abstract
A novel series of TNF inhibitors was identified based on the screening of existing MMP inhibitor libraries. Further SAR optimization led to the discovery of a novel lead compound. Its synthesis, efficacy in experimental animal models, and pharmacokinetic data are discussed.
- Published
- 2003