Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases

Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency ( K i) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK pr...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-12, Vol.20 (24), p.7283-7287
Main Authors: Girijavallabhan, Vinay M., Chen, Lei, Dai, Chaoyang, Feltz, Robert J., Firmansjah, Luke, Li, Dansu, Kim, Seong Heon, Kozlowski, Joseph A., Lavey, Brian J., Kosinski, Aneta, Piwinski, John J., Popovici-Muller, Janeta, Rizvi, Razia, Rosner, Kristin E., Shankar, Banderpalle B., Shih, Neng-Yang, Siddiqui, M. Arshad, Tong, Ling, Wong, Michael K.C., Yang, De-yi, Yang, Liping, Yu, Wensheng, Zhou, Guowei, Guo, Zhuyan, Orth, Peter, Madison, Vincent, Bian, Hong, Lundell, Daniel, Niu, Xiaoda, Shah, Himanshu, Sun, Jing, Umland, Shelby
Format: Article
Language:English
Subjects:
Acetylene - analogs & derivatives
Acetylene - pharmacokinetics
Acetylene - therapeutic use
ADAM Proteins - antagonists & inhibitors
ADAM Proteins - metabolism
ADAM17 Protein
Animals
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacokinetics
Anti-Inflammatory Agents - therapeutic use
Arthritis, Rheumatoid - drug therapy
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Dogs
Haplorhini
Humans
Hydantoin
Medical sciences
Pharmacology. Drug treatments
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacokinetics
Protease Inhibitors - therapeutic use
Rats
Rheumatoid arthritis
TACE inhibitor
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Summary:Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency ( K i) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.10.081