A series of thiazole derivatives bearing thiazolidin-4-one as non-competitive ADAMTS-5 (aggrecanase-2) inhibitors

Masakazu Atobe; Naomi Maekawara; Noriko Ishiguro; Shinya Sogame; Yoshihito Suenaga; Masashi Kawanishi; Hiroko Suzuki; Norimasa Jinno; Eiichi Tanaka; Shiro Miyoshi

doi:10.1016/j.bmcl.2013.01.121

A series of thiazole derivatives bearing thiazolidin-4-one as non-competitive ADAMTS-5 (aggrecanase-2) inhibitors

Bioorg Med Chem Lett. 2013 Apr 1;23(7):2106-10. doi: 10.1016/j.bmcl.2013.01.121. Epub 2013 Feb 9.

Authors

Masakazu Atobe¹, Naomi Maekawara, Noriko Ishiguro, Shinya Sogame, Yoshihito Suenaga, Masashi Kawanishi, Hiroko Suzuki, Norimasa Jinno, Eiichi Tanaka, Shiro Miyoshi

Affiliation

¹ Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. [email protected]

PMID: 23453070
DOI: 10.1016/j.bmcl.2013.01.121

Abstract

A series of thiazole bearing thiazolidin-4-one was discovered via high-throughput screening as non-competitive inhibitors of ADAMTS-5. Compound 31 appeared to give the best ADAMTS-5 inhibition and good selectivity over other metalloproteases.

MeSH terms

ADAM Proteins / antagonists & inhibitors*
ADAM Proteins / metabolism
ADAMTS5 Protein
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Molecular Structure
Structure-Activity Relationship
Thiazoles / chemical synthesis
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Enzyme Inhibitors
Thiazoles
ADAM Proteins
ADAMTS5 Protein
ADAMTS5 protein, human