Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.

Article Details

Citation

Copy to clipboard

Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D, Skotnicki JS

Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19.

PubMed ID

16426848 [ View in PubMed

]

Abstract

A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE	Disintegrin and metalloproteinase domain-containing protein 17	IC 50 (nM)	8	N/A	N/A	Details
4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE	Disintegrin and metalloproteinase domain-containing protein 17	IC 50 (nM)	67	N/A	N/A	Details