Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements
Journal Article
·
· Bioorg. Med. Chem. Lett.
A crystal structure of 1 bound to a Cys25Ser mutant of cathepsin S helped to elucidate the binding mode of a previously disclosed series of pyrazole-based CatS inhibitors and facilitated the design of a new class of arylalkyne analogs. Optimization of the alkyne and tetrahydropyridine portions of the pharmacophore provided potent CatS inhibitors (IC{sub 50} = 40-300 nM), and an X-ray structure of 32 revealed that the arylalkyne moiety binds in the S1 pocket of the enzyme.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1006021
- Journal Information:
- Bioorg. Med. Chem. Lett., Vol. 19, Issue (21) ; 11, 2009; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- ENGLISH
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