Synthesis and identification of conformationally constrained selective MMP inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 13, 1999, Pages 1757-1760

  Freskos, John N ^a   McDonald, Joseph J ^a   Mischke, Brent V ^a   Mullins, Patrick B ^a   Shieh, Huey Sheng ^a   Stegeman, Roderick A ^a   Stevens, Anna M ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COLLAGENASE; MATRIX METALLOPROTEINASE INHIBITOR;

ARTICLE; BINDING SITE; CONFORMATIONAL TRANSITION; DRUG CONFORMATION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

COLLAGENASES; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; INHIBITORY CONCENTRATION 50; MATRIX METALLOPROTEINASE 1; MATRIX METALLOPROTEINASE 13; MATRIX METALLOPROTEINASE 8; METALLOENDOPEPTIDASES; MODELS, CHEMICAL; MODELS, MOLECULAR;

EID: 0033526886     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00285-1     Document Type: Article

References (7)

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2. 2. Prata, M. A. Inflamm. Res. 1995, 44, 458.
3. 3. Wojtowicz-Praga, S.; Torri, J.; Johnson, M.; Steen, V.; Marshall, J.; Ness, E.; Dickson, R.; Sale, M.; Rasmussen, H. S.; Chido, T. A.; Hawkins, M. J. J. Clin. Oncol. 1998, 16, 2150.
4. 4. Mitchell, P. G.; Magna, H. A.; Reeves, L. M.; Lopresti-Morrow, L. L.; Yocum, S. A.; Posner, P. J.; Geoghegan, K. F.; Hambor, J. E. J. Clin. Invest. 1996, 3, 761.
5. 5. Freskos, J. N.; Mischke, B. V.; DeCrescenzo, G. A.; Heintz, R. M.; Getman, D. P.; Howard, S. C.; Kishore, N. N.; McDonald, J. J.; Munie, G.E.; Rangwala, S.; Swearingen, C. A.; Voliva, C.; Welsch, D. J. Bioorg. Med. Chem. Lett. 1999, 7, 943
6. 2. This is similar to conditions described by C. G. Knight, FEBS Lett. 1992, 296, 263.
7. 7. A referee suggested that the similar activity for the acyclic vs cyclic can be explained by the ring conformation of bound 8, being thermodynamically unfavorable due to the axial sulfone and that this negates any entropic advantage vs 7. We thank him for this suggestion.