Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 22, 1998, Pages 3251-3256

  Sheppard, George S ^a   Florjancic, Alan S ^a   Giesler, Jamie R ^a   Xu, Lianhong ^a   Guo, Yan ^a   Davidsen, Steven K ^a   Marcotte, Patrick A ^a   Elmore, Ildiko ^a   Albert, Daniel H ^a   Magoc, Terrance J ^a   Bouska, Jennifer J ^a   Goodfellow, Carole L ^a   Morgan, Douglas W ^a   Summers, James B ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; HYDROXAMIC ACID DERIVATIVE; KETONE; MATRIX METALLOPROTEINASE; MATRIX METALLOPROTEINASE INHIBITOR; PROTEINASE; THROMBOCYTE ACTIVATING FACTOR ANTAGONIST;

ARTHRITIS; ARTICLE; CARBOXY TERMINAL SEQUENCE; DRUG BIOAVAILABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; MONKEY; NONHUMAN; RAT; REACTION ANALYSIS; STRUCTURE ANALYSIS;

EID: 0032541993     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00597-6     Document Type: Article

References (14)

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8. 7. The indole ketone derived from phenylalanine was derivatized with (S)-phenylethylisocyanate and analyzed as 98%ee by HPLC.
9. 8. The activities of MMPs and their inhibition were monitored using a fluorescent substrate as previously described: Olejniczak, E. T.; Hajduk, P. J.; Marcotte, P. A.; Nettesheim, D. G.; Meadows, R. P.; Edalji, R.; Holtzman, T. F.; Fesik, S.W. J. Am. Chem. Soc. 1997, 119, 5828. The sources of the enzymes were as follows: MMP-1 was isolated from the culture medium of human skin fibroblasts induced with PMA; MMP-2 was isolated from the medium of HT-1080 fibrosarcoma cells induced with TNF; MMP-3 was a recombinant truncated form of the human enzyme prepared as described in: Ye, Q.-Z.; Johnson, L. L.; Hupe, D. J.; Baragi, V. Biochemistry 1992, 31, 11231; MMP-7 was aasayed using recombinant human enzyme produced in mouse Sp 2/0 cells.
10. 8. The activities of MMPs and their inhibition were monitored using a fluorescent substrate as previously described: Olejniczak, E. T.; Hajduk, P. J.; Marcotte, P. A.; Nettesheim, D. G.; Meadows, R. P.; Edalji, R.; Holtzman, T. F.; Fesik, S.W. J. Am. Chem. Soc. 1997, 119, 5828. The sources of the enzymes were as follows: MMP-1 was isolated from the culture medium of human skin fibroblasts induced with PMA; MMP-2 was isolated from the medium of HT-1080 fibrosarcoma cells induced with TNF; MMP-3 was a recombinant truncated form of the human enzyme prepared as described in: Ye, Q.-Z.; Johnson, L. L.; Hupe, D. J.; Baragi, V. Biochemistry 1992, 31, 11231; MMP-7 was aasayed using recombinant human enzyme produced in mouse Sp 2/0 cells.
11. 9. Florjancic, A. S.; Sheppard; G. S. manuscript in preparation.
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