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

A series of succinyl hydroxamate MMP inhibitors were prepared incorporating an aryl amino ketone moiety in place of the more typical C-terminal amino acid amides. Compounds of the C-terminal ketone series displayed potent inhibition of MMPs. Several compounds of the series were shown to be orally bi...

Full description

Saved in:

Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 8; no. 22; pp. 3251 - 3256
Main Authors:	Sheppard, George S., Florjancic, Alan S., Giesler, Jamie R., Xu, Lianhong, Guo, Yan, Davidsen, Steven K., Marcotte, Patrick A., Elmore, Ildiko, Albert, Daniel H., Magoc, Terrance J., Bouska, Jennifer J., Goodfellow, Carole L., Morgan, Douglas W., Summers, James B.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 17-11-1998 Elsevier
Subjects:	Analytical, structural and metabolic biochemistry Biological and medical sciences Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Gelatinases - antagonists & inhibitors Hydrolases Hydroxamic Acids - pharmacology Ketones - pharmacology Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Matrix Metalloproteinase 7 Matrix Metalloproteinase Inhibitors Medical sciences Metalloendopeptidases - antagonists & inhibitors Miscellaneous Pharmacology. Drug treatments Protease Inhibitors - pharmacology Structure-Activity Relationship Rat Lactam Monkey Non peptide compound Metalloendopeptidases Structure activity relation Primates Bicyclic compound Cyclophane Chemical synthesis Oxygen nitrogen heterocycle Molecular rigidity Enzyme Aminoamide Rodentia Oral administration Hydroxamic acid Enzyme inhibitor Bioavailability In vitro Peptidases In vivo α-Aminoacid Vertebrata Mammalia Aminoketone Animal Hydrolases Indole derivatives Pharmacokinetics
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	A series of succinyl hydroxamate MMP inhibitors were prepared incorporating an aryl amino ketone moiety in place of the more typical C-terminal amino acid amides. Compounds of the C-terminal ketone series displayed potent inhibition of MMPs. Several compounds of the series were shown to be orally bioavailable. A series of succinyl hydroxamate MMP inhibitors were prepared incorporating an aryl amino ketone moiety in place of the more typical C-terminal amino acid amides. Compounds of the C-terminal ketone series displayed potent inhibition of MMPs. Several compounds of the series were shown to be orally bioavailable.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(98)00597-6