Dipeptidyl nitrile inhibitors of Cathepsin L.
A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.
Asaad
Nabil
N
Respiratory & Inflammation Research Area, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
Bethel
Paul A
PA
Coulson
Michelle D
MD
Dawson
Jack E
JE
Ford
Susannah J
SJ
Gerhardt
Stefan
S
Grist
Matthew
M
Hamlin
Gordon A
GA
James
Michael J
MJ
Jones
Emma V
EV
Karoutchi
Galith I
GI
Kenny
Peter W
PW
Morley
Andrew D
AD
Oldham
Keith
K
Rankine
Neil
N
Ryan
David
D
Wells
Stuart L
SL
Wood
Linda
L
Augustin
Martin
M
Krapp
Stephan
S
Simader
Hannes
H
Steinbacher
Stefan
S
D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology; D002384:Catalysis; D056668:Cathepsin L / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D006801:Humans; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D008024:Ligands; D009570:Nitriles; D010455:Peptides; D011506:Proteins; D056668:Cathepsin L