Structure-activity relationships within a series of caspase inhibitors. Part 2: Heterocyclic warheads.
Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A study of their structure-activity relationship (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a cellular model of cell death is also discussed. Potent broad-spectrum caspase inhibitors have been identified.
Ullman
Brett R
BR
Idun Pharmaceuticals Inc., 9380 Judicial Drive, San Diego, CA 92121, USA. bullman@idun.com
Aja
Teresa
T
Chen
Ning
N
Diaz
Jose-Luis
JL
Gu
Xin
X
Herrmann
Julia
J
Kalish
Vincent J
VJ
Karanewsky
Donald S
DS
Kodandapani
Lalitha
L
Krebs
Joseph J
JJ
Linton
Steven D
SD
Meduna
Steven P
SP
Nalley
Kip
K
Robinson
Edward D
ED
Roggo
Silvio P
SP
Sayers
Robert O
RO
Schmitz
Albert
A
Ternansky
Robert J
RJ
Tomaselli
Kevin J
KJ
Wu
Joe C
JC
D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009284:Naphthols / Q000737:chemistry; D013329:Structure-Activity Relationship; D014633:Valine / Q000737:chemistry
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D006571:Heterocyclic Compounds; D007659:Ketones; D009284:Naphthols; C005366:naphthyl acetate; D001224:Aspartic Acid; D014633:Valine