Hydroxyoxazolidines as alpha-aminoacetaldehye equivalents: novel inhibitors of calpain.
The synthesis of [1-[(5-hydroxy-4-(phenylmethyl)-3-oxazolidinyl)carbonyl]-2-ethylpropy lcarbamic acid phenylmethyl ester (2; MDL 104,903), a potent inhibitor of calpain, is described. Synthesis of related compounds, which offer insights into the mechanism of action for 2, are also described, as is an O-acetyl prodrug derivative of 2.
Peet
N P
NP
Hoechst Marion Roussel, Inc., Bridgewater, NJ 08807, USA.
Kim
H O
HO
Marquart
A L
AL
Angelastro
M R
MR
Nieduzak
T R
TR
White
J N
JN
Friedrich
D
D
Flynn
G A
GA
Webster
M E
ME
Vaz
R J
RJ
Linnik
M D
MD
Koehl
J R
JR
Mehdi
S
S
Bey
P
P
Emary
B
B
Hwang
K K
KK
D002154:Calpain / Q000037:antagonists & inhibitors*; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D002219:Carbamates; C121656:MDL 104903; D010080:Oxazoles; D011480:Protease Inhibitors; D002154:Calpain