Cv Therapeutics, Inc.

Massachusetts Institute of Technology

Lisa Wang

Steven R Schow

Robert T Lum

Michael M Wick

Alison Joly

Suresh Kerwar

Jeff A Zablocki

Venkata Poornapragnacharyulu Palle

K Barry Sharpless

Brent K Blackburn

Chris Richard Melville

Elfaith O Elzein

Tomoyuki Shibata

Hoi-Lun Kwong

Yasuhiro Kawanami

Matthias Beller

Tatsuzo Ukita

Yasukazu Ogino

Alpha-ketoamide inhibitors of 20S proteasome

Orally active A1 adenosine receptor agonists

.alpha.-ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X.sub.2 is Ar or Ar--X.sub.3 wherein X.sub.3 is --C.dbd.O, or --CH.sub.2 CO--, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R.sub.1, and R.sub.2 are each individually selected from the side chains of the known natural .alpha.-amino acids and unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear, branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle substituted heterocycle, heteroaryl and substituted heteroaryl; X.sub.1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and ##STR1## wherein X.sub.4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R.sub.3 is selected from the known natural .alpha.-amino acids, unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear and branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl.

.alpha.-ketoamide inhibitors of 20S proteasome

Osmium-catalyzed methods of addition to an olefin are discussed. In the method of asymmetric dihydroxylation of the present invention, an olefin, a chiral ligand, an organic solvent, water, an oxidant and an osmium-containing compound are combined. In the method of asymmetric oxyamination of the present invention, an olefin, a chiral ligand, an organic solvent, water, a metallochloramine derivative, an osmium-containing compound and, optionally, a tetraalkyl ammonium compound are combined. In the method of asymmetric diamination of the present invention, an olefin, a chiral ligand, an organic solvent, a metallo-chloramine derivative, an amine and an osmium-containing compound are combined. In one embodiment, an olefin, a chiral ligand which is a polymeric dihydroquinidine derivative or a dihydroquinine derivative, acetone, water, a base, an oxidant and osmium tetroxide are combined to effect asymmetric dihydroxylation of the olefin.

Method for catalytic asymmetric dihydroxylation of olefins using

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Burlingame, CA, United States of America

Lisa Wang