Cv Therapeutics, Inc.

Telik, Inc.

Other

Michael M Wick

Steven R Schow

Robert T Lum

Alison Joly

Richard L Mackman

Suresh Kerwar

Cheri Lynn Blum

Marek G Nelson

Lisa Wang

Jeff A Zablocki

Prabha N Ibrahim

Jurg R Pfister

Songyuan Shi

George Frederic Schreiner

Jeffery A Zablocki

Louise Robinson

Reyna J Simon

Kevin T Weber

Brian T Peterson

Wenli Ma

Gail L Brown

James G Keck

David R Allen

Prabbha Ibrahim

A method of sensitizing a mammal, especially a human, to another anticancer therapy by administering a sensitizing effective amount of a GST-activated anticancer compound. A method of ameliorating a side effect of another anticancer therapy in a mammal, especially a human, by administering an ameliorating effective amount of a GST-activated anticancer compound. Pharmaceutical compositions for the methods. The GST-activated anticancer compound is preferably a compound of U.S. Pat. No. 5,556,942, and more preferably canfosfamide, especially as the hydrochloride salt.

Sensitization to another anticancer therapy and/or amelioration of a side effect of another anticancer therapy by treatment with a GST-activated anticancer compound

Sulfonylethyl and thioethyl phosphorodiamidates, their preparation and intermediates in their preparation, formulations containing them, and their pharmaceutical use. The compounds are useful for treating cancer, alone and in combination with other anticancer therapies.

Sulfonylethyl phosphorodiamidates

Compounds of the following formula are provided: In the Formula (I), Ris &#x2014;X&#x2014;R'; in which R&#x2032; is optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, and X is &#x2014;NH&#x2014;. Ris lower alkyl optionally substituted with one, two or three groups chosen from hydroxy, lower alkoxy, and halogen. And Ris &#x2014;NRR; in which Ris hydrogen and Ris lower alkyl substituted with amino; or (ii) Rand Rare both lower alkyl optionally substituted with one, two or three groups chosen from hydroxy and amino. It is to be understood that R&#x2032; is not cyclohexylmethyl, phenyl, substituted phenyl, benzyl, phenylethyl, or m-hydroxybenzyl. The compounds inhibit CDK-2 activity and are useful for treating disorders characterized by undesirable cell proliferation.

Purine inhibitors of cyclin dependent kinase 2 and I&#x3ba;B-&#x3b1;

Purine inhibitors of cyclin dependent kinase 2 & ikappabalpha

Purine inhibitors of cyclin dependent kinase 2 & IKBA

Alpha-ketoamide inhibitors of 20S proteasome

This invention is novel indanone compositions useful for inhibiting cell proliferation disorders in mammals.

Inhibition of 26S and 20S proteasome by indanones

.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

A 2,6,9-trisubstituted purine composition having the following formula: ##STR1## where X is a amino, oxo, thio, of sulfone moiety, R.sub.1 is a lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, heterocycle, hetaryl, substituted hetaryl, aralkyl, heteroaralkyl, heteroalkyl, alkyl alkenyl, alkyl alkynyl, alkyl cycloalkyl, or alkyl cycloheteroalkyl, each having from 1 to 20 carbon atoms; R.sub.2 is hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycle, hetaryl, substituted hetaryl, aralkyl, heteroaralkyl, heteroalkyl, alkyl alkenyl, alkyl alkynyl, alkyl cycloalkyl, or alkyl cycloheteroalkyl; and R.sub.3 is halogen, hydroxyl, thio, alkoxy, alkylthio, lower alkyl, --NR.sub.4 R.sub.5 or a component having the formula: ##STR2## wherein when R.sub.3 is 2-hydroxyethylamino and R.sub.2 is methyl, R.sub.1 -X is not amino, 3-methyl-2-butenylamino, benzylamino, or m-hydroxybenzyl-amino, when R.sub.3 is 2-hydroxyethylamino and R.sub.2 is isopropyl, R.sub.1 -X is not benzylamino, m-hydroxybenzylamino, or 3-methylbutylamino, when R.sub.3 is 2-hydroxyethylamino and R.sub.2 is 2-hydroxyethyl, R.sub.1 -X is not benzylamino and when R.sub.3 is selected from the group consisting of 2-propanol-2-methylamino and 2-dimethylaminoethylamino and R.sub.2 is methyl, then R.sub.1 -X is not benzylamino.

Purine inhibitors of cyclin dependent kinase 2

This invention is a method for inhibiting cell proliferation using indanones.

A substituted N.sup.6 -oxa, thia, thioxa and azacycloalkyl substituted adenosine derivative and a method for using the composition as an A.sub.1 heart adenosine receptor.

N.sup.6 mono heterocyclic substituted adenosine derivatives

Growing community of inventors

Chestnut Hill, MA, United States of America

Michael M Wick