Azabicyclo-octane inhibitors of iap

A - Human Necessities – 61 – K

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A61K 31/403 (2006.01) C07D 203/02 (2006.01) C07D 409/12 (2006.01)

Patent

CA 2558615

The invention provides novel inhibitors of IAP that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula (I) in which X1 and X2 are independently O or S; L is a bond or -C(X3)-, -C(X3)NR12, -C(X3)O- wherein X3 is O or S and R12 is H or R1; R1 is alkyl, a carbocycle, carbocycle-substituted alkyl, a heterocycle or heterocycle-substituted alkyl, wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, haloalkyl, alkoxy, alkylsulfonyl, amino, nitro, aryl and heteroaryl; R2 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, a heterocycle or heterocyclylalkyl; R3 is H or alkyl; R4 and R4' are independently H, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroaralkyl wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, alkoxy, amino and nitro; R5, and R5' are each independently H or alkyl; R6 is H or alkyl; and salts and solvates thereof.

L'invention concerne des inhibiteurs de l'IAP, utiles comme agents thérapeutiques pour le traitement de malignités. Les composés considérés, y compris leurs sels et solvats, sont représentés par la formule I : X¿1? et X¿2? sont indépendamment O ou S; L est une liaison ou -C(X¿3?)-, -C(X¿3?)NR¿12?, -C(X¿3?)O- et X¿3? est O ou S et R¿12? est H ou R¿1?; R¿1? est alkyle, carbocycle, alkyle à substitution carbocycle, hétérocycle ou alkyle à substitution hétérocycle, chacun éventuellement substitué par halogène, hydroxyle, mercapto, carboxyle, alkyle, haloalkyle, alcoxy, alkylsulfonyle, amino, nitro, aryle et hétéroaryle; R¿2? est alkyle, cycloalkyle, cycloalkylalkyle, aryle, aralkyle, hétérocycle ou hétérocyclylalkyle; R¿3? est H ou alkyle; R¿4? et R¿4'? sont indépendamment H, alkyle, aryle, aralkyle, cycloalkyle, cycloalkylalkyle, hétéroaryle, ou hétéroaralkyle, chacun éventuellement substitué par halogène, hydroxyle, mercapto, carboxyle, alkyle, alcoxy, amino et nitro; R¿5?, et R¿5'? sont chacun indépendamment H ou alkyle; R¿6? est H ou alkyle.

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