US 5,962,504 AGranted

Substituted 2-pyrrolidinone activators of PKC

AssigneeGeorgetown University

InventorsAlan P. Kozikowski, Shaomeng Wang, Lixin Qiao

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Abstract

Compounds of formula I: ##STR1## wherein R.sub.1 and R.sub.2 have any of the values defined in the specification, and their pharmaceutically acceptable salts, are PKC activators and are useful for treating diseases, such as, for example, cancer. Also disclosed are pharmaceutical compositions comprising compounds of formula I, processes for preparing compounds of formula I, and intermediates useful for preparing compounds of formula I.

Claims16

Dependent claims

A compound of formula I:

##STR22## wherein R.sup.1 and R.sup.2 are each independently (C.sub.1 -C.sub.15)alkyl, (C.sub.2 -C.sub.15)alkenyl, (C.sub.2 -C.sub.15)alkynyl, (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.10)alkyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.15)alkenyl, C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.15)alkynyl, (C.sub.1 -C.sub.15)alkoxy, (C.sub.1 -C.sub.15)alkanoyl, (C.sub.1 -C.sub.15)alkanoyloxy, aryl heteroaryl, aryl(C.sub.1 -C.sub.6)alkyl, heteroaryl(C.sub.1 -C.sub.6)alkyl, aryl(C.sub.2 -C.sub.15)alkenyl, heteroaryl(C.sub.2 -C.sub.15)alkenyl, aryl(C.sub.2 -C.sub.15)alkynyl, heteroaryl(C.sub.2 -C.sub.15)alkynyl, aryl(C.sub.1 -c.sub.15)alkoxy, heteroaryl(C.sub.1 -C.sub.15)alkoxy, aryl(C.sub.1 -C.sub.15)alkanoyl, heteroaryl(C.sub.1 -C.sub.15)alkanoyl, aryl(C.sub.1 -C.sub.15)alkanoyloxy, or heteroaryl(C.sub.1 -C.sub.15)alkanoyloxy;
wherein R.sup.1 and R.sup.2 is optionally substituted with one ore more substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.15)alkyl, )C.sub.2 -C.sub.15)alkenyl, (C.sub.2 -C.sub.15)alkynyl (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.15)alkyl, (C.sub.3 -C.sub.8)cycloalkyl-(C.sub.2 -C.sub.15)alkenyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.2 -C.sub.15)alkynyl, (C.sub.1 -C.sub.15)alkoxy, (C.sub.1 -C.sub.15)alkanoyl, (C.sub.1 -C.sub.15)alkanoyloxy, C(.dbd.O)OR.sub.a, C(.dbd.O)NR.sub.b R.sub.c, OC(.dbd.O)OR.sub.a, OC(.dbd.O)NR.sub.b R.sub.c, and NR.sub.e R.sub.f ;
and wherein any aryl or heteroaryl or R.sup.1 or R.sup.2 is optionally substituted on a non-aromatic carbon by a divalent (C.sub.2 -C.sub.7)alkylene chain to form a (C.sub.3 -C.sub.8)spirocycloalkyl;
each R.sub.a is independently hydrogen or (C.sub.1 -C.sub.6)alkyl;
each R.sub.b and R.sub.c is independently, hydrogen or (C.sub.1 -C.sub.10)alkyl;
or R.sub.b, and R.sub.c together with the nitrogen to which they are attached are a 5-6 membered heterocyclic ring;
and
each R.sub.e and R.sub.f is independently hydrogen, (C.sub.1 -C.sub.10)alkyl, (C.sub.1 -C.sub.10)alkanoyl, phenyl, benzyl, or phenethyl;
or R.sub.e and R.sub.f together with the nitrogen to which they are attached are a 5-6 membered heterocyclic ring;
or a pharmaceutically acceptable salt thereof.

7 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of formula I:

##STR22## wherein R.sup.1 and R.sup.2 are each independently (C.sub.1 -C.sub.15)alkyl, (C.sub.2 -C.sub.15)alkenyl, (C.sub.2 -C.sub.15)alkynyl, (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.10)alkyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.15)alkenyl, C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.15)alkynyl, (C.sub.1 -C.sub.15)alkoxy, (C.sub.1 -C.sub.15)alkanoyl, (C.sub.1 -C.sub.15)alkanoyloxy, aryl heteroaryl, aryl(C.sub.1 -C.sub.6)alkyl, heteroaryl(C.sub.1 -C.sub.6)alkyl, aryl(C.sub.2 -C.sub.15)alkenyl, heteroaryl(C.sub.2 -C.sub.15)alkenyl, aryl(C.sub.2 -C.sub.15)alkynyl, heteroaryl(C.sub.2 -C.sub.15)alkynyl, aryl(C.sub.1 -c.sub.15)alkoxy, heteroaryl(C.sub.1 -C.sub.15)alkoxy, aryl(C.sub.1 -C.sub.15)alkanoyl, heteroaryl(C.sub.1 -C.sub.15)alkanoyl, aryl(C.sub.1 -C.sub.15)alkanoyloxy, or heteroaryl(C.sub.1 -C.sub.15)alkanoyloxy;
wherein R.sup.1 and R.sup.2 is optionally substituted with one ore more substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.15)alkyl, )C.sub.2 -C.sub.15)alkenyl, (C.sub.2 -C.sub.15)alkynyl (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.1 -C.sub.15)alkyl, (C.sub.3 -C.sub.8)cycloalkyl-(C.sub.2 -C.sub.15)alkenyl, (C.sub.3 -C.sub.8)cycloalkyl(C.sub.2 -C.sub.15)alkynyl, (C.sub.1 -C.sub.15)alkoxy, (C.sub.1 -C.sub.15)alkanoyl, (C.sub.1 -C.sub.15)alkanoyloxy, C(.dbd.O)OR.sub.a, C(.dbd.O)NR.sub.b R.sub.c, OC(.dbd.O)OR.sub.a, OC(.dbd.O)NR.sub.b R.sub.c, and NR.sub.e R.sub.f ;
and wherein any aryl or heteroaryl or R.sup.1 or R.sup.2 is optionally substituted on a non-aromatic carbon by a divalent (C.sub.2 -C.sub.7)alkylene chain to form a (C.sub.3 -C.sub.8)spirocycloalkyl;
each R.sub.a is independently hydrogen or (C.sub.1 -C.sub.6)alkyl;
each R.sub.b and R.sub.c is independently, hydrogen or (C.sub.1 -C.sub.10)alkyl;
or R.sub.b, and R.sub.c together with the nitrogen to which they are attached are a 5-6 membered heterocyclic ring;
and
each R.sub.e and R.sub.f is independently hydrogen, (C.sub.1 -C.sub.10)alkyl, (C.sub.1 -C.sub.10)alkanoyl, phenyl, benzyl, or phenethyl;
or R.sub.e and R.sub.f together with the nitrogen to which they are attached are a 5-6 membered heterocyclic ring;
or a pharmaceutically acceptable salt thereof.

7 more elements