Compounds and methods for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-11612598-B2
Application number	US-201816230676-A
Country	US
Kind code	B2
Filing date	Dec 21, 2018
Priority date	May 26, 2005
Publication date	Mar 28, 2023
Grant date	Mar 28, 2023

Abstract

Compositions and methods relating to induction of cell death such as in cancer cells are disclosed. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds in connection with modification of procaspases such as procaspase-3 are disclosed. In various embodiments, the compounds and compositions are capable of activation of procaspase-3.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a means for enhancing the activation of procaspase-3 in a cancer cell, and a pharmaceutically acceptable carrier, wherein the means for enhancing the activation of procaspase-3 in a cancer cell is a compound of Formula ZZ:

wherein
two of R a , R b , R c , R d and R e are (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy or halogen and the remaining groups are hydrogen;
each R is independently hydrogen, halogen, alkoxy, alkenyl, or alkyl, wherein at least one R is a substituent other than hydrogen;
R 2 X is a halogen; or
X is O, S, NR 7 , CO, OCO, or OCS;
when X is O or S, R 2 is hydrogen, alkyl, aryl, R 8 CO—, R 8 OCO—, R 8 SCO, R 8 OCS— or a moiety that is removable under physiological conditions, where R 8 is alkyl or aryl;
when X is NR 7 , R 2 and R 7 are independently hydrogen, alkyl, aryl, R 8 CO—, R 8 OCO—, or a moiety that is removable under physiological conditions;
when X is CO, OCO or OCS, R 2 is hydrogen, alkyl, aryl, or a moiety that is removable under physiological conditions;

n is 1 or 2;
R 3 is halogen, alkyl, haloalkyl, alkenyl, alkenol, alkanol, or haloalkenyl;
R 4 and R 5 are N; or R 4 is N and R 5 is CH;
R 6 is hydrogen or alkyl; and
A is oxygen or sulfur;

or a salt thereof.

2. The pharmaceutical composition of claim 1 wherein A is oxygen, R 2 is hydrogen, R 3 is allyl, and R 4 and R 5 are N.

3. The pharmaceutical composition of claim 2 wherein n is 1.

4. A pharmaceutical composition comprising a means for enhancing the activation of procaspase-3 in a cancer cell, and a pharmaceutically acceptable carrier, wherein the means for enhancing the activation of procaspase-3 in a cancer cell is a compound of Formula ZZ:

wherein
two of R a , R b , R e , R d and R e are (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy or halogen and the remaining groups are hydrogen;
each R is independently hydrogen, halogen, alkoxy, alkenyl, or alkyl;
R 2 X is a halogen; or
X is O, S, NR 7 , CO, OCO, or OCS;
when X is 0 or 5, R 2 is hydrogen, alkyl, aryl, R 8 CO—, R 8 OCO—, R 8 SCO, R 8 OCS— or a moiety that is removable under physiological conditions, where R 8 is alkyl or aryl;
when X is NR 7 , R 2 and R 7 are independently hydrogen, alkyl, aryl, R 8 CO—, R 8 OCO—, or a moiety that is removable under physiological conditions;
when X is CO, OCO or OCS, R 2 is hydrogen, alkyl, aryl, or a moiety that is removable under physiological conditions;

n is 1 or 2;
R 3 is halogen, alkyl, haloalkyl, alkenyl, alkenol, alkanol, or haloalkenyl;
R 4 and R 5 are N; or R 4 is N and R 5 is CH;
R 6 is hydrogen or alkyl; and

A is oxygen or sulfur;
or a salt thereof.

5. The pharmaceutical composition of claim 4 wherein A is oxygen, R 2 is hydrogen, R 3 is allyl, R 4 and R 5 are N, and n is 1.

6. A pharmaceutical composition comprising a means for enhancing the activation of procaspase-3 in a cancer cell, and a pharmaceutically acceptable carrier, wherein the means is a procaspase-3 activating compound wherein the compound is:

Assignees

• Univ Illinois

Inventors

• Hergenrother Paul J
• Putt Karson S
• Peterson Quinn P
• Fako Valerie

Classifications

• C07D295/13

  to an acyclic saturated chain · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K31/45

  having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide · CPC title

• C07D295/15

  to an acyclic saturated chain · CPC title

• C07D295/03

  with the ring nitrogen atoms directly attached to acyclic carbon atoms · CPC title