Benzamide or benzamine compounds useful as anticancer agents for the treatment of human cancers

Patent metadata

Field	Value
Publication number	US-10112948-B2
Application number	US-201615194825-A
Country	US
Kind code	B2
Filing date	Jun 28, 2016
Priority date	Jul 6, 2015
Publication date	Oct 30, 2018
Grant date	Oct 30, 2018

Abstract

The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.

First claim

What is claimed is:

1. A compound according to Formula I-g

wherein
R 1 is selected from the group consisting of

n=0, 1, or 2;
m=0 or 1;
R 2 and R 3 can be attached at any available position on the aromatic ring and are independently selected from the group consisting of H, D, F, Cl, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 hydroxyalkyl, cycloalkyl, OR, N(R) 2 , NO 2 , N 3 , NH—C(O)—R, CN, C(O)R, C(O)OR, C(O)N(R) 2 , SR, alkylacyl, and arylacyl;
Each R is independently selected from the group consisting of H, C 1-3 alkyl, propargyl, and phenyl;
R 4 and R 5 are independently selected from the group consisting of H, C 1-6 alkyl optionally substituted with N(R) 2 , C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 hydroxyalkyl, phenyl optionally substituted with R 3 , and CH 2 OC(O)-phenyl optionally substituted with R 3 ;
R 6 and R 7 are independently selected from the group consisting of H, C 1-3 alkyl, and C(O)OMe 3 ;
such that all possible stereoisomers, including optically active isomers, are included whenever stereogenic centers are present;
or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof.

2. A compound of claim 1 according to Formula I-g

wherein
R 2 and R 3 can be attached at any available position on the aromatic ring and are independently selected from the group consisting of H, D, F, Cl, CF 3 , C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C 1 -C 3 hydroxyalkyl, C 4 -C 6 cycloalkyl, OR, N(R) 2 , NO 2 , N 3 , NH—C(O)—R, CN, C(O)R, C(O)OR, C(O)N(R) 2 , and SR;
Each R is independently selected from the group consisting of H, C 1-3 alkyl, propargyl, and phenyl;
such that all possible stereoisomers, including optically active isomers, are included whenever stereogenic centers are present;
or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof.

3. A pharmaceutical composition comprising a therapeutic amount of the compound according to claim 1 , and a pharmaceutically acceptable carrier.

4. A compound selected from the group consisting of:

such that all possible stereoisomers, including optically active isomers, are included whenever stereogenic centers are present;
or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof.

5. A compound selected from the group consisting of

such that all possible stereoisomers, including optically active isomers, are included whenever stereogenic centers are present;
or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof.

6. A compound selected from the group consisting of:

such that all possible stereoisomers, including optically active isomers, are included whenever stereogenic centers are present;
or a pharmaceutically acceptable salt, prodrug, active metabolite, or solvate thereof.

7. A pharmaceutical composition comprising a therapeutic amount of the compound according to any one of claims 4 - 6 and a pharmaceutically acceptable carrier.

Assignees

• Univ Texas

Inventors

• Debrabander Jef
• Parada Luis

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D307/14

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title

• C07D209/48

  with oxygen atoms in positions 1 and 3, e.g. phthalimide · CPC title

• C07D213/70

  Sulfur atoms · CPC title

• C07D211/14

  with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom · CPC title