Benzamide compounds

Patent metadata

Field	Value
Publication number	US-11813259-B2
Application number	US-202217656726-A
Country	US
Kind code	B2
Filing date	Mar 28, 2022
Priority date	Jan 10, 2018
Publication date	Nov 14, 2023
Grant date	Nov 14, 2023

Abstract

Compounds of Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as cancer and tumors, as well as viral infections such as HIV.

First claim

What is claimed is:

1. A method for treating a cancer or a tumor comprising administering an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an effective amount of the compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof, to a subject having the cancer or the tumor, wherein the cancer or the tumor is selected from a bladder cancer, a brain cancer, a breast cancer, a bone marrow cancer, a cervical cancer, a colorectal cancer, an esophageal cancer, a hepatocellular cancer, a lymphoblastic leukemia, a follicular lymphoma, a lymphoid malignancy of T-cell or B-cell origin, a melanoma, a myelogenous leukemia, a Hodgkin's lymphoma, a Non-Hodgkin's lymphoma, a head and neck cancer (including oral cancer), an ovarian cancer, a non-small cell lung cancer, a chronic lymphocytic leukemia, a myeloma, a prostate cancer, a small cell lung cancer, a spleen cancer, a polycythemia vera, a thyroid cancer, an endometrial cancer, a stomach cancer, a gallbladder cancer, a bile duct cancer, a testicular cancer, a neuroblastoma, an osteosarcoma, an Ewings's tumor and a Wilm's tumor, Formula (I) having the structure:

wherein:
R 1 is selected from the group consisting of hydrogen, halogen, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a substituted or unsubstituted C 1 -C 6 alkoxy, an unsubstituted mono-C 1 -C 6 alkylamine and an unsubstituted di-C 1 -C 6 alkylamine;
each R 2 is independently selected from the group consisting of halogen, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl and a substituted or unsubstituted C 3 -C 6 cycloalkyl; or
when m is 2 or 3, each R 2 is independently selected from the group consisting of halogen, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl and a substituted or unsubstituted C 3 -C 6 cycloalkyl, or two R 2 groups taken together with the atom(s) to which they are attached form a substituted or unsubstituted C 3 -C 6 cycloalkyl or a substituted or unsubstituted 3 to 6 membered heterocyclyl;
R 3 is selected from the group consisting of X—R 3A ,

R 3A is a substituted or unsubstituted 5 to 10 membered heteroaryl;
R 4 is selected from the group consisting of NO 2 , S(O)R 6 , SO 2 R 6 , halogen, cyano and an unsubstituted C 1 -C 6 haloalkyl;
R 5 is selected from the group consisting of —X 1 -(Alk 1 ) n -R 7 and —X 2 (CHR 8 )-(Alk 2 ) p -X 3 —R 9 ;
Alk 1 and Alk 2 are independently selected from an unsubstituted C 1 -C 4 alkylene and a C 1 -C 4 alkylene substituted with 1, 2 or 3 substituents independently selected from fluoro, chloro, an unsubstituted C 1 -C 3 alkyl and an unsubstituted C 1 -C 3 haloalkyl;
R 6 is selected from the group consisting of a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl and a substituted or unsubstituted C 3 -C 6 cycloalkyl;
R 7 is selected from a substituted or unsubstituted C 1 -C 6 alkoxy, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted 3 to 10 membered heterocyclyl, hydroxy, amino, a substituted or unsubstituted mono-substituted amine group, a substituted or unsubstituted di-substituted amine group, a substituted or unsubstituted N-carbamyl, a substituted or unsubstituted C-amido and a substituted or unsubstituted N-amido;
R 8 is selected from a substituted or unsubstituted 3 to 10 membered heterocyclyl(C 1 -C 6 alkyl), a substituted or unsubstituted di-C 1 -C 6 alkylamine(C 1 -C 6 alkyl) and a substituted or unsubstituted mono-C 1 -C 6 alkylamine(C 1 -C 6 alkyl);
R 9 is selected from a substituted or unsubstituted 5 to 10 membered heteroaryl and a substituted or unsubstituted C 6 -C 10 aryl;
m is 0, 1, 2 or 3;
n and p are independently selected from 0 and 1;
X 1 and X 2 are —NH—; and
X and X 3 are independently selected from the group consisting of —O—, —S— and —NH—.

2. A method for inhibiting replication of a malignant growth or a tumor comprising contacting the growth or the tumor with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising an effective amount of the compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof, wherein the malignant growth or tumor selected from an Ewings's tumor and a Wilm's tumor, or the malignant growth of tumor is due to a cancer selected from a bladder cancer, a brain cancer, a breast cancer, a bone marrow cancer, a cervical cancer, a colorectal cancer, an esophageal cancer, a hepatocellular cancer, a lymphoblastic leukemia, a follicular lymphoma, a lymphoid malignancy of T-cell or B-cell origin, a melanoma, a myelogenous leukemia, a Hodgkin's lymphoma, a Non-Hodgkin's lymphoma, a head and neck cancer (including oral cancer), an ovarian cancer, a non-small cell lung cancer, a chronic lymphocytic leukemia, a myeloma, a prostate cancer, a small cell lung cancer, a spleen cancer, a polycythemia vera, a thyroid cancer, an endometrial cancer, a stomach cancer, a gallbladder cancer, a bile duct cancer, a testicular cancer, a neuroblastoma, an osteosarcoma, Formula (I) having the structure:

wherein:
R 1 is selected from the group consisting of hydrogen, halogen, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a substituted or unsubstituted C 1 -C 6 alkoxy, an unsubstituted mono-C 1 -C 6 alkylamine and an unsubstituted di-C 1 -C 6 alkylamine;
each R 2 is independently selected from the group consisting of halogen, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl and a substituted or unsubstituted C 3 -C 6 cycloalkyl; or
when m is 2 or 3, each R 2 is independently selected from the group consisting of halogen, a substituted or unsubstituted C 1 -C 6 alkyl, a substituted or unsubstituted C 1 -C 6 haloalkyl and a substituted or unsubstituted C 3 -C 6 cycloalkyl, or two R 2 groups taken together with the atom(s) to which they are attached form a substituted or unsubstituted C 3 -C 6 cycloalkyl or a substituted or unsubstituted 3 to 6 membered heterocyclyl;
R 3 is selected from the group consisting of X—R 3A ,

R 3A is a substituted or unsubstituted 5 to 10 membered heteroaryl;
R 4 is selected from the group consisting of NO 2 , S(O)R 6 , SO 2 R 6 , halogen, cyano and an unsubstituted C 1 -C 6 haloalkyl;
R 5 is selected from the group consisting of —X 1 -(Alk 1 ) n -R 7 and —X 2 (CHR 8 )-(Alk 2 ) p -X 3 —R 9 ;
Alk 1 and Alk 2 are independently selected from an unsubstituted C 1 -C 4 alkylene and a C 1 -C 4 alkylene substituted with 1, 2 or 3 substituents independently selected from fluoro, chloro, an unsubstituted C 1 -C 3 alkyl and an unsubstituted C 1 -C 3 haloalkyl;
R 6 is selected from the group consisting of a substituted or unsubstitute

Assignees

• Recurium Ip Holdings Llc

Inventors

• Pinchman Joseph Robert
• Huang Peter Qinhua
• Bunker Kevin Duane
• Sit Rakesh Kumar
• Samatar Ahmed Abdi

Classifications

• C07C47/42

  with a six-membered ring · CPC title

• C07C49/517

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/18

  for HIV · CPC title

• C07D295/155

  with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title