Bis-amines, compositions, and uses related to CXCR4 inhibition

Patent metadata

Field	Value
Publication number	US-11517565-B2
Application number	US-202016905528-A
Country	US
Kind code	B2
Filing date	Jun 18, 2020
Priority date	Jul 16, 2015
Publication date	Dec 6, 2022
Grant date	Dec 6, 2022

Abstract

This disclosure relates bis-amine compounds disclosed herein and uses related to CXCR4 inhibition. In certain embodiments, the compounds have formula I,salts, derivatives, and prodrugs thereof wherein, A is an bridging aryl or heterocyclyl and R1 and R2 are further disclosed herein. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising compounds disclosed herein. In certain embodiments, the disclosure relates to methods of treating or preventing CXCR4 related diseases or conditions by administering an effective amount of a compound disclosed herein to a subject in need thereof.

First claim

The invention claimed is:

1. A method of treating cancer comprising administering to a subject in need thereof an effective amount of a compound of Formula IL,

salt, ester, or amide thereof wherein,
X is N or CH;
R 1 is alkyl optionally substituted with one or more, the same or different, R 10 ;
R 3 , R 4 , R 5 , R 6 , and R 7 , are each individually and independently selected from hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, benzoyl, benzyl, aryl, or heterocyclyl, wherein R 3 , R 4 , R 5 , R 6 , and R 7 are optionally substituted with one or more, the same or different, R 10 ; and
R 10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, benzoyl, benzyl, aryl, or heterocyclyl, wherein R 10 is optionally substituted with one or more, the same or different, R 11 ; and
R 11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, isopropoxy, tert-butoxy, hydoxymethyl, hydroxyethyl, thiomethyl, thioethyl, aminomethyl, aminoethyl, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, benzoyl, benzyl, carbocyclyl, aryl, or heterocyclyl;
wherein the cancer is selected from leukemia, breast cancer, kidney cancer, lung cancer, brain cancer, pancreatic cancer, ovarian cancer, melanoma, prostate cancer, multiple myeloma, non-small cell lung cancer, small cell lung cancer, colon cancer, rectal cancer, hepatocellular cancer, gastric, esophageal cancer, medulloblastoma, and glioma.

2. The method of claim 1 , wherein the compound is administering in combination with another anti-cancer agent.

3. The method of claim 1 , wherein the compound is N,N′-(pyridine-2,6-diylbis(methylene))bis(N-methyl-1-(pyridin-2-yl)methanamine) or salt thereof.

Assignees

• Univ Emory
• Univ Georgia State Res Found

Inventors

• Shim Hyunsuk
• Mooring Suazette Reid
• Bai Renren

Classifications

• C07D241/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07C2601/02

  with a three-membered ring · CPC title

• C07D213/53

  Nitrogen atoms · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07C211/29

  the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups · CPC title