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

Patent metadata

Field	Value
Publication number	US-10709697-B2
Application number	US-201615745291-A
Country	US
Kind code	B2
Filing date	Jul 13, 2016
Priority date	Jul 16, 2015
Publication date	Jul 14, 2020
Grant date	Jul 14, 2020

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 a 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 pharmaceutical composition in the form of a tablet or capsule comprising a compound of Formula IL

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, alkyl sulfonyl, aryl sulfonyl, 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, alkyl sulfonyl, aryl sulfonyl, 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, methyl sulfinyl, ethylsulfinyl, mesyl, ethyl sulfonyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, N-methyl sulfamoyl, N-ethyl sulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, benzoyl, benzyl, carbocyclyl, aryl, or heterocyclyl,
or salt, ester, amide thereof and a pharmaceutically acceptable excipient.

2. The pharmaceutical composition of claim 1 further comprising another active ingredient.

3. The pharmaceutical composition of claim 1 further comprising another anti-cancer agent.

4. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable excipient is selected from cellulose, cellulose acetate phthalate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and hydroxypropyl methylcellulose acetate succinate.

5. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable excipient is selected from dicalcium phosphate dihydrate, calcium sulfate dioxide, titanium oxide, and magnesium aluminum silicate.

6. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable excipient is selected from gelatin, sucrose, glucose, dextrose, lactose, sorbitol, mannitol, and polyethylene glycol.

7. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable excipient is selected from magnesium stearate, calcium stearate, stearic acid, and glycerol behenate.

8. A pharmaceutical composition in the form of a tablet or capsule comprising N,N′-(pyridine-2,6-diylbis(methylene))bis(N-methyl-1-(pyridin-2-yl)methanamine) or salt thereof and a pharmaceutically acceptable excipient.

9. The pharmaceutical composition of claim 8 further comprising another anti-cancer agent.

10. The pharmaceutical composition of claim 8 wherein the pharmaceutically acceptable excipient is selected from cellulose, cellulose acetate phthalate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and hydroxypropyl methylcellulose acetate succinate.

11. The pharmaceutical composition of claim 8 wherein the pharmaceutically acceptable excipient is selected from dicalcium phosphate dihydrate, calcium sulfate dioxide, titanium oxide, and magnesium aluminum silicate.

12. The pharmaceutical composition of claim 8 wherein the pharmaceutically acceptable excipient is selected from gelatin, sucrose, glucose, dextrose, lactose, sorbitol, mannitol, and polyethylene glycol.

13. The pharmaceutical composition of claim 8 wherein the pharmaceutically acceptable excipient is selected from magnesium stearate, calcium stearate, stearic acid, and glycerol behenate.

Assignees

• Univ Emory
• Univ Georgia State Res Found

Inventors

• Shim Hyunsuk
• Mooring Suazette Reid
• Bai Renren

Classifications

• C07C211/53

  having the nitrogen atom of at least one of the amino groups further bound to a hydrocarbon radical substituted by amino groups · CPC title

• C07D307/52

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

• C07C217/58

  with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain · CPC title

• C07D241/12

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

• C07D213/53

  Nitrogen atoms · CPC title