Bis-amines, compositions, and uses related to CXCR4 inhibition
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 R 1 and R 2 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.
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.