Amide-sulfamide derivatives, compositions, and uses related to CXCR4 inhibition

Patent metadata

Field	Value
Publication number	US-10669270-B2
Application number	US-201716085099-A
Country	US
Kind code	B2
Filing date	Mar 14, 2017
Priority date	Mar 14, 2016
Publication date	Jun 2, 2020
Grant date	Jun 2, 2020

Abstract

This disclosure relates amide-sulfamide 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.

First claim

The invention claimed is:

1. A compound of Formula IB

or salts thereof wherein,
R 1 is phenyl or heteroaryl wherein R 1 is optionally substituted with one or more, the same or different, R 10 ;
R 2 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, benozyl, benzyl, phenyl or 2,3-dihydrobenzofuran, wherein R 2 is optionally substituted with one or more, the same or different, R 10 ;
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, benozyl, benzyl, or phenyl.

2. The compound of claim 1 , wherein R 1 is pyrazolo[1,5-a]pyridine.

3. The compound of claim 1 , wherein R 2 is 2,4-difluorophenyl or 3,4-difluorophenyl.

4. The compound of claim 1 , wherein R 1 is pyrimidine.

5. The compound of claim 1 , wherein R 1 is 1,2,3-thiadiazole.

6. The compound of claim 1 selected from:
N-(4-((2,3-dihydrobenzofuran-5-sulfonamido)methyl)benzyl)pyrazolo[1,5-a]pyridine-2-carboxamide;
N-(4-((2,4-difluorophenylsulfonamido)methyl)benzyl)pyrimidine-5-carboxamide; and
N-(4-((3,4-difluorophenylsulfonamido)methyl)benzyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide.

7. A pharmaceutical comprising a compound of claim 1 or salt thereof and a pharmaceutically acceptable excipient, diluent, or carrier.

8. The pharmaceutical composition of claim 7 further comprising another active ingredient.

9. A compound having formula IB:

or salts thereof wherein,
R 1 is phenyl optionally substituted with one or more, the same or different, R 10 ;
R 2 is phenyl 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, benozyl, benzyl, or phenyl.

10. The compound of claim 9 which is 4-fluoro-N-(4-(((4-methylphenyl)sulfonamido)methyl)benzyl)benzamide or salts thereof.

11. A pharmaceutical comprising a compound of claim 9 or salt thereof and a pharmaceutically acceptable excipient, diluent, or carrier.

12. A compound having Formula IK:

or salts thereof wherein,
R 3 , R 4 , R 5 , R 6 , and R 7 are, individually and independently, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, benozyl, benzyl, or phenyl;
R 12 , R 13 , R 15 , and R 16 are, individually and independently, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, benozyl, benzyl, or phenyl; and
R 17 and R 18 are, individually and independently, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, benozyl, benzyl, phenyl, or heteroaryl.

13. The compound of claim 12 , wherein R 17 is heteroaryl.

14. The compound of claim 13 , wherein heteroaryl is pyrimidine.

15. The compound of claim 12 which is N-(4-(phenylsulfonamidomethyl)benzyl)-4-((pyrimidin-2-ylamino)methyl)benzamide or salts thereof.

16. A pharmaceutical comprising a compound of claim 12 or salt thereof and a pharmaceutically acceptable excipient, diluent, or carrier.

Assignees

• Univ Emory

Inventors

• Shim Hyunsuk
• Shi Qi
• Bai Renren

Classifications

• C07C311/18

  to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups · CPC title

• A61K31/505

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• C07C323/60

  with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms · CPC title

• C07D213/82

  in position 3 · CPC title

• C07D213/81

  Amides; Imides · CPC title