Chemical compounds
The present invention relates to new sulfonamide URAT-1 inhibitor compounds of formula (I) or a pharmaceutically acceptable salt thereof: to compositions containing them, to processes for their preparation and to intermediates used in such processes, and to methods of treatment, wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the description.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
R 1 is a ‘C-linked’ 6-membered heteroaryl containing one, two or three nitrogen atoms wherein said heteroaryl is optionally substituted by one, two or, three valency permitting, X 1 ;
each X 1 is independently selected from: F; CI; CN; (C 1 -C 4 )alkyl optionally substituted by one, two or three F; or (C 1 -C 4 )alkyloxy optionally substituted by one two or three F;
R 2 , R 3 and R 5 are independently selected from: H; halogen; CN; (C 1 -C 4 )alkyl optionally substituted by one, two or three F; or (C 1 -C 4 )alkyloxy optionally substituted by one, two or three F;
R 4 is selected from: halogen; CN; (C 1 -C 4 )alkyl optionally substituted by one, two or three F; or (C 1 -C 4 )alkyloxy optionally substituted by one, two or three F;
R 6 is phenyl substituted by one, two or three X 2 ; or a ‘C-linked’ 6-membered heteroaryl containing one or two nitrogen atoms wherein said heteroaryl is optionally substituted by one, two or three X 2 ;
each X 2 is independently selected from: F; CI; CN; —S(C 1 -C 4 )alkyl; —NR 7 R 8 ; (C 1 -C 6 )alkyloxy optionally substituted by one, two or three F; (C 3 -C 6 )cycloalkyloxy; (C 1 -C 6 )alkyl optionally substituted by one, two or three F; or (C 1 -C 6 )alkyl substituted by OH; and
R 7 and R 8 are independently H or (C 1 -C 4 )alkyl or, together with the nitrogen atom to which they are attached, form a saturated 4- to 6-membered nitrogen containing monocycle.
2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is a ‘C-linked’ 6-membered heteroaryl containing one or two nitrogen atoms, wherein said heteroaryl is optionally substituted by one or two X 1 .
3. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein said heteroaryl is optionally substituted by X 1 .
4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is a ‘C-linked’ pyridinyl optionally substituted by X 1 .
5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is a ‘C-linked’ pyridinyl substituted by X 1 .
6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein X 1 is F.
7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 4 is either halogen or CN, and R 2 , R 3 and R 5 are independently selected from: H; halogen; or CN.
8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 4 is CN; and each of R 2 , R 3 and R 5 are H.
9. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 6 is phenyl substituted by one, two or three X 2 .
10. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 6 is a ‘C-linked’ 6-membered heteroaryl containing one or two nitrogen atoms, wherein said heteroaryl is optionally substituted by one, two or three X 2 .
11. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein each X 2 is independently selected from: F; Cl; CN; —S(C 1 -C 3 )alkyl; (C 1 -C 4 )alkyloxy optionally substituted by one, two or three F; or (C 1 -C 4 )alkyl optionally substituted by one, two or three F.
12. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein each X 2 is independently selected from: F; Cl; CN; methoxy; or methyl.
13. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
14. The pharmaceutical composition according to claim 13 , wherein said composition further comprises one or more additional therapeutic agents.
15. A method of inhibiting URAT-1 in a human or animal in need thereof comprising administering to said human or animal a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 wherein the inhibition of URAT-1 is a human or animal is for the treatment of gout.