Modulators of CRTH2 activity
View Patent ↗Modulators of the CRTH2 receptor and their use in the treatment of various disorders, including asthma are described.
1. A compound having the formula:
wherein:
R is H, a C 1 –C 3 alkyl, optionally independently substituted with one or more halogen;
R 1 is H; a C 1 –C 6 alkyl, optionally independently substituted with one or more —OH, —NH 2 , or halogen; or a C 2 –C 6 alkenyl optionally independently substituted with one or more —OH, —NH 2 or halogen;
R 2 is a C 1 –C 6 alkyl, optionally independently substituted with one or more halogen; or a C 2 –C 6 alkenyl optionally independently substituted with one or more halogen;
R 3 is a halogen; —CN; —OH; —SH; a C 2 –C 3 alkyl, optionally independently substituted with one or more halogen; —OR 3A ; —SR 3A ; —SOR 3A ; or —S(O) 2 R 3A , wherein R 3A is a C 1 –C 3 alkyl, optionally independently substituted with one or more halogen;
m is 1, 2, 3, 4 or 5;
R 4 is H or a halogen;
R 5 is a halogen;
Y and Y′ are both H; and
R 7 is R 7A , wherein R 7A is: H or a C 1 to C 6 alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or arylalkyl optionally independently substituted with one or more halogen —OH, —C(O)OH, or —NH 3 .
2. The compound of claim 1 wherein m is 1.
3. The compound of claim 1 wherein m is 2.
4. The compound of claim 1 wherein m is 3.
5. The compound of claim 1 wherein R 3 is F; Cl; —CN; —OH; —SH; a C 2 –C 3 alkyl, optionally independently substituted with one or more F or Cl; —OR 3A ; —SR 3A ; —SOR 3A ; or —S(O) 2 R 3A , wherein R 3A is a C 1 –C 3 alkyl, optionally independently substituted with one or more F or Cl.
6. The compound of claim 5 wherein R 3 is F; Cl; —CN; —OH; —SH; or a C 2 –C 3 alkyl, optionally independently substituted with one or more F or Cl.
7. The compound of claim 5 wherein R 3 is —OR 3A ; —SR 3A ; —SOR 3A ; or —S(O) 2 R 3A , wherein R 3A is a C 1 –C 3 alkyl, optionally independently substituted with one or more F or Cl.
8. The compound of claim 1 wherein R is H.
9. The compound of claim 1 wherein R is a C 1 –C 3 alkyl, optionally independently substituted with one or more halogen.
10. The compound of claim 1 wherein R 4 is H, F or Cl.
11. The compound of claim 1 wherein R 5 is F or Cl.
12. The compound of claim 1 wherein R is H, or a C 1 –C 3 alkyl, optionally independently substituted with one or more F or Cl.
13. The compound of claim 1 wherein R 1 is H; a C 1 –C 6 alkyl, optionally independently substituted with one or more —OH, —NH 2 , F or Cl; or a C 2 –C 6 alkenyl optionally independently substituted with one or more —OH, —NH 2 , F or Cl.
14. The compound of claim 1 wherein R 2 is H; a C 1 –C 6 alkyl, optionally independently substituted with one or more F or Cl; or a C 2 –C 6 alkenyl optionally independently substituted with one or more F or Cl.
15. The compound of claim 1 wherein any halogen is selected from F and Cl.
16. The compound of claim 1 wherein R 3 is selected from: F, Cl, Br, OH, —OCH 3 , —OCH 2 CH 3 , —OCF 2 H, —OCF 3 ,—OCF 2 CF 3 , —OCF 2 CF 2 H, —CH 3 , —CF 2 H, —CF 3 , —SCH 3 , —SCF 2 H, —SCF 3 , —SCF 2 CF 3 , —SCF 2 CF 2 H, and —CN.
17. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.