Modulators of CRTH2 Activity
Modulators of the CRTH2 receptor and their use in the treatment of various disorders, including asthma are described.
1 - 69 . (canceled)
70 . A method for treating a patient suffering from a disorder associated with increased activity of the CRTH2 receptor, the method comprising administering to the patient a composition comprising a compound having the formula:
A is
R is H or a C 1 -C 3 alkyl, optionally independently substituted with one or more halogen;
n is 1,2,3 or4;
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 H; 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 1 -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 0, 1, 2, 3, 4 or 5;
R is H or a halogen;
R 5 is H or a halogen;
Y and Y′ are both H;
X is O, S, or —NR 6 , wherein R 6 is a C 1 -C 3 alkyl, optionally independently substituted with one or more halogen; and
R 7 is —OH, —OR 7A ; or R 7A , wherein R 7A is: H, a C 1 -C 6 alkyl, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, aryl, cycloalkyl, or arylalkyl optionally independently substituted with one or more halogen —OH, —C(O)OH, or —NH 3 .
71 . The method of claim 70 wherein m is 1.
72 . The method of claim 70 wherein m is 2.
73 . The method of claim 70 wherein m is 3.
74 . The method of claim 70 wherein R 3 is F; Cl; —CN; —OH; —SH; a C 1 -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.
75 . The method of claim 74 wherein R 3 is F; Cl; —CN; —OH; —SH; or a C 1 -C 3 alkyl, optionally independently substituted with one or more F or Cl.
76 . The method of claim 74 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.
77 . The method of claim 70 wherein R is H.
78 . The method of claim 70 wherein R is a C 1 -C 3 alkyl, optionally independently substituted with one or more halogen.
79 . The method of claim 70 wherein R 4 is H, F or Cl.
80 . The method of claim 70 wherein R 4 is H.
81 . The method of claim 70 wherein R 5 is halogen
82 . The method of claim 81 wherein R 5 is F or Cl.
83 . The method of claim 70 wherein R is H, or a C 1 -C 3 alkyl, optionally independently substituted with one or more F or Cl.
84 . The method of claim 70 wherein RI 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.
85 . The method of claim 70 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.
86 . The method of claim 70 wherein any halogen is selected from F and Cl.
87 . The method of claim 70 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, —SCH 3 , —SCF 2 H, —SCF 3 , —SCF 2 CF 3 , —SCF 2 CF 2 H, and —CN.
88 . The method of claim 70 wherein R 2 is methyl or ethyl.
89 . The method of claim 70 wherein R 2 is methyl.
90 . The method of claim 70 wherein the disorder is selected from: rhinitis, asthma, bronchitis, chronic inflammatory diseases of the lung, chronic obstructive pulmonary disease, and chronic sinusitis.
91 . The method of claim 70 wherein the disorder is asthma.