Method of treating functional bowel disorders
The invention relates to a method of treating at least one symptom of irritable bowel syndrome selected from the group consisting of: abnormal stool frequency, abnormal stool form, abnormal stool passage, passage of mucus and feeling of abdominal distension in a subject in need thereof. In certain embodiments, the pain and discomfort associated with irritable bowel syndrome is also reduced. The method comprises administering to a subject in need of treatment a therapeutically effective amount of a compound that has 5-HT 3 receptor antagonist activity and NorAdrenaline Reuptake Inhibitor (NARI) activity.
1 . A method of treating at least one symptom of irritable bowel syndrome selected from the group consisting of: abnormal stool frequency, abnormal stool form, abnormal stool passage, passage of mucus and feeling of abdominal distension in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound of Formula I:
wherein, R 1 and R 2 independently represent hydrogen, halogen or a C 1 -C 6 alkyl group;
or R 1 and R 2 together with the carbon atom to which they are attached form a cycloalkylene group having 5 to 6 carbon atoms;
R 3 and R 4 independently represent hydrogen or a C 1 -C 6 alkyl group;
R 5 is hydrogen, C 1 -C 6 alkyl,
or —C(O)—NH—R 6
wherein m is an integer from about 1 to about 3, X is halogen and R 6 is a C 1 -C 6 alkyl group; and
Ar is a substituted or unsubstituted phenyl, 2-thienyl or 3-thienyl group; and
n is 2 or 3; or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the irritable bowel syndrome is diarrhea predominant irritable bowel syndrome.
3 . The method of claim 1 , wherein the irritable bowel syndrome is alternating constipation/diarrhea irritable bowel syndrome.
4 . The method of claim 1 , wherein the treatment further comprises a reduction in pain or discomfort associated with irritable bowel syndrome.
5 . The method of claim 1 , wherein the subject is a human.
6 . The method of claim 5 , wherein the subject is a female.
7 . The method of claim 1 , wherein for the compound of Formula I, R 1 is a C 1 -C 6 alkyl group and Ar is a substituted phenyl.
8 . The method of claim 7 , wherein the substituted phenyl group is substituted with a halogen.
9 . The method of claim 1 , wherein for the compound of Formula I, n is 2, R 1 is a C 1 -C 6 alkyl group and Ar is a substituted phenyl.
10 . The method of claim 9 , wherein the substituted phenyl group is substituted with a halogen and R 1 is a methyl group.
11 . The method of claim 1 , wherein for the compound of Formula I, R 1 is a C 1 -C 6 alkyl group or a halogen and Ar is an unsubstituted phenyl.
12 . The method of claim 11 , wherein R 2 is hydrogen or a C 1 -C 6 alkyl group.
13 . The method of claim 1 , wherein for the compound of Formula I, n is 2, R 1 is a C 1 -C 6 alkyl group and Ar is an unsubstituted phenyl.
14 . The method of claim 13 , wherein R 2 is hydrogen or a C 1 -C 6 alkyl group
15 . A method of treating at least one symptom of irritable bowel syndrome selected from the group consisting of: abnormal stool frequency, abnormal stool form, abnormal stool passage, passage of mucus and feeling of abdominal distension in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound of Formula II:
or a pharmaceutically acceptable salt thereof.
16 . The method of claim 15 , wherein the irritable bowel syndrome is diarrhea predominant irritable bowel syndrome.
17 . The method of claim 15 , wherein the irritable bowel syndrome is alternating constipation/diarrhea irritable bowel syndrome.
18 . The method of claim 15 , wherein the treatment further comprises a reduction in pain or discomfort associated with irritable bowel syndrome.
19 . The method of claim 15 , wherein the subject is a human.
20 . The method of claim 19 , wherein the subject is a female.