METHODS OF TREATING ULCERATIVE COLITIS

1 . A method of treating ulcerative colitis, which comprises administering to a patient in need thereof a therapeutically effective amount of a potent TPH1 inhibitor.

2 . The method of claim 1 , wherein the potent TPH1 inhibitor is a compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

A is optionally substituted cycloalkyl, aryl, or heterocycle;

X is —O—, —S—, —C(O)—, —C(R 4 )═, ═C(R 4 )—, —C(R 3 R 4 )—, —C(R 4 )═C(R 4 )—, —C≡C—, —N(R 5 )—, —N(R 5 )C(O)N(R 5 )—, —C(R 3 R 4 )N(R 5 )—, —N(R 5 )C(R 3 R 4 )—, —ONC(R 3 )—, —C(R 3 )NO—, —C(R 3 R 4 )O—, —OC(R 3 R 4 )—, —S(O 2 )—, —S(O 2 )N(R 5 )—, —N(R 5 )S(O 2 )—, —C(R 3 R 4 )S(O 2 )—, or —S(O 2 )C(R 3 R 4 )—;

E is optionally substituted aryl or heterocycle;

R 1 is hydrogen or optionally substituted alkyl, aryl, or heterocycle;

R 2 is hydrogen or optionally substituted alkyl, aryl, or heterocycle;

R 3 is hydrogen, alkoxy, amino, cyano, halogen, hydroxyl, or optionally substituted alkyl;

R 4 is hydrogen, alkoxy, amino, cyano, halogen, hydroxyl, or optionally substituted alkyl or aryl;

each R 5 is independently hydrogen or optionally substituted alkyl or aryl; and

each R 10 is independently amino, cyano, halogen, hydrogen, OR 11 , SR 11 , NR 12 R 13 , or optionally substituted alkyl;

each R 11 is independently hydrogen or optionally substituted alkyl;

each R 12 is independently hydrogen or optionally substituted alkyl;

each R 13 is independently hydrogen or optionally substituted alkyl;

n is 0-3; and

q is 1-2.

3 . The method of claim 2 , wherein the compound is of the formula:

4 . The method of claim 3 , wherein the compound is of the formula:

5 . The method of claim 4 , wherein the compound is of the formula:

6 . The method of claim 5 , wherein X is —C(R 3 R 4 )O—.

7 . The method of claim 5 , wherein X is —OC(R 3 R 4 )—.

8 . The method of claim 5 , wherein A is optionally substituted aryl.

9 . The method of claim 8 , wherein A is optionally substituted biphenyl.

10 . The method of claim 5 , wherein R 1 is hydrogen.

11 . The method of claim 5 , wherein R 2 is hydrogen or lower alkyl.

12 . The method of claim 5 , wherein R 10 is amino.

13 . A method of treating ulcerative colitis, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

A is optionally substituted cycloalkyl, aryl, or heterocycle;

R 1 is hydrogen or lower alkyl;

R 2 is hydrogen or lower alkyl;

R 4 is hydrogen, alkoxy, amino, cyano, halogen, hydroxyl, or optionally substituted alkyl or aryl;

R 10 is independently amino, cyano, halogen, hydrogen, OR 11 , SR 11 , NR 12 R 13 , or optionally substituted alkyl;

R 11 is independently hydrogen or optionally substituted alkyl;

R 12 is independently hydrogen or optionally substituted alkyl; and

R 13 is independently hydrogen or optionally substituted alkyl.

14 . The method of claim 13 , wherein A is optionally substituted aryl.

15 . The method of claim 14 , wherein A is optionally substituted biphenyl.

16 . The method of claim 13 , wherein R 4 optionally substituted lower alkyl.

17 . The method of claim 16 , wherein R 4 is trifluoromethyl.

18 . The method of claim 13 , wherein R 10 is amino.

19 . A method of treating ulcerative colitis, which comprises administering to a patient in need thereof a therapeutically effective amount of (S)-2-amino-3-(4-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-methoxybiphenyl-4-yl)ethoxy)pyrimidin-4-yl)phenyl)propanoic acid or a pharmaceutically acceptable salt thereof.