Tryptophan hydroxylase inhibitors
View Patent ↗Compounds of formulae I and II are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and manage serotonin-mediated diseases and disorders:
1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
A is optionally substituted biphenyl
X is —O—, —C(R 3 R 4 )O—, or —OC(R 3 R 4 )—;
E is optionally substituted aryl or heterocycle;
R 1 is hydrogen or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle;
R 2 is hydrogen or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, 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 10 is independently amino, cyano, halogen, hydrogen, OR 11 , NR 12 R 13 , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
each R 11 is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
each R 12 is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
each R 13 is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;
n is 0-3; and
q is 1-2.
2. The compound of claim 1 , wherein R 3 is hydrogen.
3. The compound of claim 1 , wherein R 4 is independently hydrogen or optionally substituted alkyl.
4. The compound of claim 1 , wherein E is optionally substituted aryl.
5. The compound of claim 4 , wherein E is optionally substituted phenyl.
6. The compound of claim 1 , wherein R 1 is hydrogen or optionally substituted alkyl.
7. The compound of claim 1 , wherein R 2 is hydrogen or optionally substituted alkyl.
8. The compound of claim 1 , wherein n is 1.
9. A pharmaceutical formulation comprising the compound of claim 1 and a pharmaceutically acceptable excipient.