Methods for inhibiting fascin
View Patent ↗Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof.
1. A method of inhibiting fascin expression or fascin activity, comprising administering an effective amount of a fascin inhibitor to a cell with fascin expression to thereby inhibit fascin expression or fascin activity in the cell, wherein the fascin inhibitor is a compound having the following structure:
or a tautomer thereof, and/or a pharmaceutically acceptable salt thereof,
wherein
L 1 is selected from the group consisting —(C(R 8 ) 2 ) j —, —(C(R 8 ) 2 ) q —C(O)—(C(R 8 ) 2 ) r —, —(C(R 8 ) 2 ) q —C(O)N(R 8 )—(C(R 8 ) 2 ) r —, —(C(R 8 ) 2 ) q —N(R 8 )C(O)—(C(R 8 ) 2 ) r —, —(C(R 8 ) 2 ) q —N(R 8 )S(O) 2 —(C(R 8 ) 2 ) r —, —(CH 2 ) q —S(O) 2 N(R 8 )—(CH 2 ) r —, —S—, —O— and —NR 8 —;
each R 6 is independently selected from the group consisting of halo and lower alkyl optionally substituted with 1-3 halo; or two adjacent R 6 on a phenyl ring form a 5- or 6-membered cycloalkyl or heterocycloalkyl fused with the phenyl ring;
R 8 is hydrogen or lower alkyl;
j is 1, 2 or 3;
q is 0 or 1;
r is 0 or 1; and
u is 1, 2 or 3.
2. The method of claim 1 , wherein L 1 is CH 2 .
3. The method of claim 1 , wherein the fascin inhibitor is a compound having the following structure:
or a tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein R 6 is halo.
5. The method of claim 4 , wherein u is 2.
6. The method of claim 2 , wherein the cell with fascin expression is in an animal.
7. The method of claim 6 , wherein the animal is a human.