US 11,866,440 B2
Methods for inhibiting fascin
Xin-Yun Huang, New York, NY (US); and Christy Young Shue, Irvine, CA (US)
Assigned to CORNELL UNIVERSITY, Ithaca, NY (US); and NOVITA PHARMACEUTICALS, INC., New York, NY (US)
Filed by NOVITA PHARMACEUTICALS, INC., New York, NY (US); and CORNELL UNIVERSITY, Ithaca, NY (US)
Filed on Jan. 28, 2021, as Appl. No. 17/160,948.
Application 17/160,948 is a continuation of application No. 16/277,691, filed on Feb. 15, 2019, granted, now 10,941,146.
Application 16/277,691 is a continuation of application No. 13/972,649, filed on Aug. 21, 2013, granted, now 10,208,043, issued on Feb. 19, 2019.
Claims priority of provisional application 61/778,015, filed on Mar. 12, 2013.
Claims priority of provisional application 61/692,177, filed on Aug. 22, 2012.
Prior Publication US 2021/0332051 A1, Oct. 28, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/04 (2006.01); C07D 405/12 (2006.01); C07D 277/82 (2006.01); C07D 285/08 (2006.01); C07D 249/12 (2006.01); A61K 31/428 (2006.01); A61K 31/433 (2006.01); A61K 31/522 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 31/428 (2013.01); A61K 31/433 (2013.01); A61K 31/522 (2013.01); C07D 249/12 (2013.01); C07D 277/82 (2013.01); C07D 285/08 (2013.01); C07D 405/12 (2013.01)] 13 Claims
 
1. A pharmaceutical composition comprising
an amount of a compound of Formula A

OG Complex Work Unit Chemistry
or a tautomer thereof and/or a pharmaceutically acceptable salt thereof effective to inhibit fascin expression or fascin activity, and
a pharmaceutically acceptable excipient;
wherein in Formula A:
Y is N or CR;
R is hydrogen, halo, or lower alkyl;
R1 is phenyl, 5-membered heteroaryl or 6-membered heteroaryl, wherein the phenyl, 5-membered heteroaryl or 6-membered heteroaryl is optionally substituted with 1 to 3 R6;
L1 is selected from the group consisting —(C(R8)2)j—,
—(C(R8)2)q—C(O)—(C(R8)2)r—,
—(C(R8)2)q—C(O)N(R8)—(C(R8)2)r—,
—(C(R8)2)q—N(R8)C(O)—(C(R8)2)r—,
—(C(R8)2)q—N(R8)S(O)2—(C(R8)2)r—, —(CH2)q—S(O)2N(R8)—(CH2)r—, —S—,
—O—, and —NR8—;
j is 1, 2, or 3;
q is 0 or 1;
r is 0 or 1;
L2 is selected from the group consisting a covalent bond,
—C(O)N(R8)—, —N(R8)C(O)—, —N(R8)S(O)2—, and —S(O)2N(R8)—;
R5 is phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 5-membered heterocycloalkyl or 6-membered heterocycloalkyl; wherein the phenyl is substituted with 1 to 4 R2, and the 5-membered heteroaryl or 6-membered heteroaryl is optionally substituted with 1 to 4 R2, wherein each R2 is independently selected from the group consisting of lower alkyl, lower haloalkyl, —OH, —OR7, —SH, —SR7, —NR10R10, halo, cyano, nitro, —COH, —COR7, —CO2H, —CO2R7, —CoNR10R10, OCOR7, —OCO2R7, —OCONR10R10, —NR10COR10, —NR10CO2R10, —SOR7, —SO2R7, —SO2NR10R10, and —NR1SO2R7;
each R6 is independently selected from the group consisting of halo and lower alkyl optionally substituted with 1-3 halo; or two adjacent R6 on a phenyl ring form a 5- or 6-membered cycloalkyl or heterocycloalkyl fused with the phenyl ring;
R7 is lower alkyl;
R8 is hydrogen; and
each R10 is independently hydrogen or lower alkyl, or two R10 together with the atom(s) attached thereto form a 4- to 6-membered ring, with the proviso that when R5 is phenyl and L2 is a covalent bond, then R5 is substituted with 1 to 4 R2.