US 11,891,399 B2
Inhibitors of cancer invasion, attachment, and/or metastasis
Paul B. Fisher, Henrico, VA (US); Maurizio Pellecchia, Riverside, CA (US); Swadesh K. Das, Richmond, VA (US); Timothy P. Kegelman, Richmond, VA (US); Bainan Wu, Richmond, VA (US); Surya K. De, Richmond, VA (US); Jun Wei, La Jolla, CA (US); Mitchell E. Menezes, Richmond, VA (US); and Luni Emdad, Richmond, VA (US)
Assigned to VIRGINIA COMMONWEALTH UNIVERSITY, Richmond, VA (US); and SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE, La Jolla, CA (US)
Filed by VIRGINIA COMMONWEALTH UNIVERSITY, Richmond, VA (US); and SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE, La Jolla, CA (US)
Filed on Jan. 14, 2021, as Appl. No. 17/148,813.
Application 17/148,813 is a division of application No. 16/349,467, granted, now 11,008,325, previously published as PCT/US2017/061443, filed on Nov. 14, 2017.
Claims priority of provisional application 62/424,571, filed on Nov. 21, 2016.
Claims priority of provisional application 62/421,468, filed on Nov. 14, 2016.
Prior Publication US 2021/0214365 A1, Jul. 15, 2021
Int. Cl. C07D 487/04 (2006.01); C07D 495/14 (2006.01); A61P 35/04 (2006.01); A61K 45/06 (2006.01); A61K 31/519 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 31/519 (2013.01); A61K 45/06 (2013.01); A61P 35/04 (2018.01); C07D 495/14 (2013.01)] 25 Claims
 
1. A compound, or pharmaceutically acceptable salt thereof, having the formula:

OG Complex Work Unit Chemistry
wherein:
each R1 is independently halogen, —CX13, —CHX12, —CH2X1, —OCX13, —OCH2X1, —OCHX12, —CN, —SOn1R1D, —SOv1NR1AR1B, —NHC(O)NR1AR1B, —N(O)m1, —NR1AR1B, —C(O)R1C, —C(O)—OR1C, —C(O)NR1AR1B, —OR1D, —NR1ASO2R1D, —NR1AC(O)R1C, —NR1AC(O)OR1C, —NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or
two adjacent R1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R2 is hydrogen, halogen, —CX23, —CHX22, —CH2X2, —OCX23, —OCH2X2, —OCHX22, —CN, —SOn2R2D, —SOv2NR2AR2B, —NHC(O)NR2AR2B, —N(O)m2, —NR2AR2B, —C(O)R2C, —C(O)—OR2C, —C(O)NR2AR2B, OR2D, —NR2ASO2R2D, —NR2AC(O)R2C, —NR2AC(O)OR2C, —NR2AOR2C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
L1 is a bond, —S(O)2—, —N(R3)—, —O—, —S—, —C(O)—, —C(O)N(R3)—, —N(R3)C(O)—, —N(R3)C(O)NH—, —NHC(O)N(R3)—, —S(O)2N(R3)—, —N(R3)S(O)2—, —C(O)S(O)2N(R3)—, —N(R3)S(O)2C(O)—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
R3 is hydrogen, —CX33, —CHX32, —CH2X3, —CN, —C(O)R3C, —C(O)OR3C, —C(O)NR3AR3B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
L2 is a bond, —S(O)2, —N(R4)—, —O—, —S—, —C(O)—, —C(O)N(R4)—, —N(R4)C(O)—, —N(R4)C(O)NH—, —NHC(O)N(R4)—, —S(O)2N(R4)—, —N(R4)S(O)2—,—C(O)S(O)2N(R4)—, —N(R4)S(O)2C(O)—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
R4 is hydrogen, —CX43, —CHX42, —CH2X4, —CN, —C(O)R4C, —C(O)OR4C, —C(O)NR4AR4B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R4A, R4B, and R4C are each independently hydrogen, —CX3, —CN, —COOH, —CONH2, —CHX2, —CH2X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or
R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; or
R2A and R2B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; or
R3A and R3B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; or
R4A and R4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
X, X1, X2, X3, and X4 are each independently —F, —Cl, —Br, or —I;
n1 and n2 are independently an integer from 0 to 4;
m1, m2, v1, and v2 are each independently 1 or 2; and
z1 is an integer from 0 to 4;
wherein L2—R2 is not hydrogen, —OCH3, —CH3, or —Cl; or
wherein R2 is not

OG Complex Work Unit Chemistry
where
each R23 is independently halogen, —CX233, —CHX232, —CH2X23, —OCX233, —OCH2X23, —OCHX232, —CN, —SOn23R100D, —SOv23NR100AR100B, —NHC(O)NR100AR100B, —N(O)m23, —NR100AR100B, —C(O)R100C, —C(O)—OR100C, —C(O)NR100AR100B, —OR100D, —NR100ASO2R100D, —NR100AC(O)R100C, —NR100AC(O)OR100C, —NR100AOR100C, N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or
two adjacent R23 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R100A, R100B, R100C, and R100D are each independently hydrogen, —CX3, —CN, —COOH, —CONH2, —CHX2, —CH2X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or
R100A and R100B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
each X23 is independently —F, —Cl, —Br, or —I;
each n23 is independently an integer from 0 to 4;
m23 and v23 are each independently 1 or 2; and
z23 is an integer from 0 to 2.