US 12,435,047 B2
c-Abl tyrosine kinase inhibitory compound embodiments and methods of making and using the same
Juan J. Marugan, Gaithersburg, MD (US); Marc Ferrer, Potomac, MD (US); Noel T. Southall, Potomac, MD (US); Andres E. Dulcey, Gaithersburg, MD (US); Xin Hu, Frederick, MD (US); Christopher R. Dextras, Frederick, MD (US); Daniel C. Talley, Baltimore, MD (US); Alejandra Alvarez, Santiago (CL); Silvana Zanlungo, Santiago (CL); and Rommy M. Von Bernhardi, Santiago (CL)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Pontifica Universidad Catoclica de Chile, Santiago (CL)
Filed by The USA, as represented by the Secretary, Dept. of Health and Human Services, Bethesda, MD (US); and Pontificia Universidad Católica de Chile, Santiago (CL)
Filed on Mar. 30, 2023, as Appl. No. 18/128,603.
Application 18/128,603 is a division of application No. 16/976,012, granted, now 11,649,218, previously published as PCT/US2019/021434, filed on Mar. 8, 2019.
Claims priority of provisional application 62/641,126, filed on Mar. 9, 2018.
Prior Publication US 2023/0303501 A1, Sep. 28, 2023
Int. Cl. C07D 243/38 (2006.01); A61K 31/551 (2006.01); A61K 31/5513 (2006.01); A61K 31/553 (2006.01); A61K 31/554 (2006.01); A61P 25/08 (2006.01); A61P 25/28 (2006.01); A61P 33/06 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); A61P 37/00 (2006.01); C07C 201/12 (2006.01); C07C 227/22 (2006.01); C07C 319/14 (2006.01); C07D 267/18 (2006.01); C07D 267/20 (2006.01); C07D 281/16 (2006.01); C07D 401/04 (2006.01); C07D 403/04 (2006.01); C07D 409/04 (2006.01); C07D 413/04 (2006.01); C07D 413/10 (2006.01); C07D 413/14 (2006.01); C07D 417/04 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07F 5/02 (2006.01); C07F 7/08 (2006.01)
CPC C07D 243/38 (2013.01) [A61K 31/5513 (2013.01); A61K 31/553 (2013.01); A61K 31/554 (2013.01); A61P 25/08 (2018.01); A61P 25/28 (2018.01); A61P 33/06 (2018.01); A61P 35/02 (2018.01); C07C 201/12 (2013.01); C07C 227/22 (2013.01); C07C 319/14 (2013.01); C07D 267/18 (2013.01); C07D 267/20 (2013.01); C07D 281/16 (2013.01); C07D 401/04 (2013.01); C07D 403/04 (2013.01); C07D 413/04 (2013.01); C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07D 417/04 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07F 5/025 (2013.01); C07F 7/0812 (2013.01)] 19 Claims
 
1. A compound, having a structure satisfying any of Formulas IIA-IIF

OG Complex Work Unit Chemistry
or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein X is NR′, wherein R′ is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, aliphatic-aromatic, or heteroaliphatic-aromatic;
for Formulas IIA and IID, Y is oxygen, NR′, or CR′R″ wherein each R′ and R″ independently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, aliphatic-aromatic, or heteroaliphatic-aromatic;
for Formulas IIB and IIE, Y is hydrogen or NR′R″ wherein each R′ and R″ independently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, aliphatic-aromatic, or heteroaliphatic-aromatic;
for Formulas IIC and IIF, Y is hydrogen;
at least one of R1 and R3 is trifluoroalkoxy and the other of R1 and R3 is heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or boronic acid, and provided that
(a) R1 and R3 are each positioned para relative to X of Formulas IIA-IIF; or
(b)(i) for Formulas IIA and IIC, R1 is para relative to the nitrogen atom bound to R5 and R3 is para relative to the carbon atom bound to Y; (b)(ii) for Formula IIB, R1 is para relative to the imine nitrogen atom and R3 is para relative to the carbon atom bound to Y; (b)(iii) for Formulas IID and IIF, R1 is para relative to the carbon atom bound to Y and R3 is para relative to the nitrogen atom bound to R5; or (b)(iv) for Formula IIE, R1 is para relative to the carbon atom bound to Y and R3 is para relative to the imine nitrogen atom;
R2 and R4, if present, independently are aliphatic, heteroaliphatic, or halogen;
R5 is selected from hydrogen, aliphatic, heteroaliphatic, aromatic, aliphatic-aromatic, or heteroaliphatic-aromatic; and
each of n and m independently is an integer selected from 0 to 3.