US 12,168,668 B2
Compounds for the treatment of cancer and inflammatory disease
Yaron R. Hadari, Harrison, NY (US); Luca Carta, Scarsdale, NY (US); Michael Schmertzler, St. Petersburg, FL (US); Theresa M. Williams, Harleysville, PA (US); and Charles H. Reynolds, Austin, TX (US)
Assigned to SHY Therapeutics LLC, Harrison, NY (US)
Filed by SHY Therapeutics LLC, Harrison, NY (US)
Filed on Oct. 28, 2022, as Appl. No. 17/976,267.
Application 17/023,266 is a division of application No. 16/246,027, filed on Jan. 11, 2019, granted, now 10,870,657, issued on Dec. 22, 2020.
Application 17/976,267 is a continuation of application No. 17/023,266, filed on Sep. 16, 2020, granted, now 11,560,390.
Application 16/246,027 is a continuation of application No. 15/387,349, filed on Dec. 21, 2016, granted, now 10,221,191, issued on Mar. 5, 2019.
Claims priority of provisional application 62/271,185, filed on Dec. 22, 2015.
Prior Publication US 2023/0286997 A1, Sep. 14, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 495/04 (2006.01); A61K 31/52 (2006.01); A61P 29/00 (2006.01); A61P 35/00 (2006.01); C07D 221/04 (2006.01); C07D 239/94 (2006.01); C07D 265/30 (2006.01); C07D 271/06 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 407/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 473/30 (2006.01); C07D 487/04 (2006.01); C07D 495/14 (2006.01); C07D 513/04 (2006.01)
CPC C07D 495/04 (2013.01) [C07D 221/04 (2013.01); C07D 239/94 (2013.01); C07D 265/30 (2013.01); C07D 271/06 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 407/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 473/30 (2013.01); C07D 487/04 (2013.01); C07D 495/14 (2013.01)] 16 Claims
 
1. A compound of Formula VIb1:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein
R1b1 is 2-pyridyl or NH2;
R8b1 is H;
R9b1 is aryl, halo, or C(O)R4;
R4 is NR6R7; and
R6 and R7 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, or R6 and R7 are combined to form a cyclic structure including the nitrogen atom to which they are both attached,
wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, and cyclic structure are optionally substituted with one or more substituents Q independently selected from (a) deuterium, cyano, halo, and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more substituents Qa, and (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(NRa)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(═NRa)NRbRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(═NRd)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc,
wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen or deuterium or (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more substituents Qa;
wherein each Qa is independently selected from the group consisting of (a) deuterium, cyano, halo, and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) —C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(NRe)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(═NRe)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NReC(O)Rh, —NReC(O)ORf, —NReC(O)NRfRg, —NReC(═NRh)NRfRg, —NReS(O)Rh, —NReS(O)2Rh, —NReS(O)NRfRg, —NReS(O)2NRfRg, —SRe, —S(O)Re, —S(O)2Re, —S(O)NRfRg, and —S(O)2NRfRg;
wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen or deuterium or (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached form heterocyclyl;
wherein heteroaryl is a monocyclic or multicyclic aromatic ring system of about 5 to about 15 atoms, wherein one or more of the atoms in the ring system is nitrogen, oxygen, or sulfur; and
wherein heterocyclyl is a monocyclic or multicyclic non-aromatic ring system of about 5 to about 15 atoms, wherein one or more of the atoms in the ring system is nitrogen, oxygen, or sulfur.