US 12,358,918 B2
Aryl hydrocarbon receptor (AHR) activator compounds as cancer therapeutics
Steven Corsello, Boston, MA (US); Ryan Spangler, Cambridge, MA (US); Rohith Nagari, Cambridge, MA (US); Todd Golub, Cambridge, MA (US); and Amael Madec, Cambridge, MA (US)
Assigned to THE BROAD INSTITUTE, INC., Cambridge, MA (US); DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US); and INSTITUTO CARLOS SLIM DE LA SALUD, A.C., Mexico City (MX)
Appl. No. 17/293,255
Filed by THE BROAD INSTITUTE, INC., Cambridge, MA (US); DANA-FARBER CANCER INSTITUTE, INC.; and INSTITUTO CARLOS SLIM DE LA SALUD, A.C., Mexico City (MX)
PCT Filed Nov. 14, 2019, PCT No. PCT/US2019/061438
§ 371(c)(1), (2) Date May 12, 2021,
PCT Pub. No. WO2020/102506, PCT Pub. Date May 22, 2020.
Claims priority of provisional application 62/767,474, filed on Nov. 14, 2018.
Prior Publication US 2022/0017524 A1, Jan. 20, 2022
Int. Cl. C07D 487/04 (2006.01); A61K 45/06 (2006.01); C07D 471/14 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 45/06 (2013.01); C07D 471/14 (2013.01)] 3 Claims
 
1. A compound having a structure of formula I:

OG Complex Work Unit Chemistry
wherein:
R1, R2, and R3 independently represent H or Me,
wherein R1, R2, and R3 independently represent H; or
wherein R1 represents methyl and R2 and R3 each represents H; or
wherein R3 represents methyl and R1 and R2 each represents H; or
wherein both R1 and R3 represent methyl and R2 represents H; or
wherein R2 and R3 together with the other atoms to which they are bound form an optionally substituted phenyl group;
R4 represents H, methyl, or NR5R6 wherein R5 and R6 independently represent H, methyl, or phenyl, provided that only one of R5 and R6 may represent phenyl;
and wherein R7, R8, and R9 independently represent H, F, Cl, Br, methoxy, or optionally substituted C1-C3 alkyl,
X represents O or N—R10, wherein R10 represents H or methyl;
X1 represents C—O or CR4;
X2 represents N or NH;
and X3 represents CR7 or N, provided that X2 represents NH when X1 represents C═O, at least one of R7, R8, and R9 represents F, Cl, Br, methoxy, or optionally substituted C1-C3 alkyl;
and further provided that if R1, R2 and R3 independently represent H and R5 represents Cl, R4 cannot represent NR5R6 wherein R5 and R6 both represent H;
or a pharmaceutically acceptable salt, ester, amide, prodrug or stereoisomer thereof.