US 11,878,970 B2
Allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) for the treatment of disease
Erin Danielle Anderson, Arvada, CO (US); Sean Douglas Aronow, Boulder, CO (US); Nicholas A. Boyles, Hillsboro, OR (US); Xiaohong Chen, Broomfield, CO (US); Surendra Dawadi, Longmont, CO (US); Eugene R. Hickey, Danbury, CT (US); Thomas Combs Irvin, Erie, CO (US); Edward A. Kesicki, New York, NY (US); Gabrielle R. Kolakowski, Durango, CO (US); Jennifer Lynn Knight, Jersey City, NJ (US); Manoj Kumar, Broomfield, CO (US); Katelyn Frances Long, Lafayette, CO (US); Christopher Glenn Mayne, Boulder, CO (US); Johnathan Alexander McLean, Boulder, CO (US); Gerit Maria Pototschnig, San Diego, CA (US); Hua-Yu Wang, Chula Vista, CA (US); Michael Brian Welch, Westminster, CO (US); and Tien Widjaja, Lafayette, CO (US)
Assigned to PETRA PHARMA CORPORATION, New York, NY (US)
Filed by Petra Pharma Corporation, New York, NY (US)
Filed on May 26, 2022, as Appl. No. 17/825,680.
Claims priority of provisional application 63/253,352, filed on Oct. 7, 2021.
Claims priority of provisional application 63/250,592, filed on Sep. 30, 2021.
Claims priority of provisional application 63/227,493, filed on Jul. 30, 2021.
Claims priority of provisional application 63/193,917, filed on May 27, 2021.
Prior Publication US 2023/0096175 A1, Mar. 30, 2023
Int. Cl. C07D 405/04 (2006.01); C07D 405/14 (2006.01); C07D 407/04 (2006.01); C07D 413/04 (2006.01); C07D 417/04 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 491/048 (2006.01); C07D 491/052 (2006.01); C07D 495/04 (2006.01); C07D 498/04 (2006.01); C07D 513/04 (2006.01)
CPC C07D 405/04 (2013.01) [C07D 405/14 (2013.01); C07D 407/04 (2013.01); C07D 413/04 (2013.01); C07D 417/04 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 491/048 (2013.01); C07D 491/052 (2013.01); C07D 495/04 (2013.01); C07D 498/04 (2013.01); C07D 513/04 (2013.01)] 65 Claims
 
1. A compound of the Formula:

OG Complex Work Unit Chemistry
or pharmaceutically acceptable salt thereof, wherein:
R is —H or C1-C3 alkyl;
R1 is a group of the formula:

OG Complex Work Unit Chemistry
R2 is an optionally substituted bicyclic ring selected from 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, isoindolin-1-one, indolin-2-one, benzo[d]oxazol-2(3H)-one, 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one, or 2,3-dihydro-[1,4]dioxino[2,3-b]pyridine, or an optionally substituted bicyclic heteroaryl of 8 to 10 ring atoms containing 1, 2, 3, 4, or 5 ring heteroatoms independently selected from N, O, or S; wherein the optionally substituted bicyclic ring is optionally substituted with one to three substituents each independently selected from halogen and C1-C6 alkyl; the optionally substituted bicyclic heteroaryl is optionally substituted with one to three substituents each independently selected from —CN, halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, —SO2R10, —CONR10R10, —NR10R10, —NR10CO2R10, an optionally substituted C1-C6 alkyl, an optionally substituted C2-C6 alkenyl, an optionally substituted C2-C6 alkynyl, an optionally substituted C3-C5 cycloalkyl, an optionally substituted heterocycle selected from pyrrolidine, pyrrolidinone, piperidine or morpholine, an optionally substituted phenyl, an optionally substituted 1,3-benzodioxole, an optionally substituted 2,3-dihydro-1,4-benzodioxine, or an optionally substituted heteroaryl selected from pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, isoxazole, isothiazole, imidazole, oxazole, or thiazole; wherein the optionally substituted C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is each optionally substituted with a —CN, —OH, oxetanyl, or C1-C3 alkoxy; the optionally substituted C3-C5 cycloalkyl, phenyl, 1,3-benzodioxole, 2,3-dihydro-1,4-benzodioxine, heterocycle or heteroaryl is each optionally substituted with one to three substituents each independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, —SO2R10, —NR10R10, —OH or —CN;
R3 is —H, halogen, —CN, C1-C6 alkyl C1-C6 haloalkyl, C3-C5 cycloalkyl, a heterocycle of 3 to 5 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, or S, or a heteroaryl of 5 ring atoms containing 1, 2, or 3 ring heteroatoms independently selected from N, O, or S;
each of R4, R5 and R6 is independently —H, halogen, C1-C6 alkyl or C1-C6 haloalkyl;
R7 is —CN, C1-C6 alkyl or C1-C6 haloalkyl;
R8 is —H or C1-C6 alkyl;
each R9 is independently —H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C5 cycloalkyl; and
each R10 is independently —H or C1-C3 alkyl.