US 12,134,625 B2
Pyrrolo[2,1-f][1,2,4]triazines and preparation and uses thereof
Gopi Kumar Mittapalli, San Diego, CA (US); Sunil Kumar K C, San Diego, CA (US); Chi Ching Mak, San Diego, CA (US); Brian Joseph Hofilena, San Diego, CA (US); Lewis Daniel Turner, San Diego, CA (US); Brian Walter Eastman, San Diego, CA (US); Ramkrishna Reddy Vakiti, San Diego, CA (US); and Joseph Timothy Marakovits, Encinitas, CA (US)
Assigned to BioSplice Therapeutics, Inc., San Diego, CA (US)
Filed by BioSplice Therapeutics, Inc., San Diego, CA (US)
Filed on Oct. 12, 2022, as Appl. No. 17/964,489.
Claims priority of provisional application 63/347,757, filed on Jun. 1, 2022.
Claims priority of provisional application 63/254,733, filed on Oct. 12, 2021.
Prior Publication US 2023/0312605 A1, Oct. 5, 2023
Int. Cl. C07D 519/00 (2006.01); C07D 487/04 (2006.01)
CPC C07D 519/00 (2013.01) [C07D 487/04 (2013.01); C07B 2200/05 (2013.01)] 12 Claims
 
1. A compound, or a pharmaceutically acceptable salt thereof, of Formula I:

OG Complex Work Unit Chemistry
wherein:
R1 is heteroaryl optionally substituted with 1-10 R3; wherein the heteroaryl is selected from the group consisting of:

OG Complex Work Unit Chemistry
R2 is selected from the group consisting of unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-5 alkylene)pOR4, —(C1-5 alkylene)pheterocyclyl optionally substituted with 1-10 R5, -heteroaryl optionally substituted with 1-10 R6, and —(C1-5 alkylene)pcarbocyclyl optionally substituted with 1-12 R7, wherein each —(C1-5 alkylene) is, independently, optionally substituted with 1-5 halide and/or 1-3 unsubstituted —(C1-3 alkyl);
each R3 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-5 alkylene)pORB, —(C1-5 alkylene)CN, —(C1-5 alkylene)pheterocyclyl optionally substituted with 1-10 R9, -carbocyclyl optionally substituted with 1-12 R10, —(C1-5 alkylene)pheteroaryl optionally substituted with 1-10 R19, —(C1-5 alkylene)pC(═O)N(R11)2, and —C(═O)R12, wherein each —(C1-5 alkylene) is, independently, optionally substituted with 1-5 halide and/or 1-3 unsubstituted —(C1-3 alkyl);
each R4 is independently selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R5 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), -heterocyclyl optionally substituted with 1-10 R15, —(C1-5 alkylene)pOR20, —SO2R22, and —C(═O)R23, wherein the —(C1-5 alkylene) is optionally substituted with 1-5 halide and/or 1-3 unsubstituted —(C1-3 alkyl);
alternatively, two R5 attached to the same carbon atom are taken together to form a carbonyl group;
each R6 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), and —OMe;
each R is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —N(R13)2, —(C1-5 alkylene)pOR14, —(C1-5 alkylene)pheterocyclyl optionally substituted with 1-10 R15, —C(═O)R21, and —NH(═O)R22, wherein each —(C1-5 alkylene) is, independently, optionally substituted with 1-5 halide and/or 1-3 unsubstituted —(C1-3 alkyl);
each R8 is independently selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R9 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R10 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R11 is independently selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), —(C1-5 alkylene)pcarbocyclyl optionally substituted with 1-12 R16, -heterocyclyl optionally substituted with 1-10 R17, and -heteroaryl optionally substituted with 1-10 R18, wherein the —(C1-5 alkylene) is optionally substituted with 1-5 halide and/or 1-3 unsubstituted —(C1-3 alkyl);
each R12 is -heterocyclyl optionally substituted with 1-10 R17;
each R13 is independently selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R14 is independently selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), and —(C1-5 alkylene)pOR20;
each R15 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
alternatively, two R15 attached to the same carbon atom are taken together to form a carbonyl group;
each R16 is independently selected from the group consisting of halide, —OMe, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R17 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R18 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R19 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R20 is independently selected from the group consisting of H, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each R21 is independently selected from the group consisting of -heterocyclyl optionally substituted with 1-10 R17, —N(R11)2 and —OR20;
each R22 is independently selected from the group consisting of unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), and —(C1-5 alkylene)pOR20;
each R23 is independently selected from the group consisting of unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), unsubstituted —(C1-9 haloalkyl), and -carbocyclyl optionally substituted with 1-12 R24;
each R24 is independently selected from the group consisting of halide, unsubstituted —(C1-9 alkyl), unsubstituted —(C2-9 alkenyl), unsubstituted —(C2-9 alkynyl), and unsubstituted —(C1-9 haloalkyl);
each p is independently 0 or 1; and
wherein each H atom is optionally, independently replaced by 2H (D) (deuterium).