US 12,410,173 B1
Substituted pyrrolo[2,3-d]pyrimidines as inhibitors for multi-resistant cancers
Sonali Raghavan Kunjunni Kurup, Big Rapids, MI (US)
Assigned to Ferris State University, Big Rapids, MI (US)
Filed by FERRIS STATE UNIVERSITY, Big Rapids, MI (US)
Filed on Oct. 4, 2023, as Appl. No. 18/376,754.
Application 18/376,754 is a continuation of application No. 17/459,558, filed on Aug. 27, 2021, granted, now 11,814,388.
Claims priority of provisional application 63/071,446, filed on Aug. 28, 2020.
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 15 Claims
 
1. A compound of Formula (I-2):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
L1 is —NR4—R1;
R4 is H;
R1 is

OG Complex Work Unit Chemistry
(i) each R5 is independently F, Br, CH2C(O)NHC2-6 alkenyl, CH2C(O)OH, CH2NHC(O)C2-6 alkenyl, CH2-phenyl, C(O)OH, C(O)OC3-6 alkyl, C(O)OC3-6 cycloalkyl, NHC3-6 alkyl, NHC(O)C1-6 alkyl, NHC(O)C2-6 alkenyl, NHC(O)—C2-6 alkenylene-C1-6 alkylene-N(C1-10 alkyl)2, C3-6 cycloalkylamine, or phenyl; or
(ii) each R5 is independently:

OG Complex Work Unit Chemistry
each n is independently 1, 2, 3, 4, or 5;
each R7 is independently H, halo, CN, NO2, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, C(O)C1-6 alkyl, C(O)NHC1-6 alkyl, NH2, NHC1-10 alkyl, N(C1-10 alkyl)2, NHC(O)C1-6 alkyl, NHC(O)C2-6 alkenyl, NHC(O)—C2-6 alkenylene-C1-6 alkylene-N(C1-10 alkyl)2, NHS(O)2C1-10 alkyl, OH, OC1-10 alkyl, OC1-10 haloalkyl, SH, SC1-10 alkyl, S(O)C1-6 alkyl, S(O)2NHC1-6 alkyl, C3-10 cycloalkyl, C4-10 cycloalkenyl, a monocyclic 3- to 8-membered ring, or a bicyclic 6- to 12-membered ring;
wherein each monocyclic 3- to 8-membered ring or bicyclic 6- to 12-membered ring is fully saturated, partially unsaturated, or fully unsaturated;
wherein each monocyclic 3- to 8-membered ring independently contains one or more carbon atoms and optionally and independently contains one, two, or three heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; and
wherein each bicyclic 6- to 12-membered ring independently contains one or more carbon atoms and optionally and independently one, two, three, four, five, or six heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
X1 is N;
L2 is H;
X2 is N;
X3 is —NH—;
X4 is CR2;
R2 is C(O)OH or —X6R3;
X6 is —C(O)NH(CH2)m—;
R3 is phenyl, pyrazolyl, isoxazolyl, tetrazolyl, pyridinyl, or pyrimidinyl, wherein the phenyl, pyrazolyl, isoxazolyl, tetrazolyl, pyridinyl, or pyrimidinyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkyl-NH2, CH2C(O)NHC2-10 alkenyl, CH2C(O)OH, CH2NHC(O)C2-10 alkenyl, CH2-phenyl, C(O)NHC1-10 alkyl, C(O)N(C1-10 alkyl)2, C(O)NHC2-10 alkenyl, C(O)NHC(O)OC1-6 alkyl, C(O)NHC(O)OC3-6 cycloalkyl, C(O)NHC(O)Ophenyl, C(O)NHC(O)OC1-6 heteroaryl, C(O)NHpyrrolidinyl, C(O)NHpiperidinyl, C(O)NHpiperazinyl, C(O)NHphenyl, C(O)NHC1-6 heteroaryl, C(O)OH, NH2, NHC1-10 alkyl, N(C1-10 alkyl)2, NHC2-10 alkenyl, NH—C2-10 alkynylene-N(C1-10 alkyl)2, NHC(O)C1-10 alkyl, NHC(O)C2-10 alkenyl, NHC(O)—C2-10 alkenylene-C1-6 alkylene-N(C1-10 alkyl)2, NHC(O)C(O)OC1-6 alkyl, NHC(O)C(O)OC3-6 cycloalkyl, NHC(O)C(O)OC1-6 heteroaryl, NHC(O)NHC1-10 alkyl, NHC(O)N(C1-10 alkyl)2, NHC(O)NHpyrrolidinyl, NHC(O)NHpiperidinyl, NHC(O)NHpiperazinyl, NHC(O)NHphenyl, NHC(O)NHC1-6 heteroaryl, NHC(O)C3-6 cycloalkyl, NHC6-10 aryl, OH, OC1-6 alkyl, OC1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-NH2, and phenyl;
X5 is CH; and
each m is independently 1, 2, 3, 4, or 5.
 
10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.