US 12,145,931 B2
Substituted pyrrolo[2,3-c]quinolines as antimalarials
Santosh Baburao Mhaske, Pune Maharashtra (IN); Jyoti Pankaj Mahajan, Pune Maharashtra (IN); and Shanmugam Dhanasekaran, Pune Maharashtra (IN)
Assigned to COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH, New Delhi (IN)
Appl. No. 16/971,232
Filed by COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH, New Delhi (IN)
PCT Filed Feb. 19, 2019, PCT No. PCT/IN2019/050130
§ 371(c)(1), (2) Date Aug. 19, 2020,
PCT Pub. No. WO2019/159202, PCT Pub. Date Aug. 22, 2019.
Claims priority of application No. 201811006181 (IN), filed on Feb. 19, 2018.
Prior Publication US 2021/0087187 A1, Mar. 25, 2021
Int. Cl. A61K 31/437 (2006.01); A61P 33/06 (2006.01); B01D 5/00 (2006.01); B01D 11/04 (2006.01); C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 33/06 (2018.01); B01D 5/0063 (2013.01); B01D 11/0492 (2013.01)] 5 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
R1 is C1-C10 alkyl or C6-C18 aryl;
wherein the C1-C10 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, NO2, acyl, C(O)amino, C(O)OH, C(O)O(alkyl), C(O)O(cycloalkyl), C(O)O(heterocyclyl), C(O)O(aryl), C(O)O(heteroaryl), amino, alkylamino, amino (acyl), amino-C(O)amino, amino-C(O)OH, amino-C(O)O(alkyl), amino-C(O)O(cycloalkyl), amino-C(O)O(heterocyclyl), amino-C(O)O(aryl), amino-C(O)O(heteroaryl), amino-S(O)2alkyl, amino-S(O)2amino, amino-S(O)2 (alkylamino), amino-S(O)2 (acylamino), amino-S(O)2OH, amino-S(O)2O(alkyl), amino-S(O)2O(cycloalkyl), amino-S(O)2O(heterocyclyl), amino-S(O)2O(aryl), amino-S(O)2O(heteroaryl), OH, O(alkyl), O(acyl), OC(O)amino, OC(O)OH, OC(O)O(alkyl), OC(O)O(cycloalkyl), OC(O)O(heterocyclyl), OC(O)O(aryl), OC(O)O(heteroaryl), OS(O)2alkyl, OS(O)2amino, OS(O)2 (alkylamino), OS(O)2 (acylamino), OS(O)2OH, OS(O)2O(alkyl), OS(O)2O(cycloalkyl), OS(O)2O(heterocyclyl), OS(O)2O(aryl), OS(O)2O(heteroaryl), SH, S(alkyl), S(acyl), S(cycloalkyl), S(heterocyclyl), S(aryl), S(heteroaryl), S(O)alkyl, S(O)acyl, S(O)cycloalkyl, S(O)heterocyclyl, S(O)aryl, S(O)heteroaryl, S(O)2alkyl, S(O)2acyl, S(O)2amino, S(O)2 (alkylamino), S(O)2 (acylamino), S(O)2OH, S(O)2O(alkyl), S(O)2O(cycloalkyl), S(O)2O(heterocyclyl), S(O)2O(aryl), S(O)2O(heteroaryl), S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; and
wherein the C6-C18 aryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, acyl, C(O)amino, C(O)OH, C(O)O(alkyl), C(O)O(cycloalkyl), C(O)O(heterocyclyl), C(O)O(aryl), C(O)O(heteroaryl), amino, alkylamino, amino (acyl), amino-C(O)amino, amino-C(O)OH, amino-C(O)O(alkyl), amino-C(O)O(cycloalkyl), amino-C(O)O(heterocyclyl), amino-C(O)O(aryl), amino-C(O)O(heteroaryl), amino-S(O)2alkyl, amino-S(O)2amino, amino-S(O)2 (alkylamino), amino-S(O)2 (acylamino), amino-S(O)2OH, amino-S(O)2O(alkyl), amino-S(O)2O(cycloalkyl), amino-S(O)2O(heterocyclyl), amino-S(O)2O(aryl), amino-S(O)2O(heteroaryl), OH, O(alkyl), O(acyl), OC(O)amino, OC(O)OH, OC(O)O(alkyl), OC(O)O(cycloalkyl), OC(O)O(heterocyclyl), OC(O)O(aryl), OC(O)O(heteroaryl), OS(O)2alkyl, OS(O)2amino, OS(O)2 (alkylamino), OS(O)2 (acylamino), OS(O)2OH, OS(O)2O(alkyl), OS(O)2O(cycloalkyl), OS(O)2O(heterocyclyl), OS(O)2O(aryl), OS(O)2O(heteroaryl), SH, S(alkyl), S(acyl), S(cycloalkyl), S(heterocyclyl), S(aryl), S(heteroaryl), S(O)alkyl, S(O)acyl, S(O)cycloalkyl, S(O)heterocyclyl, S(O)aryl, S(O)heteroaryl, S(O)2alkyl, S(O)2acyl, S(O)2amino, S(O)2 (alkylamino), S(O)2 (acylamino), S(O)2OH, S(O)2O(alkyl), S(O)2O(cycloalkyl), S(O)2O(heterocyclyl), S(O)2O(aryl), S(O)2O(heteroaryl), S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
R2 is C1-C10 alkyl or C6-C18 aryl;
wherein the C1-C10 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, NO2, acyl, C(O)amino, C(O)OH, C(O)O(alkyl), C(O)O(cycloalkyl), C(O)O(heterocyclyl), C(O)O(aryl), C(O)O(heteroaryl), amino, alkylamino, amino (acyl), amino-C(O)amino, amino-C(O)OH, amino-C(O)O(alkyl), amino-C(O)O(cycloalkyl), amino-C(O)O(heterocyclyl), amino-C(O)O(aryl), amino-C(O)O(heteroaryl), amino-S(O)2alkyl, amino-S(O)2amino, amino-S(O)2 (alkylamino), amino-S(O)2 (acylamino), amino-S(O)2OH, amino-S(O)2O(alkyl), amino-S(O)2O(cycloalkyl), amino-S(O)2O(heterocyclyl), amino-S(O)2O(aryl), amino-S(O)2O(heteroaryl), OH, O(alkyl), O(acyl), OC(O)amino, OC(O)OH, OC(O)O(alkyl), OC(O)O(cycloalkyl), OC(O)O(heterocyclyl), OC(O)O(aryl), OC(O)O(heteroaryl), OS(O)2alkyl, OS(O)2amino, OS(O)2 (alkylamino), OS(O)2OH, OS(O)2 (acylamino), OS(O)2O(alkyl), OS(O)2O(cycloalkyl), OS(O)2O(heterocyclyl), OS(O)2O(aryl), OS(O)2O(heteroaryl), SH, S(alkyl), S(acyl), S(cycloalkyl), S(heterocyclyl), S(aryl), S(heteroaryl), S(O)alkyl, S(O)acyl, S(O)cycloalkyl, S(O)heterocyclyl, S(O)aryl, S(O)heteroaryl, S(O)2alkyl, S(O)2acyl, S(O)2amino, S(O)2 (alkylamino), S(O)2 (acylamino), S(O)2OH, S(O)2O(alkyl), S(O)2O(cycloalkyl), S(O)2O(heterocyclyl), S(O)2O(aryl), S(O)2O(heteroaryl), S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; and
wherein the C6-C18 aryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, acyl, C(O)amino, C(O)OH, C(O)O(alkyl), C(O)O(cycloalkyl), C(O)O(heterocyclyl), C(O)O(aryl), C(O)O(heteroaryl), amino, alkylamino, amino (acyl), amino-C(O)amino, amino-C(O)OH, amino-C(O)O(alkyl), amino-C(O)O(cycloalkyl), amino-C(O)O(heterocyclyl), amino-C(O)O(aryl), amino-C(O)O(heteroaryl), amino-S(O)2alkyl, amino-S(O)2amino, amino-S(O)2 (alkylamino), amino-S(O)2 (acylamino), amino-S(O)2OH, amino-S(O)2O(alkyl), amino-S(O)2O(cycloalkyl), amino-S(O)2O(heterocyclyl), amino-S(O)2O(aryl), amino-S(O)2O(heteroaryl), OH, O(alkyl), O(acyl), OC(O)amino, OC(O)OH, OC(O)O(alkyl), OC(O)O(cycloalkyl), OC(O)O(heterocyclyl), OC(O)O(aryl), OC(O)O(heteroaryl), OS(O)2alkyl, OS(O)2amino, OS(O)2 (alkylamino), OS(O)2 (acylamino), OS(O)2OH, OS(O)2O(alkyl), OS(O)2O(cycloalkyl), OS(O)2O(heterocyclyl), OS(O)2O(aryl), OS(O)2O(heteroaryl), SH, S(alkyl), S(acyl), S(cycloalkyl), S(heterocyclyl), S(aryl), S(heteroaryl), S(O)alkyl, S(O)acyl, S(O)cycloalkyl, S(O)heterocyclyl, S(O)aryl, S(O)heteroaryl, S(O)2alkyl, S(O)2acyl, S(O)2amino, S(O)2 (alkylamino), S(O)2 (acylamino), S(O)2OH, S(O)2O(alkyl), S(O)2O(cycloalkyl), S(O)2O(heterocyclyl), S(O)2O(aryl), S(O)2O(heteroaryl), S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; or
R1 and R2, taken together with the nitrogen atom to which they are attached, form a heteroaryl, wherein the heteroaryl is substituted with one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, acyl, C(O)amino, C(O)OH, C(O)O(alkyl), C(O)O(cycloalkyl), C(O)O(heterocyclyl), C(O)O(aryl), C(O)O(heteroaryl), alkylamino, amino (acyl), amino-C(O)amino, amino-C(O)OH, amino-C(O)O(alkyl), amino-C(O)O(cycloalkyl), amino-C(O)O(heterocyclyl), amino-C(O)O(aryl), amino-C(O)O(heteroaryl), amino-S(O)2alkyl, amino-S(O)2amino, amino-S(O)2 (alkylamino), amino-S(O)2 (acylamino), amino-S(O)2OH, amino-S(O)2O(alkyl), amino-S(O)2O(cycloalkyl), amino-S(O)2O(heterocyclyl), amino-S(O)2O(aryl), amino-S(O)2O(heteroaryl), OH, O(alkyl), O(acyl), OC(O)amino, OC(O)OH, OC(O)O(alkyl), OC(O)O(cycloalkyl), OC(O)O(heterocyclyl), OC(O)O(aryl), OC(O)O(heteroaryl), OS(O)2alkyl, OS(O)2amino, OS(O)2 (alkylamino), OS(O)2 (acylamino), OS(O)2O(alkyl), OS(O)2O(cycloalkyl), OS(O)2OH, OS(O)2O(heterocyclyl), OS(O)2O(aryl), OS(O)2O(heteroaryl), SH, S(alkyl), S(acyl), S(cycloalkyl), S(heterocyclyl), S(aryl), S(heteroaryl), S(O)alkyl, S(O)acyl, S(O)cycloalkyl, S(O)heterocyclyl, S(O)aryl, S(O)heteroaryl, S(O)2alkyl, S(O)2acyl, S(O)2amino, S(O)2 (alkylamino), S(O)2 (acylamino), S(O)2OH, S(O)2O(alkyl), S(O)2O(cycloalkyl), S(O)2O(heterocyclyl), S(O)2O(aryl), S(O)2O(heteroaryl), S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; and
R3 is H.
 
3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluent, or excipient and the compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.