US 12,065,439 B2
Pyrrolopyridine-aniline compounds for treatment of dermal disorders
John Kincaid, Boston, MA (US); and Matthew Duncton, Boston, MA (US)
Assigned to NFLECTION THERAPEUTICS, INC., Boston, MA (US)
Filed by NFLECTION THERAPEUTICS, INC., BOSTON, MA (US)
Filed on Aug. 11, 2021, as Appl. No. 17/399,661.
Application 17/399,661 is a division of application No. 16/615,086, granted, now 11,161,845, previously published as PCT/US2018/033547, filed on May 18, 2018.
Claims priority of provisional application 62/508,997, filed on May 19, 2017.
Claims priority of provisional application 62/663,202, filed on Apr. 26, 2018.
Prior Publication US 2022/0033399 A1, Feb. 3, 2022
Int. Cl. C07D 471/04 (2006.01); A61P 35/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 35/00 (2018.01)] 33 Claims
 
1. A method of treating a MEK-inhibitor responsive disorder, MEK-inhibitor responsive dermal disorder, MEK-mediated disorder, or a MEK-mediated dermal disorder comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula (I):

OG Complex Work Unit Chemistry
or an N-oxide, a stereoisomer, mixture of stereoisomers, and/or a pharmaceutically acceptable salt thereof,
wherein:
R1 is —OR4, —NR5R5a, or an N-linked heterocycloalkyl wherein the N-linked heterocycloalkyl is optionally substituted with one or two R10;
R2a is halo or C1-C6 alkyl;
R2 is —S—C1-C6 alkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or halo;
X1 is C1-C6 alkyl;
R3, R3a, and R3b are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —S—C1-C6 alkyl, halo, C1-C6 alkoxy, C3-C8-cycloalkyloxy, heterocycloalkyloxy, heteroaryloxy, or phenoxy wherein each phenyl and heteroaryl is independently optionally substituted with 1, 2, or 3 R6;
R4 is C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkylalkyl, C1-C6 hydroxyalkyl, or C1-C6 alkoxyalkyl;
R5 is hydrogen, C1-C6 alkyl optionally substituted with one heterocycloalkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C6-alkyl-, C1-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C6-alkyl, or —OR5b;
R5a is hydrogen or C1-C6 alkyl;
R5b is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C6-alkyl, C1-C6 hydroxyalkyl, or C1-C6 alkoxy-C1-C6-alkyl;
each R6 is independently selected from the group consisting of carboxy, C1-C6-alkoxycarbonyl, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy-C1-C6-alkyl, C3-C8 cycloalkyl, heterocycloalkyl, —OC(O)R7, —OS(O)2R7, —O—C1-C6-haloalkyl, C3-C8 cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, —NR8aS(O)2R8, —NR8aC(O)R8, —S(O)2R8, —S(O)2NR8aR8, —C(O)R8, —C(O)NR8aR8, and —C1-C6-alkylene-R6a;
each R6a is independently selected from the group consisting of C3-C8 cycloalkyl, heterocycloalkyl, —NH2, —NH(C1-C6-alkyl), —N(C1-C6-alkyl)2, —NR9aS(O)2R9, —NR9aC(O)R9, —S(O)2R9, —S(O)2NR9aR9, —C(O)R9, and —C(O)NR9aR9;
each R7 is independently selected from the group consisting of amino, C1-C6-alkylamino, di-C1-C6-alkylamino, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6-alkoxy, heterocycloalkyl, aryl, and heteroaryl;
each R8a and R9a is independently H or C1-C6 alkyl;
each R8 and R9 is independently C1-C6 alkyl, aryl, heteroaryl, C3-C8 cycloalkyl, or heterocycloalkyl; and
each R10 is independently hydrogen, halo, hydroxy, oxo, C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, amino-C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, C1-C6-alkoxy, C3-C8 cycloalkyl, heterocycloalkyl, or heteroaryl.