US Patent No. 9,695,171

3,4-DISUBSTITUTED-1 H-PYRROLO[2,3-B]PYRIDINES AND 4,5-DISUBSTITUTED-7H-PYRROLO[2,3-C]PYRIDAZINES AS LRRK2 INHIBITORS


Patent No. 9,695,171
Issue Date July 04, 2017
Title 3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines And 4,5-disubstituted-7h-pyrrolo[2,3-c]pyridazines As Lrrk2 Inhibitors
Inventorship Paul Galatsis, Newton, MA (US)
Matthew Merrill Hayward, Old Lyme, CT (US)
Bethany Lyn Kormos, Somerville, MA (US)
Travis T. Wager, Brookline, MA (US)
Lei Zhang, Auburndale, MA (US)
Jaclyn Louise Henderson, Cambridge, MA (US)
Ravi G. Kurumbail, East Lyme, CT (US)
Patrick Robert Verhoest, Newton, MA (US)
Antonia Friederike Stepan, Cambrdige, MA (US)
Assignee Pfizer Inc., New York, NY (US)

Claim of US Patent No. 9,695,171

1. A compound selected from the group consisting of:
3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
2-fluoro-3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]imidazo[1,2-b]pyridazine;
1-methyl-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carbonitrile;
1-methyl-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-imidazole-2-carbonitrile;
1-methyl-4-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazin-5-yl]-1H-pyrrole-2-carbonitrile;
4-[2-chloro-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1-methyl-1H-pyrrole-2-carbonitrile;
3-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[6-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[5-(hydroxymethyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(3-cyanophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
4-(3,6-dihydro-2H-pyran-4-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-cyano-2-fluorophenyl)-4-(dimethylamino)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-(5-fluoro-2-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluoro-5-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-methyl-3-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-fluoro-3-[6-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
6-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-2-carbonitrile;
3-(3-chlorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-chloro-5-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2,5-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2-chlorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2,3-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(5-chloro-2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
{3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}methanol;
{4-fluoro-3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}methanol;
3-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-chloro-2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(morpholin-4-yl)-3-(2,3,5-trifluorophenyl)-1H-pyrrolo[2,3-b]pyridine;
3-(3,5-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(2-chloropyridin-3-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(morpholin-4-yl)-3-phenyl-1H-pyrrolo[2,3-b]pyridine;
3-(2,4-difluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluoro-5-methylphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-fluoro-5-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(2,3-difluoro-6-methoxyphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-fluoro-5-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(5-methoxypyridin-3-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
6-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-2-carbonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-(3-cyano-2-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-(3-fluoro-5-methylphenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
4-fluoro-3-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-fluoro-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(hydroxymethyl)-5-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(4-fluorophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-methyl-3-(5-methylpyridin-3-yl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-chlorophenyl)-2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
2-methyl-4-(morpholin-4-yl)-3-phenyl-1H-pyrrolo[2,3-b]pyridine;
3-(2-fluorophenyl)-2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-(3-fluorophenyl)-2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-fluoro-5-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-ol;
4-[(2S)-2-methylmorpholin-4-yl]-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3,3-difluoropiperidin-1-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
{1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl}methanol;
3-(1-methyl-1H-pyrazol-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrrolo[2,3-b]pyridine;
N,N-dimethyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-amine;
3-(1-methyl-1H-pyrazol-4-yl)-4-(thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3,3-difluoropyrrolidin-1-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-[4-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(3-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[2-(methoxymethyl)morpholin-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
4-(morpholin-4-yl)-3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-[4-(1,4-oxazepan-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(4-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(3-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[4-(6-oxa-3-azabicyclo[3.1.1]hept-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(3R,4R)-3,4-difluoropyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-[4-(4-fluoropiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(3R)-3-fluoropyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-{4-[(2R)-2-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-[4-(pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(3S)-3-fluoropyrrolidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
3-[4-(3,3-difluoropiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-{4-[(2S)-2-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-2(1H)-one;
methyl 3-(3-cyanophenyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate;
3-[5-(cyanomethyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-[5-(methoxymethyl)-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
1-methyl-4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carboxamide;
4-[4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carbonitrile;
1-methyl-4-[2-methyl-4-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2-carbonitrile;
3-[4-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-4-phenyl-1H-pyrrolo[2,3-b]pyridine;
3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazin-5-yl]benzonitrile;
3-[3-(3-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-N-cyclopropylbenzamide;
2-fluoro-3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazin-5-yl]benzonitrile;
3-[4-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
4-(3,4-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2,5-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2,3-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3-chlorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2-fluoro-3-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
3-[3-(3-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-N-methylbenzenesulfonamide;
4-cyclopropyl-3-(2,3-difluoro-6-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;
3-[4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3,5-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(3-fluoro-4-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(2-fluoro-4-methoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
4-(furan-3-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine;
5-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,3-benzothiazole;
{3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]phenyl}acetonitrile;
3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]benzonitrile;
5-(1-methyl-1H-pyrazol-4-yl)-4-(morpholin-4-yl)-7H-pyrrolo[2,3-c]pyridazine;
4-[3-(m ethoxymethyl)phenyl]-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine; and
3-{4-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}benzonitrile;
or a pharmaceutically acceptable salt thereof.