IP Library › Granted Patent US 12,559,491

Granted Patent B2

US 12,559,491 · App. 18/043,385 · Granted Feb 24, 2026

Modified imidazopyridines as glucosylceramide synthase inhibitors

Inventors: Melissa C. Ford (Sellersville, PA); Mark E. Fraley (North Wales, PA); Kristen L.G. Jones (Oreland, PA); H. Marie Loughran (Perkasie, PA); James J. Mulhearn (Elkins, PA); Anthony J. Roecker (Harleysville, PA); Kathy M. Schirripa (Harleysville, PA); Ling Tong (Warren, NJ)

Assignee: Merck Sharp & Dohme LLC

C07D471/04 C07D519/00

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Quick Facts

Patent No.: US 12,559,491
App. No.: 18/043,385
Granted: Feb 24, 2026
Kind: B2

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Abstract

The present invention relates to Compounds of Formula I: I and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment or prophylaxis of lysosomal storage diseases, neurodegenerative disease, cystic disease, cancer, or a diseases or disorders associated with elevated levels of glucosylceramide (GlcCer), glucosylsphingosine (GlcSph) and/or other glucosylceramide-based glycosphingolipids (GSLs).

Claims (120)

1 . A compound of the formula I:

or a pharmaceutically acceptable salt thereof, wherein

X is C or N, provided that when there is one Z moiety present, then X is N;

Z is —CR 4 —,

each R 1 is independently C1-C4 alkyl, C1-C4 fluoroalkyl, —C0-C4alkylOH, cyano, C1-C4alkoxy, or halo;

each R 4 is independently hydrogen, C1-C4 alkyl, C1-C4 fluoroalkyl, —C0-C4alkylOH, cyano, C1-C4alkoxy, or halo;

is selected from

(tetrahydropuranyl)aminocarbonyl, (tetrahydro-2H-puranyl)aminocarbonyl, (1,1, 1-trifluoro-2-methylprop-2yl)aminocarbonyl, (tetrahydrofuranyl)aminocarbonyl, cyclopropylaminocarbonyl, piperazinylcarbonyl, isobutylaminocarbonyl, (3,3,3-trifluoroprop-2yl)aminocarbonyl, tertbutylaminocarbonyl, (6,7-dihydropyrrolo [3,4-b]pyridyl)carbonyl ((6,7-dihydro-5H-pyrrolo [3,4-b]pyridyl)carbonyl), 1-hydroxyethyl, 2-hydroxyprop-2yl, hydroxymethyl, dihydrooxazolyl, 4,5-dihydrooxazolyl, pyridinylaminocarbonyl, 2-pyridylaminocarbonyl, 3-pyridylaminocarbonyl, (4-pyridyl) aminocarbonyl, piperidinylaminocarbonyl, (bicyclo[2.2.2]octanyl)aminocarbonyl, cyclopentylaminocarbonyl, cyclohexylaminocarbonyl, (trifluoromethylaminomethyl)aminocarbonyl, (trifluoromethylaminoethyl)aminocarbonyl, (bicyclo[2.2.1]heptyl)aminocarbonyl, tetrahydropyranylaminocarbonyl, N-(tetrahydro-2H-pyran-3-yl)aminocarbonyl, (pyridylmethyl)aminocarbonyl, cyclobutylaminocarbonyl, (bicyclo[1.1.1]pentyl)aminocarbonyl, (azabicyclo[2.1.1]hexyl)carbonyl, (2-azabicyclo [2.1.1]hexyl)carbonyl, (oxadiazaspiro [3.5]nonyl)carbonyl, (5-oxa-2,8-diazaspiro [3.5]nonyl)carbonyl, (dioxaazaspiro [4.5]decyl)carbonyl, (2,9-dioxa-6-azaspiro [4.5]decyl)carbonyl, (dioxaazaspiro [3.5]nonyl)carbonyl, (2,5-dioxa-8-azaspiro [3.5]nonyl)carbonyl, dihydrooxazolyl, 4,5-dihydrooxazolyl, (pyridylmethyl)aminocarbonyl, (2-pyridylmethyl) aminocarbonyl, (oxetanyl)aminocarbonyl, (3-oxetanyl)aminocarbonyl, oxadiazaspiro [3.4]octenyl, 5-oxa-2,7-diazaspiro [3.4]oct-6-enyl, (pyrrolidinylethyl)aminocarbonyl, (5,6,7,8-tetrahydroimidazo[1,2-a] pyrazinyl)carbonyl, aminomethyl, (azabicyclo[3.1.0]hexyl)carbonyl, (3-azabicyclo [3.1.0]hexyl)carbonyl, cyclopropylmethyl, (tert-butyl)aminomethyl, (tetrahydropyranyl) methyl, (tetrahydro-2H-pyranyl) methyl, and cyclobutylcarbonylamino;

each R 2 is independently selected from halo, (C1-C4 fluoroalkyl) oxy, hydroxy, C1-C4 alkyl, and —(C0-C4 alkyl) O (C1-C4 alkyl); and

each R 3 is independently selected from C1-C4 alkyl, halo, oxo, cyano, amino, C1-C4 fluoroalkyl, hydroxy, —(C0-C4alkyl)O(C1-C4 alkyl), and —(C1-C4 alkyl)OH.

2 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently methyl, ethyl, propyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, hydroxy, hydroxymethyl, cyano, methoxy, ethoxy, chloro, or fluoro.

3 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently chloro, trifluoromethyl, methoxy, fluoro, or cyano.

4 . The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein each R 2 independently is chloro, fluoro, trifluoromethoxy, trifluoroethoxy, 2,2,2-trifluoroethoxy, hydroxy, methyl, ethyl, isopropyl, methoxy, ethoxy, ethoxymethyl, or methoxymethyl.

5 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 3 independently is selected from methyl, ethyl, propyl, isopropyl, butyl, fluoro, chloro, oxo, cyano, amino, trifluoromethyl, 2,2,2-trifluoroethyl, hydroxy, methoxy, ethoxy, propoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, and 2-hydroxy(prop-2yl).

6 . The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein each R 3 independently is selected from fluoro, methyl, hydroxymethyl, fluoromethyl, aminomethyl, 2-hydroxy(prop-2yl), hydroxy, cyano, methoxyethyl, methoxymethyl, trifluoromethyl and methoxy.

7 . The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein each R 4 independently is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, fluoromethyl, difluoromethyl, difluoroethyl, hydroxy, hydroxymethyl, hydroxyethyl, hydroxyisopropyl, hydroxypropyl, cyano, methoxy, ethoxy, propoxy, isopropoxy, butoxy, chloro, fluoro, and bromo.

8 . The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein each R 4 independently is hydrogen or fluoro.

9 . The compound of claim 8 or a pharmaceutically acceptable salt thereof, wherein X is C.

10 . The compound of claim 8 or a pharmaceutically acceptable salt thereof, wherein X is N.

11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from:

N-(1-hydroxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)—N-(tetrahydro-2H-pyran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(tetrahydro-2H-pyran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(1,1,1-trifluoro-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)-8-(2-(2,2,2-trifluoroethoxy)phenyl)-N-(1,1,1-trifluoropropan-2-yl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)-6-chloro-N-(tetrahydrofuran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-(1-(methoxymethyl)cyclopropyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) (3,3,4-trimethylpiperazin-1-yl) methanone;

6-chloro-N-(2-cyano-2-methylpropyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1,1,1-trifluoro-3-hydroxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)—N-(1,1,1-trifluoro-3-hydroxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1,1,1-trifluoro-3-hydroxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(1-methoxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(5,7-dihydro-6H-pyrrolo [3,4-b]pyridin-6-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanone;

N-(tert-butyl)-6-fluoro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)-6-chloro-N-(3-methyltetrahydrofuran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)-6-chloro-N-(3-methyltetrahydrofuran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(pyridin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(trans-4-fluoropiperidin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)—N-(4,4-difluoropiperidin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(4,4-difluoropiperidin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(4-(hydroxymethyl) bicyclo[2.2.2]octan-1-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(trans-3-hydroxycyclopentyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-(1-hydroxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(1-(hydroxymethyl) cyclopentyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-((1S,2R,4S)-2-fluoro-4-hydroxycyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-((1R,2S,4R)-2-fluoro-4-hydroxycyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(2-amino-3,3,3-trifluoropropyl)-6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-(trans-4-hydroxycyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-(4-hydroxybicyclo [2.2.1]heptan-1-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

cis-6-fluoro-N-(4-hydroxy-4-methylcyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

trans-6-fluoro-N-(4-hydroxy-4-methylcyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-fluoro-N-(cis-4-(hydroxymethyl)cyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-cyclopentyl-6-fluoro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(trans-4-(hydroxymethyl)cyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

8-(5-chloro-2-methoxyphenyl)-N-(4-hydroxybicyclo [2.2.1]heptan-1-yl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(cis-3-(hydroxymethyl)cyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

3-fluoro-N-(trans-4-hydroxycyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

3-fluoro-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(3-cyanotetrahydrofuran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)-6-chloro-N-(3-methyltetrahydro-2H-pyran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)-6-chloro-N-(3-methyltetrahydro-2H-pyran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(trans-4-hydroxycyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(1-hydroxy-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide;

(R)—N-(2,2,2-trifluoro-1-(pyridin-3-yl) ethyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(2,2,2-trifluoro-1-(pyridin-3-yl) ethyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-cyano-N-(trans-4-hydroxycyclohexyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-cis-3-(hydroxymethyl) cyclobutyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-fluoro-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(tetrahydro-2H-pyran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-methoxy-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-cyano-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-((3R,4R)-4-fluorotetrahydrofuran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

6-chloro-N-((3S,4R)-4-fluorotetrahydrofuran-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(3-(hydroxymethyl) bicyclo[1.1.1]pentan-1-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(1-(fluoromethyl)-2-azabicyclo [2.1.1]hexan-2-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanone;

(2-methyl-5-oxa-2,8-diazaspiro [3.5]nonan-8-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanone;

(R)-(2,6-dioxa-9-azaspiro [4.5]decan-9-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanone;

(S)-(2,6-dioxa-9-azaspiro [4.5]decan-9-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanone;

(2,5-dioxa-8-azaspiro [3.5]nonan-8-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl) methanone;

N-(pyridin-2-ylmethyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(2,2-dimethyloxetan-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-methyl-N-(2-(pyrrolidin-1-yl) ethyl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(5,6-dihydroimidazo[1,2-a] pyrazin-7 (8H)-yl) (8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanone;

N-(4-methylpyridin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

N-(4-fluoropyridin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

3-(8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamido) pyridine 1-oxide;

N-(3-cyanopyridin-4-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)((1R,5R)-6-(hydroxymethyl)-3-azabicyclo [3.1.0]hexan-3-yl) methanone;

6-fluoro-N-(pyridin-3-yl)-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridine-2-carboxamide;

(8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl) methanol;

(R) 1-(8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl) ethan-1-ol;

(S) 1-(8-(2-(2,2,2-trifluoroethoxy)phenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl) ethan-1-ol;

1-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl] ethanol;

[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-cyclopropyl-methanol;

2-(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) propan-2-ol;

2-(6-chloro-8-(4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) propan-2-ol;

(6-fluoro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) (tetrahydro-2H-pyran-4-yl) methanol;

2-(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)-5,5-dimethyl-4,5-dihydrooxazole;

6-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-2-methyl-5-oxa-2,7-diazaspiro [3.4]oct-6-ene;

(2-(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)-5-methyl-4,5-dihydrooxazol-5-yl) methanol;

[2-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-4,5-dihydrooxazol-4-yl] methanol;

[2-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-4-methyl-5H-oxazol-4-yl] methanol;

(2-(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazol-5-yl) methanamine;

2-(2-(6-chloro-8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)-4,5-dihydrooxazol-4-yl) propan-2-ol;

2-[2-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-4,5-dihydrooxazol-5-yl] propan-2-ol;

2-[2-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-5-methyl-4H-oxazol-5-yl] propan-2-ol;

2-[2-[6-chloro-8-[2-(2,2,2-trifluoroethoxy)phenyl]imidazo[1,2-a]pyridin-2-yl]-4-methyl-5H-oxazol-4-yl] propan-2-ol;

2-methyl-N-((8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methyl) propan-2-amine;

(8-(2-(2,2,2-trifluoroethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl) methanamine;

cis-3-hydroxy-N-(8-(2-(2,2,2-trifluoroethoxy)phenyl) quinolin-2-yl) cyclobutane-1-carboxamide;

trans-3-hydroxy-N-(8-(2-(2,2,2-trifluoroethoxy)phenyl) quinolin-2-yl) cyclobutane-1-carboxamide;

trans-N-(5-fluoro-8-(2-(2,2,2-trifluoroethoxy)phenyl) quinolin-2-yl)-3-hydroxycyclobutane-1-carboxamide; and

N-cis-3-hydroxycyclobutyl)-5-(2-(2,2,2-trifluoroethoxy)phenyl) isoquinoline-3-carboxamide.

12 . A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

13 . The pharmaceutical composition of claim 12 , or a pharmaceutically acceptable salt thereof, further comprising one or more additional therapeutic agents.

14 . A method for treatment of lysosomal storage diseases, kidney disease, neurodegenerative disease, diabetes related diseases, or cancers where GSL synthesis is abnormal or overexpression of GCS disrupts ceramide-induced apoptosis, which comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

15 . A method for treatment of Parkinson's Disease comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 1 .

16 . A method for treatment of a disease selected from dementia with Lewy bodies, polycystic kidney disease, renal hypertrophy, diabetes mellitus, obesity, hyperglycemia, hyperinsulemia, leukemia, papillary renal cancer, and thyroid carcinomas, comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 1 .

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 1, 2023

From: FORD, MELISSA C.; FRALEY, MARK E.; JONES, KRISTEN L.G.; LOUGHRAN, H. MARIE; MULHEARN, JAMES J.; ROECKER, ANTHONY J.; SCHIRRIPA, KATHY M.; TONG, LING

To: MERCK SHARP & DOHME CORP.

Reel/Frame 062839/0780 →

MERGER Recorded Mar 1, 2023

From: MERCK SHARP & DOHME CORP.

To: MERCK SHARP & DOHME LLC

Reel/Frame 062839/0984 →

Continuity (2)

Provisional Application 63079495 · Sep 17, 2020

Related Publication 20240018140A1 · Jan 18, 2024

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