Glucosylceramide synthase inhibitors and therapeutic methods using the same
AssigneeThe Regents of the University of Michigan
InventorsScott Larsen, Akira Abe, Liming Shu, Michael William Wilson, Richard F. Keep, James A. Shayman
Life of this patent
Estimating the term…
Abstract
Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.
Claims38
A compound having a structure
- wherein R1 is H or C1-3alkyl;
- R2 is (i) —(CH2)1-3C6H5 with the proviso that R1 is —C1-3alkyl,
- (ii) —CH2(Ra2)1,2—C6H5, wherein Ra independently is H or C1-3alkyl, with the proviso that at least one Ra is C1-3alkyl,
- wherein for (i) through (v) the C6H5 group optionally is substituted with one or two of -halo or —ORa, or
- wherein the fused ring A is a 4- to 8-membered ring, saturated or partially unsaturated, and comprising carbon atoms and optionally one or two heteroatoms selected from O, S, and NRa, and wherein the fused phenyl ring is optionally substituted with one or two substituents;
- and
- R3 is
- wherein the fused ring B is a five- or six-membered ring, saturated or partially or fully unsaturated, comprising carbon atoms and one or two heteroatoms selected from O, S, and NRa, and wherein the phenyl ring is optionally substituted with one or two substitutents;
- or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
(canceled)
(canceled)
(canceled)
(canceled)
(canceled)
A compound selected from the group consisting of N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)cinnamamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-2-phenylcyclopropanecarboxamide, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-2,3-dihydro-1H-indene-2-carboxamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-N-methyl-3-phenylpropanamide, N-((1R,2R)-1-hydroxy-1-(2-methoxyphenyl)-3-(pyrrolidin-1-yl)propan-2-yl)octanamide. 25, N-((1R,2R)-1-(3-(dimethylamino)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)octanamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-(3-fluorophenyl)propanamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-(4-fluorophenyl)propanamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-phenylbutanamide (mixture of diastereomers), N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-(2-methoxyphenyl)propanamide, N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-2-(phenylamino)acetamide, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide oxylate monohydrate, and N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-2-phenylacetamido,
- or a pharmaceutically acceptable salt thereof.
(canceled)
(canceled)
(canceled)
(canceled)
(canceled)
(canceled)
(canceled)
Dependencies are inferred from the claim text.