N-(1-hydroxy-3-(pyrrolidinyl)propan-2-yl)pyrrolidine-3-carboxamide derivatives as glucosylceramide synthase inhibitors
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Abstract
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and compounds I for use to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
5 Citations
17 Claims
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1. A compound of Formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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2. The compound of claim 1, which is according to Formula I(a):
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3. The compound of claim 1, which is according to Formula I(d1):
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4. The compound of claim 1, wherein R5 is hydroxy and R5a is hydrogen;
- optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
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5. The compound of claim 1, wherein R6 is aryl, optionally independently substituted with 1 or 2 R10 groups;
- optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
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6. The compound of claim 1, wherein R6 is heterocycloalkyl or heteroaryl, each optionally substituted with 1 or 2 R10 groups;
- optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
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7. The compound of claim 1, wherein:
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R4 is aryl or heteroaryl each of which is optionally substituted with 1 or 2 R9 groups; R5 is hydroxy, and R5a is hydrogen; R6 is alkyl, aryl, arylalkyl, arylcarbonyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl;
wherein each aryl and heteroaryl, whether alone or as part of another group, is optionally substituted with 1 or 2 R10 groups; and
wherein each heterocycloalkyl and cycloalkyl, whether alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from hydroxy, halo, haloalkyl, alkoxy, and alkyl;each R8, when present, is independently alkyl, hydroxy, alkoxy, halo, or haloalkyl; each R9, when present, is independently cyano, nitro, halo, haloalkyl, alkyl, hydroxy, alkoxy, haloalkoxy, hydroxyalkoxy, alkenyloxy, cycloalkyloxy, cycloalkylalkyloxy, cycloalkylthio, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylalkyloxy;
where each heterocycloalkyl, whether alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from alkyl, hydroxy, alkylcarbonyl, and alkoxycarbonyl;each R10, when present, is independently is cyano, halo, haloalkyl, alkyl, hydroxy, alkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aryl, aryloxy, heteroaryloxy, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylalkyloxy;
where each aryl or heteroaryl either alone or as part of another group, is independently optionally substituted with 1 or 2 halo or alkyl groups; and
each heterocycloalkyl, either alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from alkyl and hydroxy; andoptionally a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally a pharmaceutically acceptable salt thereof.
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8. The compound of claim 1, which is according to Formula I(c):
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9. The compound of claim 1, which is according to Formula I(d2):
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10. The compound of claim 1, wherein:
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R1 is N—
(R6)-pyrrolidinyl attached to the C(O) by a carbon atom;R2 and R3 together with the nitrogen to which they are attached form azetidinyl or pyrrolidinyl; R5 is hydroxy and R5a is hydrogen; and
optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
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11. The compound of claim 1, wherein R6 is aryl or heteroaryl, wherein the aryl is optionally independently substituted with 1 or 2 halo, alkyl, cycloalkyloxy, or heterocycloalkyloxy;
- and the heteroaryl is optionally independently substituted with 1 or 2 halo, alkyl, or cycloalkyloxy; and
optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
- and the heteroaryl is optionally independently substituted with 1 or 2 halo, alkyl, or cycloalkyloxy; and
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12. The compound of claim 1, wherein R6 is heterocycloalkyl optionally independently substituted with 1 or 2 halo, hydroxy, or alkyl;
- and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
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13. The compound of claim 1, wherein the compound is selected from the group consisting of
(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; -
1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-3-carboxamide;(R)-1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidine-3-carboxamide;1-cyclopentyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(2,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(2,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorobenzyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorobenzyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorobenzyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(thiazol-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(thiazol-2-yl)pyrrolidine-3-carboxamide;1-(4-chloro-3-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenethyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorophenethyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenethyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;1-cyclohexyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(5-chloropyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(5-chloropyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(5-chloropyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-butyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(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)pyrrolidine-3-carboxamide; 1-(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)pyrrolidine-3-carboxamide; (S)-1-(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)pyrrolidine-3-carboxamide; (R)-1-(2-cyclopropoxypyridin-4-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(2-cyclopropoxypyridin-4-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(2-cyclopropoxypyridin-4-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-cyclopropoxypyridin-3-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(6-cyclopropoxypyridin-3-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-6-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-7-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-7-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-7-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;(R)-1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; N-[2-(2H,3H-benzo[e]1,4-dioxan-6-yl)(1R,2R)-2-hydroxy-1-(pyrrolidinylmethyl)ethyl][1-(4-chlorophenyl)pyrrolidin-3-yl]carboxamide; (R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7, 8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7, 8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,6-dimethylpyridin-4-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,6-dimethylpyridin-4-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinoxalin-6-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinoxalin-6-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinoxalin-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1,5-naphthyridin-3-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1,5-naphthyridin-3-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7, 8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7, 8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-7-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(2-chlorobenzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-(4-chlorophenoxy)pyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-(4-chlorophenoxy)pyridin-2-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)-1-benzoyl-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-benzoyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-5-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(5-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(8-(trifluoromethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-(tert-butyl)phenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(5-chloro-6-(4-fluorophenyl)pyridin-2-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-hydroxypyrrolidine-3-carboxamide; and (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-hydroxypyrrolidine-3-carboxamide; and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
-
-
14. The compound of claim 1, wherein the compound is selected from the group consisting of:
-
(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide; N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-(trifluoromethoxy)phenyl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-isopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-isopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((1-methylpiperidin-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((1-methylpiperidin-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5-chloropyridin-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5-chloropyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-(2-(azetidin-1-yl)ethoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(4-(2-(azetidin-1-yl)ethoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-morpholinophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-morpholinophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(3-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(3-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-chloroquinolin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chlorobenzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chlorobenzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-chlorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chloro-5-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-5-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(4-fluorophenoxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-benzoyl-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chloro-3-((6-methylpyridin-2-yl)oxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-(tert-butoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(cyclohexyloxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-chloro-4′
-fluoro-[1,1′
-biphenyl]-3-yl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-(tert-butyl)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclobutoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(cyclopentyloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(cyclopropylthio)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5-chloro-6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(3-chloro-4-(vinyloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-cyanophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-cyanophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(p-tolyl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(benzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-(difluoromethoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1 R,2R)-1-(4-(difluoromethoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide; and(R)—
N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
-
-
15. The compound of claim 1, wherein the compound is selected from the group consisting of:
-
(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide; (R)-1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-(trifluoromethoxy)phenyl)pyrrolidine-3-carboxamide; (R)-1-(2,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(2,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;1-(4-chloro-3-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-isopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-isopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((1-methylpiperidin-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((1-methylpiperidin-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,2-dimethylchroman-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,2-dimethylchroman-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(4-(2-(azetidin-1-yl)ethoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(4-(2-(azetidin-1-yl)ethoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-(oxetan-3-yloxy)pyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-morpholinophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-morpholinophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(3-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(3-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;N-[2-(2H,3H-benzo[e]1,4-dioxan-6-yl)(1R,2R)-2-hydroxy-1-(pyrrolidinylmethyl)ethyl][1-(4-chlorophenyl)pyrrolidin-3-yl]carboxamide; (R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; 1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (S)-1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide; (S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chloro-5-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(4-fluorophenoxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(5-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chloro-3-((6-methylpyridin-2-yl)oxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(4-(tert-butoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-chloro-3-(cyclohexyloxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(8-(trifluoromethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(6-chloro-4′
-fluoro-[1,1′
-biphenyl]-3-yl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-(tert-butyl)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(3-chloro-4-cyclobutoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(cyclopentyloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)-1-(4-(tert-butyl)phenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-1-(benzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(cyclopropylthio)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-(vinyloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;(R)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-cyanophenyl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-cyanophenyl)pyrrolidine-3-carboxamide;(R)—
N-((1 R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(p-tolyl)pyrrolidine-3-carboxamide;(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-hydroxypyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-hydroxypyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(S)—
N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-(difluoromethoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; (R)—
N-((1 R,2R)-1-(4-(difluoromethoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide; and(R)—
N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.
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16. A pharmaceutical composition comprising the compound of claim 1, optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.
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17. A method of making a compound according to claim 1 where R5 is hydroxy and R5a is hydrogen comprising:
a) treating an intermediate of formula 100
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2. The compound of claim 1, which is according to Formula I(a):
Specification
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Current AssigneeBiomarin Pharmaceutical Incorporated (Amgen Inc.)
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Original AssigneeBiomarin Pharmaceutical Incorporated (Amgen Inc.)
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InventorsWang, Bing
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Primary Examiner(s)Padmanabhan, Sreenivasan
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Assistant Examiner(s)Karol, Jody L
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Application NumberUS15/032,613Publication NumberTime in Patent Office1,610 DaysField of SearchNoneUS Class CurrentCPC Class CodesA61P 1/04 for ulcers, gastritis or re...A61P 11/06 AntiasthmaticsA61P 13/12 of the kidneysA61P 19/02 for joint disorders, e.g. a...A61P 25/00 Drugs for disorders of the ...A61P 29/00 Non-central analgesic, anti...A61P 3/00 Drugs for disorders of the ...A61P 3/04 Anorexiants; Antiobesity ag...A61P 3/10 for hyperglycaemia, e.g. an...A61P 31/04 Antibacterial agentsA61P 35/00 Antineoplastic agentsA61P 39/00 General protective or antin...A61P 43/00 Drugs for specific purposes...A61P 9/10 for treating ischaemic or a...C07D 207/16 Carbon atoms having three b...C07D 319/16 condensed with one six-memb...C07D 401/04 directly linked by a ring-m...C07D 401/12 linked by a chain containin...C07D 401/14 containing three or more he...C07D 403/12 linked by a chain containin...C07D 405/12 : linked by a chain containin...C07D 405/14 : containing three or more he...C07D 409/04 : directly linked by a ring-m...C07D 409/12 : linked by a chain containin...C07D 409/14 : containing three or more he...C07D 417/14 : containing three or more he...C07D 471/04 : Ortho-condensed systems