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US 2019/0292203 A1Published application
Heterocyclic spiro compounds as magl inhibitors
AssigneePfizer Inc.
InventorsMichael Aaron Brodney, Christopher Ryan Butler, Laura Ann McAllister, Chistopher John Helal, Steven Victor O'Neil, Patrick Robert Verhoest
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Abstract
The present invention provides, in part, heterocyclic spiro compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
Claims20
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- ring A1 is C4-7 cycloalkyl or 4- to 7-membered heterocycloalkyl;
- R1 is R1A or R1B;
- R1A is 1,1,1,3,3,3-hexafluoropropan-2-yl-;
- R1B is 2,5-dioxopyrrolidin-1-yl-, which is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of the group consisting of halogen, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-C1-2 alkyl-, C1-4 alkoxy, and C1-4 haloalkoxy;
- each R2 is independently selected from the group consisting of halogen, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-C1-2 alkyl-, C1-4 alkoxy, and C1-4 haloalkoxy;
- each R3 is independently selected from the group consisting of —OH, oxo, halogen, —CN, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-C1-2 alkyl-, C1-4 alkoxy, and C1-4 haloalkoxy;
- R4 is selected from the group consisting of R6, —N(R5)(C(═O)R6), —N(R5)(S(═O)2R6), —C(═O)—R6, —S(═O)2R6, —NR5R6, —SO2NR5R6, and —OR6;
- R5 is selected from the group consisting of H, C1-4 alkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-C1-2 alkyl-;
- R6 is selected from the group consisting of C1-6 alkyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, (C3-10 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —CN, oxo, —OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxylalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-C1-2 alkyl-, C1-4 alkoxy, C1-4 haloalkoxy, —C(═O)C1-4 alkyl, —C(═O)OH, —C(═O)O—C1-4 alkyl, —C(═O)NHC1-4 alkyl, —C(═O)N(C1-4 alkyl)2, —OC(═O)—C1-4 alkyl, —OC(═O)O—C1-4 alkyl, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NHC(═O)C1-4 alkyl, —NHC(═O)OC1-4 alkyl, and —NHC(═O)NHC1-4 alkyl;
- t1 is 0, 1, or 2;
- t2 is 0, 1, 2, 3, or 4;
- and
- t3 is 0 or 1.
11 more elements
Dependencies are inferred from the claim text.