1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives as MAGL inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is H, —P(═O)(OR81)(OR82);
• or —S(═O)2OR90;
• each of R81, R82, and R90 is independently selected from the group consisting of H and C1-6 alkyl, wherein each of the C1-6 alkyl is optionally substituted with one or more substituents each independently selected from the group consisting of —NH2, —NH(C1-4 alkyl), and —N(C1-4 alkyl)2;
• each RS is independently selected from the group consisting of OH, oxo, halogen, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-C1-2 alkyl-, C1-4 alkoxy, and C1-4 haloalkoxy;
• n1 is 0, 1, 2, 3, 4, 5, or 6;
• the moiety of Formula M-1 of Formula I
• is a moiety of Formula M-1a, M-1b, or M-1c:
• each of R2A and R2C is, independently, —NR3S(═O)2R4, —NR3C(═O)R4;
• R5, or —OR5;
• R2B is selected from the group consisting of [4-(trifluoromethyl)-1H-pyrazol-1-yl]methyl-, (cyclopentylcarbonyl)(methyl)amino-, (tert-butylsulfonyl)(methyl)amino-, (2,2-dimethylpropanoyl)(methyl)amino-, 4-(trifluoromethyl)-1H-pyrazol-1-yl-, 4-fluoro-1H-pyrazol-1-yl-, 3-cyanophenyl-, 6-(trifluoromethyl)pyridin-2-yl-, 5-fluoropyridin-2-yl-, 4-(difluoromethyl)-1H-pyrazol-1-yl-, 4-tert-butyl-1H-pyrazol-1-yl-, 4-chlorol-1H-pyrazol-1-yl-, 4-cyclopropyl-1H-pyrazol-1-yl-, 4-methyl-1H-pyrazol-1-yl-, 2-fluorophenyl-, 4-cyano-3-fluorophenyl-, 3-cyano-4-fluorophenyl-, 5-cyano-2-fluorophenyl-, 4-cyanophenyl-, 2,6-difluorophenyl-, 2,4-difluorophenyl-, 4-fluorophenyl-, 4-(difluoromethyl)pyridin-2-yl-, 6-(difluoromethyl)pyridin-3-yl-, 5-cyanopyridin-2-yl-, 5-(difluoromethyl)pyridin-2-yl-, 5-(trifluoromethyl)pyridin-2-yl-, pyridin-2-yl-, 3-tert-butyl-1H-pyrazol-1-yl-, 3-(trifluoromethyl)-1H-pyrazol-1-yl-, 3,4-dimethyl-1H-pyrazol-1-yl-, {[(3,3-difluorocyclobutyl)methyl]sulfonyl}(methyl)amino-, [(3,3-difluorocyclobutyl)carbonyl](methyl)amino-, 1H-indazol-1-yl-, 3-cyano-2-fluorophenyl-, and 4-cyano-2-fluorophenyl-;
• each R3 is independently C1-3 alkyl;
• each R4 is independently selected from C1-6 alkyl, C3-7 cycloalkyl, (C3-7 cycloalkyl)-C1-2 alkyl-, (C6-10 aryl)-C1-2 alkyl-, (5- or 10-membered heteroaryl)-C1-2 alkyl-, 5- or 10-membered heteroaryl, and C6-10 aryl, wherein each of the selections is substituted with 0, 1, 2, or 3 halogen;
• or R3 and R4, together with the intervening moiety of “—NS(═O)2—” or “—NC(═O)—” to which they are attached, form a 4- to 10-membered heterocycloalkyl that is substituted with 0, 1, 2, 3, 4, or 5 substituents each independently selected from the group consisting of OH, oxo, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy, and wherein each of the ring-forming atoms of the 4- to 10-membered heterocycloalkyl is C, N, O, or S;
• and
• each R5 is phenyl or 5- or 6-membered heteroaryl, wherein each of the phenyl or 5- or 6-membered heteroaryl is substituted with 0, 1, 2, or 3 substituents each independently selected from the group consisting of —CN, halogen, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy, and wherein each of the ring-forming atoms of the 5- or 6-membered heteroaryl is a carbon atom or a nitrogen atom.