Carbamate compounds and of making and using same
Provided herein are carbamate compounds which may be useful in the treatment of for example, pain, solid tumors and/or obesity.
1. A compound represented by:
wherein
R s1 is independently selected for each occurrence from the group consisting of H, halogen, cyano, hydroxyl, phenyl, C 1-6 alkyl (optionally substituted by one, two, or three halogens, cyano, phenyl, or hydroxyl), and C 1-6 alkoxy (optionally substituted by one, two, or three halogens, cyano, or hydroxyl);
L 3 is —CH 2 —;
R 7 is phenyl; wherein R 7 is substituted by R a R b N— and a moiety selected from the group consisting of: halogen, C 1-6 alkyl (optionally substituted by one, two or three halogens), and C 1-6 alkoxy (optionally substituted by one, two or three halogens);
R a and R b , together with the nitrogen to which they are attached, form a saturated 4-6 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the saturated 4-6 membered heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, C 1-6 alkyl, —S(O) w —C 1-6 alkyl (where w is 0, 1 or 2), hydroxyl, —C(O)—C 1-6 alkyl, and —NH—C(O)—C 1-6 alkyl;
or a pharmaceutically acceptable salt or stereoisomer thereof.
2. The compound of claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof, wherein R a and R b , together with the nitrogen to which they are attached, form a saturated 4-6 membered heterocyclic ring selected from azetidine, pyrrolidine, piperidine, piperazine, and morpholine, and the saturated 4-6 membered heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, C 1-6 alkyl, —S(O) w —C 1-6 alkyl (where w is 0, 1 or 2), hydroxyl, —C(O)—C 1-6 alkyl, —NH 2 , and —NH—C(O)—C 1-6 alkyl.
3. The compound of claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the saturated 4-6 membered heterocyclic ring is pyrrolidine.
4. The compound of claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the saturated 4-6 membered heterocyclic ring is morpholine.
5. The compound of claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the saturated 4-6 membered heterocyclic ring is piperidine.
6. A compound selected from the group represented by: 2,5-dioxopyrrolidin-1-yl 4-(2-fluoro-4-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-methyl-4-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-bromo-2-(piperidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-bromo-2-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-methoxy-4-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-methyl-4-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-chloro-2-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-bromo-2-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-chloro-2-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(3-fluoro-4-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[4-(morpholin-4-yl)-2-(trifluoromethyl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-chloro-4-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-chloro-6-(morpholin-4-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[3-chloro-2-(morpholin-4-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-(3-acetamidopyrrolidin-1-yl)-4-chlorobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(morpholin-4-yl)-4-(trifluoromethyl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[5-chloro-2-(morpholin-4-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[3-fluoro-2-(morpholin-4-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-chloro-4-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-chloro-6-(pyrrolidin-1-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[5-chloro-2-(pyrrolidin-1-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(3-chloro-4-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[4-(morpholin-4-yl)-2-(trifluoromethoxy)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[4-(pyrrolidin-1-yl)-2-(trifluoromethoxy)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[3-chloro-2-(pyrrolidin-1-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[3-fluoro-2-(pyrrolidin-1-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[4-chloro-2-(4-methanesulfonylpiperazin-1-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(azetidin-1-yl)-4-chlorophenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(4-acetylpiperazin-1-yl)-4-chlorophenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-methyl-3-morpholinobenzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-methyl-3-(piperidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(2-methyl-3-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-fluoro-3-(pyrrolidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[5-methyl-2-(morpholin-4-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[5-methyl-2-(pyrrolidin-1-yl)phenyl]methyl}piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(4-chloro-2-(piperidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-(3-chloro-5-(piperidin-1-yl)benzyl)piperazine-1-carboxylate; 2,5-dioxopyrrolidin-1-yl 4-{[2-(propan-2-yl)-4-(pyrrolidin-1-yl)phenyl]methyl}piperazine-1-carboxylate; and 2,5-dioxopyrrolidin-1-yl 4-{[4-(morpholin-4-yl)-2-(propan-2-yl)phenyl]methyl}piperazine-1-carboxylate;
or a pharmaceutically acceptable salt or stereoisomer thereof.
7. A pharmaceutically acceptable composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.
8. A pharmaceutically acceptable composition comprising a compound of claim 6 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.
9. A method of treating pain in a patient in need thereof, comprising administering to a patient in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
10. A method of treating pain in a patient in need thereof, comprising administering to a patient in need thereof an effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt or stereoisomer thereof.