2-cyano-4-fluoropyrrolidine derivative or its salt
View Patent ↗Provided is a compound having excellent dipeptidyl peptidase IV-inhibiting activity, and a remedy based on the activity for insulin-dependent diabetes (type 1 diabetes), especially for non insulin-dependent diabetes (type 2 diabetes), insulin-resistant disorders, and obesity.
1. A 2-cyano-4-fluoropyrrolidine compound of Formula (I):
wherein A is a group of Formula (II):
wherein R 1 -B represents methanesulfonyl, formyl or acetyl which may be substituted by a group selected from the group consisting of —OH and fluoro;
R 2 represents —H, methyl or ethyl;
or a pharmaceutically acceptable salt thereof.
2. A compound selected from the group consisting of:
4-fluoro-1-({[1-(methanesulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile,
4-fluoro-1-({[4-methyl-1-(methanesulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile,
4-fluoro-1-{[(1-glycoloylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile,
4-fluoro-1-{[(1-glycoloyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile
4-fluoro-1-{[(1-fluoroacetyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine -2-carbonitrile,
4-fluoro-1-{[(1-formylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile,
4-fluoro-1-{[(1-formyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, and
4-fluoro-1-({[1-(morpholin-4-ylcarbonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile,
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutical acceptable salt thereof of claim 1 as an active ingredient, and a pharmaceutically acceptable carrier.
4. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
(2S,4S)-4-fluoro-1-({[4-methyl-1-(methanesulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile,
(2S,4S)-4-fluoro-1-{[(1-glycoloyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile,
(2S,4S)-4-fluoro-1-{[(1-fluoroacetyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, and
(2S,4S)-4-fluoro-1-{[(1-formyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile,
or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutical acceptable salt thereof of claim 4 as an active ingredient, and a pharmaceutically acceptable carrier.