Compound having ability to inhibit 11Beta-HSD1 enzyme or pharmaceutically acceptable salt thereof, method for producing same, and pharmaceutical composition containing same as active ingredient
The present invention relates to a novel compound or a pharmaceutically acceptable salt thereof inhibiting 11β-HSD1 enzyme activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. Since the compound of the present invention selectively inhibits the activity of 11β-HSD1 (11β-Hydroxysteroid dehydrogenase type 1), the compound of the invention can be effectively used as a therapeutic agent for the treatment of diseases caused by the over-activation of 11β-HSD1 such as non-insulin dependent type II diabetes, insulin resistance, obesity, lipid disorder, metabolic syndrome, and other diseases or condition mediated by the excessive activity of glucocorticoid.
1. A compound or pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of the following compounds:
(3) E-4-[1-((2-fluoro-benzenesulfonylamino)methyl)cyclopropanecarboxamido]-adamantan-1-carboxylic acid amide;
(22) E-4-[1-((2-fluoro-N-methyl-benzenesulfonylamino)methyl)cyclopropanecarboxamido]-adamantan-1-carboxylic acid amide;
(71) E-4-[2-(2-fluoro-benzenesulfonylamino)-2-methylpropanamido]-adamantan-1-carboxylic acid amide;
(84) E-4-[2-(2,6-difluoro-benzenesulfonylamino)-2-methylpropanamido]adamantan-1-carboxylic acid amide;
(113) E-sodium[3-((5-carbamoyladamantan-2-yl)carbamoyl)phenyl]-2-fluoro-3-chloro-benzenesulfonylamide; and
(119) E-4-[3-(3,5-dichloro-benzenesulfonylamino)-benzamido]-adamantan-1-carboxylic acid amide.
2. A preparation method of the compound of claim 1 containing the step of reacting the compound represented by formula 2 with the compound represented by formula 3 in the presence of an organic solvent to prepare the compound of formula 1:
wherein,
X is sulfonyl,
R 1 is
R 2 is —H,
R 3 is
R 4 is —H, —CH 3 or —Na, and
A is
3. A pharmaceutical composition for the treatment of a disease, comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient, wherein the disease is non-insulin dependent type II diabetes, insulin resistance, obesity, lipid disorder or metabolic syndrome.