SPIRO AMINIC COMPOUNDS WITH NK1 ANTAGONIST ACTIVITY
The invention concerns a spiro-amino compound of Formula (I), wherein A is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring containing 1 to 3 nitrogen atom; X is a substituent selected from the group consisting of (C 1 -C 3 )alkyl and halogen, Y is a substituent selected from the group consisting of halogen and trifluoromethyl or a pharmaceutically acceptable salt thereof for use in the treatment of pathologies which require an antagonist of the NK1 receptor.
1 . A method for the treatment of pathologies which require an antagonist of the NK1 receptor, said method comprising the step of administering a spiro-amino compound of Formula (I):
wherein
A is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring containing 1 to 3 nitrogen atom,
X is a substituent selected from the group consisting of (C 1 -C 3 )alkyl and halogen, Y is a substituent selected from the group consisting of halogen and trifluoromethyl
or a pharmaceutically acceptable salt thereof.
2 . The method according to claim 1 , wherein A of the spiro-amino compound of Formula (I) is selected from the group consisting of pyrimidinyl, pyridinyl and triazolyl, more preferably pyrimidinil.
3 . The method according to claim 1 , wherein X of the spiro-amino compound of Formula (I) is chloro, fluoro or methyl, more preferably methyl.
4 . The method according to claim 1 , wherein Y of the spiro-amino compound of Formula (I) is chloro or trifluoromethyl, more preferably chloro.
5 . The method according to claim 1 , wherein the spiro amino compound is selected from the group consisting of:
(S)-(5-chloro-2-(pyrimidin-2-yl)phenyl)(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone (compound 1);
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyridin-2-yl)phenyl)methanone (compound 2);
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyridin-2-yl)phenyl)methanone (compound 3);
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (compound 4);
(S)-(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)(5-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone (compound 5);
(S)(5-((5-chloropyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (compound 6);
(S)-(5-methyl-2-(pyrimidin-2-yl)phenyl)(5-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone (compound 7);
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone (compound 8); and
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanone (compound 9).
6 . The method according to claim 1 , wherein the pathology is selected from the group consisting of emesis, depression, eating disorders, pain, gastrointestinal disorders, inflammatory diseases and allergic disorders.
7 . A spiro-amino compound of Formula (II):
or a pharmaceutically acceptable salt thereof.
8 . A pharmaceutical composition comprising a compound of Formula (II) and a pharmaceutically acceptable carrier.
9 . (canceled)
10 . (canceled)
11 . (canceled)
12 . A method for the treatment of pathologies which require an antagonist of the NK1 receptor, said method comprising the step of administering a spiro amino compound of Formula (II) or a pharmaceutically acceptable salt thereof.
13 . The method according to claim 12 , wherein the pathology is selected from the group consisting of emesis, depression, eating disorders, pain, gastrointestinal disorders, inflammatory diseases and allergic disorders.