Spiro amino compounds suitable for the treatment of inter alia sleep disorders and drug addiction
A spiro-amino compound of Formula (VI) wherein m is 1 or 2 or 3, n is 1 or 2, R is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring comprising 1 to 3 heteroatoms selected from S, O and N, such ring being substituted with one or two substituents selected from the group consisting of (C 1 -C 3 )alkyl, halogen, (C 3 -C 5 )cycloalkyloxy, (C 1 -C 3 )alkylcarbonyl, phenyl optionally substituted with one or more halogen atoms, a 5- or 6-membered heterocycle comprising at least one nitrogen atom; P is a substituent Q or COQ, wherein Q is selected from the group consisting of phenyl, pyridyl, pyrimidyl, quinolyl, isoquinolyl, quinoxalyl, benzofuranyl, imidazotriazolyl, being such Q optionally substituted with one or more substituents selected from the group consisting of (C 1 -C 3 )alkyl, halogen, trifluoromethyl, carbammido, methylcarbammido, carboxy, methylcarboxy or a pharmaceutically acceptable salt thereof.
1. A spiro-amino compound of Formula (VI):
wherein
m is 1 or 2 or 3
n is 1 or 2,
R is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring comprising 1 to 3 heteroatoms selected from S, O and N, such ring being substituted with one or two substituents selected from the group consisting of (C 1 -C 3 )alkyl, halogen atom, (C 3 -C 5 ) cycloalkyloxy, (C 1 -C 3 ) alkyl carbonyl, phenyl optionally substituted with one or more halogen atoms, a 5- or 6-membered heterocycle comprising at least one nitrogen atom; P is a substituent Q or COQ, wherein Q is selected from the group consisting of phenyl, pyridyl, pyrimidyl, quinolyl, isoquinolyl, quinoxalyl, benzofuranyl, imidazotriazolyl, being such Q optionally substituted with one or more substituents selected from the group consisting of (C 1 -C 3 ) alkyl, halogen, trifluoromethyl, carbammido, methylcarbammido, carboxy, methylcarboxy or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein P is Q and it is a compound of Formula (VIa):
3. The compound according to claim 1 , wherein P is COQ and it is a compound of Formula (VIb):
4. The compound according to claim 1 , wherein n is 2 and m is 1.
5. The compound according to claim 1 , wherein R is phenyl or an heterocyclic ring.
6. The compound according to claim 5 , wherein when R is an heterocyclic ring this is a thiazole ring.
7. The compound according to claim 6 , wherein the thiazole ring is substituted with at least one substituent selected from the group consisting of methyl, phenyl, phenyl substituted with one or more halogens.
8. The compound according to claim 5 , wherein R is phenyl, optionally substituted with a substituent selected from cyclopropil (C 1 -C 3 ) alchyloxy, triazolil, pyrimidyl.
9. The compound according to claim 1 , wherein Q is a pyridyl ring, optionally substituted with one or more substituents selected from the group consisting of trifluoromethyl, carboxy, methyl and halogen.
10. The compound according to claim 2 , wherein m=2 and n=2.
11. The compound according to claim 2 , wherein m=3 and n=2.
12. The compound according to claim 11 , wherein Q is pyridyl substituted with trifluoromethyl or pyridyl substituted with (C 1 -C 3 )alkyl and R is 5-membered heteroaromatic ring comprising two heteroatoms selected from S, O and N, such R being substituted with one or two substituents selected from (C 1 -C 3 )alkyl and halogen.
13. The compound according to claim 2 , wherein m=1 and n=1.
14. The compound according to claim 13 , wherein Q is pyridyl substituted with one or more halogens or pyridyl substituted with (C 1 -C 3 ) alkyl and R is phenyl substituted with one or two substituent selected from (C 1 -C 3 )alkyl and a 5- or 6-membered heterocycle comprising at least one nitrogen atom.
15. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable carrier.
16. The compound according to claim 1 , said compound being selected from the group consisting of:
(±)(2-methyl-5-phenylthiazol-4-yl)(5-((6-methylpyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(R)-(2-methyl-5-phenylthiazol-4-yl)(5-(((6-methylpyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(2-methyl-5-phenylthiazol-4-yl)(5-(((6-methylpyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(±)(5-((5-chloropyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(R)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(±)(2-methyl-5-phenylthiazol-4-yl)(5-((5-(trifluoromethyl)pyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(2-methyl-5-phenylthiazol-4-yl)(5-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(±)(5-((5-chloropyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-(cyclopropylmethoxy)phenyl)methanone
(±)(5-((5-chloropyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone
(±)(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
(±)(5-((5-chloropyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone
(±)methyl 5-chloro-2-((6-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-6-azaspiro[2.5]octan-5-yl)methylamino)benzoate
(S)-(5-(((5-fluoropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(S)-(5-(((6-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(S)-(2-methyl-5-phenylthiazol-4-yl)(5-(((6-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(5-(((6-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone
(S)-(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)(5-(((6-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(2-methyl-5-phenylthiazol-4-yl)(5-(((4-methylpyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(5-(((4,6-dimethylpyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(S)-(2-methyl-5-phenylthiazol-4-yl)(5-(((5-methylpyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(5-(((4,6-difluoropyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(S)-(5-(((6-fluoropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-methyl-5-phenylthiazol-4-yl)methanone
(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
(S)-(5-methyl-2-(pyrimidin-2-yl)phenyl)(5-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(2-(2H-1,2,3-triazol-2-yl)phenyl)(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(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
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-(pyrazin-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyridin-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyridin-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-fluoro-6-(pyridin-2-yl)phenyl)methanone
(S)-[1,1′-biphenyl]-2-yl(5-(((4,6-dimethylpyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(2,5-dichlorophenyl)(5-(((4,6-dimethylpyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-[1,1′-biphenyl]-2-yl(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-[1,1′-biphenyl]-2-yl(5-(((4-methylpyrimidin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-(pyrimidin-2-yl)phenyl)methanone
(S)-(5-(((6-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone
(S)-(5-(((6-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrazin-2-yl)phenyl)methanone
(S)-(5-methyl-2-(pyrazin-2-yl)phenyl)(5-(((6-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(2-fluoro-6-(pyrimidin-2-yl)phenyl)methanone
(S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyrazin-2-yl)phenyl)methanone
(S)-(6-(((5-chloropyridin-2-yl)amino)methyl)-5-azaspiro[2.4]heptan-5-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone
(S)-(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)(6-(((6-methylpyridin-2-yl)amino)methyl)-5-azaspiro[2.4]heptan-5-yl)methanone
(S)-(6-(((5-chloropyridin-2-yl)amino)methyl)-5-azaspiro[2.4]heptan-5-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone
(±)(2-methyl-5-phenylthiazol-4-yl)(7-(((6-methylpyridin-2-yl)amino)methyl)-8-azaspiro[4.5]decan-8-yl)methanone, and
(±)(7-(((5-chloropyridin-2-yl)amino)methyl)-8-azaspiro[4.5]decan-8-yl)(2-methyl-5-phenylthiazol-4-yl)methanone.
17. Compound according to claim 16 , wherein said compound is (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone, or (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanone.