The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A 2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I).
1. A compound of the following formula:
or a pharmaceutically acceptable salt or N-oxide thereof;
wherein
A is an aryl or heteroaryl;
each of B, B 1 , and B 2 is N;
each of R 2 and R 3 is independently hydrogen, alkyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, or heteroaralkyl;
X 1 is a bond or C 1-6 alkylene, C 2-6 alkenylene, or C 2-6 alkynylene, each of which being optionally interrupted by or linked terminally to —O—, —S—, or —N(R 2 )—;
X 2 is a bond, C 1-6 alkylene, C 2-6 alkenylene, or C 2-6 alkynylene;
L is a linker selected from the group consisting of:
wherein:
each of R′ and R″ is independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, acyl, halo, hydroxy, amino, nitro, oxo, thioxo, cyano, guanadino, amidino, carboxy, sulfo, sulfoxy, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino, alkylsulfonylamino, alkoxycarbonyl, alkylcarbonyloxy, urea, thiourea, sulfamoyl, sulfamide, carbamoyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfanyl, heterocycloalkyl, heterocycloalkyloxy, heterocycloalkylsulfanyl, aryl, aryloxy, arylsulfanyl, aroyl, heteroaryl, heteroaryloxy, heteroarylsulfanyl, or heteroaroyl;
X is —C(R 2 )(R 3 )—, —N(R 2 )—, —O—, or —S—;
each of p, p1 and p2 is independently 0-2;
each of q1 and q2 is independently 0-2;
each of m1 and m2 is independently 0-2;
each of r and r1 is independently is 1-2; and
r2 is 0-1;
Y is —C(R 2 )(R 3 )—, —N(R′″)—, —O—, —S—, —SO—, —SO 2 —, —CO—, —CO 2 —, or a bond where R″′ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl; and
R 1 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl.
2. The compound of claim 1 , wherein L is
3. The compound of claim 2 , wherein L is
4. The compound of claim 3 , wherein X is —CH 2 —, p1 is 1, p2 is 1 or 2, q1 is 1, r2 is 1 or 2, each of m1 and m2 is independently 0 or 1, and each of R′ and R″ is independently hydrogen or alkyl.
5. The compound of claim 4 , wherein L is
6. The compound of claim 2 , wherein L is
7. The compound of claim 6 , wherein X is —CH 2 —, p1 is 0 or 1, p2 is 1 or 2, q1 is 1, q2 is 1 or 2, each of m1 and m2 is independently 0 or 1, and each of R′ and R″ is independently hydrogen or alkyl.
8. The compound of claim 7 , wherein L is
9. The compound of claim 2 , wherein X 1 is a bond or C 1-4 alkylene that is optionally linked terminally to —N(R 2 )—, where R 2 is hydrogen or alkyl.
10. The compound of claim 2 , wherein X 2 is a bond or C 1-4 alkylene.
11. The compound of claim 2 , wherein Y is —N(R″′)—, —O—, —S—, or a bond where R″′ is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl.
12. The compound of claim 11 , wherein R′″ is hydrogen, cycloalkylalkyl, heterocycloalkylalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl.
13. The compound of claim 2 , wherein each of R 2 and R 3 is independently hydrogen or alkyl.
14. The compound of claim 2 , wherein R 1 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl.
15. The compound of claim 2 , wherein R 1 is hydrogen, or R 1 is phenyl, furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, indolyl, isoindolyl, benzofuryl, benzothiophenyl, benzimidazolyl, benzthiazolyl, furopyridyl, or thienopyridyl; each of which being optionally substituted with C 1-4 alkyl, halo, hydroxy, C 1-4 alkoxy, or C 1-4 alkylthio.
16. The compound of claim 2 , wherein A is heteroaryl.
17. The compound of claim 3 , wherein X 1 is a bond or C 1-4 alkylene that is optionally linked terminally to —N(R 2 )—; X 2 is a bond or C 1-4 alkylene; Y is —N(R′″)—, —O—, —S—, or a bond where R″′ is hydrogen, cycloalkylalkyl, heterocycloalkylalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl; each of R 2 and R 3 is independently hydrogen or alkyl; R 1 is cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl; and A is heteroaryl.
18. The compound of claim 17 , wherein X 1 is a bond; each of R 2 and R 3 is hydrogen;
and R 1 is aryl or heteroaryl.
19. The compound of claim 17 , wherein X is —CH 2 —, p1 is 1, p2 is 1 or 2, q1 is 1, r2 is 1 or 2, each of m1 and m2 is independently 0 or 1, and each of R′ and R″ is independently hydrogen or alkyl.
20. The compound of claim 6 , wherein X 1 is a bond or C 1-4 alkylene that is optionally linked terminally to —N(R 2 )— where R 2 is hydrogen or alkyl; X 2 is a bond or C 1-4 alkylene; Y is —N(R′″)—, —O—, —S—, or a bond where R″′ is hydrogen, cycloalkylalkyl, heterocycloalkylalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl; each of R 2 and R 3 is independently hydrogen or alkyl; R 1 is cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl; and A is heteroaryl.
21. The compound of claim 20 , wherein X is —CH 2 —, p1 is 0 or 1, p2 is 1 or 2, q1 is 1, q2 is 1 or 2, each of m1 and m2 is independently 0 or 1, and each of R′ and R″ is independently hydrogen or alkyl.
22. The compound of claim 1 , said compound being selected from the group consisting of:
(7RS, 9aRS)-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol;
(6RS, 9aRS)-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-6-yl]-methanol;
(7RS, 9aRS)-[2-(5-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol;
(7RS, 9aRS)-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol;
(7RS, 9aSR)-5-[7-(3-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-N 5 -(2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS, 9aSR)—N 5 -[2-(5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethyl)-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS, 9aSR)-2-furan-2-yl-N 5 -(2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS, 9aRS)-5-(7-aminomethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-pyridin-4-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(pyrimidin-2-ylaminomethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-(7-{[(pyridin-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
2-furan-2-yl-5-[5-(5-methyl-isoxazol-3-ylmethyl)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
5-[5-(4-fluoro-benzyl)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
5-[5-(4-chloro-benzyl)-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
5-[1-(2,6-dichloro-benzyl)-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(±)-2-furan-2-yl-5-(octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(±)-2-furan-2-yl-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(S)-2-furan-2-yl-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(3S,8aS)-5-(3-benzyl-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol;
(7RS, 9aRS)-5-[7-(2,4-difluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(quinolin-6-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-(7-phenoxymethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(5,6,7,8-tetrahydro-naphthalen-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-[7-(2-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-[7-(3-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-[7-(4-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(4-methoxy-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(2,3,5-trifluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(2,4,6-trifluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(pyridin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(pyridin-4-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(4-trifluoromethyl-pyrimidin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(6-trifluoromethyl-pyrimidin-4-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(quinazolin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(isoquinolin-3-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(isoquinolin-5-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-[7-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-(7-imidazol-1-ylmethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-(7-[1,2,4]triazol-1-ylmethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-(7-tetrazol-1-ylmethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-[7-(2,4-difluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(4-methoxy-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-(7-phenoxymethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(5,6,7,8-tetrahydro-naphthalen-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(pyridin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(pyridin-4-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-[7-(benzo[1,3]dioxol-5-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(quinazolin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(quinolin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(isoquinolin-3-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(isoquinolin-5-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-[7-(2-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-[7-(4-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS, 9aRS)-[2-furan-2-yl-5-(6-phenoxymethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS, 9aRS)-[2-furan-2-yl-5-[6-(5,6,7,8-tetrahydro-naphthalen-1-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS, 9aRS)-[5-[6-(3-amino-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS, 9aRS)-[5-[6-(benzo[1,3]dioxol-5-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS, 9aRS)-[2-furan-2-yl-5-[6-(1H-indol-5-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS, 9aRS)-[1-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-6-ylmethyl]-1H-indol-5-ol;
(7RS, 9aRS)-3-amino-5-{7-[(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-6-chloro-pyrazine-2-carboxylic acid methyl ester;
(7RS, 9aRS)—N-5-[2-(3,5-difluoro-phenyl)-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS, 9aRS)—N-5-[2-(2,4-difluoro-benzyl)-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS, 9aSR)-5-(7-aminomethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(2-fluoro-benzyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(2,4-difluoro-benzyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(2,4-difluoro-benzylamino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(2,4,6-trifluoro-benzyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(2,3-difluoro-benzyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(2,6-difluoro-benzyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(3,5-difluoro-benzyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(5-chloro-furan-2-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-pyridin-2-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-pyridin-3-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-2-furan-2-yl-5-(7-{[(pyridin-3-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(2-chloro-1-methyl-4-trifluoromethyl-1H-pyrrol-3-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-cyclohexylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-furan-2-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(1H-pyrrol-2-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(5-chloro-1,3-dimethyl-1H-pyrazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-thiazol-2-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-{7-[(bis-thiophen-2-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-5-(7-{[bis-(5-methyl-thiophen-2-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-[7-(pyrimidin-2-ylaminomethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-{7-[(bis-pyridin-4-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-(7-{[(pyridin-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-{7-[(bis-pyridin-3-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-(7-{[(pyridin-3-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-{7-[(bis-furan-2-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-2-furan-2-yl-5-(7-{[(furan-2-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-(7-{[bis-(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aSR)-5-(7-{[(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(R)-2-furan-2-yl-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
2-furan-2-yl-5-(1-quinolin-2-ylmethyl-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine; and
(7RS, 9aRS)-2-furan-2-yl-5-[7-(quinolin-7-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine.
23. The compound of claim 1 , said compound being selected from the group consisting of:
(±)2-furan-2-yl-5-(octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(±)2-furan-2-yl-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS, 9aRS)-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-yl]-methanol;
(6RS, 9aRS)-[2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-6-yl]-methanol;
(7RS,9aRS)-2-Furan-2-yl-5-[7-(quinolin-6-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-Furan-2-yl-5-(7-phenoxymethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-[7-(2-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-[7-(3-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-[7-(isoquinolin-5-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-[7-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-(7-imidazol-1-ylmethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-(7-[1,2,4]triazol-1-ylmethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aSR)-2-furan-2-yl-5-[7-(quinolin-2-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(6RS,9aRS)-2-furan-2-yl-5-(6-phenoxymethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-N-5-(2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS,9aRS)-5-(7-aminomethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aSR)-5-(7-aminomethyl-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-{7-[(2,4-difluoro-benzylamino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-{7-[(bis-pyridin-4-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-(7-{[(pyridin-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-{7-[(bis-pyridin-2-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-{7-[(bis-pyridin-3-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-5-[7-(pyrimidin-2-ylaminomethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-(7-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-ylmethyl)-amino]-methyl}-octahydro-pyrido[1,2-a]pyrazin-2-yl)-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aSR)-5-{7-[(bis-pyridin-3-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(R)-2-furan-2-yl-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine; and
(7RS, 9aRS)-2-furan-2-yl-5-[7-(quinolin-7-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine.
24. The compound of claim 1 , said compound being selected from the group consisting of:
(7RS,9aRS)-2-furan-2-yl-5-[7-(quinolin-6-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-5-[7-(3-fluoro-phenoxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-2-furan-2-yl-]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine;
(7RS,9aRS)-2-furan-2-yl-N-5-(2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine;
(7RS,9aRS)-5-{7-[(bis-pyridin-3-ylmethyl-amino)-methyl]-octahydro-pyrido[1,2-a]pyrazin-2-yl}-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine; and
(7RS, 9aRS)-2-furan-2-yl-5-[7-(quinolin-7-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine.
25. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising a compound of claim 22 and a pharmaceutically acceptable carrier.
27. A method of treating Parkinson's disease in a subject, the method comprising the step of administering to said subject an effective amount of a compound of claim 1 .