Triazolo [4, 5-D] pyramidine derivatives and their use as purine receptor antagonists

1. A method of treating a disorder treatable by purine receptor blocking, wherein the method comprises administering an effective dose of a pharmaceutical composition to a subject in need of treatment of a disorder treatable by purine receptor blocking, wherein:

(a) the pharmaceutical composition comprises a compound of formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, or stereoisomer thereof, and a pharmaceutically acceptable carrier; and

(b) the compound of formula (I) has the following structure:

wherein:

R 1 is phenyl or heteroaryl, wherein the phenyl or the heteroaryl group may optionally be substituted with alkyl, alkoxy, halo or —CN;

R a is H or alkyl, R b is H or alkyl, or R a and R b together with the atom to which they are attached form a 3 to 8-membered saturated or partially saturated hydrocarbon ring or form a 4 to 8-membered saturated or partially saturated heterocylic ring comprising a ring member selected from the group consisting of 0, N(R 3 ) and S;

R 2 is H, alkyl or heterocycloalkyl, wherein the alkyl may optionally be substituted with halo, alkoxy or heterocycloalkyl, provided that R 2 is selected from heterocycloalkyl and alkyl substituted by halo, alkoxy or heterocycloalkyl when R 1 is furan-2-yl or 5-methyl-furan-2-yl and R a and R b are both H; and

R 3 is H or alkyl;

R 4 is H or alkyl; and

q is 0, 1 or 2;

wherein:

heteroaryl is a 5 or 6 membered aromatic ring, comprising one or two ring members selected from the group consisting of N, N(R 4 ), S and O;

alkyl, or the alkyl group of the alkoxy group, is a linear or branched saturated hydrocarbon containing up to 10 carbon atoms; and

heterocycloalkyl is a C-linked or N-linked 3 to 10 membered non-aromatic, monocyclic ring, wherein the heterocycloalkyl ring comprises 1, 2 or 3 ring members independently selected from N, N(R 4 ), S(O) q and O.

2. The method of claim 1 , wherein R 1 is selected from the group consisting of phenyl, 2-furanyl, 2-pyrrolyl, 2-imidazoyl, 2-oxazolyl, and 2-thiazolyl, wherein each may be optionally substituted with alkyl or alkoxy.

3. The method of claim 1 , wherein R 1 is 5-methyl-furan-2-yl.

4. The method of claim 1 , wherein R a and R b together with the atom to which they are attached form a tetrahydropyryl ring, a cyclobutyl ring, a cyclopentyl ring or a cyclohexyl ring.

5. The method of claim 1 , wherein R a and R b are independently selected from H and (C 1 -C 6 )alkyl.

6. The method of claim 1 , wherein R 2 is selected from H, (C 1 -C 4 )alkyl and tetrahydrofuranyl, wherein the (C 1 -C 4 )alkyl may optionally be substituted with fluoro, (C 1 -C 3 )alkoxy or tetrahydrofuranyl.

7. The method of claim 1 , wherein R 2 is selected from H and tetrahydrofuryl.

8. The method of claim 1 , wherein the compound is selected from the group consisting of:

(a) 7-(5-methylfuran-2-yl)-3-(6-[2-isopropyloxyethyoxy]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(b) 7-(5-methylfuran-2-yl)-3-(6-[1-hydroxy-1-methylethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(c) 7-(5-methylfuran-2-yl)-3-(6-[1-hydroxy-1-cyclopentyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(d) 7-(5-methylfuran-2-yl)-3-(6-[4-hydroxytetrahydropyran-4-yl]pyrid-2-ylmethyl)-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-5-amine;

(e) S-7-phenyl-3-(6-tetrahydrofuran-3-yl3oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(f) 7-phenyl-3-(6-[1-hydroxy-1-methylethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(g) 7-phenyl-3-(6-[1-hydroxy-1-cyclopentyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(h) 7-phenyl-3-(6-[1-hydroxycyclobutyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(i) 7-phenyl-3-(6-[methoxymethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(j) S-7-(3-methoxyphenyl)-3-(6-[tetrahydrofuran-3-yl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(k) S-7-(5-methylfuran-2-yl)-3-(6-[tetrahydrofuran-3-yl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(l) 7-(3-methoxyphenyl)-3-(6-[1-hydroxy-1-cyclopentyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(m) 7-(3-methoxyphenyl)-3-(6-[4-hydroxytetrahydropyran-4-yl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(n) 7-(3-methoxyphenyl)-3-(6-[1-hydroxycyclobutyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(o) 7-(3-methoxyphenyl)-3-(6-[methoxymethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(p) 7-(5-methylfuran-2-yl)-3-(6-[1-hydroxy-1-cyclohexyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(q) S-7-(3-cyanophenyl)-3-(6-[tetrahydrofuran-3-yl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(r) 7-(3-cyanophenyl)-3-(6-[1-hydroxy-1-methylethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(s) 7-(3-cyanophenyl)-3-(6-[4-hydroxytetrahydropyran-4-yl]pyrid-2-ylmethyl)-3-H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(t) 7-(3-cyanophenyl)-3-(6-[1-hydroxycyclobutyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(u) 7-(3-methoxyphenyl)-3-(6-[1-hydroxy-1-methylethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(v) 7-(3-cyanophenyl)-3-(6-[methoxymethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazol o[4,5-d]pyrimidin-5-amine;

(w) S-7-(4-methylthiazol-2-yl)-3-(6-[tetrahydrofuran-3-yl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(x) 7-(4-methylthiazol-2-yl)-3-(6-[1-hydroxy-1-cyclopentyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(y) 7-(4-methylthiazol-2-yl)-3-(6-[1-hydroxytetrahydropyran-4-yl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(z) 7-(5-methylfuran-2-yl)-3-(6-[1-hydroxycyclobutyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(aa) 7-(4-methylthiazol-2-yl)-3-(6-[1-hydroxycyclobutyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(bb) 7-(4-methylthiazol-2-yl)-3-(6-[methoxymethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(cc) 7-(5-methylfuran-2-yl)-3-(6-[difluoromethyloxymethyl]-pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(dd) 7-phenyl-3-(6-[4-hydroxytetrahydropyran-4-yl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(ee) 7-(5-methylfuran-2-yl)-3-(6-[2-ethoxyethoxymethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(ff) 7-(5-methylfuran-2-yl)-3-(6-[tetrahydrofuran-2-ylmethyl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(gg) 7-(5-methylfuran-2-yl)-3-(6-tetrahydrofuran-3-ylmethylloxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(hh) 7-(5-methylfuran-2-yl)-3-(6-[1-methoxy-1-methylethyl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(ii) 7-(3-cyanophenyl)-3-(6-[1-hydroxy-1-cyclopentyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(jj) 7-(5-methylfuran-2-yl)-3-(6-[2,2,2-trifluoroethyl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(kk) S-7-(thiazol-2-yl)-3-(6-[tetrahydrofuran-3-yl]oxymethylpyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine;

(ll) 7-(4-methylthiazol-2-yl)-3-(6-[1-hydroxy-1-methylethyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine; and

pharmaceutically acceptable salts and solvates thereof.

9. The method of claim 1 , wherein the purine receptors are adenosine A 2A receptors.

10. The method of claim 1 , wherein the disorder is a movement disorder selected from the group consisting of Parkinson's disease, Restless leg syndrome, nocturnal myoclonus, drug-induced Parkinsonism, postencephalitic Parkinsonism, Parkinsonism induced by poisoning, post-traumatic Parkinson's disease, progressive supernuclear palsy, Huntington's disease, multiple system atrophy, corticobasal degeneration, Wilson's disease, Hallerrorden-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, and spasticity or other disorders of the basal ganglia which result in dyskinesias.

11. The method of claim 10 , wherein the movement disorder is Parkinson's disease.

12. The method of claim 10 , further comprising administering to the subject an additional drug useful in the treatment of movement disorders.

13. The method of claim 12 , wherein the additional drug useful in the treatment of movement disorders is a drug useful in the treatment of Parkinson's disease.

14. The method of claim 13 , wherein the additional drug is L-DOPA or a dopamine agonist.

15. The method of claim 1 , wherein the disorder is selected from the group consisting of depression, a cognitive or memory impairment disorder, acute or chronic pain, AMID, and narcolepsy.

16. The method of claim 15 , wherein the cognitive or memory impairment disorder is Alzheimer's disease.