DK2782915T3 - [1,2,3]TRIAZOLO[4,5-d]PYRIMIDINDERIVATER SOM AGONISTER AF CANNABINOIDRECEPTOR-2-AGONISTER - Google Patents
[1,2,3]TRIAZOLO[4,5-d]PYRIMIDINDERIVATER SOM AGONISTER AF CANNABINOIDRECEPTOR-2-AGONISTER Download PDFInfo
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- DK2782915T3 DK2782915T3 DK12794684.6T DK12794684T DK2782915T3 DK 2782915 T3 DK2782915 T3 DK 2782915T3 DK 12794684 T DK12794684 T DK 12794684T DK 2782915 T3 DK2782915 T3 DK 2782915T3
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- triazolo
- tert
- butyl
- pyrrolidin
- pyrimidine
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Claims (18)
1. Forbindelse
med formel (I) hvor A er alkylen, hydroxyalkylen, -CH2C(0)-, -C(O)-, -SO2- eller mangler; R1 er hydrogen, alkyl, haloalkyl, hydroxyl, alkoxy, haloalkoxy, phenyl, halophenyl, alkoxyphenyl, haloalkylphenyl, haloalkoxyphenyl, cyanophenyl, hydroxyalkoxyphenyl, alkylsulfonylphenyl, alkylsulfonylaminophenyl, (halo)(haloalkyl)phenyl, (halo)(alkoxy)phenyl, cyano, cycloalkyl, cycloalkylalkoxy, amino, heterocyclyl, alkylheterocyclyl, hydroxyheterocyclyl, alkylheterocyclyl, heteroaryl, haloheteroaryl, alkylheteroaryl, (alkyl)(alkylsulfonyl)heteroaryl, (halo)(alkylamino)heteroaryl, haloalkylheteroaryl, cycloalkylheteroaryl eller nitro-benzo[l,2,5]oxadiazolylaminoheteroaryl, hvor heterocyclyl er er tre-til otte-leddet carbocyklisk ring omfattende mindst et nitrogen- eller oxygenatom, og hvor heteroaryl er pyridinyl, pyrazolyl, oxadiazolyl, furazanyl, tetrazolyl, triazolyl eller oxypyridinyl; R2 er alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkoxyalkyl, cycloalkylalkoxy, haloalkoxy, alkoxy eller alkylamino; R3 er halogen eller -NR4R5; én af R4 og R5 er hydrogen eller alkyl og den anden er alkyl eller cycloalkyl; eller R4 og R5 sammen med det nitrogenatom til hvilket de er bundet danner heterocyclyl eller substitueret heterocyclyl, hvor heterocyclyl er morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, 2-oxa-6-azaspiro[3.3]heptyl, azetidinyl, thiazolidinyl, thiomorpholinyl, dioxothiomorpholinyl, oxazepanyl, 2-oxa-6-azaspiro[3.4]octyl, 6-oxa-l-azaspiro[3.3]heptyl, 2-oxa-5-aza-spiro[3.4]octyl, isoxazolidinyl, aziridinyl eller dioxoisothiazolidinyl og hvor substitueret heterocyclyl er heterocyclyl substitueret med en til fire substituenter uafhængigt valgt fra alkyl, halogen, hydroxyl, alkoxy, hydroxyalkyl, carboxyl, alkoxyalkyl, cyano og alkylcarbonylamino; eller et farmaceutisk acceptabelt salt eller ester deraf.
2. Forbindelse ifølge krav 1, hvor A er alkylen, -CH2C(0)- eller mangler.
3. Forbindelse ifølge krav 1 eller 2, hvor A er alkylen.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor A er methylen, ethylen eller -CH(CH3)-.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4, hvor R1 er alkyl, haloalkyl, hydroxyl, alkoxy, phenyl, halophenyl, alkoxyphenyl, haloalkylphenyl, haloalkoxyphenyl, cyanophenyl, cycloalkyl, heterocyclyl, haloheteroaryl eller alkylheteroaryl, hvor heterocyclyl er oxetanyl, og hvor heteroaryl er pyridinyl eller furazanyl.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 5, hvor R1 er alkyl, haloalkyl, hydroxyl, alkoxy, phenyl, halophenyl, alkoxyphenyl, haloalkylphenyl, haloalkoxyphenyl, cyanophenyl, cycloalkyl, oxetanyl, pyridinyl, halopyridinyl eller alkylfurazanyl.
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 6, hvor R1 er trifluormethyl, phenyl, chlorphenyl, bromphenyl, cyanophenyl, cyclohexyl, pyridinyl, chlorpyridinyl, methylfurazanyl eller trifluormethylphenyl.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 7, hvor R2 er alkyl.
9. Forbindelse ifølge et hvilket som helst af kravene 1 til 8, hvor R2 er tert.-butyl.
10. Forbindelse ifølge et hvilket som helst af kravene 1 til 9, hvor R3 er -NR4R5.
11. Forbindelse ifølge et hvilket som helst af kravene 1 til 10, hvor R4 og R5 sammen med det nitrogenatom til hvilket de er bundet danner morpholinyl, halopyrrolidinyl eller hydroxypyrrolidinyl.
12. Forbindelse ifølge et hvilket som helst af kravene 1 til 11, hvor R4 og R5 sammen med det nitrogenatom til hvilket de er bundet danner morpholinyl, difluorpyrrolidinyl eller hydroxypyrrolidinyl.
13. Forbindelse ifølge et hvilket som helst af kravene 1 til 12 valgt fra 5-tert-butyl-2-(2-chlor-benzyl)-7-morpholin-4-yl-2H-[l,2,3]triazolo[4,5- d]pyrimidin; 5-tert-butyl-2-(2-chlor-4-fluor-benzyl)-7-morpholin-4-yl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-ethyl-2H-[l,2,3]triazolo[4,5- d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methoxy-ethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-yl]-ethanol; 5-tert-butyl-2-cyclohexylmethyl-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-chlor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(4-chlor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo [4,5-d]pyrimidin; 5-tert-butyl-2-(2,3-dichlor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2,4-dichlor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2,5-dichlor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2,6-dichlor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-4-fluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-6-fluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-pyridin-2-ylmethyl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-pyridin-3-ylmethyl-2H- [1.2.3] triazolo[4,5-d]pynmidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-pyridin-4-ylmethyl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2,2,2-trifluor-ethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-4,5-difluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pynmidin; 5-tert-butyl-2-(2-chlor-3,6-difluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pynmidin; 2-(2-brom-benzyl)-5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-trifluormethyl-benzyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methoxy-benzyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-trifluormethoxy-benzyl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-ylmethyl]-benzonitril; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-phenethyl-2H- [1.2.3] triazolo[4,5-d]pynmidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[[4,5- d]pyrimidin-2-yl]-l-phenyl-ethanon; 5-tert-butyl-2-[(R)-l-(2-chlor-phenyl)-ethyl]-7-(3,3-difluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo [4,5-d]pyrimidin; 5-tert-butyl-2-[(S)-l-(2-chlor-phenyl)-ethyl]-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]triazolo[4,5-d]pynmidin; 5-tert-butyl-2-(2-chlor-3-fluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-5-fluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-oxetan-3-yl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2,6-dichlor-3-fluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-pyridin-3-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(4-chlor-pyridin-3-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-chlor-pyridin-2-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo [4,5-d]pyrimidin; 5-tert-butyl-2-(2,5-dichlor-pyridin-3-ylmethyl)-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]tnazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3,6-dichlor-pyridin-2-ylmethyl)-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(4-methyl-furazan-3- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(3-methyl-[l,2,4]oxadiazol-5- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-[2-(2-chlor-phenyl)-ethyl]-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-[2-(3-chlor-phenyl)-ethyl]-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pynmidin; 5-tert-butyl-2-[2-(4-chlor-phenyl)-ethyl]-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2,4-dichlor-pyridin-3-ylmethyl)-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(R)-tetrahydro-furan-3-yl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(S)-tetrahydro-furan-3-yl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-yl]-l-(2-chlor-phenyl)-ethanon; 5-tert-butyl-2-(2,3-dichlor-6-fluor-benzyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methanesulfonyl-benzyl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-pyridin-2-yl-ethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(3-methyl-oxetan-3- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-yl]-l-(3-chlor-phenyl)-ethanon; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-yl]-l-(4-chlor-phenyl)-ethanon; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-yl]-l-pyridin-3-yl-ethanon; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2,3,6-trichlor-benzyl)-2H- [1.2.3] tnazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-3-trifluormethyl-benzyl)-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2-chlor-6-fluor-3-methoxy-benzyl)-7-(3,3-difluor-pyrrolidin- l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-pyridin-3-yl-ethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-pyridin-4-yl-ethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(2,3-dichlor-6-trifluormethyl-benzyl)-7-(3,3-difluor- pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pynmidin; 5-tert-butyl-2-(3,4-dichlor-pyridin-2-ylmethyl)-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(l,l-dioxo-lA6-thietan-3-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(l,l-dioxo-tetrahydro-lA6- thiophen-3-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-yl]-l-pyridin-2-yl-ethanon; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(5-methyl-[l,3,4]oxadiazol-2- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-chlor-pyridin-4-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(5-methyl-[l,2,4]oxadiazol-3- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(l-met hyl-lH-tetrazol-5-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pynmidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methyl-2H-[l,2,4]triazol-3-ylmethyl)-2H-[l,2,3]triazolo [4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(5-methanesulfonyl-4-methyl- 4H-[l,2,4]triazol-3-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; {3-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-ylmethyl]-5-chlor-pyndin-4-yl}-dimethyl-amin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(3-trifluormethyl-lH-pyrazol- 4-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; (S)-l-[5-tert-butyl-2-(4-methyl-furazan-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(3-chlor-pyridin-2-ylmethyl)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(3,6-dichlor-pyridin-2-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2-chlor-pyridin-3-ylmethyl)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2,3-dichlor-benzyl)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2-trifluormethyl-benzyl)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2-methanesulfonyl-benzyl)-2H-[l,2,3]triazolo[4,5-d] pyrimid in-7-yl]-pyrrolidin-3-ol; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-2H-[l,2,3]triazolo [4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(3-methyl-3H-[l,2,3]triazol-4- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(4,5-dimethyl-4H- [1.2.4] tnazol-3-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methyl-l-oxy-pyridin-3- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; (S)-l-[5-tert-butyl-2-(3,4-dichlor-pyridin-2-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(5-methyl-[l,2,4]oxadiazol-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(5-methyl-[l,3,4]oxadiazol-2-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-( 1-methyl-1 H-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2-methyl-2H-[l,2,4]triazol-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(3-methyl-3H-[l,2,3]triazol-4-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; 5-tert-butyl-2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-7-(3,3-difluor- pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; (S)-l-{5-tert-butyl-2-[2-(7-nitro-benzo[l,2,5]oxadiazol-4-ylamino)- pyridin-3-ylmethyl]-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl)-pyrrolidin-3- ol; (S)-l-[5-tert-butyl-2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-tert-butyl-2-(2,5-dimethyl-2H-[l,2,4]triazol-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2,5-dimethyl-2H- [1.2.4] triazol-3-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; (25.35) -l-[5-tert-butyl-2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-2-hydroxymethyl-pyrrolidin-3-ol; (25.35) -l-[5-tert-butyl-2-(4-methyl-furazan-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-2-hydroxymethyl-pyrrolidin-3-ol; 5-tert-butyl-2-(4-methyl-furazan-3-ylmethyl)-7-(3,3,4,4-tetrafluor- pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-7-(3,3,4,4- tetrafluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(5-methyl-[l,3,4]oxadiazol-2-ylmethyl)-7-(3,3,4,4-tetrafluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo [4,5-d]pyrimidin; 5-tert-butyl-2-(l-methyl-lH-tetrazol-5-ylmethyl)-7-(3,3,4,4-tetrafluor- pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(4,5-dimethyl-4H-[l,2,4]triazol-3-ylmethyl)-7-(3,3,4,4- tetrafluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-methyl-3H-[l,2,3]triazol-4-ylmethyl)-7-(3,3,4,4- tetrafluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-7-(2-oxa-6-aza- spiro[3.3]hept-6-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(4,5-dimethyl-4H-[l,2,4]triazol-3-ylmethyl)-7-(2-oxa-6-aza- spiro[3.3]hept-6-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5- tert-butyl-2-(2-methanesulfonyl-benzyl)-7-(2-oxa-6-aza-spiro[3.3]hept- 6- yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5- tert-butyl-2-(3-chlor-pyridin-2-ylmethyl)-7-(2-oxa-6-aza-spiro[3.3]hept- 6- yl)-2H-[l,2,3]triazolo [4,5-d]pyrimidin; (S)-l-[2-(2-chlor-benzyl)-5-(2,2,2-trifluor-ethoxy)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[5-(2,2,2-trifluor-ethoxy)-2-(2-trifluormethyl-benzyl)-2H- [l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; (S)-l-[2-(2-chlor-benzyl)-5-isopropoxy-2H-[l,2,3]triazolo[4,5-d]pyrimidin- 7- yl]-pyrrolidin-3-ol; 7-(3,3-difluor-pyrrolidin-l-yl)-5-(2,2-dimethyl-propoxy)-2-(l-methyl-lH- tetrazol-5-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; (R) -l-[5-tert-butyl-2-(l-methyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-pyrrolidin-3-ol; 1- [5-tert-biityl-2-(l-methyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol; 7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-trifluormethyl-benzyl)-5-((S)-2,2,2- trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methanesulfonyl-benzyl)-5-((S)-2,2,2- trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 2- (3-chlor-pyridin-2-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)-5-((S)-2,2,2-trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 7-(3,3-difluor-pyrrolidin-l-yl)-2-(5-methyl-[l,3,4]oxadiazol-2-ylmethyl)-5- ((S)-2,2,2-trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 7-(3,3-difluor-pyrrolidin-l-yl)-2-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-5- ((S)-2,2,2-trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 7-(3,3-difluor-pyrrolidin-l-yl)-2-(l-methyl-lH-tetrazol-5-ylmethyl)-5-((S)- 2.2.2- trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 7-(3,3-difluor-pyrrolidin-l-yl)-2-(4-methyl-furazan-3-ylmethyl)-5-((S)- 2.2.2- trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 7-(3,3-difluor-pyrrolidin-l-yl)-5-((S)-2,2,2-trifluor-l-methyl-ethoxy)-2- (3,3,3-trifluor-propyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)-5- ((S)-2,2,2-trifluor-l-methyl-ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; (S) -l-[5-tert-butyl-2-(2-chlor-benzyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R)-l-[5-tert-butyl-2-(2-chlor-benzyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrro lidin-3 -ol; (S)-l-[5-tert-butyl-2-(2-trifluormethyl-benzyl)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(2-trifluormethyl-benzyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(2-methanesulfonyl-benzyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(2-methanesulfonyl-benzyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(3-chlor-pyridin-2-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(3-chlor-pyridin-2-ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(5-methyl-[l,3,4]oxadiazol-2-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(5-methyl-[l,3,4]oxadiazol-2-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(l-methyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(l-methyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(4-methyl-furazan-3-ylmethyl)-2H- [1.2.3] tnazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(4-methyl-furazan-3-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(3,3,3-trifluor-propyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R) -l-[5-tert-butyl-2-(3,3,3-trifluor-propyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (S) -l-[5-tert-butyl-2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-3-methyl-pyrrolidin-3-ol; (R)-l-[5-tert-butyl-2-(l-cyclopropyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-3-methyl-pyrrolidin-3-ol; N-{(S)-l-[2-(2-chlor-benzyl)-5-(2,2-dimethyl-propoxy)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-yl} -acetamid; N-{(S)-l-[2-(3-chlor-pyridin-2-ylmethyl)-5-(2,2-dimethyl-propoxy)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-yl>-acetamid; tert-butyl-[7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-trifluormethyl-benzyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-5-yl]-amin; tert-butyl-[7-(3,3-difluor-pyrrolidin-l-yl)-2-(2-methanesulfonyl-benzyl)- 2H-[l,2,3]triazolo[4,5-d]pynmidin-5-yl]-amin; tert-butyl-[2-(3-chlor-pyridin-2-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin-5-yl]-amin; tert-butyl-[7-(3,3-difluor-pyrrolidin-l-yl)-2-(l-methyl-lH-tetrazol-5- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-5-yl]-amin; tert-butyl-[7-(3,3-difluor-pyrrolidin-l-yl)-2-(4-methyl-furazan-3-ylmethyl)- 2H-[l,2,3]triazolo[4,5-d]pynmidin-5-yl]-amin; N-{(S)-l-[2-(2-chlor-benzyl)-5-((S)-2,2,2-trifluor-l-methyl-ethoxy)-2H- [1.2.3] triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-yl>-acetamid; N-{(S)-l-[2-(2-trifluormethyl-benzyl)-5-((S)-2,2,2-trifluor-l-methyl- ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-yl>-acetamid; N-{(S)-l-[2-(2-Methanesulfonyl-benzyl)-5-((S)-2,2,2-trifluor-l-methyl- ethoxy)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-yl}-acetamid; N-{(S)-l-[5-tert-butylamino-2-(2-chlor-benzyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-yl}-acetamid; og (S)-l-[5-tert-butylamino-2-(l-methyl-lH-tetrazol-5-ylmethyl)-2H- [1.2.3] triazolo[4,5-d]pynmidin-7-yl]-pyrrolidin-3-ol.
14. Forbindelse ifølge et hvilket som helst af kravene 1 til 13 valgt fra 5-tert-butyl-2-(2-chlor-benzyl)-7-morpholin-4-yl-2H-[l,2,3]triazolo[4,5- d]pyrimidin; 5-tert-butyl-2-cyclohexylmethyl-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-pyridin-4-ylmethyl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(2,2,2-trifluor-ethyl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 2-(2-brom-benzyl)-5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 2-[5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-[l,2,3]triazolo[4,5- d]pyrimidin-2-ylmethyl]-benzonitril; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-phenethyl-2H- [1.2.3] triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-[(R)-l-(2-chlor-phenyl)-ethyl]-7-(3,3-difluor-pyrrolidin-l- yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(4-chlor-pyridin-3-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-chlor-pyridin-2-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)- 2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-7-(3,3-difluor-pyrrolidin-l-yl)-2-(4-methyl-furazan-3- ylmethyl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; 5-tert-butyl-2-(3-chlor-pyridin-4-ylmethyl)-7-(3,3-difluor-pyrrolidin-l-yl)-2H-[l,2,3]triazolo[4,5-d]pyrimidin; og (S)-l-[5-tert-butyl-2-(2-trifluormethyl-benzyl)-2H-[l,2,3]triazolo[4,5- d]pyrimidin-7-yl]-pyrrolidin-3-ol.
15. Fremgangsmåde til fremstillingen af en forbindelse ifølge et hvilket som helst af kravene 1 til 14 omfattende omsætning af en forbindelse med formel (A)
i tilstedeværelse af F^-A-X og en base, eller i tilstedeværelse af F^-A-OH under Mitsunobu-betingelser, hvor A og R1 til R3 er defineret ifølge et hvilket som helst af kravene 1 til 12 og hvor X er halogen eller SO2.
16. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse som terapeutisk aktivt stof.
17. Farmaceutisk sammensætning omfattende en forbindelse i overensstemmelse med et hvilket som helst af kravene 1 til 14 og en terapeutisk inert bærer.
18. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse i behandlingen eller profylakse af smerte, atherosclerose, alders-relateret makulær degeneration, diabetisk retinopati, glaukom, diabetes mellitus, inflammation, inflammatorisk tarmsygdom, iskæmi, reperfusions-skade, akut leversvigt, leverfibrose, lungefibrose, nyrefibrose, systemisk fibrose, akut transplantationsafstødning, kronisk transplantations-nefropati, diabetisk nefropati, glomerulonepfropati, cardiomyopati, hjertesvigt, myocardial iskæmi, myocardial infarkt, systemisk sclerose, termisk skade, forbrænding, hypertrofiske ar, keloider, gingivitis pyrexia, skrumpelever eller tumorer, regulering af knoglemasse, neurodegeneration, slagtilfælde, transient iskæmiske anfald eller uveitis.
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