DK3041843T3 - Triazolo[4,5-d]pyrimidinderivater som CB2-receptorantagonister - Google Patents

Triazolo[4,5-d]pyrimidinderivater som CB2-receptorantagonister Download PDF

Info

Publication number
DK3041843T3
DK3041843T3 DK14761320.2T DK14761320T DK3041843T3 DK 3041843 T3 DK3041843 T3 DK 3041843T3 DK 14761320 T DK14761320 T DK 14761320T DK 3041843 T3 DK3041843 T3 DK 3041843T3
Authority
DK
Denmark
Prior art keywords
methyl
triazolo
difluoropyrrolidin
chlorophenyl
pyrimidin
Prior art date
Application number
DK14761320.2T
Other languages
English (en)
Inventor
Stephan Roever
Mark Rogers-Evans
Matthias Nettekoven
Sébastien Schmitt
Uwe Grether
Atsushi Kimbara
Original Assignee
Hoffmann La Roche
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Application granted granted Critical
Publication of DK3041843T3 publication Critical patent/DK3041843T3/da

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (14)

1. Forbindelse med formlen (I)
hvor R1 er halogenalkyl, halogenphenyl, alkoxyphenyl, alkyl-l,2,5-oxadiazolyl, haloalkylphenyl, alkylsulfonylphenyl, halogenpyridinyl eller alkyltetrazolyl; R2 er alkylamino, cycloalkylamino, alkyloxetanylamino, (cycloalkyl)(alkyl)amino, halogenalkyloxy, alkoxy, cycloalkylalkoxy, cycloalkyloxy, oxetanyloxy, alkyloxetanylalkyloxy, alkynyloxy, alkoxyalkoxy, hydroxyalkyloxy, alkylsulfanyl, halogenalkylsulfanyl, alkylsulfonyl, hydroxyalkylsulfanyl, hydroxyalkylsulfonyl eller alkoxyalkylsulfonyl; R3 og R4 uafhængigt af hinanden er valgt blandt hydrogen, halogen, hydroxyl, alkylcarbonylamino og alkyl, forudsat at R3 og R4 ikke begge er hydrogen samtidig; og n er 1 eller 2; eller et farmaceutisk acceptabelt salt eller ester deraf; forudsat at (S)-l-[3-(4-methoxy-benzyl)-5-(2,2,2-trifluor-ethoxy)-3H-[l,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol er ekskluderet.
2. Forbindelse ifølge krav 1, hvor R1 er halogenphenyl, halogenalkylphenyl eller alkylsulfonylphenyl.
3. Forbindelse ifølge krav 1 eller 2, hvor R1 er chlorphenyl, trifluormethylphenyl eller methylsulfonylphenyl.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor R2 er alkylamino, alkoxy, halogenalkyloxy eller alkylsulfanyl.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4, hvor R2 er tert-butylamino, pentyloxy, isopropyloxy, trifluorethyloxy, trifluorpropyloxy, ethylsulfanyl eller tert-butylsulfanyl.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 5, hvor R3 og R4 uafhængigt af hinanden er valgt blandt hydrogen, halogen og hydroxyl.
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 6, hvor én af R3 og R4 er hydrogen og den anden er hydroxyl, eller hvor R3 og R4 begge er halogen samtidig.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 7, hvor én af R3 og R4 er hydrogen og den anden er hydroxyl, eller hvor R3 og R4 begge er fluor samtidig.
9. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 valgt blandt 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-N-ethyltriazolo[4,5- d]pyrimidin-5 -amin; 3-[(2-chlorphenyl)methyl]-N-cyclobutyl-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5-d]pyrimidin-5 -amin; N-tert-butyl-3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5-d]pyrimidin-5 -amin; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -yl)-N-(3 -methyloxetan-3 -yl)triazolo[4,5-d]pyrimidin-5-amin; N-tert-butyl-3 -[(2-chlorphenyl)methyl]-7-(3,3 -difluorpyrrolidin-1 -yl)-N-methyltriazolo[4,5-d]pyrimidin-5-amin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-N-(2,2- dimethylpropyl)triazolo[4,5-d]pyrimidin-5-amin; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -yl)-N-(oxetan-3 -yl)triazolo [4,5 -d]pyrimidin-5 -amin; 3 - [(2-chlorphenyl)methyl] -N-cyclobutyl-7-(3,3 -difluorpyrrolidin-1 -yl)-N -methyltriazolo[4,5-d]pyrimidin-5-amin; (3 S)-1 -[5 -(tert-butylamino)-3 - [(4-methoxyphenyl)methyl]triazolo [4,5 -d]pyrimidin-7 - yl]pyrrolidin-3-ol; N-tert-butyl-7-(3,3-difluorpyrrolidin-l-yl)-3-[(4-methoxyphenyl)methyl]triazolo[4,5-d]pyrimidin-5 -amin; N-[(3S)-l-[5-(tert-butylamino)-3-[(4-methoxyphenyl)methyl]triazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-yl]acetamid; N-tert-butyl-7 -(3,3 -difluorpyrrolidin-1 -y 1)-3 - [ [2 -(trifluormethyl)phenyl]methyl]triazolo[4,5-d]pyrimidin-5-amin; N-tert-butyl-7 -(3,3 -difluorpyrrolidin-1 -y 1)-3 - [(2 -methylsulfonylphenyl)methyl]triazolo[4,5-d]pyrimidin-5-amin; N-tert-butyl-3-[(3-chlorpyridin-2-yl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5-d]pyrimidin-5 -amin; N-tert-butyl-7 -(3,3 -difluorpyrrolidin-1 -y 1)-3 - [(1 -methyltetrazol-5 -yl)methyl]triazolo [4,5 -d]pyrimidin-5 -amin; N-tert-butyl-7 -(3,3 -difluorpyrrolidin-1 -y 1)-3 - [(4-methyl-1,2,5 -oxadiazol-3 -yl)methyl]triazolo[4,5-d]pyrimidin-5-amin; N-[(3S)-l-[5-(tert-butylamino)-3-[(3-chlorpyridin-2-yl)methyl]triazolo[4,5-d]pyrimidin- 7-yl]pyrrolidin-3-yl]acetamid; (3 S)-1 -[5 -(tert-butylamino)-3 - [(2-chlorphenyl)methyl]triazolo [4,5 -d]pyrimidin-7 -yl]pyrrolidin-3-ol; (3S)-l-[5-(tert-butylamino)-3-[(l-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-ol; (3 S)-1 -[5 -(tert-butylamino)-3 - [(4-methoxyphenyl)methyl]triazolo [4,5 -d]pyrimidin-7 -yl] -3 -methylpyrrolidin-3 -o 1; (3R)-l-[5-(tert-butylamino)-3-[(4-methoxyphenyl)methyl]triazolo[4,5-d]pyrimidin-7-yl]-3 -methylpyrrolidin-3 -o 1; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-(2,2,2- trifluorethoxy)triazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-1-yl)-5-( 1,1,1-trifluorpropan-2-yloxy)triazolo [4,5 -djpyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-[(2S)-l,l,l-trifluorpropan-2- yl]oxytriazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-5-(2,2-difluorethoxy)-7-(3,3-difluorpyrrolidin-1-yl)triazolo[4,5-d]pyrimidin; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -ethoxytriazolo [4,5 -djpyrimidin; 5-butoxy-3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5- djpyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-(2-fluorethoxy)triazolo[4,5- djpyrimidin; 3 - [(2-chlorphenyl)methyl] -5 -(cyclopropylmethoxy)-7-(3,3 -difluorpyrrolidin-1 -yl)triazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-5-cyclobutyloxy-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5- djpyrimidin; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(oxetan-3 -yloxy)triazolo [4,5 -djpyrimidin; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 - [(3 -methyloxetan-3 -yl)methoxy]triazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-[(2R)-1,1,1-trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-(2,2- dimethylpropoxy)triazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-5-(2,2-difluorpropoxy)-7-(3,3-difluorpyrrolidin-l- yl)triazolo[4,5-d]pyrimidin; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(2-methylpropoxy)triazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-propan-2-yloxytriazolo[4,5- djpyrimidin; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -prop-2 -ynoxytriazolo [4,5 -djpyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-(l-methoxypropan-2-yloxy)triazolo [4,5 -djpyrimidin; l-[3-[(2-chlorphenyl)methyl]-7-(3,3 -difluorpyrrolidin- l-yl)triazolo[4,5-d]pyrimidin-5- yl]oxy-2-methylpropan-2-ol; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -propoxytriazolo [4,5 -djpyrimidin; (3S)-l-[3-[(2-chlorphenyl)methyl]-5-(2,2,2-trifluorethoxy)triazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-ol; (3S)-l-[5-(2,2,2-trifluorethoxy)-3-[[2-(trifluormethyl)phenyl]methyl]triazolo[4,5- d]pyrimidin-7-yl]pyrrolidin-3-ol; (3S)-l-[3-[(2-chlorphenyl)methyl]-5-propan-2-yloxytriazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-ol; (3S)-l-[3-[(2-methylsulfonylphenyl)methyl]-5-propan-2-yloxytriazolo[4,5-d]pyrimidin- 7-yl]pyrrolidin-3-ol; (3S)-l-[3-[(l-methyltetrazol-5-yl)methyl]-5-propan-2-yloxytriazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-ol; 7-(3,3 -difluorpyrrolidin-1 -y 1) - 5 -(2,2 -dimethylpropoxy)-3 - [(1 -methyltetrazol-5 -yl)methyl]triazolo[4,5-d]pyrimidin; 7-(3,3 -difluorpyrrolidin-1 -y 1) - 5 -(2,2 -dimethylpropoxy)-3 -[(2-methylsulfonylphenyl)methyl]triazolo[4,5-djpyrimidin; 3 - [[7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(2,2 -dimethylpropoxy)triazolo [4,5 -djpyrimidin-3 -yl]methyl]-4-methyl-l,2,5-oxadiazol; 7-(3,3-difluorpyrrolidin-l-yl)-3-[[2-(trifluormethyl)phenyl]methyl]-5-[(2S)-1,1,1-trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; 7-(3,3-difluorpyrrolidin-1 -yl)-3-[(2-methylsulfonylphenyl)methyl]-5-[(2S)-1,1,1-trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; 3 - [(3 -chlorpyridin-2-yl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1) - 5 - [ (2 S) -1,1,1-trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; 2-[[7-(3,3-difluorpyrrolidin-l-yl)-5-[(2S)-l,l,l-trifluorpropan-2-yl]oxytriazolo[4,5- d]pyrimidin-3-yl]methyl]-5-methyl-l,3,4-oxadiazol; 5 - [[7-(3,3 -difluorpyrrolidin-1 -y 1)-5 - [(2 S)-1,1,1 -trifluorpropan-2-yl] oxytriazolo [4,5 -d]pyrimidin-3-yl]methyl]-3-methyl-l,2,4-oxadiazol; 7-(3,3-difluorpyrrolidin-l-yl)-3-[(l-methyltetrazol-5-yl)methyl]-5-[(2S)-l,l,l- trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; 3-[[7-(3,3-difluorpyrrolidin-l-yl)-5-[(2S)-l,l,l-trifluorpropan-2-yl]oxytriazolo[4,5- d]pyrimidin-3-yl]methyl]-4-methyl-l,2,5-oxadiazol; 7-(3,3 -difluorpyrrolidin-1 -yl)-5 - [(2S)-1,1,1 -trifluorpropan-2-yl] oxy-3 -(3,3,3-trifluorpropyl)triazolo[4,5-d]pyrimidin; 3 - [(1 -cyclopropyltetrazol-5 -yl)methyl]-7-(3,3 -difluorpyrrolidin-1 -yl)-5 - [(2S)-1,1,1-trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; N-[(3S)-l-[3-[(2-chlorphenyl)methyl]-5-(2,2-dimethylpropoxy)triazolo[4,5-d]pyrimidin- 7-yl]pyrrolidin-3-yl]acetamid; N-[(3S)-l-[3-[(3-chlorpyridin-2-yl)methyl]-5-(2,2-dimethylpropoxy)triazolo[4,5- d]pyrimidin-7-yl]pyrrolidin-3-yl]acetamid; N-[(3S)-l-[5-(2,2-dimethylpropoxy)-3-[(4-methyl-l,2,5-oxadiazol-3- yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-yl]acetamid; N-[(3S)-l-[3-[(2-chlorphenyl)methyl]-5-[(2S)-l,l,l-trifluorpropan-2-yl]oxytriazolo[4,5- d]pyrimidin-7-yl]pyrrolidin-3-yl]acetamid; N-[(3S)-l-[3-[[2-(trifluormethyl)phenyl]methyl]-5-[(2S)-l,l,l-trifluorpropan-2- yl]oxytriazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-yl]acetamid; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -ethylsulfanyltriazolo [4,5 -djpyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-(2,2,2- trifluorethylsulfanyl)triazolo[4,5-d]pyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-propan-2- ylsulfanyltriazolo[4,5-d]pyrimidin; 5 -tert-butylsulfanyl-3 - [(2 -chlorphenyl)methyl] -7-(3,3 -difluorpyrro lidin-1 -yl)triazolo [4,5 -djpyrimidin; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -ethylsulfonyltriazolo [4,5 -djpyrimidin; 5 -benzylsulfonyl-3 -[(2-chlorphenyl)methyl] -7-(3,3-difluorpyrrolidin-1 -yl)triazolo [4,5 -djpyrimidin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-propan-2- ylsulfonyltriazolo[4,5-d]pyrimidin; 2-[3-[(2-chlorphenyl)methyl]-7-(3,3 -difluorpyrrolidin- l-yl)triazolo[4,5-d]pyrimidin-5- yljsulfanylethanol; l-[3-[(2-chlorphenyl)methyl]-7-(3,3 -difluorpyrrolidin- l-yl)triazolo[4,5-d]pyrimidin-5-yl]sulfanylpropan-2-ol; 5-butylsulfanyl-3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5-djpyrimidin; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(2-methylpropylsulfanyl)triazolo[4,5-d]pyrimidin; 5 -butylsulfonyl-3 -[(2 -chlorphenyl)methyl]-7-(3,3 -difluorpyrrolidin-1 -yl)triazolo [4,5 -djpyrimidin; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(2-methylpropylsulfonyl)triazolo[4,5-d]pyrimidin; l-[3-[(2-chlorphenyl)methyl]-7-(3,3 -difluorpyrrolidin- l-yl)triazolo[4,5-d]pyrimidin-5-yl]sulfonylpropan-2-ol; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(2-methoxyethylsulfonyl)triazolo[4,5-d]pyrimidin og N-[(3S)-l-[5-(tert-butylamino)-3-[(2-chlorphenyl)methyl]triazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-yl]acetamid.
10. Forbindelse ifølge et hvilket som helst af kravene 1 til 9 valgt blandt N-tert-butyl-3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)triazolo[4,5- d]pyrimidin-5 -amin; N-tert-butyl-7 -(3,3 -difluorpyrrolidin-1 -y 1)-3 - [(2 -methylsulfonylphenyl)methyl]triazolo[4,5-d]pyrimidin-5-amin; 3-[(2-chlorphenyl)methyl]-7-(3,3-difluorpyrrolidin-l-yl)-5-(2,2- dimethylpropoxy)triazolo[4,5-d]pyrimidin; 3 - [(2-chlorphenyl)methylj -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -(2-methylpropoxy)triazolo[4,5-d]pyrimidin; (3S)-l-[3-[(2-chlorphenyl)methyl]-5-(2,2,2-trifluorethoxy)triazolo[4,5-d]pyrimidin-7- yl]pyrrolidin-3-ol; 7-(3,3-difhjorpyrrolidin-l-yl)-3-[[2-(trifluormethyl)phenyl]methyl]-5-[(2S)-1,1,1-trifluorpropan-2-yl]oxytriazolo[4,5-d]pyrimidin; 3 - [(2-chlorphenyl)methyl] -7-(3,3 -difluorpyrrolidin-1 -y 1)-5 -ethylsulfanyltriazolo [4,5 -djpyrimidin og 5 -tert-butylsulfanyl-3 - [(2 -chlorphenyl)methyl] -7-(3,3 -difluorpyrro lidin-1 -yl)triazolo [4,5 -d] pyrimidin.
11. Fremgangsmåde til fremstilling af en forbindelse ifølge et hvilket som helst af kravene 1 til 10, hvilken fremgangsmåde omfatter ét af følgende trin: (a) omsætning af en forbindelse med formlen (Al)
i tilstedeværelsen af en forbindelse med formlen (A2)
hvor R2 er isopropyl, cycloalkyl eller alkenyl og R1, R3, R4 og n er som defineret i et hvilket som helst af kravene 1 til 8; (b) omsætning af en forbindelse med formlen (Bl)
i tilstedeværelsen af R'CfbX, hvor X er en halogen, en hydroxyl eller en sulfonatgruppe, hvor R2 er isopropyl, cycloalkyl eller alkenyl, og hvor R3 til R4 og n er som defineret i et hvilket som helst af kravene 1 til 8;
(c) omsætning af en forbindelse med formlen (Cl)
i tilstedeværelsen af R2-H, hvor R2 er piperidinyl, alkylamino, azetidinyl, pyrrolidinyl, cycloalkylamino, alkyloxetanylamino, morpholinyl, (cycloalkyl)(alkyl)amino, halogenalkyloxy, alkoxy, cycloalkylalkoxy, cycloalkyloxy, oxetanyloxy, alkyloxetanylalkyloxy, alkynyloxy, alkoxyalkoxy, hydroxyalkyloxy, alkylsulfanyl, halogenalkylsulfanyl, alkylsulfonyl, hydroxyalkylsulfanyl, hydroxyalkylsulfonyl eller alkoxyalkylsulfonyl, og hvor R1, R3, R4 og n er som defineret i et hvilket som helst af kravene 1 til 8.
12. Forbindelse ifølge et hvilket som helst af kravene 1 til 10 til anvendelse som terapeutisk aktivt stof.
13. Farmaceutisk sammensætning, der omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 10 og en terapeutisk inert bærer.
14. Forbindelse ifølge et hvilket som helst af kravene 1 til 10 til anvendelse i behandling eller profylakse af smerte, aterosklerose, aldersrelateret makulær degeneration, diabetisk retinopati, glaukom, diabetes mellitus, inflammation, inflammatorisk tarmsygdom, iskæmi-reperfusionsskade, akut leversvigt, leverfibrose, lungefibrose, nyre fibrose, systemisk fibrose, akut allografit-afstødning, kronisk allograft-nefropati, diabetisk nefropati, glomerulonefropati, kardiomyopati, hjertesvigt, myokardieiskæmi, myokardieinfarkt, systemisk sklerose, termisk skade, forbrænding, hypertrofiske ar, keloider, gingivitis pyrexia, levercirrose eller -tumorer, regulering af knoglemassen, nervedegeneration, apopleksi, transitorisk iskæmisk attak eller uveitis.
DK14761320.2T 2013-09-06 2014-09-03 Triazolo[4,5-d]pyrimidinderivater som CB2-receptorantagonister DK3041843T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP13183385 2013-09-06
PCT/EP2014/068640 WO2015032769A1 (en) 2013-09-06 2014-09-03 Novel triazolo[4,5-d]pyrimidine derivatives

Publications (1)

Publication Number Publication Date
DK3041843T3 true DK3041843T3 (da) 2019-03-25

Family

ID=49111076

Family Applications (2)

Application Number Title Priority Date Filing Date
DK18206943.5T DK3483163T3 (da) 2013-09-06 2014-09-03 Triazolo[4,5-d]pyrimidinderivater som cb2-receptorantagonister
DK14761320.2T DK3041843T3 (da) 2013-09-06 2014-09-03 Triazolo[4,5-d]pyrimidinderivater som CB2-receptorantagonister

Family Applications Before (1)

Application Number Title Priority Date Filing Date
DK18206943.5T DK3483163T3 (da) 2013-09-06 2014-09-03 Triazolo[4,5-d]pyrimidinderivater som cb2-receptorantagonister

Country Status (31)

Country Link
US (1) US9593123B2 (da)
EP (3) EP3483163B1 (da)
JP (1) JP6441356B2 (da)
KR (3) KR102349567B1 (da)
CN (1) CN105555788B (da)
AR (1) AR097553A1 (da)
AU (1) AU2014317229B2 (da)
CA (1) CA2915766C (da)
CL (1) CL2016000495A1 (da)
CR (1) CR20160076A (da)
DK (2) DK3483163T3 (da)
EA (1) EA028335B1 (da)
ES (2) ES2883923T3 (da)
HR (2) HRP20190361T1 (da)
HU (2) HUE041760T2 (da)
IL (1) IL243092B (da)
LT (2) LT3041843T (da)
MA (1) MA38826B1 (da)
MX (2) MX391724B (da)
MY (1) MY191628A (da)
PE (2) PE20191528A1 (da)
PH (1) PH12016500250B1 (da)
PL (2) PL3041843T3 (da)
PT (2) PT3041843T (da)
RS (2) RS62234B1 (da)
SG (1) SG11201601714UA (da)
SI (2) SI3041843T1 (da)
TR (1) TR201900662T4 (da)
TW (1) TWI705966B (da)
UA (1) UA116395C2 (da)
WO (1) WO2015032769A1 (da)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015162630A1 (en) * 2014-04-25 2015-10-29 Anlon Chemical Research Organization Novel processes for preparing triazolo [4,5-d]- pyrimidines, including ticagrelor, vianew intermediates and new route of synthesis.
EP3215506B1 (en) 2014-11-07 2019-01-02 F.Hoffmann-La Roche Ag Triazolo[4,5-d]pyrimidines as agonists of the cannabinoid receptor 2
WO2017004133A1 (en) * 2015-06-29 2017-01-05 Nimbus Iris, Inc. Irak inhibitors and uses thereof
CN107001405B (zh) * 2015-11-06 2019-03-05 江苏恒瑞医药股份有限公司 制备坎格雷洛中间体的方法
MX2018014684A (es) * 2016-06-23 2019-02-28 Hoffmann La Roche Derivados de [1,2,3]triazolo[4,5-d]pirimidina con afinidad para el receptor de canabinoide de tipo 2.
CN109311886B (zh) 2016-06-23 2021-11-09 豪夫迈·罗氏有限公司 [1,2,3]三唑并[4,5-d]嘧啶衍生物
WO2017220544A1 (en) 2016-06-23 2017-12-28 F. Hoffmann-La Roche Ag Novel[1,2,3]triazolo[4,5-d]pyrimidine derivatives
WO2017220516A1 (en) * 2016-06-23 2017-12-28 F. Hoffmann-La Roche Ag Novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives
CN106478639B (zh) * 2016-09-05 2018-09-18 郑州大学 嘧啶并1,2,4–三氮唑类的lsd1抑制剂、其制备方法及应用
CN106432248B (zh) * 2016-09-27 2018-11-27 郑州大学 含嘧啶并三氮唑类lsd1抑制剂、其制备方法及应用
CN106432247B (zh) * 2016-09-27 2018-06-29 郑州大学 含有腙键的嘧啶并三氮唑类化合物、制备方法及其应用
CN106928296A (zh) * 2017-02-06 2017-07-07 上海华升生物科技有限公司 一种2‑(3,3,3‑三氟丙硫基)腺苷的合成方法
CN106928235A (zh) * 2017-05-03 2017-07-07 郑州大学 含嘧啶并三氮唑类lsd1抑制剂、其制备方法及应用
CN107033148B (zh) * 2017-05-03 2018-10-26 郑州大学 含嘧啶并三氮唑—巯基四氮唑类lsd1抑制剂、其制备方法及应用
CN109516990B (zh) * 2017-09-19 2021-06-01 天津药物研究院有限公司 嘧啶并三氮唑类化合物、其制备方法和用途
CN113582935A (zh) * 2021-08-27 2021-11-02 中国医学科学院放射医学研究所 一种炎症小体核苷酸结合寡聚化结构域样受体蛋白3抑制剂及其制备方法和应用
CN115246832B (zh) * 2022-06-15 2024-05-24 深圳湾实验室 一类去泛素化酶usp25和usp28靶向抑制剂及制备和应用
CN119912457B (zh) * 2025-03-03 2025-10-10 郑州大学 嘧啶并三氮唑类化合物及其制备方法和应用

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1012151B1 (en) 1997-09-02 2002-08-07 Bristol-Myers Squibb Pharma Company Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (crh) antagonists, useful for treating cns and stress-related disorders
WO2001058869A2 (en) 2000-02-11 2001-08-16 Bristol-Myers Squibb Company Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases
WO2006009698A2 (en) * 2004-06-17 2006-01-26 The Regents Of The University Of California Antagonizing an adenosine a2a receptor to amelioriate one or more components of addictive behavior
AR051596A1 (es) 2004-10-26 2007-01-24 Irm Llc Compuestos heterociclicos condensados nitrogenados como inhibidores de la actividad del receptor canabinoide 1; composiciones farmaceuticas que los contienen y su empleo en la preparacion de medicamentos para el tratamiento de trastornos alimentarios
CN101855222A (zh) 2007-05-10 2010-10-06 通用电气健康护理有限公司 对大麻素cb2受体具有活性的咪唑并(1,2-a)吡啶和相关化合物
CA2709784A1 (en) * 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
WO2009117444A1 (en) 2008-03-17 2009-09-24 Northeastern University Inhibitors of fatty acid amide hydrolase and monoacylglycerol lipase for modulation of cannabinoid receptors
WO2010120987A1 (en) 2009-04-17 2010-10-21 Wyeth Llc Ring fused, ureidoaryl- and carbamoylaryl-bridged morpholino-pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses
WO2013060837A1 (en) 2011-10-27 2013-05-02 Lek Pharmaceuticals D.D. Synthesis of triazolopyrimidine compounds
UA111640C2 (uk) * 2011-11-08 2016-05-25 Ф. Хоффманн-Ля Рош Аг ПОХІДНІ [1,2,3]ТРИАЗОЛО[4,5-d]ПІРИМІДИНУ ЯК АГОНІСТИ КАНАБІНОЇДНОГО РЕЦЕПТОРА 2
US9067943B2 (en) * 2011-11-25 2015-06-30 Hoffmann-La Roche Inc. [1,2,3]triazolo[4,5-D]pyrimidine derivatives
JP2015521652A (ja) 2012-07-04 2015-07-30 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ カンナビノイド受容体２アゴニストとしての新規アダマンチル誘導体
CN104837818B (zh) 2012-12-07 2017-07-14 霍夫曼-拉罗奇有限公司 可用作cb2激动剂的吡啶‑2‑酰胺
AU2013354115B2 (en) 2012-12-07 2017-10-05 F. Hoffmann-La Roche Ag Novel pyrazine derivatives as CB2 receptor agonists
PL2928868T3 (pl) 2012-12-07 2017-12-29 F.Hoffmann-La Roche Ag Pirydyno-2-amidy użyteczne jako agoniści cb2
SG10201800170YA (en) 2012-12-07 2018-02-27 Hoffmann La Roche Novel pyridine derivatives
AU2014224784B2 (en) 2013-03-07 2018-03-08 F. Hoffmann-La Roche Ag Novel pyrazol derivatives
WO2014177527A1 (en) 2013-05-02 2014-11-06 F. Hoffmann-La Roche Ag Pyrrolo[2,3-d]pyrimidine derivatives as cb2 receptor agonists
AU2014261585B2 (en) 2013-05-02 2018-03-08 F. Hoffmann-La Roche Ag Purine derivatives as CB2 receptor agonists
BR112015030824A2 (pt) 2013-06-11 2017-07-25 Hoffmann La Roche novos derivados de tetrazolona

Also Published As

Publication number Publication date
RS62234B1 (sr) 2021-09-30
HK1219277A1 (zh) 2017-03-31
RS58390B1 (sr) 2019-04-30
WO2015032769A1 (en) 2015-03-12
MA38826A1 (fr) 2016-05-31
KR20210074404A (ko) 2021-06-21
TR201900662T4 (tr) 2019-02-21
KR20160050061A (ko) 2016-05-10
PE20191528A1 (es) 2019-10-23
EA201690478A1 (ru) 2016-06-30
IL243092A0 (en) 2016-02-01
EP3943497A1 (en) 2022-01-26
PT3041843T (pt) 2019-02-26
JP6441356B2 (ja) 2018-12-19
MA38826B1 (fr) 2016-12-30
TWI705966B (zh) 2020-10-01
DK3483163T3 (da) 2021-08-30
TW201542551A (zh) 2015-11-16
US20160168158A1 (en) 2016-06-16
US9593123B2 (en) 2017-03-14
MX2016002117A (es) 2016-07-05
KR102454344B1 (ko) 2022-10-14
JP2016532707A (ja) 2016-10-20
HRP20190361T1 (hr) 2019-04-05
PL3483163T3 (pl) 2021-11-22
PL3041843T3 (pl) 2019-06-28
CA2915766C (en) 2023-09-26
MX367084B (es) 2019-08-05
AU2014317229B2 (en) 2018-11-08
CA2915766A1 (en) 2015-03-12
HUE041760T2 (hu) 2019-05-28
SI3483163T1 (sl) 2021-11-30
KR20220140651A (ko) 2022-10-18
NZ756513A (en) 2021-05-28
UA116395C2 (uk) 2018-03-12
AU2014317229A1 (en) 2016-01-07
NZ715085A (en) 2021-05-28
EP3483163B1 (en) 2021-06-23
CN105555788A (zh) 2016-05-04
MY191628A (en) 2022-07-04
PH12016500250A1 (en) 2016-05-16
AR097553A1 (es) 2016-03-23
IL243092B (en) 2019-06-30
EP3041843B1 (en) 2019-01-02
EA028335B1 (ru) 2017-11-30
SG11201601714UA (en) 2016-04-28
PT3483163T (pt) 2021-08-24
CR20160076A (es) 2016-04-01
MX2019009100A (es) 2019-09-16
HUE055201T2 (hu) 2021-11-29
EP3483163A3 (en) 2019-07-24
HRP20211322T1 (hr) 2021-11-26
SI3041843T1 (sl) 2019-04-30
KR102349567B1 (ko) 2022-01-11
EP3041843A1 (en) 2016-07-13
LT3041843T (lt) 2019-03-12
PH12016500250B1 (en) 2019-09-13
ES2883923T3 (es) 2021-12-09
CL2016000495A1 (es) 2016-10-07
PE20160691A1 (es) 2016-07-28
CN105555788B (zh) 2018-11-23
EP3483163A2 (en) 2019-05-15
MX391724B (es) 2025-03-21
LT3483163T (lt) 2021-09-10
ES2714094T3 (es) 2019-05-27

Similar Documents

Publication Publication Date Title
DK3041843T3 (da) Triazolo[4,5-d]pyrimidinderivater som CB2-receptorantagonister
DK2782915T3 (da) [1,2,3]TRIAZOLO[4,5-d]PYRIMIDINDERIVATER SOM AGONISTER AF CANNABINOIDRECEPTOR-2-AGONISTER
EP3215506B1 (en) Triazolo[4,5-d]pyrimidines as agonists of the cannabinoid receptor 2
DK2991987T3 (da) Purinderivativer som CB2-receptoragonister
DK2991988T3 (da) Pyrrolo[2,3-d]pyrimidinderivater som CB2-receptoragonister
NZ756513B2 (en) Novel triazolo[4,5-d]pyrimidine derivatives
BR122020008944B1 (pt) Novos derivados de triazolo [4,5-d] pirimidina
BR112016004934B1 (pt) Novos derivados de triazolo [4,5-d] pirimidina
NZ715085B2 (en) Novel triazolo[4,5-d]pyrimidine derivatives
HK1219277B (zh) 三唑并[4，5-d]嘧啶衍生物
HK1236027B (zh) 作爲大麻素受体2的激动剂的三唑并[4，5-d]嘧啶类