HRP20191139T1 - Derivati etinila kao modulatori metabotropnih glutamatnih receptora - Google Patents
Derivati etinila kao modulatori metabotropnih glutamatnih receptora Download PDFInfo
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- HRP20191139T1 HRP20191139T1 HRP20191139TT HRP20191139T HRP20191139T1 HR P20191139 T1 HRP20191139 T1 HR P20191139T1 HR P20191139T T HRP20191139T T HR P20191139TT HR P20191139 T HRP20191139 T HR P20191139T HR P20191139 T1 HRP20191139 T1 HR P20191139T1
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- Croatia
- Prior art keywords
- phenyl
- compound
- hexahydropyrimidine
- dione
- difluoro
- Prior art date
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- 102000016193 Metabotropic glutamate receptors Human genes 0.000 title 1
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 title 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 23
- 150000003839 salts Chemical class 0.000 claims 13
- 125000004076 pyridyl group Chemical group 0.000 claims 12
- 125000000217 alkyl group Chemical group 0.000 claims 9
- 239000002253 acid Substances 0.000 claims 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 6
- 230000003287 optical effect Effects 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- JQTTVBBQZKSMKH-SANMLTNESA-N (3S)-3'-[2,6-difluoro-4-(2-pyridin-3-ylethynyl)phenyl]-1'-methylspiro[1,2-dihydroindene-3,6'-1,3-diazinane]-2',4'-dione Chemical compound FC1=C(C(=CC(=C1)C#CC=1C=NC=CC=1)F)N1C(N([C@@]2(CCC3=CC=CC=C23)CC1=O)C)=O JQTTVBBQZKSMKH-SANMLTNESA-N 0.000 claims 1
- GCTGBTIYBHWYFT-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1,1'-dimethylspiro[1,3-diazinane-6,4'-5,6,7,8-tetrahydrocyclohepta[c]pyrazole]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCCCC=1N(N=CC=12)C)C)=O GCTGBTIYBHWYFT-MHZLTWQESA-N 0.000 claims 1
- RDYFWSWITUAFNE-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1,1'-dimethylspiro[1,3-diazinane-6,4'-6,7-dihydro-5H-indole]-2,4-dione Chemical compound CN1C=CC2=C1CCC[C@]21CC(=O)N(C(=O)N1C)C1=C(F)C=C(C=C1F)C#CC1=CC=CC=C1 RDYFWSWITUAFNE-MHZLTWQESA-N 0.000 claims 1
- KAUSIRYAUVTWDN-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1,2'-dimethylspiro[1,3-diazinane-6,4'-5,6,7,8-tetrahydrocyclohepta[c]pyrazole]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCCCC1=NN(C=C12)C)C)=O KAUSIRYAUVTWDN-MHZLTWQESA-N 0.000 claims 1
- PQEZBKHIJYKKFV-SANMLTNESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1,2'-dimethylspiro[1,3-diazinane-6,4'-6,7-dihydro-5H-indazole]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@@]2(CC1=O)C1=CN(N=C1CCC2)C)C)=O PQEZBKHIJYKKFV-SANMLTNESA-N 0.000 claims 1
- DPTPJUBSDCGSEH-NDEPHWFRSA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-ethylspiro[1,3-diazinane-6,8'-6,7-dihydro-5H-isoquinoline]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCCC=1C=CN=CC=12)CC)=O DPTPJUBSDCGSEH-NDEPHWFRSA-N 0.000 claims 1
- XIGZGUNDXPCNJD-VWLOTQADSA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,4'-1,5,6,7-tetrahydroindazole]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@@]2(CC1=O)C=1C=NNC=1CCC2)C)=O XIGZGUNDXPCNJD-VWLOTQADSA-N 0.000 claims 1
- YKSSJLFOPGPZKN-SANMLTNESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,4'-2,3-dihydropyrano[2,3-b]pyridine]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCOC1=NC=CC=C12)C)=O YKSSJLFOPGPZKN-SANMLTNESA-N 0.000 claims 1
- VQFAUHJPOOWPCF-SANMLTNESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,4'-5,6,7,8-tetrahydro-1H-cyclohepta[c]pyrazole]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCCCC=1NN=CC=12)C)=O VQFAUHJPOOWPCF-SANMLTNESA-N 0.000 claims 1
- FXLNLNIFGVNEBK-SANMLTNESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,5'-6,7-dihydrocyclopenta[b]pyridine]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCC1=NC=CC=C12)C)=O FXLNLNIFGVNEBK-SANMLTNESA-N 0.000 claims 1
- ANGRQMLXDYFWQR-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,5'-7,8-dihydro-6H-isoquinoline]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@@]2(CC1=O)C=1C=CN=CC=1CCC2)C)=O ANGRQMLXDYFWQR-MHZLTWQESA-N 0.000 claims 1
- CMFHEUJVSQXEFR-SANMLTNESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,5'-7,8-dihydro-6H-quinazoline]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@@]2(CC1=O)C=1C=NC=NC=1CCC2)C)=O CMFHEUJVSQXEFR-SANMLTNESA-N 0.000 claims 1
- ZOLJSTICBXZCNS-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,5'-7,8-dihydro-6H-quinoline]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@@]2(CC1=O)C=1C=CC=NC=1CCC2)C)=O ZOLJSTICBXZCNS-MHZLTWQESA-N 0.000 claims 1
- BASKATXGQBKLBA-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,8'-6,7-dihydro-5H-isoquinoline]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC1=CC=CC=C1)F)N1C(N([C@]2(CC1=O)CCCC=1C=CN=CC=12)C)=O BASKATXGQBKLBA-MHZLTWQESA-N 0.000 claims 1
- APMCYLNNKFINAI-AREMUKBSSA-N (6S)-3-[2,6-difluoro-4-(2-pyridin-3-ylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,4'-1,3-dihydroisochromene]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC=1C=NC=CC=1)F)N1C(N([C@@]2(COCC3=CC=CC=C23)CC1=O)C)=O APMCYLNNKFINAI-AREMUKBSSA-N 0.000 claims 1
- MTYDRISEUXFPDE-MHZLTWQESA-N (6S)-3-[2,6-difluoro-4-(2-pyridin-3-ylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,4'-2,3-dihydro-1H-naphthalene]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC=1C=NC=CC=1)F)N1C(N([C@@]2(CCCC3=CC=CC=C23)CC1=O)C)=O MTYDRISEUXFPDE-MHZLTWQESA-N 0.000 claims 1
- GLFVBDNUHFGLOX-SANMLTNESA-N (6S)-3-[2,6-difluoro-4-(2-pyridin-3-ylethynyl)phenyl]-1-methylspiro[1,3-diazinane-6,4'-2,3-dihydrochromene]-2,4-dione Chemical compound FC1=C(C(=CC(=C1)C#CC=1C=NC=CC=1)F)N1C(N([C@]2(CC1=O)CCOC1=CC=CC=C12)C)=O GLFVBDNUHFGLOX-SANMLTNESA-N 0.000 claims 1
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 206010003805 Autism Diseases 0.000 claims 1
- 208000020706 Autistic disease Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 206010047700 Vomiting Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 230000036506 anxiety Effects 0.000 claims 1
- 229910000024 caesium carbonate Inorganic materials 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
- 230000008673 vomiting Effects 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-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
- A61K31/527—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim spiro-condensed
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/22—Anxiolytics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- 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
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/20—Spiro-condensed systems
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- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Claims (15)
1. Spoj, naznačen time, da je predstavljen formulom I
u kojoj
R1 je niži alkil, pri čemu niži alkil znači alkilna skupina s 1 do 7 atoma ugljika;
R2 je fenil ili piridinil, gdje atom dušika u piridinilskoj skupini može zauzimati različite položaje;
n je 0, 1 ili 2;
V/U su neovisno jedan od drugog O ili CH2, pri čemu V i U ne mogu istovremeno biti O;
L je 5- ili 6-eročlana heteroarilna skupina, koja se bira između
ili
;
ili njegova farmaceutski prihvatljiva sol ili kiselinska adicijska sol, njegova racemična smjesa ili njezini odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.
2. Spoj formule IA prema patentnom zahtjevu 1,
naznačen time, da
R1 je niži alkil;
R2 je fenil ili piridinil, gdje atom dušika u piridinilskoj skupini može zauzimati različite položaje;
L je 5- ili 6-eročlana heteroarilna skupina, koja se bira između
ili
ili njegova farmaceutski prihvatljiva sol ili kiselinska adicijska sol, njegova racemična smjesa ili njezini odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.
3. Spoj formule IA prema patentnim zahtjevima 1 i 2, naznačen time, da su spojevi sljedeći
(8S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[6,7-dihidro-5H-izokinolin-8,6'-heksahidropirimidin]-2',4'-dion,
(6S)-3-[2,6-difluoro-4-[2-(3-piridil)etinil]fenil]-1-metil-spiro[heksahidropirimidin-6,1'-tetralin]-2,4-dion,
(5S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[7,8-dihidro-6H-kinolin-5,6'-heksahidropirimidin]-2',4'-dion,
(5S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[7,8-dihidro-6H-izokinolin-5,6'-heksahidropirimidin]-2',4'-dion,
(5S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[7,8-dihidro-6H-kinazolin-5,6'-heksahidropirimidin]-2',4'-dion,
(8S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-etil-spiro[6,7-dihidro-5H-izokinolin-8,6'-heksahidropirimidin]-2',4'-dion,
(4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[1,5,6,7-tetrahidroindazol-4,6'-heksahidropirimidin]-2',4'-dion,
(4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1',2-dimetil-spiro[6,7-dihidro-5H-indazol-4,6'-heksahidropirimidin]-2',4'-dion ili
(4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1,1'-dimetil-spiro[6,7-dihidro-5H-indazol-4,6'-heksahidropirimidin]-2',4'-dion.
4. Spoj formule IB prema patentnom zahtjevu 1,
naznačen time, da
R1 je niži alkil;
R2 je fenil ili piridinil, gdje atom dušika u piridinilskoj skupini može zauzimati različite položaje;
L je 5- ili 6-eročlana heteroarilna skupina, koja se bira između
ili
;
ili njegova farmaceutski prihvatljiva sol ili kiselinska adicijska sol, njegova racemična smjesa ili njezini odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.
5. Spoj formule IB prema patentnim zahtjevima 1 i 4, naznačen time, da su spojevi sljedeći
(6S)-3-[2,6-difluoro-4-[2-(3-piridil)etinil]fenil]-1-metil-spiro[heksahidropirimidin-6,1'-indan]-2,4-dion ili
(5S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[6,7-dihidrociklopenta[b]piridin-5,6'-heksahidropirimidin]-2',4'-dion.
6. Spoj formule IC prema patentnom zahtjevu 1,
naznačen time, da
R1 je niži alkil;
R² je fenil ili piridinil, gdje atom dušika u piridinilskoj skupini može zauzimati različite položaje;
L je 5- ili 6-eročlana heteroarilna skupina, koja se bira između
ili
;
ili njegova farmaceutski prihvatljiva sol ili kiselinska adicijska sol, njegova racemična smjesa ili njezini odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.
7. Spoj formule IC prema patentnim zahtjevima 1 i 6, naznačen time da su spojevi sljedeći
(4S)-3'-[2,6-difluoro-4-[2-(3-piridil)etinil]fenil]-1'-metil-spiro[kroman-4,6'-heksahidropirimidin]-2',4'-dion ili (4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[2,3-dihidropirano[2,3−b]piridin-4,6'-heksahidropirimidin]-2',4'-dion.
8. Spoj formule ID prema patentnom zahtjevu 1,
naznačen time, da
R1 je niži alkil;
R² je fenil ili piridinil, gdje atom dušika u piridinilskoj skupini može zauzimati različite položaje;
L je 5- ili 6-eročlana heteroarilna skupina, koja se bira između
ili
;
ili njegova farmaceutski prihvatljiva sol ili kiselinska adicijska sol, njegova racemična smjesa ili njezini odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.
9. Spoj formule ID prema patentnim zahtjevima 1 i 8, naznačen time, da spoj je sljedeći
(6S)-3-[2,6-difluoro-4-[2-(3-piridil)etinil]fenil]-1-metil-spiro[heksahidropirimidin-6,4'-izokroman]-2,4-dion.
10. Spoj formule IE prema patentnom zahtjevu 1,
naznačen time, da
R1 je niži alkil;
R2 je fenil ili piridinil, gdje atom dušika u piridinilskoj skupini može zauzimati različite položaje;
L je 5- ili 6-eročlana heteroarilna skupina, koja se bira između
ili
;
ili njegova farmaceutski prihvatljiva sol ili kiselinska adicijska sol, njegova racemična smjesa ili njezini odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.
11. Spoj formule IE prema patentnim zahtjevima 1 i 10, naznačen time, da su spojevi sljedeći
(4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1'-metil-spiro[5,6,7,8-tetrahidro-1H-ciklohepta[c]pirazol-4,6'-heksahidropirimidin]-2',4'-dion, (4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1,1'-dimetil-spiro[5,6,7,8-tetrahidrociklohepta[c]pirazol-4,6'-heksahidropirimidin]-2',4'-dion ili (4S)-3'-[2,6-difluoro-4-(2-feniletinil)fenil]-1',2-dimetil-spiro[5,6,7,8-tetrahidrociklohepta[c]pirazol-4,6'-heksahidropirimidin]-2',4'-dion.
12. Postupak proizvodnje spoja formule I kako je definiran u bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, da postupak obuhvaća:
a) alkilaciju spoja formule
s R1-I u prisutnosti NaH ili Cs2CO3 u DMF u spoj formule
pri čemu R1 je niži alkil, a preostali supstituenti su opisani gore, ili ako je potrebno, pretvaranje dobivenih spojeva u farmaceutski prihvatljive kiselinske adicijske soli.
13. Spoj formule I prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, da se upotrebljava kao terapeutski aktivne tvari.
14. Spoj formule I prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, da se upotrebljava u liječenju Parkinsonove bolesti, tjeskobe, povraćanja, opsesivnog kompulzivnog poremećaja, autizma, karcinoma, depresije i dijabetesa tipa 2.
15. Farmaceutski pripravak, naznačen time, da obuhvaća spoj formule I prema bilo kojem od patentnih zahtjeva 1 do 11, zajedno s farmaceutski prihvatljivim pomoćnim tvarima.
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| EP16739442.8A EP3322701B1 (en) | 2015-07-15 | 2016-07-11 | Ethynyl derivatives as metabotropic glutamate receptor modulators |
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| JP (1) | JP6761821B2 (hr) |
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| CA (1) | CA2984711C (hr) |
| CL (1) | CL2018000036A1 (hr) |
| CO (1) | CO2017011174A2 (hr) |
| CR (1) | CR20180022A (hr) |
| DK (1) | DK3322701T3 (hr) |
| ES (1) | ES2733468T3 (hr) |
| HR (1) | HRP20191139T1 (hr) |
| HU (1) | HUE045145T2 (hr) |
| IL (1) | IL255096B (hr) |
| LT (1) | LT3322701T (hr) |
| MA (1) | MA42442B1 (hr) |
| MX (1) | MX2018000592A (hr) |
| PE (1) | PE20180356A1 (hr) |
| PH (1) | PH12018500106A1 (hr) |
| PL (1) | PL3322701T3 (hr) |
| PT (1) | PT3322701T (hr) |
| RS (1) | RS58929B1 (hr) |
| RU (1) | RU2721776C9 (hr) |
| SI (1) | SI3322701T1 (hr) |
| TR (1) | TR201909160T4 (hr) |
| TW (1) | TWI612962B (hr) |
| UA (1) | UA120463C2 (hr) |
| WO (1) | WO2017009275A1 (hr) |
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| CN107652289B (zh) | 2012-06-13 | 2020-07-21 | 因塞特控股公司 | 作为fgfr抑制剂的取代的三环化合物 |
| JP6449244B2 (ja) | 2013-04-19 | 2019-01-09 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｆｇｆｒ抑制剤としての二環式複素環 |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| WO2016134320A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| LT3322701T (lt) | 2015-07-15 | 2019-07-10 | F. Hoffmann-La Roche Ag | Etinilo dariniai kaip metabotropinių glutamato receptorių moduliatoriai |
| PL3484889T3 (pl) | 2016-07-18 | 2020-12-28 | F. Hoffmann-La Roche Ag | Pochodne etynylu |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| SG11202010882XA (en) | 2018-05-04 | 2020-11-27 | Incyte Corp | Salts of an fgfr inhibitor |
| DK3788047T3 (da) | 2018-05-04 | 2024-09-16 | Incyte Corp | Faste former af en FGFR-inhibitor og fremgangsmåder til fremstilling deraf |
| CN112566906A (zh) | 2018-07-26 | 2021-03-26 | 多曼治疗学公司 | 取代的喹唑啉酮衍生物和它们作为mglur4的正变构调节剂的用途 |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| MX2022004513A (es) | 2019-10-14 | 2022-07-19 | Incyte Corp | Heterociclos biciclicos como inhibidores de los receptores del factor de crecimiento de fibroblastos (fgfr). |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| BR112022010664A2 (pt) | 2019-12-04 | 2022-08-16 | Incyte Corp | Derivados de um inibidor de fgfr |
| JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤としての三環式複素環 |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4323405A1 (en) | 2021-04-12 | 2024-02-21 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
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