HRP20100477T1 - Kemijski spojevi - Google Patents
Kemijski spojevi Download PDFInfo
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- HRP20100477T1 HRP20100477T1 HR20100477T HRP20100477T HRP20100477T1 HR P20100477 T1 HRP20100477 T1 HR P20100477T1 HR 20100477 T HR20100477 T HR 20100477T HR P20100477 T HRP20100477 T HR P20100477T HR P20100477 T1 HRP20100477 T1 HR P20100477T1
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- 150000001875 compounds Chemical class 0.000 title claims abstract 38
- 238000000034 method Methods 0.000 claims abstract 9
- 206010028980 Neoplasm Diseases 0.000 claims abstract 6
- 201000011510 cancer Diseases 0.000 claims abstract 6
- 238000011282 treatment Methods 0.000 claims abstract 4
- -1 nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl Chemical group 0.000 claims 30
- 150000003839 salts Chemical class 0.000 claims 22
- 125000000217 alkyl group Chemical group 0.000 claims 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 11
- 239000001257 hydrogen Substances 0.000 claims 11
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 9
- 125000005843 halogen group Chemical group 0.000 claims 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 8
- 229910052799 carbon Inorganic materials 0.000 claims 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 8
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 7
- 125000001589 carboacyl group Chemical group 0.000 claims 7
- 229910052757 nitrogen Inorganic materials 0.000 claims 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 6
- 125000004452 carbocyclyl group Chemical group 0.000 claims 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 5
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 206010006187 Breast cancer Diseases 0.000 claims 4
- 208000026310 Breast neoplasm Diseases 0.000 claims 4
- 206010027406 Mesothelioma Diseases 0.000 claims 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 201000001441 melanoma Diseases 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 238000011321 prophylaxis Methods 0.000 claims 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 206010065859 Congenital fibrosarcoma Diseases 0.000 claims 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 2
- 206010062904 Hormone-refractory prostate cancer Diseases 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 206010070665 Mesoblastic nephroma Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 2
- 206010029260 Neuroblastoma Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 206010033701 Papillary thyroid cancer Diseases 0.000 claims 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 206010038389 Renal cancer Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 2
- 125000004423 acyloxy group Chemical group 0.000 claims 2
- 230000001028 anti-proliverative effect Effects 0.000 claims 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 2
- 201000010881 cervical cancer Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 201000010982 kidney cancer Diseases 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 2
- 230000003248 secreting effect Effects 0.000 claims 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- FDVYXPGZCFFAOV-KRWDZBQOSA-N (2r)-2-[5-[(5-cyclopropyl-1h-pyrazol-3-yl)amino]imidazo[4,5-b]pyridin-3-yl]-2-(4-fluorophenyl)ethanol Chemical compound C1([C@H](CO)N2C3=NC(NC4=NNC(=C4)C4CC4)=CC=C3N=C2)=CC=C(F)C=C1 FDVYXPGZCFFAOV-KRWDZBQOSA-N 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- WEMUXEAHYIJLLC-LBPRGKRZSA-N 6-chloro-3-[(1s)-1-(4-fluorophenyl)ethyl]-n-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical class N1C(OC(C)C)=CC(NC=2C(=CC=3N=CN(C=3N=2)[C@@H](C)C=2C=CC(F)=CC=2)Cl)=N1 WEMUXEAHYIJLLC-LBPRGKRZSA-N 0.000 claims 1
- AEYYBNYJLOJJRE-NSHDSACASA-N 6-chloro-n-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(1s)-1-(4-fluorophenyl)ethyl]imidazo[4,5-b]pyridin-5-amine Chemical class C1([C@H](C)N2C3=NC(NC4=NNC(=C4)C4CC4)=C(Cl)C=C3N=C2)=CC=C(F)C=C1 AEYYBNYJLOJJRE-NSHDSACASA-N 0.000 claims 1
- GTQWPQWZQDJIDK-LBPRGKRZSA-N 6-fluoro-3-[(1s)-1-(4-fluorophenyl)ethyl]-n-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical class N1C(OC(C)C)=CC(NC=2C(=CC=3N=CN(C=3N=2)[C@@H](C)C=2C=CC(F)=CC=2)F)=N1 GTQWPQWZQDJIDK-LBPRGKRZSA-N 0.000 claims 1
- PGJIKVGJKHTQEB-NSHDSACASA-N 6-fluoro-3-[(1s)-1-(4-fluorophenyl)ethyl]-n-(5-methyl-1h-pyrazol-3-yl)imidazo[4,5-b]pyridin-5-amine Chemical class C1([C@H](C)N2C3=NC(NC4=NNC(C)=C4)=C(F)C=C3N=C2)=CC=C(F)C=C1 PGJIKVGJKHTQEB-NSHDSACASA-N 0.000 claims 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 201000005619 esophageal carcinoma Diseases 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- ZJKJHYMHERVKGZ-LBPRGKRZSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-3-[(1s)-1-(4-fluorophenyl)ethyl]imidazo[4,5-b]pyridin-5-amine Chemical compound C1([C@H](C)N2C3=NC(NC4=NNC(=C4)C4CC4)=CC=C3N=C2)=CC=C(F)C=C1 ZJKJHYMHERVKGZ-LBPRGKRZSA-N 0.000 claims 1
- GBEMGSXBITUWBG-NSHDSACASA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-6-fluoro-3-[(1s)-1-(4-fluorophenyl)ethyl]imidazo[4,5-b]pyridin-5-amine Chemical class C1([C@H](C)N2C3=NC(NC4=NNC(=C4)C4CC4)=C(F)C=C3N=C2)=CC=C(F)C=C1 GBEMGSXBITUWBG-NSHDSACASA-N 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 235000010288 sodium nitrite Nutrition 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
Classifications
-
- 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
- C07D471/04—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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Spoj formule (I): naznačen time da: R1 i R2 su nezavisno odabrani od vodika, halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkila, C2-6alkenila, C2-6alkinila, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoila, C1-6alkilsulfonilamino, karbociklila ili heterociklila; pri čemu R1 i R2 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R7; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom iz R8;X1, X2 i X3 su nezavisno =N- ili =CR9-;R3 i R9 su nezavisno odabrani od vodika, halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkil, C2-6alkenil, C2-6alkinil, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoila, C1-6alkilsulfonilamino, karbociklila-R10- ili heterociklila-R11-; pri čemu R3 i R9 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R12; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R13;R4 i R5 su nezavisno odabrani od vodika, halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkil, C2-6alkenil, C2-6alkinil, C1-6alkoksi, C1-6alkanoil, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoil, C1-6alkilsulfonilamino, karbociklila ili heterociklila; pri čemu R4 i R5 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R14; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R15;A je direktna veza ili C1-2alkilen; pri čemu navedeni C1-2alkilen može biti opcijski supstituiran sa jednim ili više R16;prsten C je karbociklil ili heterociklil; pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R17;R6 je odabran od halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkila, C2-6alkenila, C2-6alkinila, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)zamino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6al
Claims (22)
1. Spoj formule (I):
[image]
naznačen time da:
R1 i R2 su nezavisno odabrani od vodika, halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkila, C2-6alkenila, C2-6alkinila, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoila, C1-6alkilsulfonilamino, karbociklila ili heterociklila; pri čemu R1 i R2 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R7; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom iz R8;
X1, X2 i X3 su nezavisno =N- ili =CR9-;
R3 i R9 su nezavisno odabrani od vodika, halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkil, C2-6alkenil, C2-6alkinil, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoila, C1-6alkilsulfonilamino, karbociklila-R10- ili heterociklila-R11-; pri čemu R3 i R9 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R12; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R13;
R4 i R5 su nezavisno odabrani od vodika, halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkil, C2-6alkenil, C2-6alkinil, C1-6alkoksi, C1-6alkanoil, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoil, C1-6alkilsulfonilamino, karbociklila ili heterociklila; pri čemu R4 i R5 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R14; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R15;
A je direktna veza ili C1-2alkilen; pri čemu navedeni C1-2alkilen može biti opcijski supstituiran sa jednim ili više R16;
prsten C je karbociklil ili heterociklil; pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R17;
R6 je odabran od halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkila, C2-6alkenila, C2-6alkinila, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)zamino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)zsulfamoila, C1-6alkilsulfonilamino, karbociklila ili heterociklila; pri čemu R6 može biti opcijski supstituiran na ugljiku sa jednim ili više R18; i pri čemu ako navedeni heterociklil sadrži
-NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R19;
n je 0, 1, 2 ili 3; pri čemu vrijednosti R6 mogu biti iste ili različite;
R7, R12, R14, R16 i R18 su nezavisno odabrani od halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkila, C2-6alkenila, C2-6alkinila, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoila, C1-6alkilsulfonilamino, karbociklila-R20- ili heterociklila-R21-; pri čemu R7, R12, R14, R16 i R18 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R22; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R23;
R8, R13, R15, R17, R19 i R23 su nezavisno odabrani od C1-6alkila, C1-6alkanoila, C1-6alkilsulfonila, C1-6alkoksikarbonila, karbamoila, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)karbamoila, benzila, benziloksikarbonila, benzoila i fenilsulfonila; pri čemu R8, R13, R15, R17, R19 i R23 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R24;
R22 i R24 su nezavisno odabrani od halo, nitro, cijano, hidroksi, trifluorometoksi, amino, karboksi, karbamoila, merkapto, sulfamoila, C1-6alkila, C2-6alkenila, C2-6alkinila, C1-6alkoksi, C1-6alkanoila, C1-6alkanoiloksi, N-(C1-6alkil)amino, N,N-(C1-6alkil)2amino, C1-6alkanoilamino, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)2karbamoila, C1-6alkilS(O)a pri čemu a je 0 do 2, C1-6alkoksikarbonila, N-(C1-6alkil)sulfamoila, N,N-(C1-6alkil)2sulfamoila, C1-6alkilsulfonilamino, karbociklila ili heterociklila; pri čemu R22 i R24 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R25; i pri čemu ako navedeni heterociklil sadrži -NH- skupinu taj dušik može biti opcijski supstituiran sa skupinom odabranom od R26;
R10, R11, R20 i R21 su nezavisno odabrani od direktne veze, -O-, -N(Rz7)-, -C(O)-, -N(R28)C(O)-, -C(O)N(R29)-, -S(O)s-, -SO2N(R30)- ili -N(R31)SO2-; pri čemu R27, R28, R29, R30 i R31 su nezavisno odabrani od vodika ili C1-6alkila i s je 0-2;
R25 je odabran od halo, nitro, cijano, hidroksi, trifluorometoksi, trifluorometila, amino, karboksi, karbamoila, merkapto, sulfamoila, metila, etila, metoksi, etoksi, acetila, acetoksi, metilamino, etilamino, dimetilamino, dietilamino, N-metil-N-etilamino, acetilamino, N-metilkarbamoila, N-etilkarbamoila, N,N-dimetilkarbamoila, N,N-dietilkarbamoila, N-metil-N-etilkarbamoila, metiltio, etiltio, metilsulfinila, etilsulfinila, mesila, etilsulfonila, metoksikarbonila, etoksikarbonila, N-metilsulfamoila, N-etilsulfamoila, N,N-dimetilsulfamoila, N,N-dietilsulfamoila ili N-metil-N-etilsulfamoila; i
R26 je odabran od C1-6alkila, C1-6alkanoila, C1-6alkilsulfonila, C1-6alkoksikarbonila, karbamoila, N-(C1-6alkil)karbamoila, N,N-(C1-6alkil)karbamoila, benzila, benziloksikarbonila, benzoila i fenilsulfonila;
ili njegova farmaceutski prihvatljiva sol.
2. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema zahtjevu 1 naznačen time da je R1 odabran od C1-6alkila, C1-6alkoksi ili karbociklila.
3. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema zahtjevu 1 ili zahtjevu 2 naznačen time da R2 je vodik.
4. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-3 naznačen time da R3 i R9 su nezavisno odabrani od vodika, halo, hidroksi i C1-6alkila.
5. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-4 naznačen time da R4 i R5 su nezavisno odabrani od vodika ili C1-6alkila; pri čemu R4 i R5 nezavisno jedan od drugoga mogu biti opcijski supstituirani na ugljiku sa jednim ili više R14; pri čemu R14 je hidroksi.
6. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-5 naznačen time da A je direktna veza.
7. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-6 naznačen time da Prsten C je fenil.
8. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-7 naznačen time da R6 je halo.
9. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-8 naznačen time da n je 0 ili 1.
10. Spoj formule (I):
[image]
naznačen time da:
R1 je odabran od metila, t-butila, izopropoksi ili ciklopropila;
R2 je vodik;
X1, X2 i X3 su nezavisno =N- ili =CR9-;
R3 i R9 su nezavisno odabrani od vodika, fluoro, kloro, hidroksi i metila;
R4 i R5 su nezavisno odabrani od vodika, metila ili hidroksimetila;
A je a direktna veza;
Prsten C je fenil;
R6 je fluoro; i
n je 1;
ili njegova farmaceutski prihvatljiva sol.
11. Spoj formule (I):
[image]
odabran od:
(S)-N-(5-ciklopropil-1H-pirazol-3-il)-3-(1-(4-fluorofenil)etil)-3H-imidazo[4,5-b]piridin-5-amina;
(R)-2-(5-(5-ciklopropil-1H-pirazol-3-ilamino)-3H-imidazo[4,5-b]piridin-3-il)-2-(4-fluorofenil)etanola;
(S)-6-kloro-N-(5-ciklopropil-1H-pirazol-3-il)-3-(1-(4-fluorofenil)etil)-3H-imidazo[4,5-b]piridin-5-amina;
(R)-2-(6-kloro-5-(5-ciklopropil-1H-pirazol-3-ilamino)-3H-imidazo[4,5-b]piridin-3-il)-2-(4-fluorofenil)etanola;
(R)-2-(6-kloro-5-(5-metil-1H-pirazol-3-ilamino)-3H-imidazo[4,5-b]piridin-3-il)-2-(4-fluorofenil)etanola;
(S)-6-fluoro-3-(1-(4-fluorofenil)etil)-N-(5-metil-1H-pirazol-3-il)-3H-imidazo[4,5-b]piridin-5-amina;
(R)-2-(5-(5-ciopropil-1H-pirazol-3-ilamino)-6-fluoro-3H-imidazo[4,5-b]piridin-3-il)-2-(4-fluorofenil)etanola;
(S)-N-(5-ciklopropil-1H-pirazol-3-il)-6-fluoro-3-(1-(4-fluorofenil)etil)-3H-imidazo[4,5-b]piridin-5-amina;
(S)-6-fluoro-3-(1-(4-fluorofenil)etil)-N-(5-izopropoksi-1H-pirazol-3-il)-3H-imidazo[4,5-b]piridin-5-amina; i
(S)-6-kloro-3-(1-(4-fluorofenil)etil)-N-(5-izopropoksi-1H-pirazol-3-il)-3H-imidazo[4,5-b]piridin-5-amina;
ili njegova farmaceutski prihvatljiva sol.
12. Postupak za dobivanje spoja formule (I) ili njegove farmaceutski prihvatljive soli, pri čemu su varijabilne skupine, ukoliko nije drugačije navedeno, definirane prema zahtjevu 1, koji postupak je naznačen time da:
postupak a) reakcijom spoja formule (II):
[image]
pri čemu Pg je dušikova zaštitna skupina; sa spojem formule (III):
[image]
pri čemu L je skupina koja mijenja mjesto;
postupak b) za spojeve formule (I) pri čemu R4 je hidroksimetil i R5 je vodik; reakcijom spoja formule (II) sa epoksidom formule (IV):
[image]
postupak c) za spojeve formule (I) pri čemu X1 je =CR9-; reakcijom spoja formule (V):
[image]
sa spojem formule (VI):
[image]
postupak d) za spojeve formule (I) pri čemu X1 je =N-; reakcijom spoja formule (V) sa vodenom otopinom NaNO2;
postupak e) reakcijom spoja formule (VII):
[image]
pri čemu L je skupina koja mijenja mjesto; sa aminom formule (VIII):
[image]
pri čemu Pg je dušikova zaštitna skupina;
postupak f) reakcijom spoja formule (IX):
[image]
sa spojem formule (X):
[image]
pri čemu L je skupina koja mijenja mjesto;
i nakon toga ako je potrebno:
i) pretvaranja spoja formule (I) u drugi spoj formule (I);
ii) uklanjanja bilo koje zaštitne skupine
iii) formiranja farmaceutski prihvatljive soli.
13. Spoj formule (I) ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-11 naznačen time da je za uporabu kao lijek.
14. Uporaba spoja formule (I), ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1-11, naznačena time da je za proizvodnju lijeka za inhibiciju Trk aktivnosti.
15. Uporaba spoja formule (I), ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1-11, naznačena time da je za proizvodnju lijeka za liječenje ili za profilaksu raka.
16. Uporaba prema zahtjevu 15 naznačena time da je navedeni rak odabran od: kongenitalnog fibrosarkoma, mezoblastičnog nefroma, mezotelioma, akutne mijeloblastične leukemije, akutne limfocitne leukemije, multiplog mijeloma, melanoma, osofagealnog karcinoma, mijeloma, hepatocelularnog raka, raka gušterače, raka grlića maternice, Ewingovog sarkoma, neuroblastoma, Kaposijevog sarkoma, karcinoma jajnika, raka dojke uključujući sekretorni rak dojke , raka debelog crijeva, raka prostate uključujući i hormonski refraktorni rak prostate, raka mokraćnog mjehura, melanoma, karcinoma pluća - karcinoma pluća ne-malih stanica (NSCLC), i karcinoma pluća malih stanica (SCLC), karcinoma želuca, tumora glave i vrata, raka bubrega, limfoma, raka štitnjače uključujući i papilarni karcinom štitnjače, mezotelioma i leukemije.
17. Uporaba spoja formule (I), ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1-11, naznačena time da je za proizvodnju lijeka za dobivanje anti-proliferativnog djelovanja.
18. Farmaceutski pripravak naznačen time da sadrži spoj formule (I), ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1-11, zajedno sa barem jednim farmaceutski prihvatljivim nosačem, otapalom ili ekscipijentom.
19. Spoj formule (I), ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-11, naznačen time da je za inhibiciju Trk aktivnosti.
20. Spoj formule (I), ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-11, naznačen time da je za liječenje ili za profilaksu raka.
21. Spoj formule (I), ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-11, naznačen time da je za dobivanje anti-proliferativnog djelovanja.
22. Spoj formule (I), ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-11, naznačen time da je za liječenje ili za profilaksu raka pri čemu je navedeni rak odabran od kongenitalnog fibrosarkoma, mezoblastičnog nefroma, mezotelioma, akutne mijeloblastične leukemije, akutne limfocitne leukemije, multiplog mijeloma, melanoma, osofagealnog karcinoma, mijeloma, hepatocelularnog raka, raka gušterače, raka grlića maternice, Ewingovog sarkoma, neuroblastoma, Kaposijevog sarkoma, karcinoma jajnika, raka dojke uključujući sekretorni rak dojke, raka debelog crijeva, raka prostate uključujući i hormonski refraktorni rak prostate, raka mokraćnog mjehura, melanoma, karcinoma pluća - karcinoma pluća ne-malih stanica (NSCLC), i karcinoma pluća malih stanica (SCLC), karcinoma želuca, tumora glave i vrata, raka bubrega, limfoma, raka štitnjače uključujući i papilarni karcinom štitnjače, mezotelioma i leukemije.
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US6399780B1 (en) * | 1999-08-20 | 2002-06-04 | Cephalon, Inc. | Isomeric fused pyrrolocarbazoles and isoindolones |
CN100436452C (zh) * | 2000-12-21 | 2008-11-26 | 沃泰克斯药物股份有限公司 | 可用作蛋白激酶抑制剂的吡唑化合物 |
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EP1430053B1 (en) * | 2001-09-27 | 2006-10-25 | SmithKline Beecham Corporation | AZAOXOINDOLE DERIVATIVES AS Trk PROTEIN KINASE INHIBITORS FOR THE TREATMENT OF CANCER AND CHRONIC PAIN |
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- 2006-02-15 US US11/816,376 patent/US7622482B2/en not_active Expired - Fee Related
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AU2006215394A1 (en) | 2006-08-24 |
PT1853602E (pt) | 2010-08-25 |
US7622482B2 (en) | 2009-11-24 |
DK1853602T3 (da) | 2010-09-20 |
NO20073790L (no) | 2007-09-03 |
AU2006215394B2 (en) | 2009-10-08 |
ES2347172T3 (es) | 2010-10-26 |
MX2007009842A (es) | 2007-08-23 |
NZ561526A (en) | 2010-11-26 |
HK1113352A1 (en) | 2008-10-03 |
CY1110900T1 (el) | 2015-06-10 |
EP1853602B1 (en) | 2010-07-14 |
KR20070104936A (ko) | 2007-10-29 |
EP1853602A1 (en) | 2007-11-14 |
US20090137624A1 (en) | 2009-05-28 |
BRPI0608160A2 (pt) | 2010-11-09 |
WO2006087538A1 (en) | 2006-08-24 |
CA2598076A1 (en) | 2006-08-24 |
JP2008530191A (ja) | 2008-08-07 |
DE602006015431D1 (de) | 2010-08-26 |
IL184872A0 (en) | 2007-12-03 |
PL1853602T3 (pl) | 2010-11-30 |
SI1853602T1 (sl) | 2010-11-30 |
ATE473975T1 (de) | 2010-07-15 |
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