HRP20120824T1 - Derivati 4-(3-aminopirazol) pirimidina za uporabu kao inhibitori tirozin kinaze u lijeäśenju karcinoma - Google Patents
Derivati 4-(3-aminopirazol) pirimidina za uporabu kao inhibitori tirozin kinaze u lijeäśenju karcinoma Download PDFInfo
- Publication number
- HRP20120824T1 HRP20120824T1 HRP20120824TT HRP20120824T HRP20120824T1 HR P20120824 T1 HRP20120824 T1 HR P20120824T1 HR P20120824T T HRP20120824T T HR P20120824TT HR P20120824 T HRP20120824 T HR P20120824T HR P20120824 T1 HRP20120824 T1 HR P20120824T1
- Authority
- HR
- Croatia
- Prior art keywords
- cancer
- formula
- compound
- pharmaceutically acceptable
- fluoropyrimidin
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims 10
- 201000011510 cancer Diseases 0.000 title claims 8
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 title 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 14
- 206010041067 Small cell lung cancer Diseases 0.000 claims 8
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 8
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 8
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 8
- 238000000034 method Methods 0.000 claims 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims 5
- 206010005003 Bladder cancer Diseases 0.000 claims 4
- 206010006187 Breast cancer Diseases 0.000 claims 4
- 208000026310 Breast neoplasm Diseases 0.000 claims 4
- 206010009944 Colon cancer Diseases 0.000 claims 4
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 4
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 4
- 206010025323 Lymphomas Diseases 0.000 claims 4
- 206010027406 Mesothelioma Diseases 0.000 claims 4
- 241001465754 Metazoa Species 0.000 claims 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 4
- 206010029260 Neuroblastoma Diseases 0.000 claims 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 4
- 206010033128 Ovarian cancer Diseases 0.000 claims 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 4
- 206010060862 Prostate cancer Diseases 0.000 claims 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 4
- 206010038389 Renal cancer Diseases 0.000 claims 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- -1 chloro, bromo, N-methyl-N-mesylamino Chemical group 0.000 claims 4
- 208000029742 colonic neoplasm Diseases 0.000 claims 4
- 239000003085 diluting agent Substances 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 206010017758 gastric cancer Diseases 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 201000010536 head and neck cancer Diseases 0.000 claims 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 4
- 201000010982 kidney cancer Diseases 0.000 claims 4
- 208000032839 leukemia Diseases 0.000 claims 4
- 201000005202 lung cancer Diseases 0.000 claims 4
- 208000020816 lung neoplasm Diseases 0.000 claims 4
- 201000001441 melanoma Diseases 0.000 claims 4
- 201000000050 myeloid neoplasm Diseases 0.000 claims 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 4
- 201000011549 stomach cancer Diseases 0.000 claims 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 201000010881 cervical cancer Diseases 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 201000004101 esophageal cancer Diseases 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 201000002528 pancreatic cancer Diseases 0.000 claims 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 208000032027 Essential Thrombocythemia Diseases 0.000 claims 2
- 241000282412 Homo Species 0.000 claims 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 claims 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- 206010028561 Myeloid metaplasia Diseases 0.000 claims 2
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 claims 2
- 208000014767 Myeloproliferative disease Diseases 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- 208000005485 Thrombocytosis Diseases 0.000 claims 2
- 208000017733 acquired polycythemia vera Diseases 0.000 claims 2
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 206010028537 myelofibrosis Diseases 0.000 claims 2
- 208000037244 polycythemia vera Diseases 0.000 claims 2
- 208000003476 primary myelofibrosis Diseases 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 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 1
- QVRNOZLSUAECTA-NSHDSACASA-N 2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(3-methoxy-1h-pyrazol-5-yl)-6-morpholin-4-ylpyrimidine-2,4-diamine Chemical compound N1C(OC)=CC(NC=2N=C(N[C@@H](C)C=3N=CC(F)=CN=3)N=C(C=2)N2CCOCC2)=N1 QVRNOZLSUAECTA-NSHDSACASA-N 0.000 claims 1
- VQLGDEFHXMDXJG-LBPRGKRZSA-N 2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(5-methyl-1h-pyrazol-3-yl)-6-morpholin-4-ylpyrimidine-2,4-diamine Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=C(C=1)N2CCOCC2)=NC=1NC=1C=C(C)NN=1 VQLGDEFHXMDXJG-LBPRGKRZSA-N 0.000 claims 1
- QNBLPUFFJOANGD-JTQLQIEISA-N 2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-5-methyl-4-n-(5-methyl-1h-pyrazol-3-yl)pyrimidine-2,4-diamine Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=1)=NC=C(C)C=1NC=1C=C(C)NN=1 QNBLPUFFJOANGD-JTQLQIEISA-N 0.000 claims 1
- PFXXPRYKFJNBAN-QMMMGPOBSA-N 4-n-(5-cyclopropyl-1h-pyrazol-3-yl)-5-fluoro-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]pyrimidine-2,4-diamine Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=1)=NC=C(F)C=1NC(=NN1)C=C1C1CC1 PFXXPRYKFJNBAN-QMMMGPOBSA-N 0.000 claims 1
- WMZWKZSZFLNJAR-ZETCQYMHSA-N 5-bromo-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(3-methoxy-1h-pyrazol-5-yl)pyrimidine-2,4-diamine Chemical compound N1C(OC)=CC(NC=2C(=CN=C(N[C@@H](C)C=3N=CC(F)=CN=3)N=2)Br)=N1 WMZWKZSZFLNJAR-ZETCQYMHSA-N 0.000 claims 1
- UXPJEUHRPHLFQP-JTQLQIEISA-N 5-chloro-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(3-methoxy-1h-pyrazol-5-yl)-6-morpholin-4-ylpyrimidine-2,4-diamine Chemical compound N1C(OC)=CC(NC=2C(=C(N3CCOCC3)N=C(N[C@@H](C)C=3N=CC(F)=CN=3)N=2)Cl)=N1 UXPJEUHRPHLFQP-JTQLQIEISA-N 0.000 claims 1
- KWKMYGPZQBMLGC-ZETCQYMHSA-N 5-chloro-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(3-methoxy-1h-pyrazol-5-yl)pyrimidine-2,4-diamine Chemical compound N1C(OC)=CC(NC=2C(=CN=C(N[C@@H](C)C=3N=CC(F)=CN=3)N=2)Cl)=N1 KWKMYGPZQBMLGC-ZETCQYMHSA-N 0.000 claims 1
- PDOQBOJDRPLBQU-QMMMGPOBSA-N 5-chloro-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(5-methyl-1h-pyrazol-3-yl)pyrimidine-2,4-diamine Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=1)=NC=C(Cl)C=1NC=1C=C(C)NN=1 PDOQBOJDRPLBQU-QMMMGPOBSA-N 0.000 claims 1
- VYJBUWRWDPVJKR-QMMMGPOBSA-N 5-chloro-4-n-(5-cyclopropyl-1h-pyrazol-3-yl)-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]pyrimidine-2,4-diamine Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=1)=NC=C(Cl)C=1NC(=NN1)C=C1C1CC1 VYJBUWRWDPVJKR-QMMMGPOBSA-N 0.000 claims 1
- KDEZEJSFZUZWID-JTQLQIEISA-N 5-fluoro-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(3-methoxy-1h-pyrazol-5-yl)-6-morpholin-4-ylpyrimidine-2,4-diamine Chemical compound N1C(OC)=CC(NC=2C(=C(N3CCOCC3)N=C(N[C@@H](C)C=3N=CC(F)=CN=3)N=2)F)=N1 KDEZEJSFZUZWID-JTQLQIEISA-N 0.000 claims 1
- RDRRGPBIENGEQJ-QMMMGPOBSA-N 5-fluoro-2-n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-n-(5-methyl-1h-pyrazol-3-yl)pyrimidine-2,4-diamine Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=1)=NC=C(F)C=1NC=1C=C(C)NN=1 RDRRGPBIENGEQJ-QMMMGPOBSA-N 0.000 claims 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000004452 carbocyclyl group Chemical group 0.000 claims 1
- 208000019065 cervical carcinoma Diseases 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000005619 esophageal carcinoma Diseases 0.000 claims 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- DTLAYCCMAHHIRT-QMMMGPOBSA-N n-[5-chloro-2-[[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]amino]-6-[(3-methoxy-1h-pyrazol-5-yl)amino]pyrimidin-4-yl]-n-methylmethanesulfonamide Chemical compound N1C(OC)=CC(NC=2C(=C(N(C)S(C)(=O)=O)N=C(N[C@@H](C)C=3N=CC(F)=CN=3)N=2)Cl)=N1 DTLAYCCMAHHIRT-QMMMGPOBSA-N 0.000 claims 1
- KBTUOAYIXOOSIP-VIFPVBQESA-N n-[5-chloro-2-[[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-4-yl]-n-methylmethanesulfonamide Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=C(C=1Cl)N(C)S(C)(=O)=O)=NC=1NC=1C=C(C)NN=1 KBTUOAYIXOOSIP-VIFPVBQESA-N 0.000 claims 1
- AKEDZKNCKDIFIS-VIFPVBQESA-N n-[5-fluoro-2-[[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-4-yl]-n-methylmethanesulfonamide Chemical compound N([C@@H](C)C=1N=CC(F)=CN=1)C(N=C(C=1F)N(C)S(C)(=O)=O)=NC=1NC=1C=C(C)NN=1 AKEDZKNCKDIFIS-VIFPVBQESA-N 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 210000004291 uterus Anatomy 0.000 claims 1
Classifications
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (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)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (15)
1. Spoj formule (I):
[image]
ili njegova farmaceutski prihvatljiva sol,
naznačen time da:
R1 je odabran iz skupine koja sadrži C1-6alkil, C1-6alkoksi, 3-5-člani karbociklil i N,N-(C1-6alkil)2amino, pri čemu R1 može proizvoljno biti supstituiran na ugljiku sa jednim ili više R6;
R2 je odabran iz skupine koja sadrži vodik, halo, nitro, i C1-6alkil, pri čemu R2 može proizvoljno biti supstituiran na ugljiku sa jednim ili više R8;
R3 je odabran iz skupine koja sadrži vodik, fluoro, kloro, bromo, N-metil-N-mezilamino i morfolino;
R4 je C1-6alkil;
R5 je halo;
R6 je halo;
R8 je halo; i
n= 1.
2. Spoj formule (I),
[image]
ili njegova farmaceutski prihvatljiva sol, prema zahtjevu 1, naznačen time da
R1 je odabran iz skupine koja sadrži metil, metoksi, trifluoroetoksi, izopropoksi, ciklopropil, i N,N-dimetilamino;
R2 je kloro;
R3 je vodik;
R4 je metil;
R5 je fluoro; i
n je 1.
3. Spoj formule (I), prema zahtjevu 1, naznačen time da je odabran iz skupine koja sadrži:
N-{5-fluoro-2-{[(1S)-1-(5-fluoropirimidin-2-il)etil]amino}-6-[(5-metil-1H-pirazol-3-il)amino]pirimidin-4-il}-N-metilmetansulfonamid;
5-Fluoro-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metil-1H-pirazol-3-il)pirimidin-2,4-diamin;
5-Kloro-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metoksi-1H-pirazol-3-il)pirimidin-2,4-diamin;
N2-[(1S)-1-(5-Fluoropirimidin-2-il)etil]-N4-(5-metil-1H-pirazol-3-il)-6-morfolin-4-ilpirimidin-2,4-diamin;
5-Kloro-N4-(5-ciklopropil-1H-pirazol-3-il)-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]pirimidin-2,4-diamin;
5-bromo-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metoksi-1H-pirazol-3-il)pirimidin-2,4-diamin;
N4-(5-Ciklopropil-1H-pirazol-3-il)-5-fluoro-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]pirimidin-2,4-diamin;
N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-5-metil-N4-(5-metil-1H-pirazol-3-il)pirimidin-2,4-diamin;
N-{5-kloro-2-{[(1S)-1-(5-fluoropirimidin-2-il)etil]amino}-6-[(5-metoksi-1H-pirazol-3-il)amino]pirimidin-4-il}-N-metilmetansulfonamid;
N-{5-kloro-2-{[(1S)-1-(5-fluoropirimidin-2-il)etil]amino}-6-[(5-metil-1H-pirazol-3-il)amino]pirimidin-4-il}-N-metilmetansulfonamid;
N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metoksi-1H-pirazol-3-il)-6-morfolin-4-ilpirimidin-2,4-diamin;
5-kloro-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metoksi-1H-pirazol-3-il)-6-morfolin-4-ilpirimidin-2,4-diamin; i
5-fluoro-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metoksi-1H-pirazol-3-il)-6-morfolin-4-ilpirimidin-2,4-diamin;
ili njegova farmaceutski prihvatljiva sol.
4. Spoj formule (I), prema zahtjevu 1, naznačen time da spoj je 5-Kloro-N2-[(1S)-1-(5-fluoropirimidin-2-il)etil]-N4-(5-metil-1H-pirazol-3-il)pirimidin-2,4-diamin ili njegova farmaceutski prihvatljiva sol.
5. Postupak za dobivanje spoja prema bilo kojem od zahtjeva 1-4, ili njegova farmaceutski prihvatljiva sol, naznačen time da su varijabilne skupine, osim ako nije drugačije naznačeno, kako je definirano u zahtjevu 1, te navedeni postupak sadrži:
postupak a) reakciju pirimidina sa Formulom (II):
[image]
pri čemu L je odlazeća skupina; sa pirazol aminom sa Formulom (III):
[image]
ili
postupak b) reakciju pirimidina sa Formulom (IV):
[image]
pri čemu L je odlazeća skupina; sa spojem formule (V):
[image]
postupak c) reakciju spoja formule (VI):
[image]
sa spojem formule (VII):
[image]
pri čemu X je atom kisika i q je 1; ili X je atom dušika i q je 2; te pri čemu svaki R20 neovisno predstavlja C1-6alkil skupinu; ili
postupak d) reakciju spoja formule (VIII):
[image]
sa hidrazinom; ili
te zatim ako je potrebno:
i) pretvaranje spoja formule (I) u drugi spoj formule (I);
ii) uklanjanje bilo kojih zaštitnih skupina;
iii) formiranje farmaceutski prihvatljive soli.
6. Farmaceutski pripravak naznačen time da sadrži:
spoj formule (I), ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1-4; te
barem jedan farmaceutski prihvatljiv nosač, razrjeđivač, ili pomoćnu tvar.
7. Spoj formule (I), ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1-4, naznačen time da je za uporabu kao lijek.
8. Uporaba spoja formule (I), ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1-4, naznačena time da je za proizvodnju lijeka za uporabu kod liječenja mijeloproliferativnih poremećaja, mijelodisplastičnog sindroma, te karcinoma kod toplokrvne životinje kao što je čovjek.
9. Uporaba spoja formule (I), ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1-4, naznačena time da je za proizvodnju lijeka za uporabu kod liječenja kronične mijeloidne leukemije, policitemije vera, esencijalne trombocitemije, trombocitemije, mijeloidne metaplazije sa mijelofibrozom, idiopatske mijelofibroze, kronične mijelomonocitne leukemije i hipereozinofilnog sindroma, mijelodisplastičnih sindroma i karcinoma odabranih od karcinoma jednjaka, mijeloma, hepatocelularnog karcinoma, karcinoma gušterače, karcinoma grlića maternice, Ewingovog sarkoma, neuroblastoma, Kaposijevog sarkoma, karcinoma jajnika, raka dojke, karcinoma debelog crijeva, karcinoma prostate, karcinoma mjehura, melanoma, karcinoma pluća - karcinoma pluća ne-malih stanica (NSCLC) i karcinoma pluća malih stanica (SCLC), raka želuca, karcinoma glave i vrata, mezotelioma, karcinoma bubrega, limfoma i leukemije.
10. Uporaba spoja formule (I), ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1-4, naznačena time da je za proizvodnju lijeka za uporabu kod liječenja karcinoma.
11. Uporaba prema zahtjevu 10, naznačena time da je navedeni karcinom odabran iz skupine koja sadrži karcinom jednjaka, mijelom, hepatocelularni karcinom, karcinom gušterače, karcinom grlića maternice, Ewingov sarkom, neuroblastom, Kaposijev sarkom, karcinom jajnika, rak dojke, karcinom debelog crijeva, karcinom prostate, karcinom mjehura, melanom, karcinom pluća - karcinom pluća ne-malih stanica (NSCLC) i karcinom pluća malih stanica (SCLC), rak želuca, karcinom glave i vrata, mezoteliom, karcinom bubrega, limfom i leukemiju.
12. Farmaceutski pripravak naznačen time da sadrži:
a. spoj formule (I), ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1-4; i
b. barem jedan farmaceutski prihvatljiv razrjeđivač ili nosač,
za uporabu kod liječenja mijeloproliferativnih poremećaja, mijelodisplastičnog sindroma, te karcinoma kod toplokrvne životinje kao što je čovjek.
13. Farmaceutski pripravak naznačen time da sadrži:
spoj formule (I), ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1-4; i
barem jedan farmaceutski prihvatljiv razrjeđivač ili nosač,
za uporabu kod liječenja kronične mijeloidne leukemije, policitemije vera, esencijalne trombocitemije, trombocitemije, mijeloidne metaplazije sa mijelofibrozom, idiopatske mijelofibroze, kronične mijelomonocitne leukemije i hipereozinofilnog sindroma, mijelodisplastičnih sindroma i karcinoma odabranih od karcinoma jednjaka, mijeloma, hepatocelularnog karcinoma, karcinoma gušterače, karcinoma grlića maternice, Ewingovog sarkoma, neuroblastoma, Kaposijevog sarkoma, karcinoma jajnika, raka dojke, karcinoma debelog crijeva, karcinoma prostate, karcinoma mjehura, melanoma, karcinoma pluća - karcinoma pluća ne-malih stanica (NSCLC) i karcinoma pluća malih stanica (SCLC), raka želuca, karcinoma glave i vrata, mezotelioma, karcinoma bubrega, limfoma, i leukemije kod toplokrvne životinje kao što je čovjek.
14. Farmaceutski pripravak naznačen time da sadrži
spoj formule (I), ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1-4; i
barem jedan farmaceutski prihvatljiv razrjeđivač ili nosač,
za uporabu kod liječenja karcinoma kod toplokrvne životinje kao što je čovjek.
15. Farmaceutski pripravak prema zahtjevu 14, naznačen time da je navedeni karcinom odabran iz skupine koja sadrži karcinom jednjaka, mijelom, hepatocelularni karcinom, karcinom gušterače, karcinom grlića maternice, Ewingov sarkom, neuroblastom, Kaposijev sarkom, karcinom jajnika, rak dojke, karcinom debelog crijeva, karcinom prostate, karcinom mjehura, melanom, karcinom pluća - karcinom pluća ne-malih stanica (NSCLC) i karcinom pluća malih stanica (SCLC), rak želuca, karcinom glave i vrata, mezoteliom, karcinom bubrega, limfom i leukemiju.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US73129905P | 2005-10-28 | 2005-10-28 | |
US80306106P | 2006-05-24 | 2006-05-24 | |
PCT/GB2006/003978 WO2007049041A1 (en) | 2005-10-28 | 2006-10-26 | 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20120824T1 true HRP20120824T1 (hr) | 2012-11-30 |
Family
ID=37575154
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20120824TT HRP20120824T1 (hr) | 2005-10-28 | 2012-10-15 | Derivati 4-(3-aminopirazol) pirimidina za uporabu kao inhibitori tirozin kinaze u lijeäśenju karcinoma |
Country Status (22)
Country | Link |
---|---|
US (3) | US20080287475A1 (hr) |
EP (2) | EP1945631B8 (hr) |
JP (1) | JP2009513615A (hr) |
KR (1) | KR20080063846A (hr) |
AR (1) | AR056210A1 (hr) |
AU (1) | AU2006307657B2 (hr) |
BR (1) | BRPI0618011A2 (hr) |
CA (1) | CA2626375A1 (hr) |
DK (1) | DK1945631T3 (hr) |
EC (1) | ECSP088450A (hr) |
ES (1) | ES2391783T3 (hr) |
HR (1) | HRP20120824T1 (hr) |
IL (1) | IL190935A0 (hr) |
MX (1) | MX2008005398A (hr) |
NO (1) | NO20081893L (hr) |
NZ (1) | NZ567584A (hr) |
PL (1) | PL1945631T3 (hr) |
PT (1) | PT1945631E (hr) |
RU (1) | RU2463302C2 (hr) |
TW (1) | TW200800963A (hr) |
UY (1) | UY29886A1 (hr) |
WO (1) | WO2007049041A1 (hr) |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1343781B1 (en) * | 2000-12-05 | 2008-09-03 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
PT2383268E (pt) * | 2005-02-04 | 2015-12-21 | Astrazeneca Ab | Derivados de pirazolilaminopiridina úteis como inibidores de quinase |
PT1853588E (pt) * | 2005-02-16 | 2008-08-25 | Astrazeneca Ab | Compostos químicos |
KR20080015409A (ko) * | 2005-05-16 | 2008-02-19 | 아스트라제네카 아베 | 티로신 키나제 억제제로서 유용한 피라졸릴아미노피리미딘 유도체 |
EP1945631B8 (en) * | 2005-10-28 | 2013-01-02 | AstraZeneca AB | 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer |
PT3184526T (pt) | 2005-12-13 | 2018-12-19 | Incyte Holdings Corp | Derivados de pirrolo[2,3-d]pirimidina como inibidores da cinase janus |
AU2007287428B2 (en) | 2006-08-24 | 2011-08-11 | Astrazeneca Ab | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
WO2008061370A1 (en) * | 2006-11-24 | 2008-05-29 | Mcmaster University | Diagnostic method to detect endometriosis |
CN101679429A (zh) * | 2007-04-18 | 2010-03-24 | 阿斯利康(瑞典)有限公司 | 5-氨基吡唑-3-基-3h-咪唑并[4,5-b]吡啶衍生物及其治疗癌的用途 |
ES2369596T3 (es) * | 2007-05-04 | 2011-12-02 | Astrazeneca Ab | Derivados de amino-tiazolil-pirimidina y su uso para el tratamiento del cáncer. |
UA99459C2 (en) * | 2007-05-04 | 2012-08-27 | Астразенека Аб | 9-(pyrazol-3-yl)- 9h-purine-2-amine and 3-(pyraz0l-3-yl)-3h-imidazo[4,5-b]pyridin-5-amine derivatives and their use for the treatment of cancer |
US20080312259A1 (en) | 2007-06-13 | 2008-12-18 | Incyte Corporation | SALTS OF THE JANUS KINASE INHIBITOR (R)-3-(4-(7H-PYRROLO[2,3-d]PYRIMIDIN-4-YL)-1H-PYRAZOL-1-YL)-3-CYCLOPENTYLPROPANENITRILE |
JP5508260B2 (ja) | 2007-07-09 | 2014-05-28 | アストラゼネカ アクチボラグ | mTORキナーゼおよび/またはP13Kに関連する病気に用いられるモルホリノピリミジン誘導体 |
WO2009007753A2 (en) * | 2007-07-11 | 2009-01-15 | Astrazeneca Ab | 4- (3-aminopyrazole) -pyrimidine derivativee and their use as tyrosine kinase inhibitors for the treatment of cancer |
WO2009013545A2 (en) * | 2007-07-26 | 2009-01-29 | Astrazeneca Ab | Chemical compounds |
TW200906818A (en) * | 2007-07-31 | 2009-02-16 | Astrazeneca Ab | Chemical compounds |
EA020777B1 (ru) | 2007-11-16 | 2015-01-30 | Инсайт Корпорейшн | 4-пиразолил-n-арилпиримидин-2-амины, 4-пиразолил-n-пиразолилпиримидин-2-амины и 4-пиразолил-n-пиридилпиримидин-2-амины в качестве ингибиторов киназ janus |
WO2009095712A2 (en) * | 2008-01-29 | 2009-08-06 | Astrazeneca Ab | Chemical compounds |
CA2727073A1 (en) * | 2008-06-11 | 2009-12-17 | Astrazeneca Ab | Tricyclic 2,4-diamin0-l,3,5-triazine derivatives useful for the treatment of cancer and myeloproliferative disorders |
UY32055A (es) * | 2008-08-19 | 2010-03-26 | Astrazeneca Ab | Derivados sustituidos de la 5-Halo-N2-[sustituido](1-metil-1H-imidazol-4-il)pirimidin-2,-diamina y sus sales farmacéuticamente aceptables, procesos de preparación, composiciones y aplicaciones. |
RU2011116928A (ru) * | 2008-09-30 | 2012-11-20 | Астразенека Аб (Se) | Гетероциклические ингибиторы jак киназы |
CN106967070A (zh) | 2009-05-22 | 2017-07-21 | 因塞特控股公司 | 作为jak抑制剂的化合物 |
ES2487542T3 (es) | 2009-05-22 | 2014-08-21 | Incyte Corporation | Derivados de N-(hetero)aril-pirrolidina de pirazol-4-il-pirrolo[2,3-d]pirimidinas y pirrol-3-il-pirrolo[2,3-d]pirimidinas como inhibidores de cinasas Janus |
US8933227B2 (en) | 2009-08-14 | 2015-01-13 | Boehringer Ingelheim International Gmbh | Selective synthesis of functionalized pyrimidines |
EP2464633A1 (en) | 2009-08-14 | 2012-06-20 | Boehringer Ingelheim International GmbH | Regioselective preparation of 2-amino-5-trifluoromethylpyrimidine derivatives |
AR078012A1 (es) | 2009-09-01 | 2011-10-05 | Incyte Corp | Derivados heterociclicos de las pirazol-4-il- pirrolo (2,3-d) pirimidinas como inhibidores de la quinasa janus |
TWI766281B (zh) | 2010-03-10 | 2022-06-01 | 美商英塞特控股公司 | 作為jak1抑制劑之哌啶-4-基三亞甲亞胺衍生物 |
PE20130216A1 (es) | 2010-05-21 | 2013-02-27 | Incyte Corp | Formulacion topica para un inhibidor de jak |
SA111320519B1 (ar) | 2010-06-11 | 2014-07-02 | Astrazeneca Ab | مركبات بيريميدينيل للاستخدام كمثبطات atr |
BR112013008420A2 (pt) | 2010-10-07 | 2016-06-28 | Takeda Pharmaceutical | composto, medicamento, e, uso do composito |
JP2012102088A (ja) * | 2010-10-14 | 2012-05-31 | Sumitomo Chemical Co Ltd | ヘテロ芳香環化合物およびその有害生物防除用途 |
AR083933A1 (es) | 2010-11-19 | 2013-04-10 | Incyte Corp | Derivados de pirrolopiridina y pirrolopirimidina sustituidos con ciclobutilo como inhibidores de jak |
JP5917544B2 (ja) | 2010-11-19 | 2016-05-18 | インサイト・ホールディングス・コーポレイションIncyte Holdings Corporation | Jak阻害剤としての複素環置換ピロロピリジンおよびピロロピリミジン |
EA201490042A1 (ru) | 2011-06-20 | 2014-10-30 | Инсайт Корпорейшн | Азетидинил-фенил-, пиридил- или пиразинилкарбоксамидные производные как ингибиторы jak |
EP2554544A1 (en) * | 2011-08-01 | 2013-02-06 | Almirall, S.A. | Pyridin-2(1h)-one derivatives as jak inhibitors |
TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為jak抑制劑之環己基氮雜環丁烷衍生物 |
US8637537B2 (en) | 2011-08-25 | 2014-01-28 | Genentech, Inc. | Serine/threonine kinase inhibitors |
CN103781779B (zh) * | 2011-09-05 | 2016-06-08 | 浙江海正药业股份有限公司 | 具有蛋白激酶抑制活性的4-取代-(3-取代-1h-吡唑-5-氨基)-嘧啶衍生物及其用途 |
UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
BR112014015549A8 (pt) * | 2011-12-22 | 2017-07-04 | Hoffmann La Roche | composto, método de inibição da atividade pak1, método para o tratamento, processo, composição, utilização de um composto e invenção |
AR091079A1 (es) | 2012-05-18 | 2014-12-30 | Incyte Corp | Derivados de pirrolopirimidina y pirrolopiridina sustituida con piperidinilciclobutilo como inhibidores de jak |
SG11201503695XA (en) | 2012-11-15 | 2015-06-29 | Incyte Corp | Sustained-release dosage forms of ruxolitinib |
HUE057262T2 (hu) | 2013-03-06 | 2022-04-28 | Incyte Holdings Corp | Eljárás és köztitermékek JAK inhibitor elõállítására |
US9655854B2 (en) | 2013-08-07 | 2017-05-23 | Incyte Corporation | Sustained release dosage forms for a JAK1 inhibitor |
US9498467B2 (en) | 2014-05-30 | 2016-11-22 | Incyte Corporation | Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1 |
HRP20220738T1 (hr) | 2014-08-11 | 2022-08-19 | Acerta Pharma B.V. | Terapijske kombinacije inhibitora btk, inhibitora pd-1 i/ili inhibitora pd-l1 |
HUE056329T2 (hu) | 2014-08-11 | 2022-02-28 | Acerta Pharma Bv | BTK-inhibitor és BCL-2-inhibitor terápiás kombinációi |
KR20180058719A (ko) | 2015-09-25 | 2018-06-01 | 디잘 (지앙수) 파마슈티칼 씨오., 리미티드 | Jak를 억제하기 위한 화합물 및 방법 |
AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
CN112105608B (zh) | 2018-01-30 | 2023-07-14 | 因赛特公司 | 制备(1-(3-氟-2-(三氟甲基)异烟碱基)哌啶-4-酮)的方法 |
AU2019245420A1 (en) | 2018-03-30 | 2020-11-12 | Incyte Corporation | Treatment of hidradenitis suppurativa using JAK inhibitors |
TWI759829B (zh) * | 2019-08-23 | 2022-04-01 | 財團法人生物技術開發中心 | 作為第iii型受體酪胺酸激酶抑制劑之雜環吡唑衍生物 |
US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
Family Cites Families (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2426180A1 (de) | 1974-05-29 | 1975-12-18 | Bayer Ag | Verfahren zum faerben von polyurethankunststoffen |
US4485284A (en) | 1982-01-11 | 1984-11-27 | Advanced Moisture Technology, Inc. | Apparatus and process for microwave moisture analysis |
HU206337B (en) | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
CA2104053C (en) | 1992-08-31 | 1999-04-13 | Miguel A. Cacho | Automated fluid bed process |
US5543520A (en) | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
US5935966A (en) | 1995-09-01 | 1999-08-10 | Signal Pharmaceuticals, Inc. | Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions |
CA2230896A1 (en) | 1995-09-01 | 1997-03-13 | Signal Pharmaceuticals, Inc. | Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions |
GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
EP0880508B1 (en) | 1996-02-13 | 2003-04-16 | AstraZeneca AB | Quinazoline derivatives as vegf inhibitors |
ATE211134T1 (de) | 1996-03-05 | 2002-01-15 | 4-anilinochinazolin derivate | |
GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
WO1998044341A1 (de) | 1997-03-27 | 1998-10-08 | Glatt Gmbh | Verfahren zum überwachen und/oder steuern und regeln eines granulations-, agglomerations-, instantisierungs-, coating- und trocknungsprozesses in einer wirbelschicht oder einer bewegten schüttung durch bestimmung der produktfeuchte sowie lufttechnischer apparat zur durchführung des verfahrens |
JP2002502379A (ja) * | 1997-05-22 | 2002-01-22 | ジー.ディー.サール アンド カンパニー | p38キナーゼインヒビターとしての3(5)−ヘテロアリール置換ピラゾール |
GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
NZ506417A (en) | 1998-02-17 | 2003-05-30 | Tularik Inc | Anti-viral pyrimidine derivatives |
US6247246B1 (en) | 1998-05-27 | 2001-06-19 | Denver Instrument Company | Microwave moisture analyzer: apparatus and method |
ES2274634T3 (es) | 1998-08-29 | 2007-05-16 | Astrazeneca Ab | Compuestos de pirimidina. |
WO2000014552A1 (en) | 1998-09-03 | 2000-03-16 | Malcam Ltd. | Moisture measurement device using microwaves |
US6227041B1 (en) | 1998-09-17 | 2001-05-08 | Cem Corporation | Method and apparatus for measuring volatile content |
NZ511116A (en) | 1998-11-10 | 2003-08-29 | Janssen Pharmaceutica Nv | HIV replication inhibiting pyrimidines |
WO2000035455A1 (en) | 1998-12-15 | 2000-06-22 | Telik, Inc. | Heteroaryl-aryl ureas as igf-1 receptor antagonists |
GB9828511D0 (en) | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
GB9900334D0 (en) | 1999-01-07 | 1999-02-24 | Angiogene Pharm Ltd | Tricylic vascular damaging agents |
GB9900752D0 (en) | 1999-01-15 | 1999-03-03 | Angiogene Pharm Ltd | Benzimidazole vascular damaging agents |
GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
DE19917785A1 (de) | 1999-04-20 | 2000-10-26 | Bayer Ag | 2,4-Diamino-pyrimidin-Derivate |
IT1306704B1 (it) | 1999-05-26 | 2001-10-02 | Sirs Societa Italiana Per La R | Anticorpi monoclonali e suoi derivati sintetici o biotecnologici ingrado di agire come molecole antagoniste per il ngf. |
GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
US6399780B1 (en) | 1999-08-20 | 2002-06-04 | Cephalon, Inc. | Isomeric fused pyrrolocarbazoles and isoindolones |
PL355639A1 (en) | 1999-09-10 | 2004-05-04 | Merck & Co, Inc. | Tyrosine kinase inhibitors |
IL148801A0 (en) | 1999-09-24 | 2002-09-12 | Janssen Pharmaceutica Nv | Antiviral compositions |
US6455525B1 (en) | 1999-11-04 | 2002-09-24 | Cephalon, Inc. | Heterocyclic substituted pyrazolones |
WO2001047921A1 (en) | 1999-12-28 | 2001-07-05 | Pharmacopeia, Inc. | Pyrimidine and triazine kinase inhibitors |
CA2400447C (en) | 2000-02-17 | 2008-04-22 | Amgen Inc. | Kinase inhibitors |
GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
US7034019B2 (en) | 2000-05-08 | 2006-04-25 | Janssen Pharmaceutica N.V. | Prodrugs of HIV replication inhibiting pyrimidines |
KR20030013433A (ko) | 2000-05-31 | 2003-02-14 | 아스트라제네카 아베 | 혈관 손상 활성을 가진 인돌 유도체 |
AU6623301A (en) | 2000-07-07 | 2002-01-21 | Angiogene Pharm Ltd | Colchinol derivatives as vascular damaging agents |
EE200300015A (et) | 2000-07-07 | 2004-10-15 | Angiogene Pharmaceuticals Limited | Kolhinooli derivaadid kui angiogeneesi inhibiitorid |
JP2004507526A (ja) | 2000-08-31 | 2004-03-11 | ファイザー・プロダクツ・インク | ピラゾール誘導体及びそのプロテインキナーゼ阻害剤としての使用 |
WO2002020513A1 (en) | 2000-09-01 | 2002-03-14 | Glaxo Group Limited | Oxindole derivatives |
WO2002020479A1 (en) | 2000-09-01 | 2002-03-14 | Glaxo Group Limited | Substituted oxindole derivatives as tyrosine kinase inhibitors |
US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
KR100876069B1 (ko) | 2000-09-15 | 2008-12-26 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제 억제제로서 유용한 피라졸 화합물 및 이를 포함하는 약제학적 조성물 |
US6610677B2 (en) | 2000-09-15 | 2003-08-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
US6613776B2 (en) | 2000-09-15 | 2003-09-02 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
CA2433018A1 (en) | 2000-12-21 | 2002-06-27 | Joel C. Barrish | Thiazolyl inhibitors of tec family tyrosine kinases |
MXPA03005610A (es) | 2000-12-21 | 2003-10-06 | Vertex Pharma | Compuestos de pirazol utiles como inhibidores de la proteina cinasa. |
SE0101675D0 (sv) | 2001-05-11 | 2001-05-11 | Astrazeneca Ab | Novel composition |
EP1423380B1 (en) | 2001-08-03 | 2010-12-15 | Vertex Pharmaceuticals Incorporated | Pyrazole-derived kinase inhibitors and uses thereof |
EP1423382B1 (en) | 2001-08-03 | 2008-04-16 | Vertex Pharmaceuticals Incorporated | Pyrazole-derived kinase inhibitors and uses thereof |
JP2005508337A (ja) | 2001-09-27 | 2005-03-31 | スミスクライン ビーチャム コーポレーション | 化合物 |
US6747461B2 (en) | 2001-10-25 | 2004-06-08 | Pioneer Hi-Bred International, Inc. | Apparatus and method for monitoring drying of an agricultural porous medium such as grain or seed |
SE0104140D0 (sv) | 2001-12-07 | 2001-12-07 | Astrazeneca Ab | Novel Compounds |
JP2003231687A (ja) | 2002-02-04 | 2003-08-19 | Japan Tobacco Inc | ピラゾリル縮合環化合物及びその医薬用途 |
US7262200B2 (en) | 2002-10-25 | 2007-08-28 | Vertex Pharmaceuticals Incorporated | Indazolinone compositions useful as kinase inhibitors |
ES2338545T3 (es) * | 2002-12-20 | 2010-05-10 | Pfizer Products Inc. | Derivados de pirimidina para el tratamiento del crecimiento celular anormal. |
MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
ATE508129T1 (de) | 2004-03-30 | 2011-05-15 | Vertex Pharma | Als inhibitoren von jak und anderen proteinkinasen geeignete azaindole |
WO2005103010A2 (en) | 2004-04-21 | 2005-11-03 | Astrazeneca Ab | Pyrazole derivatives useful for the treatment of cancer |
WO2005105814A1 (en) | 2004-04-28 | 2005-11-10 | Incyte Corporation | Tetracyclic inhibitors of janus kinases |
ES2354824T3 (es) | 2004-11-04 | 2011-03-18 | Vertex Pharmaceuticals, Inc. | Pirazolo[1,5-a]pirimidinas útiles como inhibidores de proteínas cinasas. |
PT2383268E (pt) | 2005-02-04 | 2015-12-21 | Astrazeneca Ab | Derivados de pirazolilaminopiridina úteis como inibidores de quinase |
MX2007009842A (es) | 2005-02-16 | 2007-08-23 | Astrazeneca Ab | Compuestos quimicos. |
PT1853588E (pt) | 2005-02-16 | 2008-08-25 | Astrazeneca Ab | Compostos químicos |
EP1877057A1 (en) | 2005-04-27 | 2008-01-16 | AstraZeneca AB | Use of pyrazolyl-pyrimidine derivatives in the treatment of pain |
CA2607727A1 (en) | 2005-04-28 | 2006-11-09 | Mitsubishi Tanabe Pharma Corporation | Cyanopyridine derivative and use thereof as medicine |
CN101218229A (zh) | 2005-05-05 | 2008-07-09 | 阿斯利康(瑞典)有限公司 | 吡唑基-氨基取代的嘧啶及其在癌症治疗中的应用 |
KR20080015409A (ko) | 2005-05-16 | 2008-02-19 | 아스트라제네카 아베 | 티로신 키나제 억제제로서 유용한 피라졸릴아미노피리미딘 유도체 |
EP1945631B8 (en) * | 2005-10-28 | 2013-01-02 | AstraZeneca AB | 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer |
EP1951715B1 (en) | 2005-11-03 | 2013-09-04 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
EP2044063A1 (en) | 2006-06-30 | 2009-04-08 | Astra Zeneca AB | Pyrimidine derivatives useful in the treatment of cancer |
TW200823196A (en) | 2006-11-01 | 2008-06-01 | Astrazeneca Ab | New use |
TW200826937A (en) | 2006-11-01 | 2008-07-01 | Astrazeneca Ab | New use |
-
2006
- 2006-10-26 EP EP06794902A patent/EP1945631B8/en active Active
- 2006-10-26 AU AU2006307657A patent/AU2006307657B2/en not_active Ceased
- 2006-10-26 NZ NZ567584A patent/NZ567584A/en not_active IP Right Cessation
- 2006-10-26 JP JP2008537190A patent/JP2009513615A/ja active Pending
- 2006-10-26 PT PT06794902T patent/PT1945631E/pt unknown
- 2006-10-26 TW TW095139565A patent/TW200800963A/zh unknown
- 2006-10-26 ES ES06794902T patent/ES2391783T3/es active Active
- 2006-10-26 MX MX2008005398A patent/MX2008005398A/es not_active Application Discontinuation
- 2006-10-26 EP EP11177767A patent/EP2388259A1/en not_active Withdrawn
- 2006-10-26 DK DK06794902.4T patent/DK1945631T3/da active
- 2006-10-26 WO PCT/GB2006/003978 patent/WO2007049041A1/en active Application Filing
- 2006-10-26 PL PL06794902T patent/PL1945631T3/pl unknown
- 2006-10-26 KR KR1020087011816A patent/KR20080063846A/ko not_active Application Discontinuation
- 2006-10-26 CA CA002626375A patent/CA2626375A1/en not_active Abandoned
- 2006-10-26 RU RU2008120848/04A patent/RU2463302C2/ru not_active IP Right Cessation
- 2006-10-26 US US12/091,382 patent/US20080287475A1/en not_active Abandoned
- 2006-10-26 BR BRPI0618011-6A patent/BRPI0618011A2/pt not_active IP Right Cessation
- 2006-10-27 AR ARP060104713A patent/AR056210A1/es not_active Application Discontinuation
- 2006-10-27 UY UY29886A patent/UY29886A1/es not_active Application Discontinuation
-
2008
- 2008-04-17 IL IL190935A patent/IL190935A0/en unknown
- 2008-04-22 NO NO20081893A patent/NO20081893L/no not_active Application Discontinuation
- 2008-05-14 EC EC2008008450A patent/ECSP088450A/es unknown
-
2010
- 2010-02-26 US US12/713,695 patent/US8088784B2/en not_active Expired - Fee Related
-
2011
- 2011-12-01 US US13/308,584 patent/US20120071480A1/en not_active Abandoned
-
2012
- 2012-10-15 HR HRP20120824TT patent/HRP20120824T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
US20120071480A1 (en) | 2012-03-22 |
NZ567584A (en) | 2011-08-26 |
TW200800963A (en) | 2008-01-01 |
AU2006307657B2 (en) | 2010-10-28 |
US20100160325A1 (en) | 2010-06-24 |
KR20080063846A (ko) | 2008-07-07 |
WO2007049041A1 (en) | 2007-05-03 |
EP1945631B1 (en) | 2012-08-08 |
US20080287475A1 (en) | 2008-11-20 |
PT1945631E (pt) | 2012-10-15 |
PL1945631T3 (pl) | 2012-12-31 |
IL190935A0 (en) | 2009-09-22 |
ECSP088450A (es) | 2008-06-30 |
CA2626375A1 (en) | 2007-05-03 |
JP2009513615A (ja) | 2009-04-02 |
EP2388259A1 (en) | 2011-11-23 |
BRPI0618011A2 (pt) | 2011-08-16 |
DK1945631T3 (da) | 2012-10-22 |
AU2006307657A1 (en) | 2007-05-03 |
ES2391783T3 (es) | 2012-11-29 |
EP1945631B8 (en) | 2013-01-02 |
RU2463302C2 (ru) | 2012-10-10 |
WO2007049041A8 (en) | 2012-11-01 |
NO20081893L (no) | 2008-05-20 |
EP1945631A1 (en) | 2008-07-23 |
UY29886A1 (es) | 2007-05-31 |
AR056210A1 (es) | 2007-09-26 |
RU2008120848A (ru) | 2009-12-10 |
US8088784B2 (en) | 2012-01-03 |
MX2008005398A (es) | 2008-09-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20120824T1 (hr) | Derivati 4-(3-aminopirazol) pirimidina za uporabu kao inhibitori tirozin kinaze u lijeäśenju karcinoma | |
AU2015331166B2 (en) | Compounds and compositions for modulating EGFR mutant kinase activities | |
ES2873001T3 (es) | Heterociclaminas como inhibidores de PI3K | |
ES2904544T3 (es) | Compuestos de indazol como inhibidores de la cinasa FGFR, preparación y uso de los mismos | |
JP2019535664A5 (hr) | ||
RU2345996C1 (ru) | Аннелированные азагетероциклические амиды, включающие пиримидиновый фрагмент, способ их получения и применения | |
JP6084291B2 (ja) | Fgfr阻害剤の間歇投与用抗腫瘍剤 | |
HRP20211362T1 (hr) | Heterociklički spojevi kao inhibitori ret kinaze | |
CA3043540C (en) | 2-substituted aromatic ring-pyrimidine derivative and preparation and application thereof | |
RU2006121337A (ru) | Производные пиразола и их применение в качестве ингибиторов рецепторных тирозинкиназ | |
JP2018532760A5 (hr) | ||
HRP20170311T1 (hr) | Novi spojevi pirolopirimidina kao inhibitori protein kinaza | |
EP4093406A1 (en) | Enhancement of anti-tumor activity of shp2 inhibitor pyrimidinone in combination with novel cancer medicines in cancers | |
HRP20220599T1 (hr) | Heterociklički spojevi kao inhibitori pi3k-gama | |
HRP20170349T1 (hr) | Novi derivati pirola, postupak njihove priprave i farmaceutski pripravci koji ih sadrže | |
HRP20240293T1 (hr) | Derivati kinazolina kao protutumorska sredstva | |
HRP20140814T1 (hr) | Inhibitori jak2 i njihova uporaba za lijeäśenje mijeloproliferativnih bolesti i karcinoma | |
HRP20131051T1 (hr) | Inhibitori proteinskih kinaza | |
JP2013523889A5 (hr) | ||
RU2011116447A (ru) | Модуляторы амилоида бета | |
CN102695416A (zh) | 激酶抑制剂 | |
CN113993866A (zh) | 杂芳基衍生物、其制备方法、及含其作为有效成分的药物组合物 | |
CA2861010A1 (en) | Heterocyclic compounds and uses as anticancer agents | |
EA034558B1 (ru) | 4-ИМИДАЗО[1,5-a]ПИРИДАЗИН-1-ИЛ-БЕНЗАМИДЫ В КАЧЕСТВЕ Btk-ИНГИБИТОРОВ | |
El-Damasy et al. | Design, synthesis, in-vitro antiproliferative activity and kinase profile of new picolinamide based 2-amido and ureido quinoline derivatives |