AU2009302360B2 - Imidazopyridazinecarbonitriles useful as kinase inhibitors - Google Patents
Imidazopyridazinecarbonitriles useful as kinase inhibitors Download PDFInfo
- Publication number
- AU2009302360B2 AU2009302360B2 AU2009302360A AU2009302360A AU2009302360B2 AU 2009302360 B2 AU2009302360 B2 AU 2009302360B2 AU 2009302360 A AU2009302360 A AU 2009302360A AU 2009302360 A AU2009302360 A AU 2009302360A AU 2009302360 B2 AU2009302360 B2 AU 2009302360B2
- Authority
- AU
- Australia
- Prior art keywords
- amino
- imidazo
- carbonitrile
- pyridazine
- cyclopropylamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 229940043355 kinase inhibitor Drugs 0.000 title description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 163
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 430
- 125000000217 alkyl group Chemical group 0.000 claims description 220
- -1 3 -Cyano-5-(trifluoromethyl)phenyl Chemical group 0.000 claims description 129
- 125000000623 heterocyclic group Chemical group 0.000 claims description 101
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 73
- 229910052799 carbon Inorganic materials 0.000 claims description 69
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
- YLXWTAXPOOYRSL-UHFFFAOYSA-N imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1=CC=NN2C(C#N)=CN=C21 YLXWTAXPOOYRSL-UHFFFAOYSA-N 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 60
- PJESVVYWPFAJCS-UHFFFAOYSA-N pyridazine-3-carbonitrile Chemical compound N#CC1=CC=CN=N1 PJESVVYWPFAJCS-UHFFFAOYSA-N 0.000 claims description 56
- 229910052794 bromium Inorganic materials 0.000 claims description 55
- 229910052801 chlorine Inorganic materials 0.000 claims description 52
- 229910052731 fluorine Inorganic materials 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 229910052702 rhenium Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 229910052705 radium Inorganic materials 0.000 claims description 34
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 33
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 31
- 229910021481 rutherfordium Inorganic materials 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 claims description 25
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 10
- 101150105130 RORB gene Proteins 0.000 claims description 10
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 10
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 229910052701 rubidium Inorganic materials 0.000 claims description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 8
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 8
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 6
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 5
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims description 4
- 101150073096 NRAS gene Proteins 0.000 claims description 4
- 239000002254 cytotoxic agent Substances 0.000 claims description 4
- 229940127089 cytotoxic agent Drugs 0.000 claims description 4
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- JHBIUJPZHKBEPQ-UHFFFAOYSA-N n-[3-[(8-anilino-3-cyanoimidazo[1,2-b]pyridazin-6-yl)amino]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(NC2=NN3C(C#N)=CN=C3C(NC=3C=CC=CC=3)=C2)=C1 JHBIUJPZHKBEPQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 210000001685 thyroid gland Anatomy 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- RZPKWDDURQVWRG-UHFFFAOYSA-N 3-[[6-(3-acetamido-4-methylanilino)-3-cyanoimidazo[1,2-b]pyridazin-8-yl]amino]-n-[2-(dimethylamino)ethyl]benzamide Chemical compound CN(C)CCNC(=O)C1=CC=CC(NC=2C3=NC=C(N3N=C(NC=3C=C(NC(C)=O)C(C)=CC=3)C=2)C#N)=C1 RZPKWDDURQVWRG-UHFFFAOYSA-N 0.000 claims description 2
- QQUIUHWOULMUPW-UHFFFAOYSA-N 6-(5-cyano-2-methoxyanilino)-8-(2,2,2-trifluoroethylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound COC1=CC=C(C#N)C=C1NC1=NN2C(C#N)=CN=C2C(NCC(F)(F)F)=C1 QQUIUHWOULMUPW-UHFFFAOYSA-N 0.000 claims description 2
- NIHOARPLDKSGFI-UHFFFAOYSA-N 6-[4-fluoro-3-(1,2,4-triazol-4-yl)anilino]-8-[(5-methoxypyridin-2-yl)amino]imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N1=CC(OC)=CC=C1NC1=CC(NC=2C=C(C(F)=CC=2)N2C=NN=C2)=NN2C1=NC=C2C#N NIHOARPLDKSGFI-UHFFFAOYSA-N 0.000 claims description 2
- DOUYOXMJHLRMTQ-UHFFFAOYSA-N 8-(cyclopropylamino)-6-[4-morpholin-4-yl-3-(1,2,4-triazol-4-yl)anilino]imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C=1C(NC=2C=C(C(N3CCOCC3)=CC=2)N2C=NN=C2)=NN2C(C#N)=CN=C2C=1NC1CC1 DOUYOXMJHLRMTQ-UHFFFAOYSA-N 0.000 claims description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
- 208000000172 Medulloblastoma Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- VJPQCIWEUVOSDD-UHFFFAOYSA-N n-[3-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 VJPQCIWEUVOSDD-UHFFFAOYSA-N 0.000 claims description 2
- SGBSNJVNEDAJFN-UHFFFAOYSA-N n-[5-[[3-cyano-8-(2-hydroxyethylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-2-methylphenyl]acetamide Chemical compound C1=C(C)C(NC(=O)C)=CC(NC2=NN3C(C#N)=CN=C3C(NCCO)=C2)=C1 SGBSNJVNEDAJFN-UHFFFAOYSA-N 0.000 claims description 2
- VIDMEUWDGBRTKR-UHFFFAOYSA-N n-[5-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-2-(trifluoromethoxy)phenyl]acetamide Chemical compound C1=C(OC(F)(F)F)C(NC(=O)C)=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 VIDMEUWDGBRTKR-UHFFFAOYSA-N 0.000 claims description 2
- YPHTZCUITGMBSO-UHFFFAOYSA-N n-[5-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-2-methylphenyl]acetamide Chemical compound C1=C(C)C(NC(=O)C)=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 YPHTZCUITGMBSO-UHFFFAOYSA-N 0.000 claims description 2
- ZGUQIQORODEQBT-UHFFFAOYSA-N n-[5-[[8-(azetidin-3-ylamino)-3-cyanoimidazo[1,2-b]pyridazin-6-yl]amino]-2-methylphenyl]acetamide Chemical compound C1=C(C)C(NC(=O)C)=CC(NC2=NN3C(C#N)=CN=C3C(NC3CNC3)=C2)=C1 ZGUQIQORODEQBT-UHFFFAOYSA-N 0.000 claims description 2
- 229940127084 other anti-cancer agent Drugs 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 3
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 3
- 108010011222 cyclo(Arg-Pro) Proteins 0.000 claims 3
- STKQWHQDRAQKIG-UHFFFAOYSA-N n-[5-[[3-cyano-8-(2-methoxyethylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-2-methylphenyl]acetamide Chemical compound N=1N2C(C#N)=CN=C2C(NCCOC)=CC=1NC1=CC=C(C)C(NC(C)=O)=C1 STKQWHQDRAQKIG-UHFFFAOYSA-N 0.000 claims 2
- QGEZIXBUQONEOG-UHFFFAOYSA-N 1-[3-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]phenyl]-3-methylurea Chemical compound CNC(=O)NC1=CC=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 QGEZIXBUQONEOG-UHFFFAOYSA-N 0.000 claims 1
- TYHYESDUJZRBKS-UHFFFAOYSA-N 2,3-dihydroindole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)CCC2=C1 TYHYESDUJZRBKS-UHFFFAOYSA-N 0.000 claims 1
- WRPNOGUHLLWRTM-UHFFFAOYSA-N 2-[5-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-2-methylphenyl]acetamide Chemical compound C1=C(CC(N)=O)C(C)=CC=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 WRPNOGUHLLWRTM-UHFFFAOYSA-N 0.000 claims 1
- JMTVADAFUJKUGH-UHFFFAOYSA-N 2-[5-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-2-methylphenyl]acetic acid Chemical compound C1=C(CC(O)=O)C(C)=CC=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 JMTVADAFUJKUGH-UHFFFAOYSA-N 0.000 claims 1
- IPYLVZFHJMUSFE-UHFFFAOYSA-N 2-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]-1,3-thiazole-5-carbonitrile Chemical compound S1C(C#N)=CN=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 IPYLVZFHJMUSFE-UHFFFAOYSA-N 0.000 claims 1
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 claims 1
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 claims 1
- LLLLFBIQGQJRDZ-UHFFFAOYSA-N 3-[[3-cyano-6-[3-methoxy-5-(5-methyltetrazol-1-yl)anilino]imidazo[1,2-b]pyridazin-8-yl]amino]-n-[2-(dimethylamino)ethyl]benzamide Chemical compound C=1C(N2C(=NN=N2)C)=CC(OC)=CC=1NC(=NN1C(C#N)=CN=C11)C=C1NC1=CC=CC(C(=O)NCCN(C)C)=C1 LLLLFBIQGQJRDZ-UHFFFAOYSA-N 0.000 claims 1
- OEWOMLTZHHMWLV-UHFFFAOYSA-N 3-[[3-cyano-8-(cyclopropylamino)imidazo[1,2-b]pyridazin-6-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 OEWOMLTZHHMWLV-UHFFFAOYSA-N 0.000 claims 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims 1
- MCBZOKZCENKAGK-UHFFFAOYSA-N 6-(3-aminoanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound NC1=CC=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 MCBZOKZCENKAGK-UHFFFAOYSA-N 0.000 claims 1
- HRUYYTNLOCPEMB-UHFFFAOYSA-N 6-(3-cyano-2-fluoroanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1=CC=C(C#N)C(F)=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 HRUYYTNLOCPEMB-UHFFFAOYSA-N 0.000 claims 1
- FKPTZDJAURXWKO-UHFFFAOYSA-N 6-(3-cyano-4-methylanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1=C(C#N)C(C)=CC=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 FKPTZDJAURXWKO-UHFFFAOYSA-N 0.000 claims 1
- ZIVLUPIQFWETAV-UHFFFAOYSA-N 6-(3-cyano-5-fluoroanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N#CC1=CC(F)=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 ZIVLUPIQFWETAV-UHFFFAOYSA-N 0.000 claims 1
- IASVXSDFXAWLDK-UHFFFAOYSA-N 6-(3-cyano-5-fluoroanilino)-8-(pyridin-2-ylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N#CC1=CC(F)=CC(NC2=NN3C(C#N)=CN=C3C(NC=3N=CC=CC=3)=C2)=C1 IASVXSDFXAWLDK-UHFFFAOYSA-N 0.000 claims 1
- DCHQRIGPHJGZHY-UHFFFAOYSA-N 6-(3-cyanoanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C=1C(NC=2C=C(C=CC=2)C#N)=NN2C(C#N)=CN=C2C=1NC1CC1 DCHQRIGPHJGZHY-UHFFFAOYSA-N 0.000 claims 1
- LATUZQQCMJOKJW-UHFFFAOYSA-N 6-(4-chloro-3-cyanoanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=CC=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 LATUZQQCMJOKJW-UHFFFAOYSA-N 0.000 claims 1
- BNAQQZJFEOVLFS-UHFFFAOYSA-N 6-(5-cyano-2-methoxyanilino)-8-(cyclobutylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound COC1=CC=C(C#N)C=C1NC1=NN2C(C#N)=CN=C2C(NC2CCC2)=C1 BNAQQZJFEOVLFS-UHFFFAOYSA-N 0.000 claims 1
- VJTUZMKWQGEZPL-UHFFFAOYSA-N 6-(5-cyano-2-methylanilino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound CC1=CC=C(C#N)C=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 VJTUZMKWQGEZPL-UHFFFAOYSA-N 0.000 claims 1
- NLLUIPZINBHBSO-UHFFFAOYSA-N 6-[3-cyano-4-(4-methylpiperazin-1-yl)anilino]-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1CN(C)CCN1C(C(=C1)C#N)=CC=C1NC1=NN2C(C#N)=CN=C2C(NC2CC2)=C1 NLLUIPZINBHBSO-UHFFFAOYSA-N 0.000 claims 1
- VBWNBAHLTKPJDB-UHFFFAOYSA-N 6-[3-cyano-4-(trifluoromethoxy)anilino]-8-(2-methoxyethylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N=1N2C(C#N)=CN=C2C(NCCOC)=CC=1NC1=CC=C(OC(F)(F)F)C(C#N)=C1 VBWNBAHLTKPJDB-UHFFFAOYSA-N 0.000 claims 1
- LDJVHGQIQBWIKJ-UHFFFAOYSA-N 6-[3-cyano-5-(trifluoromethyl)anilino]-8-(2-morpholin-4-ylethylamino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N#CC1=CC(C(F)(F)F)=CC(NC2=NN3C(C#N)=CN=C3C(NCCN3CCOCC3)=C2)=C1 LDJVHGQIQBWIKJ-UHFFFAOYSA-N 0.000 claims 1
- YJIFXBLTLFJSSN-UHFFFAOYSA-N 8-(2-methoxyethylamino)-6-[3-methoxy-5-(1,2,4-triazol-4-yl)anilino]imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N=1N2C(C#N)=CN=C2C(NCCOC)=CC=1NC(C=1)=CC(OC)=CC=1N1C=NN=C1 YJIFXBLTLFJSSN-UHFFFAOYSA-N 0.000 claims 1
- MMGAIEKGWLULMA-UHFFFAOYSA-N 8-(2-methoxyethylamino)-6-[4-morpholin-4-yl-3-(1,2,4-triazol-4-yl)anilino]imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound N=1N2C(C#N)=CN=C2C(NCCOC)=CC=1NC(C=C1N2C=NN=C2)=CC=C1N1CCOCC1 MMGAIEKGWLULMA-UHFFFAOYSA-N 0.000 claims 1
- LMGHCPABWFHCGY-UHFFFAOYSA-N 8-(cyclopropylamino)-6-(3-imidazol-1-ylanilino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C=1C(NC=2C=C(C=CC=2)N2C=NC=C2)=NN2C(C#N)=CN=C2C=1NC1CC1 LMGHCPABWFHCGY-UHFFFAOYSA-N 0.000 claims 1
- KOIZTLRNGMBSHO-UHFFFAOYSA-N 8-(cyclopropylamino)-6-(3-methylsulfonylanilino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound CS(=O)(=O)C1=CC=CC(NC2=NN3C(C#N)=CN=C3C(NC3CC3)=C2)=C1 KOIZTLRNGMBSHO-UHFFFAOYSA-N 0.000 claims 1
- JIKQAZRTCQELMY-UHFFFAOYSA-N 8-(cyclopropylamino)-6-(3-pyridin-4-ylanilino)imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C=1C(NC=2C=C(C=CC=2)C=2C=CN=CC=2)=NN2C(C#N)=CN=C2C=1NC1CC1 JIKQAZRTCQELMY-UHFFFAOYSA-N 0.000 claims 1
- MAPVUFLTUVGHLL-UHFFFAOYSA-N 8-(cyclopropylamino)-6-[(1-methylsulfonylindol-6-yl)amino]imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1=C2N(S(=O)(=O)C)C=CC2=CC=C1NC(=NN1C(C#N)=CN=C11)C=C1NC1CC1 MAPVUFLTUVGHLL-UHFFFAOYSA-N 0.000 claims 1
- NTHXXZQWQLXFSZ-UHFFFAOYSA-N 8-(cyclopropylamino)-6-[(4-methyl-3-oxo-1,4-benzoxazin-6-yl)amino]imidazo[1,2-b]pyridazine-3-carbonitrile Chemical compound C1=C2N(C)C(=O)COC2=CC=C1NC(=NN1C(C#N)=CN=C11)C=C1NC1CC1 NTHXXZQWQLXFSZ-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10404508P | 2008-10-09 | 2008-10-09 | |
| US61/104,045 | 2008-10-09 | ||
| PCT/US2009/059968 WO2010042699A1 (en) | 2008-10-09 | 2009-10-08 | Imidazopyridazinecarbonitriles useful as kinase inhibitors |
Publications (2)
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| AU2009302360A1 AU2009302360A1 (en) | 2010-04-15 |
| AU2009302360B2 true AU2009302360B2 (en) | 2014-12-11 |
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| EP (1) | EP2350081B1 (OSRAM) |
| JP (1) | JP5560278B2 (OSRAM) |
| KR (1) | KR20110075010A (OSRAM) |
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| AR (1) | AR073818A1 (OSRAM) |
| AU (1) | AU2009302360B2 (OSRAM) |
| BR (1) | BRPI0920135A2 (OSRAM) |
| CA (1) | CA2739782A1 (OSRAM) |
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| PE (1) | PE20110411A1 (OSRAM) |
| PL (1) | PL2350081T3 (OSRAM) |
| PT (1) | PT2350081E (OSRAM) |
| SI (1) | SI2350081T1 (OSRAM) |
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| TW (1) | TWI491610B (OSRAM) |
| WO (1) | WO2010042699A1 (OSRAM) |
| ZA (1) | ZA201102423B (OSRAM) |
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| US8389527B2 (en) * | 2008-02-06 | 2013-03-05 | Bristol-Myers Squibb Company | Substituted imidazopyridazines useful as kinase inhibitors |
| TWI491610B (zh) * | 2008-10-09 | 2015-07-11 | 必治妥美雅史谷比公司 | 作為激酶抑制劑之咪唑并嗒腈 |
| TWI541243B (zh) | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
| US9587033B2 (en) | 2010-11-15 | 2017-03-07 | University Of Florida Research Foundation, Inc. | Therapeutic and diagnostic applications targeting TNK-1 |
| CA2821837A1 (en) | 2010-12-17 | 2012-06-21 | Bayer Intellectual Property Gmbh | 2-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| WO2012080229A1 (en) | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | Imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment hyperproliferative disorders |
| WO2012080234A1 (en) | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | Substituted 6-imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| EP2701507A1 (en) * | 2011-04-26 | 2014-03-05 | Merck Sharp & Dohme Corp. | Heterocyclic compounds as b-raf inhibitors for treatment of cancer |
| US9512126B2 (en) | 2012-03-14 | 2016-12-06 | Bayer Intellectual Property Gmbh | Substituted imidazopyridazines |
| EP2827869A4 (en) | 2012-03-23 | 2015-09-23 | Dennis Brown | COMPOSITIONS AND METHODS FOR IMPROVING THE THERAPEUTIC BENEFIT OF INDIRUBIN AND ANALOGUE THEREOF, WITH MEISOINDIGO |
| TW201414737A (zh) * | 2012-07-13 | 2014-04-16 | 必治妥美雅史谷比公司 | 作爲激酶抑制劑之咪唑并三□甲腈 |
| WO2014020041A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
| TW201437211A (zh) * | 2013-03-01 | 2014-10-01 | Bayer Pharma AG | 經取代咪唑并嗒□ |
| AP2015008898A0 (en) | 2013-06-11 | 2015-12-31 | Bayer Pharma AG | Prodrug derivatives of substituted triazolopyridines |
| CN105764502A (zh) | 2013-07-26 | 2016-07-13 | 现代化制药公司 | 改善比生群及其类似物及衍生物的治疗益处的组合方法 |
| TW201542550A (zh) * | 2013-09-06 | 2015-11-16 | Lexicon Pharmaceuticals Inc | 吡唑并［１，５－ａ］嘧啶基化合物、包含彼之組合物以及使用彼之方法 |
| AR097543A1 (es) * | 2013-09-06 | 2016-03-23 | Lexicon Pharmaceuticals Inc | COMPUESTOS BASADOS EN IMIDAZO[1,2-b]PIRIDAZINA, COMPOSICIONES QUE LOS COMPRENDEN Y SUS MÉTODOS DE USO |
| GB201403536D0 (en) * | 2014-02-28 | 2014-04-16 | Cancer Rec Tech Ltd | Inhibitor compounds |
| JP6843135B2 (ja) | 2015-11-18 | 2021-03-17 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ＩＬ−１２、ＩＬ−２３および／またはＩＦＮα応答のモジュレーターとして有用なイミダゾピリダジン化合物 |
| US10227344B2 (en) | 2016-06-24 | 2019-03-12 | Polaris Pharmaceuticals, Inc. | CK2 inhibitors, compositions and methods thereof |
| MA45940B1 (fr) * | 2016-08-10 | 2024-12-31 | Takeda Pharmaceutical Company Limited | Composé hétérocyclique |
| JP7012082B2 (ja) | 2016-11-17 | 2022-01-27 | ブリストル－マイヤーズ スクイブ カンパニー | Ｉｌ－１２、ｉｌ－２３および／またはｉｆｎ－アルファのイミダゾピリダジン調節剤 |
| JP7129420B6 (ja) | 2017-03-30 | 2024-02-02 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | Ｈｐｋ１阻害剤としてのイソキノリン |
| EP3700904B1 (en) | 2017-10-24 | 2023-07-19 | Bayer AG | 4h-pyrrolo[3,2-c]pyridin-4-one derivatives |
| CN109988150B (zh) | 2017-12-29 | 2022-04-12 | 江苏中旗科技股份有限公司 | N-烷基-n-氰基烷基苯甲酰胺类化合物及其应用 |
| BR112020013313B1 (pt) | 2017-12-29 | 2023-10-31 | Jiangsu Flag Chemical Industry Co., Ltd | Composto de pirazolamida de fórmula geral i, composto de fórmula ii, método para preparar um composto de fórmula geral i, uso do composto de fórmula geral i, composição inseticida e método para controlar pragas |
| WO2019128871A1 (zh) | 2017-12-29 | 2019-07-04 | 江苏中旗科技股份有限公司 | N-烷基-n-氰基烷基苯甲酰胺类化合物及其应用 |
| CN111867581B (zh) * | 2018-01-29 | 2023-12-26 | 默克专利股份有限公司 | Gcn2抑制剂及其用途 |
| PE20211275A1 (es) | 2018-07-09 | 2021-07-19 | Boehringer Ingelheim Animal Health Usa Inc | Compuestos heterociclicos antihelminticos |
| US11612606B2 (en) | 2018-10-03 | 2023-03-28 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
| ES2987809T3 (es) | 2019-03-05 | 2024-11-18 | Bristol Myers Squibb Co | Compuestos de imidazopiridazina útiles como moduladores de las respuestas de IL-12, IL-23 y/o IFN alfa |
| KR20220002890A (ko) | 2019-03-19 | 2022-01-07 | 뵈링거 잉겔하임 애니멀 헬스 유에스에이 인코포레이티드 | 구충성 아자-벤조티오펜 및 아자-벤조푸란 화합물 |
| CN117986251A (zh) | 2019-04-24 | 2024-05-07 | 拜耳股份有限公司 | 4H-吡咯并[3,2-c]吡啶-4-酮化合物 |
| CA3137611A1 (en) | 2019-04-24 | 2020-10-29 | Bayer Aktiengesellschaft | 4h-pyrrolo[3,2-c]pyridin-4-one derivatives |
| EP3959212A1 (en) | 2019-04-24 | 2022-03-02 | Bayer Aktiengesellschaft | 4h-pyrrolo[3,2-c]pyridin-4-one compounds |
| WO2021198020A1 (en) | 2020-03-31 | 2021-10-07 | Bayer Aktiengesellschaft | 3-(anilino)-2-[3-(3-alkoxy-pyridin-4-yl]-1,5,6,7-tetrahydro-4h-pyrrolo[3,2-c]pyridin-4-one derivatives as egfr inhibitors for the treatment of cancer |
| MX2022015038A (es) | 2020-05-29 | 2023-01-04 | Boehringer Ingelheim Animal Health Usa Inc | Compuestos heterociclicos como anthelminticos. |
| MX2023009094A (es) * | 2021-02-03 | 2023-08-09 | Sanofi Sa | Derivados de imidazo[4,5-d]piridazina, su preparacion y su aplicacion terapeutica. |
| PE20250675A1 (es) | 2021-11-01 | 2025-03-04 | Boehringer Ingelheim Vetmedica Gmbh | Compuestos de pirrolopiridazina como antihelminticos |
| IL314397A (en) * | 2022-01-25 | 2024-09-01 | Kinnate Biopharma Inc | CDK4/6 kinase inhibitors |
| WO2024039767A1 (en) * | 2022-08-18 | 2024-02-22 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Imidazo[1,2-b]pyridazine inhibitors of cyclin-dependent kinases |
| CN115947756B (zh) * | 2022-12-13 | 2025-08-01 | 西湖大学 | 一种芳基卤代物和多氟烷基醇直接偶联合成多氟烷基芳基醚的方法 |
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- 2009-10-08 MX MX2011003304A patent/MX2011003304A/es active IP Right Grant
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007038314A2 (en) * | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
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