ES2540962T3 - Derivados de azaindoles como inhibidores de las proteína cinasas Abl y Src - Google Patents
Derivados de azaindoles como inhibidores de las proteína cinasas Abl y Src Download PDFInfo
- Publication number
- ES2540962T3 ES2540962T3 ES10710439.0T ES10710439T ES2540962T3 ES 2540962 T3 ES2540962 T3 ES 2540962T3 ES 10710439 T ES10710439 T ES 10710439T ES 2540962 T3 ES2540962 T3 ES 2540962T3
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- ES
- Spain
- Prior art keywords
- group
- polysubstituted
- methyl
- optionally mono
- pyrrolo
- Prior art date
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- 102000001253 Protein Kinase Human genes 0.000 title claims description 19
- 108060006633 protein kinase Proteins 0.000 title claims description 19
- 239000003112 inhibitor Substances 0.000 title description 61
- 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 224
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 60
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 53
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 47
- 125000005843 halogen group Chemical group 0.000 claims abstract description 41
- 125000003118 aryl group Chemical group 0.000 claims abstract description 40
- 125000000565 sulfonamide group Chemical group 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims abstract description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 7
- 125000003368 amide group Chemical group 0.000 claims abstract description 5
- 125000004185 ester group Chemical group 0.000 claims abstract description 5
- -1 imidazyl group Chemical group 0.000 claims description 113
- 102000020233 phosphotransferase Human genes 0.000 claims description 80
- 108091000080 Phosphotransferase Proteins 0.000 claims description 79
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 66
- 101100268648 Mus musculus Abl1 gene Proteins 0.000 claims description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 33
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 19
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- 229910052801 chlorine Inorganic materials 0.000 claims description 19
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- KBOWEPWOSHLMGE-UHFFFAOYSA-N methyl 5-amino-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound NC1=CN=C2NC(C(=O)OC)=CC2=C1 KBOWEPWOSHLMGE-UHFFFAOYSA-N 0.000 claims description 17
- NMMIHXMBOZYNET-UHFFFAOYSA-N Methyl picolinate Chemical compound COC(=O)C1=CC=CC=N1 NMMIHXMBOZYNET-UHFFFAOYSA-N 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
- 150000001408 amides Chemical class 0.000 claims description 14
- 238000000746 purification Methods 0.000 claims description 14
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 13
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical group CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 12
- WWCIKRATXUMSLS-UHFFFAOYSA-N methyl 5-nitro-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound [O-][N+](=O)C1=CN=C2NC(C(=O)OC)=CC2=C1 WWCIKRATXUMSLS-UHFFFAOYSA-N 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 11
- 150000001263 acyl chlorides Chemical class 0.000 claims description 11
- 125000005412 pyrazyl group Chemical group 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
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- 125000001544 thienyl group Chemical group 0.000 claims description 9
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- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical class C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 7
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 7
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
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- 102000001332 SRC Human genes 0.000 claims description 6
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- 230000009471 action Effects 0.000 claims description 5
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- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- OEYPDGZCSFPTBF-UHFFFAOYSA-N methyl 5-[(2-bromobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1Br OEYPDGZCSFPTBF-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- ZWXCSTVTBKAEAD-UHFFFAOYSA-N 2-bromo-n-[2-(methoxymethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound C=1N=C2NC(COC)=CC2=CC=1NC(=O)C1=CC=CC=C1Br ZWXCSTVTBKAEAD-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- DHIHZLGSYHTLMS-UHFFFAOYSA-N 3-methoxy-1h-indazole Chemical compound C1=CC=C2C(OC)=NNC2=C1 DHIHZLGSYHTLMS-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
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- 229940043355 kinase inhibitor Drugs 0.000 claims description 3
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- OPMOBCCZILYPTP-UHFFFAOYSA-N 2-bromo-n-[2-[(4-hydroxyanilino)methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound C1=CC(O)=CC=C1NCC1=CC2=CC(NC(=O)C=3C(=CC=CC=3)Br)=CN=C2N1 OPMOBCCZILYPTP-UHFFFAOYSA-N 0.000 claims description 2
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- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
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- CYOZJGAFKCEXBD-UHFFFAOYSA-N 5-[(2-bromobenzoyl)amino]-n-[3-(dimethylamino)propyl]-1h-pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound C=1N=C2NC(C(=O)NCCCN(C)C)=CC2=CC=1NC(=O)C1=CC=CC=C1Br CYOZJGAFKCEXBD-UHFFFAOYSA-N 0.000 claims 1
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- MUEAFINVGVSIJM-UHFFFAOYSA-N methyl 5-(propanoylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound CCC(=O)NC1=CN=C2NC(C(=O)OC)=CC2=C1 MUEAFINVGVSIJM-UHFFFAOYSA-N 0.000 description 1
- KVVSEHVSCHEWNZ-UHFFFAOYSA-N methyl 5-(pyridin-4-ylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC1=CC=NC=C1 KVVSEHVSCHEWNZ-UHFFFAOYSA-N 0.000 description 1
- CVNGIJDNTWLTPR-UHFFFAOYSA-N methyl 5-(thiophen-2-ylmethylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CS1 CVNGIJDNTWLTPR-UHFFFAOYSA-N 0.000 description 1
- CMUUMIKNQANVSF-UHFFFAOYSA-N methyl 5-(thiophene-2-carbonylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CS1 CMUUMIKNQANVSF-UHFFFAOYSA-N 0.000 description 1
- INHKTKGJEIKALZ-UHFFFAOYSA-N methyl 5-[(2,6-dichlorobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=C(Cl)C=CC=C1Cl INHKTKGJEIKALZ-UHFFFAOYSA-N 0.000 description 1
- DJCLBOJZORFUMR-UHFFFAOYSA-N methyl 5-[(2,6-dichlorophenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=C(Cl)C=CC=C1Cl DJCLBOJZORFUMR-UHFFFAOYSA-N 0.000 description 1
- MOEQLLUONDJIIJ-UHFFFAOYSA-N methyl 5-[(2-bromophenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1Br MOEQLLUONDJIIJ-UHFFFAOYSA-N 0.000 description 1
- UVFLAWMNLLGDNC-UHFFFAOYSA-N methyl 5-[(2-chloro-6-methylbenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=C(C)C=CC=C1Cl UVFLAWMNLLGDNC-UHFFFAOYSA-N 0.000 description 1
- KNTPBVJWLVSQOV-UHFFFAOYSA-N methyl 5-[(2-chloro-6-methylphenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=C(C)C=CC=C1Cl KNTPBVJWLVSQOV-UHFFFAOYSA-N 0.000 description 1
- KENHMYXWDPBTAU-UHFFFAOYSA-N methyl 5-[(2-ethylpyrazol-3-yl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound CCN1N=CC=C1CNC1=CN=C(NC(=C2)C(=O)OC)C2=C1 KENHMYXWDPBTAU-UHFFFAOYSA-N 0.000 description 1
- MDMLHBBPUVVDII-UHFFFAOYSA-N methyl 5-[(2-methoxybenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1OC MDMLHBBPUVVDII-UHFFFAOYSA-N 0.000 description 1
- XHNJVFQIMAESOO-UHFFFAOYSA-N methyl 5-[(2-methoxyphenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1OC XHNJVFQIMAESOO-UHFFFAOYSA-N 0.000 description 1
- NSRFIEYUXOOISZ-UHFFFAOYSA-N methyl 5-[(2-methylbenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1C NSRFIEYUXOOISZ-UHFFFAOYSA-N 0.000 description 1
- ONXVBFWIQSGWAH-UHFFFAOYSA-N methyl 5-[(2-methylphenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1C ONXVBFWIQSGWAH-UHFFFAOYSA-N 0.000 description 1
- VVHXNKYRTPCMBO-UHFFFAOYSA-N methyl 5-[(3-bromobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC(Br)=C1 VVHXNKYRTPCMBO-UHFFFAOYSA-N 0.000 description 1
- SSAOJTZTWPNCBO-UHFFFAOYSA-N methyl 5-[(3-cyanobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC(C#N)=C1 SSAOJTZTWPNCBO-UHFFFAOYSA-N 0.000 description 1
- QSLXNAZCAJSVIR-UHFFFAOYSA-N methyl 5-[(6-methyl-1h-indol-5-yl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC(C(=C1)C)=CC2=C1NC=C2 QSLXNAZCAJSVIR-UHFFFAOYSA-N 0.000 description 1
- PRGAKQWPQRXYMK-UHFFFAOYSA-N methyl 5-[4-(methylcarbamoyl)anilino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=CC(C(=O)NC)=CC=C1NC1=CN=C(NC(=C2)C(=O)OC)C2=C1 PRGAKQWPQRXYMK-UHFFFAOYSA-N 0.000 description 1
- SIUOVOCGMYQPIB-UHFFFAOYSA-N methyl 5-[[2-(trifluoromethyl)benzoyl]amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1C(F)(F)F SIUOVOCGMYQPIB-UHFFFAOYSA-N 0.000 description 1
- MFAPLYWBOUSVJJ-UHFFFAOYSA-N methyl 5-[[2-(trifluoromethyl)phenyl]methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1C(F)(F)F MFAPLYWBOUSVJJ-UHFFFAOYSA-N 0.000 description 1
- OBWMULCASPZKTP-UHFFFAOYSA-N methyl 5-[[4-(chloromethyl)benzoyl]amino]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC(NC(=O)C=2C=CC(CCl)=CC=2)=C1 OBWMULCASPZKTP-UHFFFAOYSA-N 0.000 description 1
- OHIHEJTUXNQOPM-UHFFFAOYSA-N methyl 6-aminopyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(N)=N1 OHIHEJTUXNQOPM-UHFFFAOYSA-N 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- YRWYLPAVVWDGGS-UHFFFAOYSA-N n,n-dimethoxypropan-1-amine Chemical compound CCCN(OC)OC YRWYLPAVVWDGGS-UHFFFAOYSA-N 0.000 description 1
- ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 description 1
- AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
- PNEJDIFQKCQXPM-UHFFFAOYSA-N n-[2-[[bis(2-methoxyethyl)amino]methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]-2-bromobenzamide Chemical compound C=1N=C2NC(CN(CCOC)CCOC)=CC2=CC=1NC(=O)C1=CC=CC=C1Br PNEJDIFQKCQXPM-UHFFFAOYSA-N 0.000 description 1
- VSSWZOOAQIXYDI-UHFFFAOYSA-N n-[3-(hydroxymethyl)-4-methylphenyl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(CO)C(C)=CC=2)C=C1 VSSWZOOAQIXYDI-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- JCSQXEINQFERDM-UHFFFAOYSA-N n-benzyl-1h-indazol-3-amine Chemical compound N=1NC2=CC=CC=C2C=1NCC1=CC=CC=C1 JCSQXEINQFERDM-UHFFFAOYSA-N 0.000 description 1
- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 208000015768 polyposis Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20227909P | 2009-02-12 | 2009-02-12 | |
| FR0900631 | 2009-02-12 | ||
| US202279P | 2009-02-12 | ||
| FR0900631A FR2941948B1 (fr) | 2009-02-12 | 2009-02-12 | Derives d'azaindoles en tant qu'inhibiteur des proteines kinases abl et src |
| PCT/IB2010/000593 WO2010092489A1 (en) | 2009-02-12 | 2010-02-12 | Derivatives of azaindoles as inhibitors of protein kinases abl and src |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2540962T3 true ES2540962T3 (es) | 2015-07-15 |
Family
ID=40886859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10710439.0T Active ES2540962T3 (es) | 2009-02-12 | 2010-02-12 | Derivados de azaindoles como inhibidores de las proteína cinasas Abl y Src |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8580815B2 (enExample) |
| EP (1) | EP2396325B1 (enExample) |
| JP (1) | JP5583698B2 (enExample) |
| AU (1) | AU2010212560B2 (enExample) |
| CA (1) | CA2751478A1 (enExample) |
| DK (1) | DK2396325T3 (enExample) |
| ES (1) | ES2540962T3 (enExample) |
| FR (1) | FR2941948B1 (enExample) |
| HR (1) | HRP20150697T8 (enExample) |
| HU (1) | HUE024989T2 (enExample) |
| PL (1) | PL2396325T3 (enExample) |
| PT (1) | PT2396325E (enExample) |
| SI (1) | SI2396325T1 (enExample) |
| SM (1) | SMT201500175B (enExample) |
| WO (1) | WO2010092489A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ME03000B (me) * | 2012-12-21 | 2018-10-20 | Plexxikon Inc | Jedinjenja i metode modulacije kinaze i povezane indikacije |
| FR3000493A1 (fr) * | 2012-12-28 | 2014-07-04 | Oribase Pharma | Nouveaux inhibiteurs de proteines kinases |
| FR3000494B1 (fr) * | 2012-12-28 | 2015-08-21 | Oribase Pharma | Nouveaux derives d'azaindoles en tant qu'inhibiteurs de proteines kinases |
| FR3000492B1 (fr) * | 2012-12-28 | 2015-09-11 | Oribase Pharma | Nouveaux derives azaindole en tant qu'inhibiteurs multikinases |
| US10722484B2 (en) | 2016-03-09 | 2020-07-28 | K-Gen, Inc. | Methods of cancer treatment |
| MA49014A (fr) * | 2017-03-21 | 2020-02-05 | Arbutus Biopharma Corp | Dihydroindène-4-carboxamides substitués, leurs analogues et procédés d'utilisation correspondant |
| AU2021263383A1 (en) | 2020-04-29 | 2022-11-24 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| CN111943947B (zh) * | 2020-07-24 | 2021-04-30 | 重庆文理学院 | 1H-吡咯[2,3-b]吡啶衍生物及其合成方法与应用 |
| CA3196620A1 (en) | 2020-10-05 | 2022-04-14 | Enliven Therapeutics, Inc. | 5- and 6-azaindole compounds for inhibition of bcr-abl tyrosine kinases |
| WO2022076973A1 (en) * | 2020-10-05 | 2022-04-14 | Enliven Therapeutics, Inc. | 7-azaindole compounds for inhibition of bcr-abl tyrosine kinases |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0330043D0 (en) * | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions comprising them |
| GB0330042D0 (en) | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions them |
| TW200616632A (en) * | 2004-06-17 | 2006-06-01 | Plexxikon Inc | Compounds modulating c-kit activity and uses therefor |
| US7361764B2 (en) | 2004-07-27 | 2008-04-22 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| NZ553267A (en) | 2004-07-27 | 2010-09-30 | Sgx Pharmaceuticals Inc | Pyrrolo-pyridine kinase modulators |
| US7709645B2 (en) | 2004-07-27 | 2010-05-04 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| WO2006104971A1 (en) * | 2005-03-28 | 2006-10-05 | Bristol-Myers Squibb Company | Atp competitive kinase inhibitors |
| BRPI0716477A2 (pt) | 2006-09-06 | 2014-03-18 | Hoffmann La Roche | Derivados heteroarila como inibidores de quinase protéica |
| JP5244118B2 (ja) * | 2006-11-10 | 2013-07-24 | ブリストル−マイヤーズ スクイブ カンパニー | 新規キナーゼ阻害剤 |
| WO2008144253A1 (en) * | 2007-05-14 | 2008-11-27 | Irm Llc | Protein kinase inhibitors and methods for using thereof |
| WO2009111278A2 (en) * | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Raf inhibitor compounds and methods of use thereof |
| HUE035798T2 (en) * | 2008-11-03 | 2018-05-28 | Syntarga Bv | CC-1065 analogues and conjugates |
-
2009
- 2009-02-12 FR FR0900631A patent/FR2941948B1/fr not_active Expired - Fee Related
-
2010
- 2010-02-12 HR HRP20150697TT patent/HRP20150697T8/hr unknown
- 2010-02-12 AU AU2010212560A patent/AU2010212560B2/en not_active Ceased
- 2010-02-12 EP EP10710439.0A patent/EP2396325B1/en not_active Not-in-force
- 2010-02-12 PT PT107104390T patent/PT2396325E/pt unknown
- 2010-02-12 JP JP2011549698A patent/JP5583698B2/ja not_active Expired - Fee Related
- 2010-02-12 US US13/148,988 patent/US8580815B2/en not_active Expired - Fee Related
- 2010-02-12 WO PCT/IB2010/000593 patent/WO2010092489A1/en not_active Ceased
- 2010-02-12 HU HUE10710439A patent/HUE024989T2/en unknown
- 2010-02-12 ES ES10710439.0T patent/ES2540962T3/es active Active
- 2010-02-12 DK DK10710439.0T patent/DK2396325T3/en active
- 2010-02-12 CA CA2751478A patent/CA2751478A1/en not_active Abandoned
- 2010-02-12 SI SI201030964T patent/SI2396325T1/sl unknown
- 2010-02-12 PL PL10710439T patent/PL2396325T3/pl unknown
-
2015
- 2015-07-22 SM SM201500175T patent/SMT201500175B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US8580815B2 (en) | 2013-11-12 |
| DK2396325T3 (en) | 2015-06-29 |
| EP2396325B1 (en) | 2015-04-01 |
| SI2396325T1 (sl) | 2015-08-31 |
| FR2941948A1 (fr) | 2010-08-13 |
| JP5583698B2 (ja) | 2014-09-03 |
| US20110312959A1 (en) | 2011-12-22 |
| PT2396325E (pt) | 2015-08-21 |
| AU2010212560B2 (en) | 2016-01-21 |
| FR2941948B1 (fr) | 2013-04-05 |
| HRP20150697T8 (xx) | 2015-11-06 |
| WO2010092489A1 (en) | 2010-08-19 |
| HRP20150697T1 (hr) | 2015-08-14 |
| AU2010212560A1 (en) | 2011-08-11 |
| JP2012517465A (ja) | 2012-08-02 |
| SMT201500175B (it) | 2015-09-07 |
| EP2396325A1 (en) | 2011-12-21 |
| CA2751478A1 (en) | 2010-08-19 |
| PL2396325T3 (pl) | 2015-10-30 |
| HUE024989T2 (en) | 2016-01-28 |
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