JP2014503567A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2014503567A5 JP2014503567A5 JP2013550833A JP2013550833A JP2014503567A5 JP 2014503567 A5 JP2014503567 A5 JP 2014503567A5 JP 2013550833 A JP2013550833 A JP 2013550833A JP 2013550833 A JP2013550833 A JP 2013550833A JP 2014503567 A5 JP2014503567 A5 JP 2014503567A5
- Authority
- JP
- Japan
- Prior art keywords
- carboxamide
- quinazoline
- pyrrolo
- formula
- dihydro
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 28
- 229910052739 hydrogen Inorganic materials 0.000 claims 17
- 239000001257 hydrogen Substances 0.000 claims 17
- 125000003118 aryl group Chemical group 0.000 claims 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims 11
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 10
- 125000000623 heterocyclic group Chemical group 0.000 claims 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 8
- 238000000034 method Methods 0.000 claims 8
- -1 - alkyl Chemical group 0.000 claims 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 150000002431 hydrogen Chemical group 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 229940127089 cytotoxic agent Drugs 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 108091000080 Phosphotransferase Proteins 0.000 claims 2
- 230000002378 acidificating effect Effects 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 102000020233 phosphotransferase Human genes 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- ZXOFAHRGRROAQR-UHFFFAOYSA-N 1-(isocyanomethylsulfonyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1S(=O)(=O)C[N+]#[C-] ZXOFAHRGRROAQR-UHFFFAOYSA-N 0.000 claims 1
- SNFGHOGDCXZSGY-UHFFFAOYSA-N 2-(4-bromo-2-methoxyanilino)-n-(2,6-diethylphenyl)-8,9-dimethyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=C(C)N(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(Br)C=C1OC SNFGHOGDCXZSGY-UHFFFAOYSA-N 0.000 claims 1
- JPYAEEZHLANFOV-UHFFFAOYSA-N 2-(4-bromo-2-methoxyanilino)-n-(2,6-diethylphenyl)-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=CN(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(Br)C=C1OC JPYAEEZHLANFOV-UHFFFAOYSA-N 0.000 claims 1
- HCUXMELTHAQYDN-MUUNZHRXSA-N 2-(4-bromo-2-methoxyanilino)-n-[(1s)-2-(1,3-dioxoisoindol-2-yl)-1-phenylethyl]-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound COC1=CC(Br)=CC=C1NC1=NC=C(CCC2=C3N(C)C=C2C(=O)N[C@H](CN2C(C4=CC=CC=C4C2=O)=O)C=2C=CC=CC=2)C3=N1 HCUXMELTHAQYDN-MUUNZHRXSA-N 0.000 claims 1
- CQNXJSHIMDAHNX-UHFFFAOYSA-N 2-(dimethylamino)-8-methyl-6,9-dihydro-5h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(N(C)C)=NC=C2CCC2=C1NC(C)=C2C(N)=O CQNXJSHIMDAHNX-UHFFFAOYSA-N 0.000 claims 1
- NKTVIWIDORBNHH-UHFFFAOYSA-N 2-(dimethylamino)-8-methyl-9h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(N(C)C)=NC=C2C=CC2=C1NC(C)=C2C(N)=O NKTVIWIDORBNHH-UHFFFAOYSA-N 0.000 claims 1
- RJGLNSNPZNKTGL-UHFFFAOYSA-N 2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-8,9-dimethyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C=1C=C(NC=2N=C3C=4N(C)C(C)=C(C(N)=O)C=4CCC3=CN=2)C(OC)=CC=1N1CCN(C)CC1 RJGLNSNPZNKTGL-UHFFFAOYSA-N 0.000 claims 1
- BWJORBLWBGOLQL-UHFFFAOYSA-N 2-amino-8-phenyl-9h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound N1C(C2=NC(N)=NC=C2C=C2)=C2C(C(=O)N)=C1C1=CC=CC=C1 BWJORBLWBGOLQL-UHFFFAOYSA-N 0.000 claims 1
- UXWNPSLXAXDXKK-UHFFFAOYSA-N 2-amino-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C1CC2=CN=C(N)N=C2C2=C1C(C(N)=O)=CN2C UXWNPSLXAXDXKK-UHFFFAOYSA-N 0.000 claims 1
- KVWLHWMGSYRLAU-UHFFFAOYSA-N 2-amino-9-methyl-8-phenyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound NC(=O)C=1C=2CCC3=CN=C(N)N=C3C=2N(C)C=1C1=CC=CC=C1 KVWLHWMGSYRLAU-UHFFFAOYSA-N 0.000 claims 1
- OXBHOAOVRFUPJX-UHFFFAOYSA-N 2-amino-9-methyl-8-phenylpyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound NC(=O)C=1C2=CC=C3C=NC(N)=NC3=C2N(C)C=1C1=CC=CC=C1 OXBHOAOVRFUPJX-UHFFFAOYSA-N 0.000 claims 1
- CCYINSRXXFXUST-UHFFFAOYSA-N 2-methyl-6,9-dihydro-5h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(C)=NC=C2CCC2=C1NC=C2C(N)=O CCYINSRXXFXUST-UHFFFAOYSA-N 0.000 claims 1
- YQUFJQISWIFZLH-UHFFFAOYSA-N 2-methylsulfanyl-6,9-dihydro-5h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2CCC2=C1NC=C2C(N)=O YQUFJQISWIFZLH-UHFFFAOYSA-N 0.000 claims 1
- QZODUKPIHBQCBB-UHFFFAOYSA-N 2-methylsulfanyl-9-piperidin-4-yl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C1=2C3=NC(SC)=NC=C3CCC=2C(C(N)=O)=CN1C1CCNCC1 QZODUKPIHBQCBB-UHFFFAOYSA-N 0.000 claims 1
- ZWVHBACWMIHSNL-UHFFFAOYSA-N 2-methylsulfanyl-9-piperidin-4-ylpyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C1=2C3=NC(SC)=NC=C3C=CC=2C(C(N)=O)=CN1C1CCNCC1 ZWVHBACWMIHSNL-UHFFFAOYSA-N 0.000 claims 1
- JCICCACMYITOCI-UHFFFAOYSA-N 2-methylsulfanyl-9-propan-2-yl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2CCC2=C1N(C(C)C)C=C2C(N)=O JCICCACMYITOCI-UHFFFAOYSA-N 0.000 claims 1
- XHEYSFJJPSXTHP-UHFFFAOYSA-N 2-methylsulfanyl-9h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2C=CC2=C1NC=C2C(N)=O XHEYSFJJPSXTHP-UHFFFAOYSA-N 0.000 claims 1
- KGKDUDXNIIDOCV-UHFFFAOYSA-N 8-methyl-2-methylsulfanyl-6,9-dihydro-5h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2CCC2=C1NC(C)=C2C(N)=O KGKDUDXNIIDOCV-UHFFFAOYSA-N 0.000 claims 1
- DGFIPMBMVVDMPR-UHFFFAOYSA-N 8-methyl-2-methylsulfanyl-9-propan-2-yl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2CCC2=C1N(C(C)C)C(C)=C2C(N)=O DGFIPMBMVVDMPR-UHFFFAOYSA-N 0.000 claims 1
- UKHAILBNXALNFF-UHFFFAOYSA-N 8-methyl-2-methylsulfanyl-9h-pyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2C=CC2=C1NC(C)=C2C(N)=O UKHAILBNXALNFF-UHFFFAOYSA-N 0.000 claims 1
- IJFXPCHHRYCYMT-UHFFFAOYSA-N 9-(2-hydroxyethyl)-2-methylsulfanyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2CCC2=C1N(CCO)C=C2C(N)=O IJFXPCHHRYCYMT-UHFFFAOYSA-N 0.000 claims 1
- MNTKEWDJIACGNK-UHFFFAOYSA-N 9-(2-hydroxyethyl)-8-methyl-2-methylsulfanyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2CCC2=C1N(CCO)C(C)=C2C(N)=O MNTKEWDJIACGNK-UHFFFAOYSA-N 0.000 claims 1
- LVYDNZIZBIQXIS-UHFFFAOYSA-N 9-(2-hydroxyethyl)-8-methyl-2-methylsulfanylpyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2C=CC2=C1N(CCO)C(C)=C2C(N)=O LVYDNZIZBIQXIS-UHFFFAOYSA-N 0.000 claims 1
- JYCIIVNGEUKVMV-UHFFFAOYSA-N 9-(3-amino-2,2-dimethylpropyl)-2-methylsulfanylpyrrolo[3,2-h]quinazoline-7-carboxamide;hydrochloride Chemical compound Cl.C12=NC(SC)=NC=C2C=CC2=C1N(CC(C)(C)CN)C=C2C(N)=O JYCIIVNGEUKVMV-UHFFFAOYSA-N 0.000 claims 1
- JYHABUQXZXZOLO-UHFFFAOYSA-N 9-ethyl-2-methylsulfanylpyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C1=NC(SC)=NC2=C3N(CC)C=C(C(N)=O)C3=CC=C21 JYHABUQXZXZOLO-UHFFFAOYSA-N 0.000 claims 1
- UECMCGVVQAQYOJ-UHFFFAOYSA-N 9-methyl-2-methylsulfanylpyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound C12=NC(SC)=NC=C2C=CC2=C1N(C)C=C2C(N)=O UECMCGVVQAQYOJ-UHFFFAOYSA-N 0.000 claims 1
- CXMXBFQRJAIBDD-UHFFFAOYSA-N 9H-cyclohepta[d]pyrimidine-8-carboxamide Chemical compound N1=CN=CC2=C1CC(=CC=C2)C(=O)N CXMXBFQRJAIBDD-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- FRANNCVVJFQWOT-TXEJJXNPSA-N C1=2C3=NC(SC)=NC=C3C=CC=2C(C(N)=O)=CN1[C@@H]1CC[C@H](N)CC1 Chemical compound C1=2C3=NC(SC)=NC=C3C=CC=2C(C(N)=O)=CN1[C@@H]1CC[C@H](N)CC1 FRANNCVVJFQWOT-TXEJJXNPSA-N 0.000 claims 1
- BRAYMNJVFKIQLD-TXEJJXNPSA-N C1=2C3=NC(SC)=NC=C3CCC=2C(C(N)=O)=CN1[C@@H]1CC[C@H](N)CC1 Chemical compound C1=2C3=NC(SC)=NC=C3CCC=2C(C(N)=O)=CN1[C@@H]1CC[C@H](N)CC1 BRAYMNJVFKIQLD-TXEJJXNPSA-N 0.000 claims 1
- VTSDHOBIBSBOEN-UHFFFAOYSA-N Cl.CSC1=NC2=C3C(=CC=C2C=N1)C(=CN3)C(=O)N Chemical compound Cl.CSC1=NC2=C3C(=CC=C2C=N1)C(=CN3)C(=O)N VTSDHOBIBSBOEN-UHFFFAOYSA-N 0.000 claims 1
- 101000678466 Homo sapiens 40S ribosomal protein S27 Proteins 0.000 claims 1
- 101001019502 Homo sapiens Alpha-L-iduronidase Proteins 0.000 claims 1
- 101000659223 Homo sapiens Dual specificity protein kinase TTK Proteins 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 101100297651 Mus musculus Pim2 gene Proteins 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 1
- GFPDONVWLDXBHG-UHFFFAOYSA-N NC1=NC=2C3=C(CCC2C=N1)C(=CN3C)C(=O)NC3=C(C=C(C=C3)N3CCN(CC3)C)OC Chemical compound NC1=NC=2C3=C(CCC2C=N1)C(=CN3C)C(=O)NC3=C(C=C(C=C3)N3CCN(CC3)C)OC GFPDONVWLDXBHG-UHFFFAOYSA-N 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
- 101001001642 Xenopus laevis Serine/threonine-protein kinase pim-3 Proteins 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 238000011319 anticancer therapy Methods 0.000 claims 1
- 238000009104 chemotherapy regimen Methods 0.000 claims 1
- 239000002131 composite material Substances 0.000 claims 1
- 239000000824 cytostatic agent Substances 0.000 claims 1
- 230000001085 cytostatic effect Effects 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000008482 dysregulation Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- ISJSUWAGGVIHDZ-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-8,9-dimethyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=C(C)N(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCN(C)CC2)C=C1OC ISJSUWAGGVIHDZ-UHFFFAOYSA-N 0.000 claims 1
- HRLWNUGLIWNXQQ-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[2-methoxy-4-(4-pyrrolidin-1-ylpiperidin-1-yl)anilino]-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=CN(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCC(CC2)N2CCCC2)C=C1OC HRLWNUGLIWNXQQ-UHFFFAOYSA-N 0.000 claims 1
- ILEDQKOHCPIFFS-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[4-[3-(dimethylamino)propyl-methylamino]-2-methoxyanilino]-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=CN(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N(C)CCCN(C)C)C=C1OC ILEDQKOHCPIFFS-UHFFFAOYSA-N 0.000 claims 1
- YXROSHBBKYVTDI-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[4-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methoxyanilino]-8,9-dimethyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=C(C)N(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCN(CCO)CC2)C=C1OC YXROSHBBKYVTDI-UHFFFAOYSA-N 0.000 claims 1
- LYFDXTJJPSDFMS-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[4-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methoxyanilino]-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=CN(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCN(CCO)CC2)C=C1OC LYFDXTJJPSDFMS-UHFFFAOYSA-N 0.000 claims 1
- SWEYDUSNJPBSGO-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-8,9-dimethyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=C(C)N(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCC(CC2)N(C)C)C=C1OC SWEYDUSNJPBSGO-UHFFFAOYSA-N 0.000 claims 1
- PTUKZCQTLIICLP-UHFFFAOYSA-N n-(2,6-diethylphenyl)-2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-9-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=CN(C)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCC(CC2)N(C)C)C=C1OC PTUKZCQTLIICLP-UHFFFAOYSA-N 0.000 claims 1
- GKHAZTHWYXEFJA-UHFFFAOYSA-N n-(2,6-diethylphenyl)-9-(methoxymethyl)-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-8-methyl-5,6-dihydropyrrolo[3,2-h]quinazoline-7-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)C1=C(C)N(COC)C(C2=N3)=C1CCC2=CN=C3NC1=CC=C(N2CCN(C)CC2)C=C1OC GKHAZTHWYXEFJA-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000004952 protein activity Effects 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- TYHCBIKGTCZFTK-UHFFFAOYSA-N quinazoline-7-carboxamide Chemical compound C1=NC=NC2=CC(C(=O)N)=CC=C21 TYHCBIKGTCZFTK-UHFFFAOYSA-N 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims 1
- 230000005747 tumor angiogenesis Effects 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11152190 | 2011-01-26 | ||
| EP11152190.2 | 2011-01-26 | ||
| PCT/EP2012/050773 WO2012101032A1 (en) | 2011-01-26 | 2012-01-19 | Tricyclic pyrrolo derivatives, process for their preparation and their use as kinase inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015203440A Division JP6118383B2 (ja) | 2011-01-26 | 2015-10-15 | 三環系ピロロ誘導体、その調製方法およびそのキナーゼ阻害剤としての使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014503567A JP2014503567A (ja) | 2014-02-13 |
| JP2014503567A5 true JP2014503567A5 (https=) | 2015-03-05 |
| JP5925809B2 JP5925809B2 (ja) | 2016-05-25 |
Family
ID=45562287
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013550833A Active JP5925809B2 (ja) | 2011-01-26 | 2012-01-19 | 三環系ピロロ誘導体、その調製方法およびそのキナーゼ阻害剤としての使用 |
| JP2015203440A Active JP6118383B2 (ja) | 2011-01-26 | 2015-10-15 | 三環系ピロロ誘導体、その調製方法およびそのキナーゼ阻害剤としての使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015203440A Active JP6118383B2 (ja) | 2011-01-26 | 2015-10-15 | 三環系ピロロ誘導体、その調製方法およびそのキナーゼ阻害剤としての使用 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8975267B2 (https=) |
| EP (1) | EP2668190B1 (https=) |
| JP (2) | JP5925809B2 (https=) |
| CN (1) | CN103339134B (https=) |
| BR (1) | BR112013018515B1 (https=) |
| ES (1) | ES2602791T3 (https=) |
| RU (1) | RU2591191C2 (https=) |
| WO (1) | WO2012101032A1 (https=) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| EP2614065B1 (en) * | 2010-12-17 | 2017-04-19 | Nerviano Medical Sciences S.r.l. | Substituted pyrazolo-quinazoline derivatives as kinase inhibitors |
| ES2602791T3 (es) | 2011-01-26 | 2017-02-22 | Nerviano Medical Sciences S.R.L. | Derivados de pirrolo tricíclicos, proceso para su preparación y su uso como inhibidores de cinasa |
| GB201216017D0 (en) | 2012-09-07 | 2012-10-24 | Cancer Rec Tech Ltd | Inhibitor compounds |
| GB201216018D0 (en) | 2012-09-07 | 2012-10-24 | Cancer Rec Tech Ltd | Pharmacologically active compounds |
| JP6437452B2 (ja) | 2013-01-14 | 2018-12-12 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｐｉｍキナーゼ阻害剤として有用な二環式芳香族カルボキサミド化合物 |
| RS60244B1 (sr) | 2013-01-15 | 2020-06-30 | Incyte Holdings Corp | Jedinjenja tiazolkarboksamida i piridinkarboksamida korisna kao inhibitori pim kinaze |
| CN105658653A (zh) | 2013-08-23 | 2016-06-08 | 因赛特公司 | 可用作pim激酶抑制剂的呋喃并-和噻吩并-吡啶甲酰胺化合物 |
| GB201403536D0 (en) | 2014-02-28 | 2014-04-16 | Cancer Rec Tech Ltd | Inhibitor compounds |
| KR102359214B1 (ko) | 2014-04-04 | 2022-02-07 | 델 마 파마슈티컬스 | 폐의 비소세포 암종 및 난소암을 치료하기 위한 디안하이드로갈락티톨 및 이의 유사체 또는 유도체 |
| US9856258B2 (en) | 2014-04-07 | 2018-01-02 | Netherlands Translational Research Center B.V. | (5,6-dihydro)pyrimido[4,5-E]indolizines |
| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| FI3283642T3 (fi) | 2015-04-17 | 2024-01-11 | Crossfire Oncology Holding B V | Prognostisia biomarkkereita ttk-inhibiittorikemoterapiaan |
| ITRM20150212A1 (it) * | 2015-05-15 | 2016-11-15 | Univ Degli Studi Di Palermo | 4,5,6,9-tetraidropirrolo[2',3':3,4] cicloepta[1,2-d] isossazoli, procedimento per la loro produzione e loro uso come antitumorali |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| BR112018000808A2 (pt) | 2015-07-16 | 2018-09-04 | Array Biopharma Inc | compostos de pirazolo[1,5-a]piridina substituída como inibidores de ret cinase |
| CN105130980B (zh) * | 2015-09-09 | 2018-05-22 | 沈阳药科大学 | N-3-苯并咪唑噻唑胺类衍生物及其制备方法与应用 |
| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| US9920032B2 (en) | 2015-10-02 | 2018-03-20 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| CN108697708A (zh) | 2015-10-26 | 2018-10-23 | 洛克索肿瘤学股份有限公司 | Trk抑制剂抗性癌症中的点突变以及与此相关的方法 |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| ES2987474T3 (es) | 2016-04-04 | 2024-11-15 | Loxo Oncology Inc | Formulaciones líquidas de (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-IL)-pirazolo[1,5-A]pirimidin-3-IL)-3-hidroxipirrolidina-1-carboxamida |
| RS65988B1 (sr) | 2016-04-04 | 2024-10-31 | Loxo Oncology Inc | Postupak lečenja pedijatrijskih karcinoma |
| ES2836222T3 (es) | 2016-05-18 | 2021-06-24 | Loxo Oncology Inc | Preparación de (S)-N-(5-((R)-2-(2,5-difluorofenil)pirrolidin-1-il)pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| TWI752098B (zh) | 2016-10-10 | 2022-01-11 | 美商亞雷生物製藥股份有限公司 | 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| US11168090B2 (en) | 2017-01-18 | 2021-11-09 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyrazines as RET kinase inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| JP7175026B2 (ja) * | 2017-04-01 | 2022-11-18 | 晟科薬業（江蘇）有限公司 | プロテインキナーゼ阻害剤としての１ｈ－イミダゾ［４，５－ｈ］キナゾリン系化合物 |
| GB201709840D0 (en) | 2017-06-20 | 2017-08-02 | Inst Of Cancer Research: Royal Cancer Hospital | Methods and medical uses |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| CN111615514B (zh) | 2018-01-18 | 2022-10-11 | 奥瑞生物药品公司 | 作为ret激酶抑制剂的取代的吡唑并[4,3-c]吡啶化合物 |
| WO2019143991A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | SUBSTITUTED PYRAZOLO[3,4-d]PYRIMIDINE COMPOUNDS AS RET KINASE INHIBITORS |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| US12109193B2 (en) | 2018-07-31 | 2024-10-08 | Loxo Oncology Inc. | Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide |
| EP3849986B1 (en) | 2018-09-10 | 2022-06-08 | Array Biopharma, Inc. | Fused heterocyclic compounds as ret kinase inhibitors |
| EP3898615A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| WO2020131627A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
| KR102866207B1 (ko) * | 2019-08-02 | 2025-09-29 | 청두 사이노젠 바이오-파마슈티컬 테크놀로지 코., 엘티디. | 단백질 키나제 억제제로 작용하는 1h-[1, 2, 3]트리아졸로[4, 5-h] 퀴나졸린 화합물 |
| EP4069369A4 (en) | 2019-12-06 | 2024-02-14 | Schrödinger, Inc. | CYCLIC COMPOUNDS AND METHODS OF USE |
| IL294214B2 (en) | 2019-12-27 | 2026-04-01 | Schrodinger Inc | Cyclic compounds and methods for using them |
| JP2023541047A (ja) | 2020-09-10 | 2023-09-27 | シュレーディンガー， インコーポレイテッド | がんの治療のための複素環式ペリ縮環ｃｄｃ７キナーゼ阻害剤 |
| CN114685520B (zh) * | 2020-12-25 | 2024-08-30 | 武汉誉祥医药科技有限公司 | 三并环化合物及其药物组合物和应用 |
| EP4284804A1 (en) | 2021-01-26 | 2023-12-06 | Schrödinger, Inc. | Tricyclic compounds useful in the treatment of cancer, autoimmune and inflammatory disorders |
| TW202300150A (zh) | 2021-03-18 | 2023-01-01 | 美商薛定諤公司 | 環狀化合物及其使用方法 |
| AU2022408915A1 (en) * | 2021-12-15 | 2024-06-27 | Sillajen, Inc. | Methods of treating neoplastic diseases |
| MX2024007452A (es) * | 2021-12-15 | 2024-07-09 | Sillajen Inc | Composiciones farmaceuticas que comprenden beta-ciclodextrinas modificadas. |
| WO2025059027A1 (en) | 2023-09-11 | 2025-03-20 | Schrödinger, Inc. | Cyclopenta[e]pyrazolo[1,5-a]pyrimidine derivatives as malt1 inhibitors |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL115833A (en) | 1994-11-25 | 1998-10-27 | Zeneca Ltd | 6,6-Dihalo-3,3-dimethyl-5-hydroxy-7,7,7-trifluoroheptanoic acids and their alkyl esters useful as intermediates for insecticides and their preparation |
| MY125533A (en) * | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| BR0307796A (pt) | 2002-02-19 | 2004-12-21 | Pharmacia Corp | Derivados tricìclicos de pirazol para o tratamento de inflamação |
| PT1636236E (pt) * | 2003-05-22 | 2013-12-16 | Nerviano Medical Sciences Srl | Derivados de pirazol-quinazolina, processo para sua preparação e sua utilização como inibidores de cinase |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| EP2118102B1 (en) * | 2006-11-28 | 2013-06-12 | Nerviano Medical Sciences S.r.l. | Tricyclic indoles and (4,5-dihydro) indoles |
| ES2383084T3 (es) | 2006-12-04 | 2012-06-18 | Jiangsu Simcere Pharmaceutical R&D Co., Ltd. | Derivados de 3-pirrolo[b]ciclohexilen-2-dihidroindolinona y usos de los mismos |
| PT2125822E (pt) * | 2006-12-21 | 2015-01-30 | Nerviano Medical Sciences Srl | Derivados de pirazol-quinazolina substituídos, processo para sua preparação e seu uso como inibidores da quinase |
| CN101687869A (zh) * | 2007-07-16 | 2010-03-31 | 诺瓦提斯公司 | 作为mk2抑制剂的四环内酰胺衍生物 |
| EP2240029A4 (en) | 2008-01-07 | 2012-08-22 | Synta Pharmaceuticals Corp | COMPOUNDS FOR USE AGAINST INFLAMMATORY AND IMMUNOMIC DISEASES |
| US8546410B2 (en) * | 2008-05-05 | 2013-10-01 | Abbvie Inc. | Heteroaryl-fused macrocyclic pyrimidine derivatives |
| MX2010013843A (es) * | 2008-06-26 | 2011-01-21 | Nerviano Medical Sciences Srl | Pirazolo-quinazolinas. |
| US8946226B2 (en) * | 2008-07-29 | 2015-02-03 | Nerviano Medical Sciences S.R.L. | Use of CDK inhibitor for the treatment of glioma |
| EP2320903B1 (en) * | 2008-07-29 | 2017-01-18 | Nerviano Medical Sciences S.r.l. | THERAPEUTIC COMBINATION COMPRISING A CDKs INHIBITOR AND AN ANTINEOPLASTIC AGENT |
| JP2012509859A (ja) * | 2008-11-24 | 2012-04-26 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 中皮腫の治療のためのｃｄｋ阻害物質 |
| JP5650193B2 (ja) * | 2009-03-20 | 2015-01-07 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 胸腺腫の治療のためのキナーゼ阻害剤の使用 |
| EP2424868B1 (en) * | 2009-04-29 | 2018-01-10 | Nerviano Medical Sciences S.r.l. | Cdk inhibitor salts |
| AR076784A1 (es) * | 2009-05-26 | 2011-07-06 | Nerviano Medical Sciences Srl | Combinacion terapeutica que comprende un inhibidor de plk1 y un agente antineoplasico |
| JP5851990B2 (ja) * | 2009-07-29 | 2016-02-03 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | Ｐｌｋ阻害剤の塩 |
| EP2598508B1 (en) * | 2010-07-30 | 2015-04-22 | Nerviano Medical Sciences S.r.l. | Isoxazolo-quinazolines as modulators of protein kinase activity |
| EP2614065B1 (en) * | 2010-12-17 | 2017-04-19 | Nerviano Medical Sciences S.r.l. | Substituted pyrazolo-quinazoline derivatives as kinase inhibitors |
| ES2602791T3 (es) | 2011-01-26 | 2017-02-22 | Nerviano Medical Sciences S.R.L. | Derivados de pirrolo tricíclicos, proceso para su preparación y su uso como inhibidores de cinasa |
-
2012
- 2012-01-19 ES ES12702207.7T patent/ES2602791T3/es active Active
- 2012-01-19 CN CN201280006541.4A patent/CN103339134B/zh active Active
- 2012-01-19 EP EP12702207.7A patent/EP2668190B1/en active Active
- 2012-01-19 BR BR112013018515-5A patent/BR112013018515B1/pt active IP Right Grant
- 2012-01-19 WO PCT/EP2012/050773 patent/WO2012101032A1/en not_active Ceased
- 2012-01-19 US US13/980,168 patent/US8975267B2/en active Active
- 2012-01-19 JP JP2013550833A patent/JP5925809B2/ja active Active
- 2012-01-19 RU RU2013139353/04A patent/RU2591191C2/ru active
-
2015
- 2015-01-30 US US14/609,534 patent/US9309253B2/en active Active
- 2015-10-15 JP JP2015203440A patent/JP6118383B2/ja active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2014503567A5 (https=) | ||
| JP2016053042A5 (https=) | ||
| JP7380507B2 (ja) | Ｓｔｉｎｇ作動化合物 | |
| US11578054B2 (en) | Compounds useful as immunomodulators | |
| AU2018360854B2 (en) | Modulators of the integrated stress pathway | |
| RU2013139353A (ru) | Трициклические пирролопроизводные, способ их получения и их применение в качестве ингибиторов киназы | |
| JP6898868B2 (ja) | Ｈｐｋ１阻害剤およびそれを用いる方法 | |
| JP5886411B2 (ja) | 新規のピリミジン誘導体 | |
| US20240173307A1 (en) | Modulators of the integrated stress pathway | |
| JP2021512150A5 (https=) | ||
| KR20190041471A (ko) | 케모카인 수용체 조절제 및 이의 용도 | |
| KR20180017013A (ko) | K-Ras 조절제 | |
| RU2015118647A (ru) | Аминопиримидиновые соединения в качестве ингибиторов содержащих т790м мутантных egfr | |
| US12090149B2 (en) | SMAD3 inhibitors | |
| JP2016501251A (ja) | がんの治療のための新規二環フェニル−ピリジン／ピラジン | |
| CN106458930A (zh) | 2‑氨基嘧啶类化合物及其药物组合物和应用 | |
| RU2012130929A (ru) | Гетероциклические соединения в качестве ингибиторов янус-киназы | |
| WO2020010003A1 (en) | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS | |
| KR20220028075A (ko) | 티로신 키나제 비-수용체 1 (tnk1) 억제제 및 그의 용도 | |
| CN116635390A (zh) | 作为血清素1b受体调节剂的强效和选择性化合物 | |
| US10730878B2 (en) | Fused quinoline compounds as PI3K/mTOR inhibitors | |
| CN103002899A (zh) | 作为pi3k抑制剂用于治疗抗增殖障碍的哌嗪子基三嗪化合物 | |
| JP2016513726A (ja) | がん細胞成長阻害剤としてのテトラヒドロイソキノリン−２−イル−（キナゾリン−４−イル）メタノン化合物 | |
| KR102939670B1 (ko) | Pdl1 체크포인트 억제제로서의 헤테로고리 면역조절제 | |
| CN121399105A (zh) | 杂芳族dhodh抑制剂 |