JP7101165B2 - 特定の化学的実体、組成物、および方法 - Google Patents
特定の化学的実体、組成物、および方法 Download PDFInfo
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- JP7101165B2 JP7101165B2 JP2019508173A JP2019508173A JP7101165B2 JP 7101165 B2 JP7101165 B2 JP 7101165B2 JP 2019508173 A JP2019508173 A JP 2019508173A JP 2019508173 A JP2019508173 A JP 2019508173A JP 7101165 B2 JP7101165 B2 JP 7101165B2
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- JP
- Japan
- Prior art keywords
- quinazoline
- phenyl
- acrylamide
- pyridin
- benzamide
- 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.)
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- 239000000203 mixture Substances 0.000 title claims description 80
- 238000000034 method Methods 0.000 title claims description 42
- 150000005829 chemical entities Chemical class 0.000 title description 37
- -1 nitro, carboxy Chemical group 0.000 claims description 950
- 150000001875 compounds Chemical class 0.000 claims description 208
- 229910052739 hydrogen Inorganic materials 0.000 claims description 141
- 239000001257 hydrogen Substances 0.000 claims description 133
- 125000001072 heteroaryl group Chemical group 0.000 claims description 124
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 122
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 119
- 150000002431 hydrogen Chemical group 0.000 claims description 90
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 83
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 65
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 64
- 206010028980 Neoplasm Diseases 0.000 claims description 56
- 125000003107 substituted aryl group Chemical group 0.000 claims description 55
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 125000004043 oxo group Chemical group O=* 0.000 claims description 40
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 39
- 125000002252 acyl group Chemical group 0.000 claims description 37
- 102200048928 rs121434568 Human genes 0.000 claims description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 102200048955 rs121434569 Human genes 0.000 claims description 35
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 35
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 34
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 34
- 201000011510 cancer Diseases 0.000 claims description 33
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 claims description 33
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 31
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 29
- 125000004104 aryloxy group Chemical group 0.000 claims description 28
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 24
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 20
- UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical group ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 claims description 19
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 18
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 230000035772 mutation Effects 0.000 claims description 11
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 8
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 8
- 201000002510 thyroid cancer Diseases 0.000 claims description 8
- 206010009944 Colon cancer Diseases 0.000 claims description 7
- 206010033128 Ovarian cancer Diseases 0.000 claims description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
- 208000029742 colonic neoplasm Diseases 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000012472 biological sample Substances 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 102200048796 rs28929495 Human genes 0.000 claims description 4
- 102200048979 rs28929495 Human genes 0.000 claims description 4
- 102200048929 rs121913444 Human genes 0.000 claims description 3
- XNZGQNPRCCMRNI-UHFFFAOYSA-N 1-[3-[2-amino-6-(2-fluoro-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=C(C=C(C=C1)OC1=NC=CC=C1)F)C1CN(CC1)C(C=C)=O XNZGQNPRCCMRNI-UHFFFAOYSA-N 0.000 claims description 2
- KDOIKONQYLKWKJ-UHFFFAOYSA-N 1-[3-[2-amino-6-(2-methoxy-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=C(C=C(C=C1)OC1=NC=CC=C1)OC)C1CN(CC1)C(C=C)=O KDOIKONQYLKWKJ-UHFFFAOYSA-N 0.000 claims description 2
- YTHKZJKFFRYRPD-UHFFFAOYSA-N 1-[3-[2-amino-6-[4-(4-cyclopropylpyridin-2-yl)oxyphenyl]quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=CC=C(C=C1)OC1=NC=CC(=C1)C1CC1)C1CN(CC1)C(C=C)=O YTHKZJKFFRYRPD-UHFFFAOYSA-N 0.000 claims description 2
- YWAIUVIGWDUVJA-UHFFFAOYSA-N 1-[3-[6-(2-fluoro-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound FC1=C(C=CC(=C1)OC1=NC=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O YWAIUVIGWDUVJA-UHFFFAOYSA-N 0.000 claims description 2
- LVVGQWUCDMZJJZ-UHFFFAOYSA-N 1-[3-[6-(2-methoxy-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound COC1=C(C=CC(=C1)OC1=NC=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O LVVGQWUCDMZJJZ-UHFFFAOYSA-N 0.000 claims description 2
- DJWJGVMGQUPQEK-UHFFFAOYSA-N 1-[3-[6-(3-methoxy-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound COC=1C=C(C=CC=1OC1=NC=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O DJWJGVMGQUPQEK-UHFFFAOYSA-N 0.000 claims description 2
- SDGGVEXZBCHGPT-UHFFFAOYSA-N 1-[3-[6-(4-pyridin-2-yloxyphenyl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound N1=C(C=CC=C1)OC1=CC=C(C=C1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O SDGGVEXZBCHGPT-UHFFFAOYSA-N 0.000 claims description 2
- JKYWWHVASMBZPA-UHFFFAOYSA-N 1-[3-[6-(5-cyclopropylpyridin-3-yl)quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound C1(CC1)C=1C=C(C=NC=1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O JKYWWHVASMBZPA-UHFFFAOYSA-N 0.000 claims description 2
- UAZUPEYDPJZYKG-UHFFFAOYSA-N 1-[3-[6-[2-fluoro-4-(3-fluoropyridin-2-yl)oxyphenyl]quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound FC1=C(C=CC(=C1)OC1=NC=CC=C1F)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O UAZUPEYDPJZYKG-UHFFFAOYSA-N 0.000 claims description 2
- LLKLYSAGRVDQNY-UHFFFAOYSA-N 1-[3-[6-[3-(3-cyclopropylanilino)phenyl]quinazolin-8-yl]piperidin-1-yl]prop-2-en-1-one Chemical compound C1(CC1)C=1C=C(C=CC=1)NC=1C=C(C=CC=1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CCC1)C(C=C)=O LLKLYSAGRVDQNY-UHFFFAOYSA-N 0.000 claims description 2
- XPWCJKLQDCYRRM-UHFFFAOYSA-N 1-[3-[6-[4-(4-cyclopropylpyridin-2-yl)oxy-2-fluorophenyl]quinazolin-8-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound C1(CC1)C1=CC(=NC=C1)OC1=CC(=C(C=C1)C=1C=C2C=NC=NC2=C(C=1)C1CN(CC1)C(C=C)=O)F XPWCJKLQDCYRRM-UHFFFAOYSA-N 0.000 claims description 2
- DZZFDZUOZJBHFI-UHFFFAOYSA-N 2-[3-fluoro-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]phenoxy]pyridine-4-carbonitrile Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=C(C=C(OC=2C=C(C#N)C=CN=2)C=C1)F DZZFDZUOZJBHFI-UHFFFAOYSA-N 0.000 claims description 2
- RVXLXDZMUSIRRY-UHFFFAOYSA-N 2-[4-[2-amino-8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]phenoxy]pyridine-4-carbonitrile Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC(=NC=12)N)C1=CC=C(OC=2C=C(C#N)C=CN=2)C=C1 RVXLXDZMUSIRRY-UHFFFAOYSA-N 0.000 claims description 2
- NDHNIFVAKQQGCQ-UHFFFAOYSA-N 3-[3-[8-(1-prop-2-enoylpiperidin-3-yl)quinazolin-6-yl]anilino]benzonitrile Chemical compound C(C=C)(=O)N1CC(CCC1)C=1C=C(C=C2C=NC=NC=12)C=1C=C(C=CC=1)NC=1C=C(C#N)C=CC=1 NDHNIFVAKQQGCQ-UHFFFAOYSA-N 0.000 claims description 2
- YRDXJCQMKODHPC-UHFFFAOYSA-N 3-[5-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]pyridin-2-yl]oxybenzonitrile Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C=1C=CC(=NC=1)OC=1C=C(C#N)C=CC=1 YRDXJCQMKODHPC-UHFFFAOYSA-N 0.000 claims description 2
- VZWRASJMLKPNKJ-UHFFFAOYSA-N 5-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]pyridine-3-carbonitrile Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C=1C=NC=C(C#N)C=1 VZWRASJMLKPNKJ-UHFFFAOYSA-N 0.000 claims description 2
- MHGZPOILOSWDNS-UHFFFAOYSA-N N-(4-cyanopyridin-2-yl)-2-fluoro-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=CC(=C(C(=O)NC2=NC=CC(=C2)C#N)C=C1)F MHGZPOILOSWDNS-UHFFFAOYSA-N 0.000 claims description 2
- LMFBXJXEUKKTSA-UHFFFAOYSA-N N-(4-cyanopyridin-2-yl)-2-methoxy-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=CC(=C(C(=O)NC2=NC=CC(=C2)C#N)C=C1)OC LMFBXJXEUKKTSA-UHFFFAOYSA-N 0.000 claims description 2
- NVDXYGLCAICPCU-UHFFFAOYSA-N N-(4-cyanopyridin-2-yl)-3-fluoro-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=C(C=C(C(=O)NC2=NC=CC(=C2)C#N)C=C1)F NVDXYGLCAICPCU-UHFFFAOYSA-N 0.000 claims description 2
- TWTORNQZBLWXFT-UHFFFAOYSA-N N-(4-cyanopyridin-2-yl)-3-methoxy-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=C(C=C(C(=O)NC2=NC=CC(=C2)C#N)C=C1)OC TWTORNQZBLWXFT-UHFFFAOYSA-N 0.000 claims description 2
- YDFRMYULKBTIML-UHFFFAOYSA-N N-(4-cyclopropylpyridin-2-yl)-2-fluoro-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=CC(=C(C(=O)NC2=NC=CC(=C2)C2CC2)C=C1)F YDFRMYULKBTIML-UHFFFAOYSA-N 0.000 claims description 2
- CPKZGGJVZCXTEB-UHFFFAOYSA-N N-(4-cyclopropylpyridin-2-yl)-2-methoxy-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=CC(=C(C(=O)NC2=NC=CC(=C2)C2CC2)C=C1)OC CPKZGGJVZCXTEB-UHFFFAOYSA-N 0.000 claims description 2
- GKPGXEOYTWDWRW-UHFFFAOYSA-N N-(4-cyclopropylpyridin-2-yl)-3-fluoro-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=C(C=C(C(=O)NC2=NC=CC(=C2)C2CC2)C=C1)F GKPGXEOYTWDWRW-UHFFFAOYSA-N 0.000 claims description 2
- PHLMIWREANFZGR-UHFFFAOYSA-N N-(4-cyclopropylpyridin-2-yl)-3-methoxy-4-[8-(1-prop-2-enoylpyrrolidin-3-yl)quinazolin-6-yl]benzamide Chemical compound C(C=C)(=O)N1CC(CC1)C=1C=C(C=C2C=NC=NC=12)C1=C(C=C(C(=O)NC2=NC=CC(=C2)C2CC2)C=C1)OC PHLMIWREANFZGR-UHFFFAOYSA-N 0.000 claims description 2
- ZSLPGTSEWBCFPS-UHFFFAOYSA-N N-[3-(2,6-diphenylquinazolin-8-yl)phenyl]prop-2-enamide Chemical compound C1(=CC=CC=C1)C1=NC2=C(C=C(C=C2C=N1)C1=CC=CC=C1)C=1C=C(C=CC=1)NC(C=C)=O ZSLPGTSEWBCFPS-UHFFFAOYSA-N 0.000 claims description 2
- YGPABYQIECHROT-UHFFFAOYSA-N N-[3-(6-pyridin-2-ylquinazolin-8-yl)phenyl]prop-2-enamide Chemical compound N1=C(C=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O YGPABYQIECHROT-UHFFFAOYSA-N 0.000 claims description 2
- GELOZYOGIRXTBY-UHFFFAOYSA-N N-[3-[2-amino-6-(2-fluoro-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=C(C=C(C=C1)OC1=NC=CC=C1)F)C=1C=C(C=CC=1)NC(C=C)=O GELOZYOGIRXTBY-UHFFFAOYSA-N 0.000 claims description 2
- QMBDURQRANLPOF-UHFFFAOYSA-N N-[3-[2-amino-6-(2-methoxy-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=C(C=C(C=C1)OC1=NC=CC=C1)OC)C=1C=C(C=CC=1)NC(C=C)=O QMBDURQRANLPOF-UHFFFAOYSA-N 0.000 claims description 2
- ITDXMYADOCRWRB-UHFFFAOYSA-N N-[3-[2-amino-6-(3-fluoro-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=CC(=C(C=C1)OC1=NC=CC=C1)F)C=1C=C(C=CC=1)NC(C=C)=O ITDXMYADOCRWRB-UHFFFAOYSA-N 0.000 claims description 2
- FVTXZHAHLYZKFK-UHFFFAOYSA-N N-[3-[2-amino-6-(5-fluoropyridin-3-yl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C=1C=NC=C(C=1)F)C=1C=C(C=CC=1)NC(C=C)=O FVTXZHAHLYZKFK-UHFFFAOYSA-N 0.000 claims description 2
- PJXLRBDFTIZNJC-UHFFFAOYSA-N N-[3-[2-amino-6-(5-methoxypyridin-3-yl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C=1C=NC=C(C=1)OC)C=1C=C(C=CC=1)NC(C=C)=O PJXLRBDFTIZNJC-UHFFFAOYSA-N 0.000 claims description 2
- JPFCTSWIDVMACO-UHFFFAOYSA-N N-[3-[2-amino-6-[4-(4-cyanopyridin-2-yl)oxyphenyl]quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=CC=C(C=C1)OC1=NC=CC(=C1)C#N)C=1C=C(C=CC=1)NC(C=C)=O JPFCTSWIDVMACO-UHFFFAOYSA-N 0.000 claims description 2
- PLJURPWJKLDCOF-UHFFFAOYSA-N N-[3-[2-amino-6-[4-(4-cyclopropylpyridin-2-yl)oxyphenyl]quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound NC1=NC2=C(C=C(C=C2C=N1)C1=CC=C(C=C1)OC1=NC=CC(=C1)C1CC1)C=1C=C(C=CC=1)NC(C=C)=O PLJURPWJKLDCOF-UHFFFAOYSA-N 0.000 claims description 2
- HBNDQDSPRUMKID-UHFFFAOYSA-N N-[3-[6-(2-chlorophenyl)-2-phenylquinazolin-8-yl]phenyl]prop-2-enamide Chemical compound ClC1=C(C=CC=C1)C=1C=C2C=NC(=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O)C1=CC=CC=C1 HBNDQDSPRUMKID-UHFFFAOYSA-N 0.000 claims description 2
- KQCLOTFDUJSFPF-UHFFFAOYSA-N N-[3-[6-(2-cyanopyridin-4-yl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound C(#N)C1=NC=CC(=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O KQCLOTFDUJSFPF-UHFFFAOYSA-N 0.000 claims description 2
- BQYNEICTDIJRKB-UHFFFAOYSA-N N-[3-[6-(2-cyclopropylpyridin-4-yl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound C1(CC1)C1=NC=CC(=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O BQYNEICTDIJRKB-UHFFFAOYSA-N 0.000 claims description 2
- RDHHNNSMLWSPLA-UHFFFAOYSA-N N-[3-[6-(2-fluoro-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound FC1=C(C=CC(=C1)OC1=NC=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O RDHHNNSMLWSPLA-UHFFFAOYSA-N 0.000 claims description 2
- JTGFFBSVAASDRL-UHFFFAOYSA-N N-[3-[6-(2-methoxy-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound COC1=C(C=CC(=C1)OC1=NC=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O JTGFFBSVAASDRL-UHFFFAOYSA-N 0.000 claims description 2
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- KSUVZFMEVFWJSA-UHFFFAOYSA-N N-[3-[6-(3-methoxy-4-pyridin-2-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound COC=1C=C(C=CC=1OC1=NC=CC=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O KSUVZFMEVFWJSA-UHFFFAOYSA-N 0.000 claims description 2
- GSFXLSBIPKBPBJ-UHFFFAOYSA-N N-[3-[6-(4-pyridin-3-yloxyphenyl)quinazolin-8-yl]phenyl]prop-2-enamide Chemical compound N1=CC(=CC=C1)OC1=CC=C(C=C1)C=1C=C2C=NC=NC2=C(C=1)C=1C=C(C=CC=1)NC(C=C)=O GSFXLSBIPKBPBJ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pyridine Compounds (AREA)
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| US10947201B2 (en) | 2015-02-17 | 2021-03-16 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| EP4006035B1 (en) | 2016-08-15 | 2023-11-22 | Neupharma, Inc. | Quinazoline derivatives as tyrosine kinase inhibitors for the treatment of cancer |
| CN110386921A (zh) * | 2018-04-23 | 2019-10-29 | 南京药捷安康生物科技有限公司 | 成纤维细胞生长因子受体抑制剂化合物 |
| WO2020097398A1 (en) | 2018-11-07 | 2020-05-14 | Dana-Farber Cancer Institute, Inc. | Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof |
| CN111574521A (zh) * | 2019-02-18 | 2020-08-25 | 深圳市塔吉瑞生物医药有限公司 | 取代的芳香稠合环衍生物及其组合物及用途 |
| MA56022A (fr) * | 2019-05-31 | 2022-04-06 | Chiesi Farm Spa | Dérivés d'amino quinazoline servant d'inhibiteurs de p2x3 |
| CN110724143B (zh) * | 2019-10-09 | 2021-03-23 | 清华大学 | 一种靶向btk蛋白降解化合物的制备及其在治疗自身免疫系统疾病与肿瘤中的应用 |
| GB201915831D0 (en) * | 2019-10-31 | 2019-12-18 | Cancer Research Tech Ltd | Compounds, compositions and therapeutic uses thereof |
| WO2021102361A1 (en) * | 2019-11-22 | 2021-05-27 | The Regents Of The University Of California | Caspase 6 inhibitors and uses thereof |
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| AU2017312561A1 (en) | 2019-03-07 |
| JP2022058912A (ja) | 2022-04-12 |
| CN109843858A (zh) | 2019-06-04 |
| EP3497087B1 (en) | 2021-11-10 |
| US12018002B2 (en) | 2024-06-25 |
| WO2018035061A1 (en) | 2018-02-22 |
| JP2019526550A (ja) | 2019-09-19 |
| US20200172495A1 (en) | 2020-06-04 |
| EP4006035A1 (en) | 2022-06-01 |
| EP3497087A4 (en) | 2020-07-29 |
| EP4006035B1 (en) | 2023-11-22 |
| US20180072688A1 (en) | 2018-03-15 |
| CN109843858B (zh) | 2023-05-05 |
| US11208388B2 (en) | 2021-12-28 |
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