CN115697996A - 烯基嘧啶类化合物、其制备方法与应用 - Google Patents
烯基嘧啶类化合物、其制备方法与应用 Download PDFInfo
- Publication number
- CN115697996A CN115697996A CN202180041038.1A CN202180041038A CN115697996A CN 115697996 A CN115697996 A CN 115697996A CN 202180041038 A CN202180041038 A CN 202180041038A CN 115697996 A CN115697996 A CN 115697996A
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- CN
- China
- Prior art keywords
- piperidinyl
- methyl
- pyrazolyl
- formyl
- ethyl
- 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.)
- Pending
Links
- -1 Alkenyl pyrimidine compound Chemical class 0.000 title claims abstract description 3930
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000012453 solvate Substances 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 5
- 230000001404 mediated effect Effects 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 939
- 125000003386 piperidinyl group Chemical group 0.000 claims description 521
- 229910052739 hydrogen Inorganic materials 0.000 claims description 472
- 239000001257 hydrogen Substances 0.000 claims description 472
- 150000002431 hydrogen Chemical class 0.000 claims description 268
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 213
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 212
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 claims description 151
- 125000001424 substituent group Chemical group 0.000 claims description 125
- 125000004193 piperazinyl group Chemical group 0.000 claims description 98
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 92
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 91
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 83
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 68
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 67
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 55
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 48
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 48
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 48
- 239000011737 fluorine Substances 0.000 claims description 48
- 229910052731 fluorine Inorganic materials 0.000 claims description 48
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 44
- 239000000460 chlorine Substances 0.000 claims description 44
- 229910052801 chlorine Inorganic materials 0.000 claims description 44
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 41
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 41
- 229910052794 bromium Inorganic materials 0.000 claims description 41
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 40
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 40
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 36
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims description 36
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 29
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 230000035772 mutation Effects 0.000 claims description 25
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 24
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- 125000002883 imidazolyl group Chemical group 0.000 claims description 24
- 125000006262 isopropyl amino sulfonyl group Chemical group 0.000 claims description 24
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 24
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 23
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims description 22
- 125000003777 thiepinyl group Chemical group 0.000 claims description 21
- 125000005348 fluorocycloalkyl group Chemical group 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 19
- 229940002612 prodrug Drugs 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 11
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 9
- OZEVNJINVVOGGU-UHFFFAOYSA-N CCCNS(=O)=O Chemical group CCCNS(=O)=O OZEVNJINVVOGGU-UHFFFAOYSA-N 0.000 claims description 8
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- CWJSHJJYOPWUGX-UHFFFAOYSA-N chlorpropham Chemical compound CC(C)OC(=O)NC1=CC=CC(Cl)=C1 CWJSHJJYOPWUGX-UHFFFAOYSA-N 0.000 claims description 8
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 6
- VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical compound CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical compound CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000006257 n-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])OC(*)=O 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 11
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 9
- 201000005202 lung cancer Diseases 0.000 claims 9
- 208000020816 lung neoplasm Diseases 0.000 claims 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 230000002378 acidificating effect Effects 0.000 claims 3
- 229910052751 metal Inorganic materials 0.000 claims 3
- 239000002184 metal Substances 0.000 claims 3
- 229910052763 palladium Inorganic materials 0.000 claims 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 238000005859 coupling reaction Methods 0.000 claims 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 1
- 229910000024 caesium carbonate Inorganic materials 0.000 claims 1
- 229960005395 cetuximab Drugs 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 claims 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims 1
- 229910000105 potassium hydride Inorganic materials 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- 239000012312 sodium hydride Substances 0.000 claims 1
- 229910000104 sodium hydride Inorganic materials 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 102000001301 EGF receptor Human genes 0.000 abstract description 18
- 108060006698 EGF receptor Proteins 0.000 abstract description 18
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 102000020233 phosphotransferase Human genes 0.000 abstract description 2
- 150000001721 carbon Chemical group 0.000 description 14
- 230000000694 effects Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 229940121647 egfr inhibitor Drugs 0.000 description 2
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960003278 osimertinib Drugs 0.000 description 1
- DUYJMQONPNNFPI-UHFFFAOYSA-N osimertinib Chemical compound COC1=CC(N(C)CCN(C)C)=C(NC(=O)C=C)C=C1NC1=NC=CC(C=2C3=CC=CC=C3N(C)C=2)=N1 DUYJMQONPNNFPI-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- 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
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Abstract
Description
Claims (11)
- PCT国内申请,权利要求书已公开。
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CN202010510345 | 2020-06-08 | ||
CN2020105103457 | 2020-06-08 | ||
CN2021105907886 | 2021-05-28 | ||
CN202110590788 | 2021-05-28 | ||
PCT/CN2021/098539 WO2021249324A1 (zh) | 2020-06-08 | 2021-06-07 | 烯基嘧啶类化合物、其制备方法与应用 |
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CL (1) | CL2022003477A1 (zh) |
IL (1) | IL298864A (zh) |
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WO2022100688A1 (zh) * | 2020-11-13 | 2022-05-19 | 南京红云生物科技有限公司 | Hpk1激酶调节剂、其制备方法与应用 |
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GB0321710D0 (en) * | 2003-09-16 | 2003-10-15 | Novartis Ag | Organic compounds |
CN110944989B (zh) * | 2017-07-19 | 2021-06-25 | 正大天晴药业集团股份有限公司 | 作为egfr激酶抑制剂的芳基磷氧化合物 |
CN109575045B (zh) * | 2017-09-28 | 2021-02-12 | 南京红云生物科技有限公司 | 噻吩并嘧啶类化合物、其制备方法、药用组合物及其应用 |
WO2020216371A1 (zh) * | 2019-04-26 | 2020-10-29 | 江苏先声药业有限公司 | Egfr抑制剂及其应用 |
CN112538072B (zh) * | 2019-09-21 | 2024-02-06 | 齐鲁制药有限公司 | 氨基嘧啶类egfr抑制剂 |
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2021
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BR112022024937A2 (pt) | 2022-12-27 |
US20230212147A1 (en) | 2023-07-06 |
AU2021288300A1 (en) | 2023-02-02 |
CL2022003477A1 (es) | 2023-08-25 |
MX2022015659A (es) | 2023-02-27 |
EP4166553A1 (en) | 2023-04-19 |
KR20230022976A (ko) | 2023-02-16 |
TW202214590A (zh) | 2022-04-16 |
CA3186484A1 (en) | 2021-12-16 |
WO2021249324A1 (zh) | 2021-12-16 |
JP2023528170A (ja) | 2023-07-04 |
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