TW202415648A - 稠環類kif18a抑制劑化合物、藥物組合物及其製備方法和用途 - Google Patents
稠環類kif18a抑制劑化合物、藥物組合物及其製備方法和用途 Download PDFInfo
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- TW202415648A TW202415648A TW112137065A TW112137065A TW202415648A TW 202415648 A TW202415648 A TW 202415648A TW 112137065 A TW112137065 A TW 112137065A TW 112137065 A TW112137065 A TW 112137065A TW 202415648 A TW202415648 A TW 202415648A
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- ring
- alkyl
- alkoxy
- compound
- nitrile
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- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
- 239000003112 inhibitor Substances 0.000 title claims description 9
- 125000003367 polycyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 43
- 101001091231 Homo sapiens Kinesin-like protein KIF18A Proteins 0.000 claims abstract description 31
- 102100034895 Kinesin-like protein KIF18A Human genes 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 229940126262 KIF18A Drugs 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 22
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 229940079593 drug Drugs 0.000 claims abstract description 19
- 230000001404 mediated effect Effects 0.000 claims abstract description 4
- -1 nitrile C1-12 alkyl Chemical group 0.000 claims description 241
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 229910052757 nitrogen Inorganic materials 0.000 claims description 65
- 150000002825 nitriles Chemical class 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000004122 cyclic group Chemical group 0.000 claims description 22
- 150000001721 carbon Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 10
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 7
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical group C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 5
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 201000002313 intestinal cancer Diseases 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 2
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical group CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 claims description 2
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical group C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 2
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- 102000029749 Microtubule Human genes 0.000 abstract description 5
- 108091022875 Microtubule Proteins 0.000 abstract description 5
- 210000004688 microtubule Anatomy 0.000 abstract description 5
- 238000011282 treatment Methods 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
- 239000000243 solution Substances 0.000 description 90
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 82
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- 230000015572 biosynthetic process Effects 0.000 description 46
- 239000000203 mixture Substances 0.000 description 46
- 238000003786 synthesis reaction Methods 0.000 description 46
- 230000002829 reductive effect Effects 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 239000000706 filtrate Substances 0.000 description 40
- 239000012074 organic phase Substances 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
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- 239000012071 phase Substances 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000002619 bicyclic group Chemical group 0.000 description 12
- 239000012043 crude product Substances 0.000 description 11
- FDAKNRLXSJBEFL-UHFFFAOYSA-N dicyclohexyl-[2-propan-2-yloxy-6-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound CC(C)Oc1cccc(c1P(C1CCCCC1)C1CCCCC1)-c1c(cc(cc1C(C)C)C(C)C)C(C)C FDAKNRLXSJBEFL-UHFFFAOYSA-N 0.000 description 11
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- BLGJHQMNSBYLEZ-UHFFFAOYSA-N 2-hydroxyethanesulfonamide Chemical compound NS(=O)(=O)CCO BLGJHQMNSBYLEZ-UHFFFAOYSA-N 0.000 description 8
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 229910000024 caesium carbonate Inorganic materials 0.000 description 8
- 125000002950 monocyclic group Chemical group 0.000 description 8
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
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- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
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- 241001465754 Metazoa Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
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- 229940098779 methanesulfonic acid Drugs 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 125000003003 spiro group Chemical group 0.000 description 6
- NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 5
- IDGDUKPISDZPDY-UHFFFAOYSA-N 6-azoniaspiro[2.5]octane;chloride Chemical compound Cl.C1CC11CCNCC1 IDGDUKPISDZPDY-UHFFFAOYSA-N 0.000 description 5
- WVIIMZNLDWSIRH-UHFFFAOYSA-N cyclohexylcyclohexane Chemical group C1CCCCC1C1CCCCC1 WVIIMZNLDWSIRH-UHFFFAOYSA-N 0.000 description 5
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- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 4
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- DDVIBOYOSCQHPQ-UHFFFAOYSA-N methyl 4-bromo-2,6-difluoro-3-nitrobenzoate Chemical compound COC(=O)C1=C(F)C=C(Br)C([N+]([O-])=O)=C1F DDVIBOYOSCQHPQ-UHFFFAOYSA-N 0.000 description 4
- SJOUHYCDSMKYHH-UHFFFAOYSA-N methyl 5,7-dichloro-[1,2,4]triazolo[1,5-a]pyridine-8-carboxylate Chemical compound COC(=O)C1=C(Cl)C=C(Cl)N2N=CN=C12 SJOUHYCDSMKYHH-UHFFFAOYSA-N 0.000 description 4
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- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 3
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- ZGPXEDXDXDDBEM-UHFFFAOYSA-N 3-(2-bromo-4-fluoro-5-methoxyphenyl)propanoic acid Chemical compound COC1=CC(CCC(O)=O)=C(Br)C=C1F ZGPXEDXDXDDBEM-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 3
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- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Public Health (AREA)
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| CN2022112170258 | 2022-09-30 | ||
| CN202211217025 | 2022-09-30 | ||
| CN202211406766 | 2022-11-10 | ||
| CN2022114067660 | 2022-11-10 | ||
| CN2023101253514 | 2023-02-16 | ||
| CN202310125351 | 2023-02-16 | ||
| CN202311219723 | 2023-09-20 | ||
| CN2023112197236 | 2023-09-20 |
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| TW202415648A true TW202415648A (zh) | 2024-04-16 |
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| WO (1) | WO2024067675A1 (fr) |
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| TW202416973A (zh) | 2022-08-18 | 2024-05-01 | 美商雅客森醫療公司 | Ｋｉｆ１８ａ抑制劑及其用途 |
| WO2025026392A1 (fr) * | 2023-08-02 | 2025-02-06 | 上海湃隆生物科技有限公司 | Inhibiteur de kinésine kif18a et son utilisation |
| TW202506675A (zh) * | 2023-08-08 | 2025-02-16 | 美商富曼西公司 | 用於防治和對抗無脊椎有害生物的連接的雙環化合物 |
| WO2025190325A1 (fr) * | 2024-03-13 | 2025-09-18 | 海南先声再明医药股份有限公司 | Combinaison pharmaceutique d'inhibiteur de kif18a et d'inhibiteur de tubuline et son utilisation |
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| US10044745B1 (en) * | 2015-10-12 | 2018-08-07 | Palantir Technologies, Inc. | Systems for computer network security risk assessment including user compromise analysis associated with a network of devices |
| US12459932B2 (en) * | 2018-12-20 | 2025-11-04 | Amgen Inc. | KIF18A inhibitors |
| CA3123227A1 (fr) * | 2018-12-20 | 2020-06-25 | Amgen Inc. | Amides d'heteroaryle utiles en tant qu'inhibiteurs de kif18a |
| EP3897852A1 (fr) * | 2018-12-20 | 2021-10-27 | Amgen Inc. | Inhibiteurs de kif18a |
| AU2020324963A1 (en) * | 2019-08-02 | 2022-02-24 | Amgen Inc. | KIF18A inhibitors |
| WO2021026098A1 (fr) * | 2019-08-02 | 2021-02-11 | Amgen Inc. | Inhibiteurs de kif18a |
| JP7756070B2 (ja) * | 2019-08-02 | 2025-10-17 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤としてのピリジン誘導体 |
| WO2023217230A1 (fr) * | 2022-05-13 | 2023-11-16 | 上海湃隆生物科技有限公司 | Inhibiteur de kinésine kif18a et son utilisation |
| CN116535400B (zh) * | 2023-04-26 | 2024-08-16 | 上海湃隆生物科技有限公司 | 氮杂螺环化合物及其应用 |
-
2023
- 2023-09-27 CN CN202380035332.0A patent/CN119072473A/zh active Pending
- 2023-09-27 TW TW112137065A patent/TW202415648A/zh unknown
- 2023-09-27 WO PCT/CN2023/121929 patent/WO2024067675A1/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CN119072473A (zh) | 2024-12-03 |
| WO2024067675A1 (fr) | 2024-04-04 |
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