JP2018520202A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018520202A5 JP2018520202A5 JP2018503190A JP2018503190A JP2018520202A5 JP 2018520202 A5 JP2018520202 A5 JP 2018520202A5 JP 2018503190 A JP2018503190 A JP 2018503190A JP 2018503190 A JP2018503190 A JP 2018503190A JP 2018520202 A5 JP2018520202 A5 JP 2018520202A5
- Authority
- JP
- Japan
- Prior art keywords
- group
- substituted
- alkyl group
- unsubstituted
- independently
- 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
- 125000000217 alkyl group Chemical group 0.000 claims 113
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 75
- 238000006467 substitution reaction Methods 0.000 claims 47
- 150000001875 compounds Chemical class 0.000 claims 36
- 125000003545 alkoxy group Chemical group 0.000 claims 33
- 125000005842 heteroatom Chemical group 0.000 claims 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 24
- 229910052799 carbon Inorganic materials 0.000 claims 17
- -1 alkyl groups Pyrimidine compounds Chemical class 0.000 claims 16
- 229910052736 halogen Inorganic materials 0.000 claims 15
- 150000002367 halogens Chemical class 0.000 claims 15
- 238000000034 method Methods 0.000 claims 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 14
- 229910052757 nitrogen Inorganic materials 0.000 claims 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 13
- 230000002503 metabolic effect Effects 0.000 claims 13
- 239000002207 metabolite Substances 0.000 claims 13
- 239000003960 organic solvent Substances 0.000 claims 13
- 229910052760 oxygen Inorganic materials 0.000 claims 13
- 239000001301 oxygen Substances 0.000 claims 13
- 239000002243 precursor Substances 0.000 claims 13
- 150000003839 salts Chemical class 0.000 claims 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 12
- 125000004432 carbon atom Chemical group C* 0.000 claims 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 12
- 229940002612 prodrug Drugs 0.000 claims 12
- 239000000651 prodrug Substances 0.000 claims 12
- 239000002585 base Substances 0.000 claims 10
- 125000004431 deuterium atom Chemical group 0.000 claims 8
- 229910052805 deuterium Inorganic materials 0.000 claims 7
- 125000001424 substituent group Chemical group 0.000 claims 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 5
- 150000001721 carbon Chemical group 0.000 claims 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims 5
- 229910052731 fluorine Inorganic materials 0.000 claims 5
- 239000011737 fluorine Substances 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 125000004429 atom Chemical group 0.000 claims 4
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 125000003277 amino group Chemical group 0.000 claims 3
- 239000002552 dosage form Substances 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 229910052740 iodine Inorganic materials 0.000 claims 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 208000026935 allergic disease Diseases 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- 229940125877 compound 31 Drugs 0.000 claims 2
- 238000006482 condensation reaction Methods 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 208000026278 immune system disease Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 claims 1
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229940126657 Compound 17 Drugs 0.000 claims 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- 208000011231 Crohn disease Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 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
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 229940044683 chemotherapy drug Drugs 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 claims 1
- 229940125833 compound 23 Drugs 0.000 claims 1
- 229940125878 compound 36 Drugs 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 208000030381 cutaneous melanoma Diseases 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 229960004275 glycolic acid Drugs 0.000 claims 1
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 230000001035 methylating effect Effects 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 206010028537 myelofibrosis Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 150000003230 pyrimidines Chemical class 0.000 claims 1
- 238000006268 reductive amination reaction Methods 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 201000003708 skin melanoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 238000003419 tautomerization reaction Methods 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical group C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 0 C1[C@@](CC2)*3[C@]2C13 Chemical compound C1[C@@](CC2)*3[C@]2C13 0.000 description 4
- YXCDCLUCEYSYKE-WAOQWHTKSA-N C/C(/OC)=C(\C=C/C=C)/c1cc(F)cc(C)c1/N=C(\N=C)/Cl Chemical compound C/C(/OC)=C(\C=C/C=C)/c1cc(F)cc(C)c1/N=C(\N=C)/Cl YXCDCLUCEYSYKE-WAOQWHTKSA-N 0.000 description 1
- NDYWWOAGDGFZMW-UHFFFAOYSA-N C/C=S(/C)\c(cc1)cc(OC)c1-c1cccc(cn2)c1nc2Cl Chemical compound C/C=S(/C)\c(cc1)cc(OC)c1-c1cccc(cn2)c1nc2Cl NDYWWOAGDGFZMW-UHFFFAOYSA-N 0.000 description 1
- TWAJWBFPRCENHQ-UHFFFAOYSA-N CCC1=C(C)OCO1 Chemical compound CCC1=C(C)OCO1 TWAJWBFPRCENHQ-UHFFFAOYSA-N 0.000 description 1
- MCZVZNNHDQXBAY-UHFFFAOYSA-N COc1ccccc1-c1cccc(cn2)c1nc2Cl Chemical compound COc1ccccc1-c1cccc(cn2)c1nc2Cl MCZVZNNHDQXBAY-UHFFFAOYSA-N 0.000 description 1
- UYWOONXZYCNXCP-UHFFFAOYSA-N Cc([s]c(CN1)c2N=C1Cl)c2-c(ccc(C)c1)c1OC Chemical compound Cc([s]c(CN1)c2N=C1Cl)c2-c(ccc(C)c1)c1OC UYWOONXZYCNXCP-UHFFFAOYSA-N 0.000 description 1
- BGQUPQPMLRRPPS-UHFFFAOYSA-N Cc([s]c(cn1)c2nc1Cl)c2-c(ccc(F)c1)c1OC Chemical compound Cc([s]c(cn1)c2nc1Cl)c2-c(ccc(F)c1)c1OC BGQUPQPMLRRPPS-UHFFFAOYSA-N 0.000 description 1
- DODMROWOSJXWCG-UHFFFAOYSA-N Cc1c(C2C=CC=C3C2OCC3)c2nc(Cl)ncc2[s]1 Chemical compound Cc1c(C2C=CC=C3C2OCC3)c2nc(Cl)ncc2[s]1 DODMROWOSJXWCG-UHFFFAOYSA-N 0.000 description 1
- OAYWRBMJFWIYMR-UHFFFAOYSA-N Cc1c(C2C=CC=CC2OC)c(nc(nc2)Cl)c2[s]1 Chemical compound Cc1c(C2C=CC=CC2OC)c(nc(nc2)Cl)c2[s]1 OAYWRBMJFWIYMR-UHFFFAOYSA-N 0.000 description 1
- LQSQPVHPPSIFOR-LESIGDGNSA-N Cc1c(C2C=CC=C[C@H]2N(C)S(C)=O)c2nc(Cl)ncc2[s]1 Chemical compound Cc1c(C2C=CC=C[C@H]2N(C)S(C)=O)c2nc(Cl)ncc2[s]1 LQSQPVHPPSIFOR-LESIGDGNSA-N 0.000 description 1
- KTAVWSSNNVHJHQ-UHFFFAOYSA-N Clc1nc(c(-c2cccc3c2OCC3)ccc2)c2cn1 Chemical compound Clc1nc(c(-c2cccc3c2OCC3)ccc2)c2cn1 KTAVWSSNNVHJHQ-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510430641.5 | 2015-07-21 | ||
| CN201510430641 | 2015-07-21 | ||
| PCT/CN2016/090798 WO2017012559A1 (zh) | 2015-07-21 | 2016-07-21 | 稠环嘧啶类化合物、中间体、其制备方法、组合物和应用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018520202A JP2018520202A (ja) | 2018-07-26 |
| JP2018520202A5 true JP2018520202A5 (enExample) | 2018-09-06 |
| JP6875372B2 JP6875372B2 (ja) | 2021-05-26 |
Family
ID=57833793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018503190A Active JP6875372B2 (ja) | 2015-07-21 | 2016-07-21 | 縮合環ピリミジン系化合物、中間体、その製造方法、組成物及び応用 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US10494378B2 (enExample) |
| EP (1) | EP3354653B1 (enExample) |
| JP (1) | JP6875372B2 (enExample) |
| KR (1) | KR102591886B1 (enExample) |
| CN (1) | CN106366093B (enExample) |
| AU (1) | AU2016295594B2 (enExample) |
| CA (1) | CA2993096C (enExample) |
| MX (1) | MX379383B (enExample) |
| RU (1) | RU2732576C2 (enExample) |
| WO (1) | WO2017012559A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109305944B (zh) * | 2017-07-28 | 2022-09-02 | 深圳睿熙生物科技有限公司 | 布鲁顿酪氨酸激酶的抑制剂 |
| CN110551142B (zh) * | 2018-05-31 | 2023-05-12 | 上海再极医药科技有限公司 | 一种稠环嘧啶类化合物的盐、晶型及其制备方法和应用 |
| KR20210058817A (ko) * | 2018-07-23 | 2021-05-24 | 셀젠 콴티셀 리서치, 인크. | 브로모도메인 억제제의 제조 방법 |
| CN111978331B (zh) * | 2019-05-21 | 2023-06-20 | 上海再极医药科技有限公司 | 一种flt3和fgfr激酶抑制剂的制备方法 |
| WO2021148010A1 (zh) * | 2020-01-22 | 2021-07-29 | 南京明德新药研发有限公司 | 吡唑并杂芳环类化合物及其应用 |
| US12473300B2 (en) * | 2020-03-06 | 2025-11-18 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd. | Thienopyrimidine derivative and preparation method therefor |
| US20230192653A1 (en) * | 2020-03-13 | 2023-06-22 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd. | Novel Therapeutic Methods |
| CN116621843B (zh) * | 2022-06-13 | 2024-05-24 | 四川大学华西医院 | 一种dna甲基转移酶1抑制剂及其制备方法和用途 |
| TW202417423A (zh) * | 2022-07-18 | 2024-05-01 | 美商依安彼克醫療有限公司 | 喹唑啉化合物及使用方法 |
| TW202408522A (zh) * | 2022-08-25 | 2024-03-01 | 大陸商廣州再極醫藥科技有限公司 | 一種稠環嘧啶類化合物的用途 |
| CN116836171B (zh) * | 2023-06-30 | 2024-06-04 | 凌科药业(杭州)有限公司 | 一种磺酰胺类化合物及其应用 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5110347A (en) * | 1990-11-26 | 1992-05-05 | E. I Du Pont De Nemours And Company | Substituted fused heterocyclic herbicides |
| US5633218A (en) * | 1995-05-24 | 1997-05-27 | E. I. Du Pont De Nemours And Company | Herbicidal benzodioxoles and benzodioxanes |
| ES2270867T3 (es) * | 1999-09-23 | 2007-04-16 | Astrazeneca Ab | Compuestos de quinazolina terapeuticos. |
| NZ567851A (en) * | 2005-11-01 | 2011-09-30 | Targegen Inc | Bi-aryl meta-pyrimidine inhibitors of kinases |
| AR060358A1 (es) * | 2006-04-06 | 2008-06-11 | Novartis Vaccines & Diagnostic | Quinazolinas para la inhibicion de pdk 1 |
| KR101533461B1 (ko) * | 2006-04-26 | 2015-07-02 | 에프. 호프만-라 로슈 아게 | Ｐｉ３ｋ저해제로 유용한 티에노［3,2-ｄ］피리미딘 유도체 |
| US8354408B2 (en) * | 2007-11-15 | 2013-01-15 | Ym Biosciences Australia Pty Ltd | N-containing heterocyclic compounds |
| CA2748943A1 (en) * | 2009-02-09 | 2010-08-12 | Supergen, Inc. | Pyrrolopyrimidinyl axl kinase inhibitors |
| TWI468402B (zh) * | 2009-07-31 | 2015-01-11 | 必治妥美雅史谷比公司 | 降低β－類澱粉生成之化合物 |
| KR101147550B1 (ko) * | 2009-10-22 | 2012-05-17 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 가지는 2,7-치환된 티에노［3,2-ｄ］피리미딘 화합물 |
| WO2011079231A1 (en) * | 2009-12-23 | 2011-06-30 | Gatekeeper Pharmaceutical, Inc. | Compounds that modulate egfr activity and methods for treating or preventing conditions therewith |
| EP2611812A1 (en) * | 2010-09-01 | 2013-07-10 | Ambit Biosciences Corporation | Thienopyridine and thienopyrimidine compounds and methods of use thereof |
| TW201309655A (zh) * | 2011-01-28 | 2013-03-01 | 必治妥美雅史谷比公司 | 降低β－類澱粉生成之化合物 |
| EP2882746B1 (en) * | 2012-08-07 | 2016-12-07 | Merck Patent GmbH | Pyridopyrimidine derivatives as protein kinase inhibitors |
| GB201216017D0 (en) * | 2012-09-07 | 2012-10-24 | Cancer Rec Tech Ltd | Inhibitor compounds |
| NZ718190A (en) * | 2013-08-23 | 2017-10-27 | Neupharma Inc | Substituted quinazolines for inhibiting kinase activity |
| JO3805B1 (ar) * | 2013-10-10 | 2021-01-31 | Araxes Pharma Llc | مثبطات كراس جي12سي |
| JO3556B1 (ar) * | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| EP3270694A4 (en) * | 2015-02-17 | 2018-09-05 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| SG11201706869XA (en) * | 2015-03-24 | 2017-09-28 | Shanghai Yingli Pharm Co Ltd | Condensed ring derivative, and preparation method, intermediate, pharmaceutical composition and use thereof |
| AU2016251253B2 (en) * | 2015-04-24 | 2020-07-09 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd | Condensed-ring pyrimidylamino derivative, preparation method therefor, and intermediate, pharmaceutical composition and applications thereof |
-
2016
- 2016-07-21 RU RU2018103332A patent/RU2732576C2/ru active
- 2016-07-21 AU AU2016295594A patent/AU2016295594B2/en active Active
- 2016-07-21 CA CA2993096A patent/CA2993096C/en active Active
- 2016-07-21 MX MX2018000945A patent/MX379383B/es unknown
- 2016-07-21 CN CN201610579459.0A patent/CN106366093B/zh active Active
- 2016-07-21 KR KR1020187004890A patent/KR102591886B1/ko active Active
- 2016-07-21 EP EP16827250.8A patent/EP3354653B1/en active Active
- 2016-07-21 JP JP2018503190A patent/JP6875372B2/ja active Active
- 2016-07-21 WO PCT/CN2016/090798 patent/WO2017012559A1/zh not_active Ceased
- 2016-07-21 US US15/746,254 patent/US10494378B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018520202A5 (enExample) | ||
| RU2018103332A (ru) | Пиримидиновое соединение с конденсированными кольцами, его промежуточное соединение, способ получения, композиция и применение | |
| CA2861150C (en) | Morphinan derivative | |
| US10954199B2 (en) | Process methods for phosphatidylinositol 3-kinase inhibitors | |
| EP2903614B1 (en) | Novel compounds, their synthesis and their uses | |
| US20220251089A1 (en) | Cyclic iminopyrimidine derivatives as kinase inhibitors | |
| US12528803B2 (en) | Inhibitors of αvβ6 integrin | |
| US11827637B2 (en) | Azaindole derivatives and their use as ERK kinase inhibitors | |
| JP2015512438A (ja) | 新規なアルファ２アドレナリン受容体アゴニスト | |
| JP2014040426A (ja) | ［５−（４，６−ジメチル−１ｈ−ベンゾイミダゾール−２−イル）−４−メチル−ピリミジン−２−イル］−［３−（１−メチル−ピペリジン−４−イル）−プロピル］−アミンの結晶性ヘミタートレート | |
| US12492212B2 (en) | Substituted pyrazolecarboxamides as sting activators | |
| JP2020517676A5 (enExample) | ||
| CN109134432B (zh) | 氘代抗抑郁药物 | |
| JP7607799B2 (ja) | ６員芳香族ヘテロ尿素環の誘導体及びその使用 | |
| RU2817349C1 (ru) | Производные аминопиримидинила | |
| JP2023543006A (ja) | １Ｈ－ピロロ［２，３－ｃ］ピリジン系化合物及びその使用 | |
| US10323043B2 (en) | Derivatives of macrocyclic N-aryl-tricyclopyrimidine-2-amine polyethers as inhibitors of FTL3 and JAK | |
| US11655252B2 (en) | Aminopyrimidinyl derivatives | |
| KR20150078018A (ko) | 암 치료 효과를 갖는 신규한 이속사졸 화합물 | |
| EA046338B1 (ru) | СОЕДИНЕНИЯ 1H-ПИРРОЛО[2,3-с]ПИРИДИНА И ИХ ПРИМЕНЕНИЕ | |
| KR20160136454A (ko) | 니코틴 중독의 예방 또는 치료를 위한 접합체 및 그를 제조하는 연관 방법 | |
| WO2013191244A1 (ja) | ピリドピリミジン－４－オン誘導体 |