JP7458987B2 - イミダゾピリジノン化合物 - Google Patents
イミダゾピリジノン化合物 Download PDFInfo
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- JP7458987B2 JP7458987B2 JP2020546064A JP2020546064A JP7458987B2 JP 7458987 B2 JP7458987 B2 JP 7458987B2 JP 2020546064 A JP2020546064 A JP 2020546064A JP 2020546064 A JP2020546064 A JP 2020546064A JP 7458987 B2 JP7458987 B2 JP 7458987B2
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- Prior art keywords
- reference example
- methyl
- alkyl
- pyridin
- title compound
- Prior art date
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- JXXWJMUPNZDILL-UHFFFAOYSA-N imidazo[4,5-b]pyridin-2-one Chemical class C1=CC=NC2=NC(=O)N=C21 JXXWJMUPNZDILL-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 427
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- -1 cyano, hydroxy Chemical group 0.000 claims description 52
- 125000005843 halogen group Chemical group 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 48
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 489
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
- 239000000203 mixture Substances 0.000 description 215
- 239000011541 reaction mixture Substances 0.000 description 212
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 148
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 144
- 230000002829 reductive effect Effects 0.000 description 116
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
- 239000012156 elution solvent Substances 0.000 description 98
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 89
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 73
- 238000010898 silica gel chromatography Methods 0.000 description 73
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 65
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- 238000000034 method Methods 0.000 description 53
- 239000000243 solution Substances 0.000 description 51
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- 239000012044 organic layer Substances 0.000 description 47
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 44
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
- 238000004440 column chromatography Methods 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 29
- DWOZNANUEDYIOF-UHFFFAOYSA-L 4-ditert-butylphosphanyl-n,n-dimethylaniline;dichloropalladium Chemical compound Cl[Pd]Cl.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 DWOZNANUEDYIOF-UHFFFAOYSA-L 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- 238000012360 testing method Methods 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- 239000002585 base Substances 0.000 description 19
- 239000003814 drug Substances 0.000 description 19
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- XYZWMVYYUIMRIZ-UHFFFAOYSA-N 4-bromo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(Br)C=C1 XYZWMVYYUIMRIZ-UHFFFAOYSA-N 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 17
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 15
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 15
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 14
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 229910000029 sodium carbonate Inorganic materials 0.000 description 13
- 210000002429 large intestine Anatomy 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 206010009900 Colitis ulcerative Diseases 0.000 description 11
- 101710111663 Egl nine homolog 1 Proteins 0.000 description 11
- 102100037249 Egl nine homolog 1 Human genes 0.000 description 11
- 238000006751 Mitsunobu reaction Methods 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 201000006704 Ulcerative Colitis Diseases 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 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 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 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 10
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000010751 Ullmann type reaction Methods 0.000 description 9
- 235000010290 biphenyl Nutrition 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 9
- UEBFLTZXUXZPJO-UHFFFAOYSA-N 1-methylimidazole-2-carbaldehyde Chemical compound CN1C=CN=C1C=O UEBFLTZXUXZPJO-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 8
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 7
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 7
- JDYVLWWFVYNMTN-UHFFFAOYSA-N 3-methylpyridine-2-carbaldehyde Chemical compound CC1=CC=CN=C1C=O JDYVLWWFVYNMTN-UHFFFAOYSA-N 0.000 description 7
- 101000881648 Homo sapiens Egl nine homolog 1 Proteins 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 210000001072 colon Anatomy 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 102000053692 human EGLN1 Human genes 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- NXYICUMSYKIABQ-UHFFFAOYSA-N 1-iodo-4-phenylbenzene Chemical group C1=CC(I)=CC=C1C1=CC=CC=C1 NXYICUMSYKIABQ-UHFFFAOYSA-N 0.000 description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 206010009887 colitis Diseases 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 6
- 229960004963 mesalazine Drugs 0.000 description 6
- 125000004076 pyridyl group Chemical group 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 6
- PQCXFUXRTRESBD-UHFFFAOYSA-N (4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C=C1 PQCXFUXRTRESBD-UHFFFAOYSA-N 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- FLXVRBSKKVMMQQ-UHFFFAOYSA-N methyl 2-formylpyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C=O)=C1 FLXVRBSKKVMMQQ-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 230000035699 permeability Effects 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 208000004232 Enteritis Diseases 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 4
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
- ALLIZEAXNXSFGD-UHFFFAOYSA-N 1-methyl-2-phenylbenzene Chemical group CC1=CC=CC=C1C1=CC=CC=C1 ALLIZEAXNXSFGD-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QDKIYDGHCFZBGC-UHFFFAOYSA-N 2-fluoro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1F QDKIYDGHCFZBGC-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- BMTZEAOGFDXDAD-UHFFFAOYSA-M 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium;chloride Chemical compound [Cl-].COC1=NC(OC)=NC([N+]2(C)CCOCC2)=N1 BMTZEAOGFDXDAD-UHFFFAOYSA-M 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- ZFUTWKQTEYLBKA-UHFFFAOYSA-N 5-bromo-1-methylimidazole-2-carbaldehyde Chemical compound CN1C(Br)=CN=C1C=O ZFUTWKQTEYLBKA-UHFFFAOYSA-N 0.000 description 3
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- AMGWMUWASGFYKS-JTQLQIEISA-N tert-butyl (3S)-3-[(3-amino-5-methoxypyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound NC=1C(=NC=C(C=1)OC)N[C@@H]1CN(CC1)C(=O)OC(C)(C)C AMGWMUWASGFYKS-JTQLQIEISA-N 0.000 description 1
- ZNUSCNKAVRYUIV-JTQLQIEISA-N tert-butyl (3S)-3-[(5-methoxy-3-nitropyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound COC=1C=C(C(=NC=1)N[C@@H]1CN(CC1)C(=O)OC(C)(C)C)[N+](=O)[O-] ZNUSCNKAVRYUIV-JTQLQIEISA-N 0.000 description 1
- AUYUAPUDZDMZIW-NSHDSACASA-N tert-butyl (3S)-3-[(5-methyl-3-nitropyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound CC=1C=C(C(=NC=1)N[C@@H]1CN(CC1)C(=O)OC(C)(C)C)[N+](=O)[O-] AUYUAPUDZDMZIW-NSHDSACASA-N 0.000 description 1
- WRTMESNWRKGKJP-INIZCTEOSA-N tert-butyl (3S)-3-[1-(4-chlorophenyl)-2-oxoimidazo[4,5-b]pyridin-3-yl]pyrrolidine-1-carboxylate Chemical compound ClC1=CC=C(C=C1)N1C(N(C2=NC=CC=C21)[C@@H]1CN(CC1)C(=O)OC(C)(C)C)=O WRTMESNWRKGKJP-INIZCTEOSA-N 0.000 description 1
- BALPRXOMLYKKMM-QFIPXVFZSA-N tert-butyl (3S)-3-[1-[4-(4-fluorophenyl)phenyl]-2-oxoimidazo[4,5-b]pyridin-3-yl]pyrrolidine-1-carboxylate Chemical compound FC1=CC=C(C=C1)C1=CC=C(C=C1)N1C(N(C2=NC=CC=C21)[C@@H]1CN(CC1)C(=O)OC(C)(C)C)=O BALPRXOMLYKKMM-QFIPXVFZSA-N 0.000 description 1
- MMZXZUWQKNUKPF-NRFANRHFSA-N tert-butyl (3S)-3-[1-[4-(4-hydroxyphenyl)phenyl]-2-oxoimidazo[4,5-b]pyridin-3-yl]pyrrolidine-1-carboxylate Chemical compound OC1=CC=C(C=C1)C1=CC=C(C=C1)N1C(N(C2=NC=CC=C21)[C@@H]1CN(CC1)C(=O)OC(C)(C)C)=O MMZXZUWQKNUKPF-NRFANRHFSA-N 0.000 description 1
- QDAMAXOSAKBVDQ-QFIPXVFZSA-N tert-butyl (3S)-3-[1-[4-(4-methoxyphenyl)phenyl]-2-oxoimidazo[4,5-b]pyridin-3-yl]pyrrolidine-1-carboxylate Chemical compound COC1=CC=C(C=C1)C1=CC=C(C=C1)N1C(N(C2=NC=CC=C21)[C@@H]1CN(CC1)C(=O)OC(C)(C)C)=O QDAMAXOSAKBVDQ-QFIPXVFZSA-N 0.000 description 1
- ILLSIIVHFYOOJM-SNVBAGLBSA-N tert-butyl (3r)-3-[(3-nitropyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@H]1NC1=NC=CC=C1[N+]([O-])=O ILLSIIVHFYOOJM-SNVBAGLBSA-N 0.000 description 1
- CMIBWIAICVBURI-SSDOTTSWSA-N tert-butyl (3r)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)C1 CMIBWIAICVBURI-SSDOTTSWSA-N 0.000 description 1
- ILLSIIVHFYOOJM-JTQLQIEISA-N tert-butyl (3s)-3-[(3-nitropyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1NC1=NC=CC=C1[N+]([O-])=O ILLSIIVHFYOOJM-JTQLQIEISA-N 0.000 description 1
- GSPQESXGLJJNKV-JTQLQIEISA-N tert-butyl (3s)-3-[2-oxo-6-(trifluoromethyl)-1h-imidazo[4,5-b]pyridin-3-yl]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1N1C(=O)NC2=CC(C(F)(F)F)=CN=C21 GSPQESXGLJJNKV-JTQLQIEISA-N 0.000 description 1
- NXXJZGSMPJFPBX-NRFANRHFSA-N tert-butyl 2-[[(3S)-3-[1-(4-ethenylphenyl)-2-oxoimidazo[4,5-b]pyridin-3-yl]pyrrolidin-1-yl]methyl]-3-methylimidazole-4-carboxylate Chemical compound CN1C(=NC=C1C(=O)OC(C)(C)C)CN1C[C@H](CC1)N1C(N(C=2C1=NC=CC=2)C1=CC=C(C=C1)C=C)=O NXXJZGSMPJFPBX-NRFANRHFSA-N 0.000 description 1
- VFAJCZHBOJFVTO-UHFFFAOYSA-N tert-butyl 2-formyl-3-methylimidazole-4-carboxylate Chemical compound Cn1c(C=O)ncc1C(=O)OC(C)(C)C VFAJCZHBOJFVTO-UHFFFAOYSA-N 0.000 description 1
- YJHNPTOFDITELE-UHFFFAOYSA-N tert-butyl 3-(2-oxo-1H-imidazo[4,5-b]pyridin-3-yl)azetidine-1-carboxylate Chemical compound O=C1NC=2C(=NC=CC=2)N1C1CN(C1)C(=O)OC(C)(C)C YJHNPTOFDITELE-UHFFFAOYSA-N 0.000 description 1
- PFRMKJHFVJJKHF-UHFFFAOYSA-N tert-butyl 3-[(3-aminopyridin-2-yl)amino]azetidine-1-carboxylate Chemical compound NC=1C(=NC=CC=1)NC1CN(C1)C(=O)OC(C)(C)C PFRMKJHFVJJKHF-UHFFFAOYSA-N 0.000 description 1
- KLKHBWAMXFYYRV-UHFFFAOYSA-N tert-butyl 3-[(3-nitropyridin-2-yl)amino]azetidine-1-carboxylate Chemical compound [N+](=O)([O-])C=1C(=NC=CC=1)NC1CN(C1)C(=O)OC(C)(C)C KLKHBWAMXFYYRV-UHFFFAOYSA-N 0.000 description 1
- WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 1
- ZYWHOQMDGIKRJV-QHCPKHFHSA-N tert-butyl 3-methyl-2-[[(3S)-3-[1-(4-morpholin-4-ylphenyl)-2-oxoimidazo[4,5-b]pyridin-3-yl]pyrrolidin-1-yl]methyl]imidazole-4-carboxylate Chemical compound CN1C(=NC=C1C(=O)OC(C)(C)C)CN1C[C@H](CC1)N1C(N(C=2C1=NC=CC=2)C1=CC=C(C=C1)N1CCOCC1)=O ZYWHOQMDGIKRJV-QHCPKHFHSA-N 0.000 description 1
- GGYAOVIUEIGSBZ-QHCPKHFHSA-N tert-butyl 3-methyl-2-[[(3S)-3-[2-oxo-1-(4-phenoxyphenyl)imidazo[4,5-b]pyridin-3-yl]pyrrolidin-1-yl]methyl]imidazole-4-carboxylate Chemical compound CN1C(=NC=C1C(=O)OC(C)(C)C)CN1C[C@H](CC1)N1C(N(C=2C1=NC=CC=2)C1=CC=C(C=C1)OC1=CC=CC=C1)=O GGYAOVIUEIGSBZ-QHCPKHFHSA-N 0.000 description 1
- HMMRNUODMUVXTJ-UHFFFAOYSA-N tert-butyl 3-methylimidazole-4-carboxylate Chemical compound CN1C=NC=C1C(=O)OC(C)(C)C HMMRNUODMUVXTJ-UHFFFAOYSA-N 0.000 description 1
- FSBNQEJPFLWDBD-UHFFFAOYSA-N tert-butyl 4-[(3-aminopyridin-2-yl)amino]-4-methylpiperidine-1-carboxylate Chemical compound NC=1C(=NC=CC=1)NC1(CCN(CC1)C(=O)OC(C)(C)C)C FSBNQEJPFLWDBD-UHFFFAOYSA-N 0.000 description 1
- DMBKWEHXTOCLTC-UHFFFAOYSA-N tert-butyl 4-amino-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(N)CC1 DMBKWEHXTOCLTC-UHFFFAOYSA-N 0.000 description 1
- GJEKNTKJLYDGSV-UHFFFAOYSA-N tert-butyl 4-methyl-4-(2-oxo-1H-imidazo[4,5-b]pyridin-3-yl)piperidine-1-carboxylate Chemical compound CC1(CCN(CC1)C(=O)OC(C)(C)C)N1C(NC=2C1=NC=CC=2)=O GJEKNTKJLYDGSV-UHFFFAOYSA-N 0.000 description 1
- GEHVFEKJXYYILF-UHFFFAOYSA-N tert-butyl 4-methyl-4-[(3-nitropyridin-2-yl)amino]piperidine-1-carboxylate Chemical compound CC1(CCN(CC1)C(=O)OC(C)(C)C)NC1=NC=CC=C1[N+](=O)[O-] GEHVFEKJXYYILF-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61K31/435—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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cosmetics (AREA)
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| JP2018171839 | 2018-09-13 | ||
| PCT/JP2019/035792 WO2020054788A1 (ja) | 2018-09-13 | 2019-09-12 | イミダゾピリジノン化合物 |
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| EP (1) | EP3808747B1 (https=) |
| JP (1) | JP7458987B2 (https=) |
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| HU (1) | HUE069830T2 (https=) |
| IL (1) | IL281391B2 (https=) |
| MX (1) | MX2021003027A (https=) |
| MY (1) | MY207239A (https=) |
| NZ (1) | NZ773786A (https=) |
| PH (1) | PH12021550512A1 (https=) |
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| JP2021143176A (ja) * | 2020-03-12 | 2021-09-24 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物の製造方法 |
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| JP7414550B2 (ja) * | 2020-01-23 | 2024-01-16 | キッセイ薬品工業株式会社 | （ヘテロ）アリールイミダゾロン化合物 |
| US20230107927A1 (en) | 2020-02-28 | 2023-04-06 | First Wave Bio, Inc. | Methods of treating iatrogenic autoimmune colitis |
| CA3169000A1 (en) * | 2020-03-11 | 2021-09-16 | Hideki Takeuchi | Crystal of imidazopyridinone compound or salt thereof |
| CN117402178B (zh) * | 2023-12-15 | 2024-03-08 | 英矽智能科技(上海)有限公司 | 作为jak抑制剂和phd抑制剂的嘧啶类化合物 |
| WO2025264818A1 (en) * | 2024-06-20 | 2025-12-26 | Raythera, Inc. | Stat6 modulators and methods of uses thereof |
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| WO2001072751A1 (en) | 2000-03-29 | 2001-10-04 | Knoll Gesellschaft Mit Beschraenkter Haftung | Pyrrolopyrimidines as tyrosine kinase inhibitors |
| JP2002526500A (ja) | 1998-09-18 | 2002-08-20 | ビーエーエスエフ アクチェンゲゼルシャフト | プロテインキナーゼ阻害剤としてのピロロピリミジン |
| JP2007505127A (ja) | 2003-09-11 | 2007-03-08 | ケミア，インコーポレイテッド | サイトカイン阻害剤 |
| JP2008533121A (ja) | 2005-03-15 | 2008-08-21 | ファイザー株式会社 | Ｃｂ２受容体リガンドとしてのベンズイミダゾロン誘導体 |
| JP2010503654A (ja) | 2006-09-12 | 2010-02-04 | ファイザー・プロダクツ・インク | ベンゾイミダゾロン誘導体 |
| JP2011037814A (ja) | 2009-08-14 | 2011-02-24 | Synstar Japan Co Ltd | マラリア原虫疾患予防又は治療用の５−ヘテロ環置換イミノ−９−ジアルキルアミノベンゾ［ａ］フェノキサチン化合物又はその塩とアーテミシニン誘導体との組み合わせ |
| JP2011519857A (ja) | 2008-04-28 | 2011-07-14 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | プロリルヒドロキシラーゼ阻害物質としてのベンゾイミダゾール |
| WO2011096490A1 (ja) | 2010-02-04 | 2011-08-11 | 第一三共株式会社 | イミダゾピリジン－２－オン誘導体 |
| WO2014181813A1 (ja) | 2013-05-10 | 2014-11-13 | 武田薬品工業株式会社 | 複素環化合物 |
| WO2015052765A1 (ja) | 2013-10-08 | 2015-04-16 | 日立マクセル株式会社 | 投射型映像表示装置、操作検出装置及び投射型映像表示方法 |
| WO2015139619A1 (zh) | 2014-03-18 | 2015-09-24 | 北京韩美药品有限公司 | 作为RORγ调节剂的化合物 |
| WO2018036469A1 (zh) | 2016-08-22 | 2018-03-01 | 南京明德新药研发股份有限公司 | Pde4抑制剂 |
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