JP7034512B2 - キナーゼ阻害剤としてのヘテロアリール化合物 - Google Patents
キナーゼ阻害剤としてのヘテロアリール化合物 Download PDFInfo
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- JP7034512B2 JP7034512B2 JP2020549595A JP2020549595A JP7034512B2 JP 7034512 B2 JP7034512 B2 JP 7034512B2 JP 2020549595 A JP2020549595 A JP 2020549595A JP 2020549595 A JP2020549595 A JP 2020549595A JP 7034512 B2 JP7034512 B2 JP 7034512B2
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- amino
- oxy
- phenyl
- ethyl
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- -1 Heteroaryl compound Chemical class 0.000 title claims description 219
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 195
- 150000001875 compounds Chemical class 0.000 claims description 127
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 123
- 229910052739 hydrogen Inorganic materials 0.000 claims description 93
- 239000001257 hydrogen Substances 0.000 claims description 93
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 79
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 57
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 53
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 46
- 150000002367 halogens Chemical group 0.000 claims description 46
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 41
- 150000002431 hydrogen Chemical group 0.000 claims description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 27
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 25
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 25
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 20
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 5
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- OFDVABAUFQJWEZ-UHFFFAOYSA-N 3-pyridin-3-ylpyridine Chemical compound C1=CN=CC(C=2C=NC=CC=2)=C1 OFDVABAUFQJWEZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- TVOIRWXYIRYKGJ-UHFFFAOYSA-N 1,1-dioxo-1-benzothiophene-6-carboxamide Chemical compound NC(=O)C1=CC=C2C=CS(=O)(=O)C2=C1 TVOIRWXYIRYKGJ-UHFFFAOYSA-N 0.000 claims description 2
- DUIFMLVGDSKWED-UHFFFAOYSA-N 1,1-dioxothiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1(=O)=O DUIFMLVGDSKWED-UHFFFAOYSA-N 0.000 claims description 2
- IPEGSDNDXHMCNH-UHFFFAOYSA-N 1-benzothiophene-6-carboxamide Chemical compound NC(=O)C1=CC=C2C=CSC2=C1 IPEGSDNDXHMCNH-UHFFFAOYSA-N 0.000 claims description 2
- LDBLGZFDZQMPAR-OAHLLOKOSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]phenyl]-3-propan-2-yloxybenzamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(C1=CC(=CC=C1)OC(C)C)=O)Cl LDBLGZFDZQMPAR-OAHLLOKOSA-N 0.000 claims description 2
- WUVRCJGAPKKUMA-GOSISDBHSA-N N-[3-[(1R)-1-[2-amino-5-(1-methylpyrazol-4-yl)pyridin-3-yl]oxyethyl]phenyl]-3,5-dimethylbenzamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(C1=CC(=CC(=C1)C)C)=O)C=1C=NN(C=1)C WUVRCJGAPKKUMA-GOSISDBHSA-N 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229940127557 pharmaceutical product Drugs 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- ILZTVYIGJUKEBA-UHFFFAOYSA-N 5-(1-methylpyrazol-4-yl)pyridin-2-amine Chemical compound C1=NN(C)C=C1C1=CC=C(N)N=C1 ILZTVYIGJUKEBA-UHFFFAOYSA-N 0.000 claims 2
- HUSYTLMIRXITQS-UHFFFAOYSA-N 1,3-benzodioxole-5-carboxamide Chemical compound NC(=O)C1=CC=C2OCOC2=C1 HUSYTLMIRXITQS-UHFFFAOYSA-N 0.000 claims 1
- NLPDMBSLKMVISZ-UHFFFAOYSA-N CC(C1(C=CC=CC1)N1C=C(C)SC1C(N)=O)OC1=CC(Cl)=CN=C1N Chemical compound CC(C1(C=CC=CC1)N1C=C(C)SC1C(N)=O)OC1=CC(Cl)=CN=C1N NLPDMBSLKMVISZ-UHFFFAOYSA-N 0.000 claims 1
- AVTKRDQDOBXORL-GFCCVEGCSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]-4-chlorophenyl]-2-chloro-3-methylbenzamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1Cl)NC(C1=C(C(=CC=C1)C)Cl)=O)Cl AVTKRDQDOBXORL-GFCCVEGCSA-N 0.000 claims 1
- MBJVZBAHDZXJKT-CYBMUJFWSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]phenyl]-1,1-dioxo-1-benzothiophene-6-carboxamide Chemical compound S1(C2=C(C=C1)C=CC(=C2)C(=O)NC1=CC(=CC=C1)[C@@H](C)OC=1C(=NC=C(C=1)Cl)N)(=O)=O MBJVZBAHDZXJKT-CYBMUJFWSA-N 0.000 claims 1
- NUTGTXVVLPLRSS-CYBMUJFWSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiophene-6-carboxamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(=O)C=1C=CC2=C(S(CC2)(=O)=O)C=1)Cl NUTGTXVVLPLRSS-CYBMUJFWSA-N 0.000 claims 1
- LBWVNBKWUPTWDJ-OAHLLOKOSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]phenyl]-1-methyl-3,4-dihydro-2H-quinoline-7-carboxamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(=O)C1=CC=C2CCCN(C2=C1)C)Cl LBWVNBKWUPTWDJ-OAHLLOKOSA-N 0.000 claims 1
- RYORRAAKRYRJII-CQSZACIVSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]phenyl]-3-cyclopropylbenzamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(C1=CC(=CC=C1)C1CC1)=O)Cl RYORRAAKRYRJII-CQSZACIVSA-N 0.000 claims 1
- SIRXUSHVPXOANZ-CQSZACIVSA-N N-[3-[(1R)-1-(2-amino-5-chloropyridin-3-yl)oxyethyl]phenyl]-3-ethynylbenzamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(C1=CC(=CC=C1)C#C)=O)Cl SIRXUSHVPXOANZ-CQSZACIVSA-N 0.000 claims 1
- NSJUOFWRFCVECC-QGZVFWFLSA-N N-[3-[(1R)-1-[2-amino-5-(1-methylpyrazol-4-yl)pyridin-3-yl]oxyethyl]phenyl]-2,3-dihydro-1H-indene-5-carboxamide Chemical compound NC1=NC=C(C=C1O[C@H](C)C=1C=C(C=CC=1)NC(=O)C=1C=C2CCCC2=CC=1)C=1C=NN(C=1)C NSJUOFWRFCVECC-QGZVFWFLSA-N 0.000 claims 1
- 150000003857 carboxamides Chemical class 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- YMNAJWHTELQUJU-UHFFFAOYSA-N quinoline-6-carboxamide Chemical compound N1=CC=CC2=CC(C(=O)N)=CC=C21 YMNAJWHTELQUJU-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 230000015572 biosynthetic process Effects 0.000 description 57
- 238000003786 synthesis reaction Methods 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- 238000000034 method Methods 0.000 description 47
- 239000000203 mixture Substances 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 238000004440 column chromatography Methods 0.000 description 37
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 36
- 239000007787 solid Substances 0.000 description 33
- 229910052799 carbon Inorganic materials 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 125000000753 cycloalkyl group Chemical group 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 17
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 108091000080 Phosphotransferase Proteins 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 102000020233 phosphotransferase Human genes 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 13
- 125000005843 halogen group Chemical group 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 12
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 11
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- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 10
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 10
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- 150000003839 salts Chemical class 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
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- 125000005842 heteroatom Chemical group 0.000 description 9
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OPMWQSDBBSURGY-UHFFFAOYSA-N tert-butyl n-[3-(hydroxymethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CO)=C1 OPMWQSDBBSURGY-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
- 125000003441 thioacyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
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- 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
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Description
本願は、2018年3月15日に提出された中国特許出願第201810212171.9号及び2018年7月26日に提出された第201810835038.9号の優先権を主張し、両者の全内容は引用することによって本願に組み込まれる。
Aは、N、CR2から選ばれ、
R1は、水素、C1-C5アルキル基、C3-C6シクロアルキル基、C(O)C1-C3アルキル基、S(O)2(C1-C3)アルキル基、S(O)2(C3-C6)シクロアルキル基から選ばれ、
R2は、水素、ハロゲン、OH、NR5R6、シアノ基、C1-C5アルキル基から選ばれ、
R3は、水素、ハロゲン、C6-C12アリール基、5-12員のヘテロアリール基、ヒドロキシ基、ニトロ基、シアノ基、O(C1-C5)アルキル基、(C1-C5)ヘテロアルキル基、O(C3-C6)シクロアルキル基、O(C3-C6)ヘテロシクロアルキル基、(C1-C3)アルキル(C3-C6)ヘテロシクロアルキル基、C2-C5アルケニル基、C2-C5アルキニル基、C3-C7シクロアルキル基、C3-C6ヘテロシクロアルキル基、NR5R6、C(O)R8、P(O)R8R9、S(O)n(C1-C3)アルキル基、S(O)n(C3-C6)シクロアルキル基から選ばれ、ここで、n=0,1,2であり、R3の水素のそれぞれは1つ又は複数のR7によって独立して任意に置換され、且つ隣接するR7は4~12員環を形成でき、
Qは、CHR5CHR6、O、OC(R5R6)、C(R5R6)、CO、NR5C(O)、NR5S(O)2、CH=CH、C≡C、S(O)n、S(O)n(C1-C3)アルキル基から選ばれ、ここで、n=0,1,2であり、
Zは、C6-C10アリール基、5~10員のヘテロアリール基から選ばれ、その環上の水素はR4によって置換されてよく、
Xは、O(C0-C3)アルキル基、NR5(C0-C3)アルキル基、NR5C(O)、NR5S(O)2、C(O)NR5、S(O)2NR5、N(R5)C(O)N(R6)、N(R5)C(S)N(R6)から選ばれ、
Wは、C6-C12アリール基、5-12員のヘテロアリール基から選ばれ、その環上の水素は1つ又は複数のR7によって独立して置換されてよく、
R4は、ハロゲン、OH、シアノ基、O(C1-C5)アルキル基、C1-C5アルキル基から選ばれ、
R5及びR6は、水素、C1-C3アルキル基、C3-C6シクロアルキル基、C(O)C1-C3アルキル基、S(O)2(C1-C3)アルキル基、S(O)2(C3-C6)シクロアルキル基から独立して選ばれ、又はR5とR6が結合して3~6員環が形成され、又はR1がR5及びR6の一方と結合して5~7員環が形成され、
R7は、水素、ハロゲン、C6-C12アリール基、5-12員のヘテロアリール基、ヒドロキシ基、ニトロ基、シアノ基、(C1-C5)アルキル基、O(C1-C6)アルキル基、(C1-C5)ヘテロアルキル基、O(C3-C7)シクロアルキル基、O(C3-C6)ヘテロシクロアルキル基、(C1-C3)アルキル(C3-C6)ヘテロシクロアルキル基、C2-C5アルケニル基、C2-C5アルキニル基、C3-C6シクロアルキル基、C3-C6ヘテロシクロアルキル基、NR5R6、C(O)R8、P(O)R8R9、S(O)n(C1-C3)アルキル基、S(O)n(C3-C6)シクロアルキル基から選ばれ、ここで、n=0,1,2であり、且つ2つの隣接するR7は4~12員環を形成できる。
R2は、水素、ハロゲン、OH、NR5R6、シアノ基、C1-C5アルキル基から選ばれ、
Qは、CHR5CHR6、O、OC(R5R6)、C(R5R6)、CO、NR5C(O)、NR5S(O)2、CH=CH、C≡C、S(O)n、S(O)n(C1-C3)アルキル基から選ばれ、ここで、n=0,1,2であり、
Zは、ベンゼン環、ピリジンから選ばれ、その環上の水素はR4によって置換されてよく、
Xは、O(C0-C3)アルキル基、NR5(C0-C3)アルキル基、NR5C(O)、NR5S(O)2、C(O)NR5、S(O)2NR5、N(R5)C(O)N(R6)、N(R5)C(S)N(R6)から選ばれ、
R4は、ハロゲン、OH、シアノ基、O(C1-C5)アルキル基、C1-C5アルキル基から選ばれ、
R5及びR6は、水素、C1-C3アルキル基から独立してから選ばれ、又はR5とR6が結合して3~6員環が形成される。
当該好ましい実施形態のいくつかの実施形態において、Zはベンゼン環、ピリジンから選ばれ、その環上の水素は1つ又は複数のR4によって独立して置換されてよく、且つR4はハロゲン、OH、シアノ基、O(C1-C3)アルキル基、C1-C3アルキル基から選ばれる。いくつかの更なる実施形態において、Zはベンゼン環、ピリジンから選ばれ、その環上の水素は1つ又は複数のR4によって独立して置換されてよく、且つR4はハロゲン、OH、シアノ基、O(C1-C3)アルキル基、C1-C3アルキル基から選ばれ、QはOC(R5R6)に選ばれ、ここでR5及びR6は水素、C1-C3アルキル基から独立して選ばれ、又はR5とR6が結合して3~6員環が形成される。更なる実施形態において、Zはベンゼン環、ピリジンから選ばれ、その環上の水素は1つ又は複数のR4によって独立して置換されてよく、且つR4はハロゲン、OH、シアノ基、O(C1-C3)アルキル基、C1-C3アルキル基から選ばれ、QはOC(R5R6)に選ばれ、ここでR5及びR6の一方は水素であり、他方はC1-C3アルキル基から選ばれる。
Wは、C6-C10アリール基、5~10員のヘテロアリール基から選ばれ、その環上の水素は1つ又は複数のR7によって独立して置換されてよく、
R7は、水素、ハロゲン、ヒドロキシ基、ニトロ基、シアノ基、O(C1-C3)アルキル基、(C1-C5)ヘテロアルキル基、O(C3-C6)シクロアルキル基、O(C3-C6)ヘテロシクロアルキル基、C1-C5アルキル基、C=C、C≡C、C3-C6シクロアルキル基、C3-C6ヘテロシクロアルキル基、NR5R6、C(O)(C1-C2)アルキル基、C(O)O(C1-C2)アルキル基、P(O)(C1-C2アルキル)2基、SO2(C1-C3)アルキル基、SO2シクロプロピル基、S(C1-C3)アルキル基から選ばれ、且つ2つの隣接するR7は5~7員環を形成でき、
R5及びR6は、水素、C1-C3アルキル基、C3-C6シクロアルキル基、C(O)C1-C3アルキル基、S(O)2(C1-C3)アルキル基、S(O)2(C3-C6)シクロアルキル基から独立して選ばれ、又はR5とR6が結合して3~6員環が形成される。
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-3-メチルベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-3-フルオロベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-3-クロロベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-2-フルオロ-5-メチルベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-2-フルオロベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)ベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-5-フルオロ-2-メチルベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-5-メチルニコチンアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-5-フルオロニコチンアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)フェニル)-5-クロロニコチンアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-クロロベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-フルオロ-5-メチルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-5-メチルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メトキシベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-クロロニコチンアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルニコチンアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シアノベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-トリフルオロメトキシベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-トリフルオロメチルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-3-メチルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジクロロベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,5-ジクロロベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジクロロベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[d][1,3]ジオキソール-5-ベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-ブロモベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-C≡Cベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メトキシベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シアノベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,5-ジクロロベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-C≡Cベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(イソプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(シクロプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルホスホリル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルニコチンアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-フルオロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-イソプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-イソプロポキシベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(エチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-3-メトキシベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-ヒドロキシシクロペンチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-ヒドロキシシクロブチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-4-クロロフェニル)-2-クロロ-3-メチルベンズアミド
N-(3-((R)-1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-((2-ヒドロキシシクロヘキシル)アミノ)ベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-フルオロフェニル)-2-クロロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-ヒドロキシシクロヘキシル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-4-((4-メチルピペラジン-1-イル)メチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-3-((4-メチルピペラジン-1-イル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-4-(4-メチルピペラジン-1-イル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-メトキシ-5-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-((4-メチルピペラジン-1-イル)メチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(シクロプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(イソプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(シクロペンチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)キノリン-3-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)イソキノリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)キノリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ピロリジン-1-イルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-シクロプロピルニコチンアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)ピリジン-3-イル)-2-クロロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-シアノシクロプロピル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロブチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ピロリジン-1-イル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-4-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-5-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[d][1,3]ジオキソール-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-フルオロピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-メチルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-(トリフルオロメチル)ピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-(トリフルオロメチル)ピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-6-(トリフルオロメチル)ピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルスルホニル)ベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-メチルフェニル)-3-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-6-メチルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-クロロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-フルオロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロ-1H-インデン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-6-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-フルオロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-クロロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,5-ジメチルベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-トリル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-4-フルオロフェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-4-クロロフェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(6-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-ピリジン)-2-イル)-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-4-メチルフェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-メチルフェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(4-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)ピリジン-2-イル)-3-メチルベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-クロロフェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-フルオロフェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-フェニル)-3-(メチルスルホニル)-4-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[b]チオフェン-5-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[b]チオフェン-6-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)-5-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチル-5-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1,5-ジメチル-1H-ピラゾール-3-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルチアゾール-2-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-(tert-ブチル)-1H-ピラゾール-4-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-(イソプロピル)-1H-ピラゾール-4-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1H-インダゾール-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾフラン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1H-インドール-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-(tert-ブチル)イソキサゾール-3-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-7-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1,2,3,4-テトラヒドロキノリン-7-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチルインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-2-オキソインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1,3-ジヒドロイソベンゾフラン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,5-ジメチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-6-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)-4-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)-5-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチル-5-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)-4-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2’,3’-ジヒドロスピロ[シクロプロパン-1,1’-インデン]-6’-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-1-メチルインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-クロロ-3-(ジメチルアミノ)ベンズアミド
メチル(R)-3-((3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)カルバモイル)ベンゾエート
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-イソプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロ-1H-インデン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-エチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-5-イソプロピルニコチンアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1H-インドール-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[b]チオフェン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,3-ジメチル-1,3-ジヒドロイソベンゾフラン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2H-スピロ[ベンゾフラン-3,1’-シクロプロパン]-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾフラン-5-カルボキサミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-トリフルオロメチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3,4-ジメチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3,5-ジメチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)-4-メチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-1-メチルインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-(ピペリジン-4-イル)-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-シクロプロピル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-エチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチルピペリジン-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(4-ヒドロキシ-3-メトキシフェニル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-6’-(4-メチルピペラジン-1-イル)-[3,3’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,4’-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
N-(3-(((5-クロロ-2-(メチルアミノ)ピリジン-3-イル)オキシ)メチル)フェニル)-3-メチルベンズアミド
N-(3-(((2-アミノピリジン-3-イル)オキシ)メチル)フェニル)-3-メチルベンズアミド
5-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)-N-((6-(トリフルオロメチル)ピリジン-3-イル)メチル)ピリジン-2-アミン
5-クロロ-3-((3-メトキシ-4-((4-メトキシベンジル)オキシ)ベンジル)オキシ)ピリジン-2-アミン
5-クロロ-3-(3-メトキシ-4-((4-メトキシベンジル)オキシ)フェノキシ)ピリジン-2-アミン
N-(3-(((3-アミノ-6-クロロピペラジン-2-イル)オキシ)メチル)フェニル)-3-メチルベンズアミド
5-クロロ-3-((3-メトキシ-4-((4-メトキシベンジル)オキシ)ベンジル)オキシ)ピペラジン-2-アミン
5-クロロ-3-(3-メトキシ-4-((4-メトキシベンジル)オキシ)フェノキシ)ピペラジン-2-アミン
(S)-N-(3-(1-((3-アミノ-6-クロロピペラジン-2-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
5-クロロ-3-((6-((4-メトキシベンジル)オキシ)ピリジン-3-イル)メトキシ)ピリジン-2-アミン
(E)-5-クロロ-3-(3-メトキシ-4-((4-メトキシベンジル)オキシ)スチリル)ピリジン-2-アミン
(E)-N-(3-(2-(2-アミノ-5-クロロピリジン-3-イル)ビニル)フェニル)-3-メチルベンズアミド
N-(3-(2-(2-アミノ-5-クロロピリジン-3-イル)シクロプロピル)フェニル)-3-メチルベンズアミド
N-(3-(2-((2-アミノ-5-クロロピリジン-3-イル)オキシ)プロパン)-2-イル)フェニル)-3-メチルベンズアミド
N-(3-(2-((2-アミノ-5-クロロピリジン-3-イル)オキシ)プロパン)-2-イル)フェニル)-2-クロロ-5-メチルベンズアミド
N-(3-(2-((2-アミノ-5-クロロピリジン-3-イル)オキシ)プロパン)-2-イル)フェニル)-3-メトキシベンズアミド
N-(3-(2-((2-アミノ-5-クロロピリジン-3-イル)オキシ)プロパン)-2-イル)フェニル)-2-クロロ-3-メチルベンズアミド
N-(3-(2-((2-アミノ-5-クロロピリジン-3-イル)オキシ)プロパン)-2-イル)フェニル)-2,5-ジクロロベンズアミド
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロプロピル)フェニル)-3-メチルベンズアミド
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロブチル)フェニル)-3-メチルベンズアミド
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロペンチル)フェニル)-3-メチルベンズアミド
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロヘキシル)フェニル)-3-メチルベンズアミド
5-クロロ-3-((5-メトキシ-6-((4-メトキシベンジル)オキシ)ピリジン-3-イル)オキシ)ピリジン-2-アミン
5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-N-((6-(トリフルオロメチル)ピリジン-3-イル)メチル)ピリジン-2-アミン
4-((4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-メトキシフェノキシ)メチル)ベンゾニトリル
5-クロロ-3-(3-メトキシ-4-((4-トリフルオロメチル)ベンジル)オキシ)フェノキシ)ピリジン-2-アミン
4-(((5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-3-メトキシピリジン-2-イル)オキシ)メチル)ベンゾニトリル
5-クロロ-3-((6-((4-クロロベンジル)オキシ)-5-メトキシピリジン-3-イル)オキシ)ピリジン-2-アミン
N-(4-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-3-メトキシベンズアミド
N-(4-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-4-メトキシベンズアミド
N-(4-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-4-シアノベンズアミド
N-(3-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-3-メチルベンズアミド
N-(3-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-3-メトキシベンズアミド
N-(3-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-3-クロロベンズアミド
N-(3-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-3-トリフルオロメトキシベンズアミド
N-(3-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-4-メチルベンズアミド
N-(3-((2-アミノ-5-クロロピリジン)-3-イル)オキシ)フェニル)-3-(メチルスルホニル)ベンズアミド
N-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(1-ヒドロキシシクロペンチル)ベンズアミド
N-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-シクロプロピルベンズアミド
N-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(1-シアノシクロプロピル)ベンズアミド
N-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-メチルピリジン-1-イル)ベンズアミド
N-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-フルオロフェニル)-3-メトキシベンズアミド
N-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-クロロフェニル)-3-メトキシベンズアミド
N-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-メチルフェニル)-3-メトキシベンズアミド
N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-フルオロフェニル)-3-メトキシベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)-2-フルオロフェニル)-3-メトキシベンズアミド
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)-4-フルオロフェニル)-3-メトキシベンズアミド
(R)-N-(3-(1-((5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
(R)-N-(3-(1-((6-クロロピラジン-2-イル)オキシ)エチル)フェニル)-3-(トリフルオロメチル)ベンズアミド
(R)-1-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-3-(4-メチルフェニル)尿素
(R)-1-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-3-(3-メチルフェニル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(m-トリル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-トリル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-(メチルスルホニル)フェニル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(m-トリル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-トリル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-メチルフェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-3-メチルフェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-3-フルオロフェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-フルオロフェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-メチルフェニル)-3-(4-トリル)尿素
1-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-クロロフェニル)-3-(4-トリル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-(ジメチルアミノ)フェニル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(4-(メトキシ)フェニル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(2,3-ジヒドロベンゾ[b]チオフェン-5-イル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(ベンゾ[b]チオフェン-5-イル)尿素
1-(3-((2-アミノ-5-クロロピリジン-3-イル)オキシ)フェニル)-3-(1-(tert-ブチル)-1H-ピラゾール-4-イル)尿素
1-(3-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)フェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(3-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)フェニル)-3-(4-トリル)尿素
1-(3-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)フェニル)-3-(4-(メチルスルホニル)フェニル)尿素
1-(4-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)フェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(4-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)-2-フルオロフェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(3-((6-アミノ-[3,3’-ビピリジン-5-イル)オキシ)フェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
1-(3-((6-アミノ-[3,3’-ビピリジン-5-イル)オキシ)フェニル)-3-(4-トリル)尿素
1-(3-((6-アミノ-[3,3’-ビピリジン-5-イル)オキシ)フェニル)-3-(4-(メチルスルホニル)フェニル)尿素
1-(4-((6-アミノ-[3,3’-ビピリジン-5-イル)オキシ)フェニル)-3-(4-クロロ-3-(トリフルオロメチル)フェニル)尿素
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-5-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-シクロプロピル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-クロロ-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-フルオロ-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シアノ-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1,3-ジメチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-(2-(ジメチルアミノ)-2-オキソエチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(3-メチル-1H-ピラゾール-5-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N1-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)イソフタルアミド
N-(3-((R)-1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルフィニル)ベンズアミド
N-(3-((S)-1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルフィニル)ベンズアミド
(S)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(S)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(S)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)-4-メチルベンズアミド
(S)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルチオ)ベンズアミド
(S)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルチオ)ベンズアミド
(1)親化合物の遊離塩基と、塩酸、臭化水素酸、硝酸、リン酸、硫酸、過塩素酸等の無機酸、又は酢酸、シュウ酸、(D)もしくは(L)リンゴ酸、マレイン酸、メタンスルホン酸、エタンスルホン酸、p-トルエンスルホン酸、サリチル酸、酒石酸、クエン酸、コハク酸、マロン酸等の有機酸が反応して得た酸付加塩、
(2)親化合物に存在する酸性プロトンが、アルカリ金属イオン、アルカリ土類イオン又はアルミニウムイオン等の金属イオンによって置換されることにより、又は、エタノールアミン、ジエタノールアミン、トリエタノールアミン、トロメタミン、N-メチルグルカミン等の有機塩基と配位することにより形成された塩、が含まれる。
次に、いくつかの実施例を用いて、本発明に係る化合物の製造をさらに説明するが、本発明はこれらの実施例に限定されない。
2-アミノ-3-ヒドロキシ-5-クロロピリジンの合成:
3-((3-アミノベンジル)オキシ)-5-クロロピリジン-2-アミンの合成:
化合物20~29の合成:
フラスコに9(57mg、0.2mmol)、R-COOH(1.2当量、0.24mmol)、EDCI(58mg、0.3mmol)とDMAP(5mg、0.04mmol)のDCM(5mL)溶液をこの順に加え、攪拌しながらDIPEA(77mg、0.6mmol)を加える。室温で一晩攪拌して反応させ、次にカラムクロマトグラフィーによって精製して、生成物を得る。
(S)-(3-(1-ヒドロキシエチル)フェニル)tert-ブチルカルバメートの合成:
化合物54~71の合成:
化合物72~164の合成は、化合物54~71の手順と同様である。
化合物168~195の合成:
化合物199~208の合成は、化合物168~195の手順と同様である。
(R)-N-(3-(1-((2-アミノ-5-(1-(ピペリジン-4-イル)-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミドの合成:
化合物212~217の合成は、化合物168~195の手順と同様である。
化合物222~226の合成:
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミドの合成:
N-(3-(((5-クロロ-2-(メチルアミノ)ピリジン-3-イル)オキシ)メチル)フェニル)-3-メチルベンズアミドの合成:
N-(3-(((2-アミノピリジン-3-イル)オキシ)メチル)フェニル)-3-メチルベンズアミドの合成:
5-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)-N-((6-(トリフルオロメチル)ピリジン-3-イル)メチル)ピリジン-2-アミンの合成
5-クロロ-3-((3-メトキシ-4-((4-メトキシベンジル)オキシ)ベンジル)オキシ)ピリジン-2-アミンの合成
5-クロロ-3-(3-メトキシ-4-((4-メトキシベンジル)オキシ)フェノキシ)ピリジン-2-アミンの合成:
N-(3-(((3-アミノ-6-クロロピペラジン-2-イル)オキシ)メチル)フェニル)-3-メチルベンズアミドの合成:
5-クロロ-3-((3-メトキシ-4-((4-メトキシベンジル)オキシ)ベンジル)オキシ)ピペラジン-2-アミンの合成:
5-クロロ-3-(3-メトキシ-4-((4-メトキシベンジル)オキシ)フェノキシ)ピペラジン-2-アミンの合成:
化合物256~258の合成は、実施例18の手順と同様である。
5-クロロ-3-((6-((4-メトキシベンジル)オキシ)ピリジン-3-イル)メトキシ)ピリジン-2-アミンの合成:
(E)-5-クロロ-3-(3-メトキシ-4-((4-メトキシベンジル)オキシ)スチリル)ピリジン-2-アミンの合成:
(E)-N-(3-(2-(2-アミノ-5-クロロピリジン-3-イル)ビニル)フェニル)-3-メチルベンズアミドの合成:
N-(3-(2-(2-アミノ-5-クロロピリジン-3-イル)シクロプロピル)フェニル)-3-メチルベンズアミドの合成:
化合物272~275の合成:
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロプロピル)フェニル)-3-メチルベンズアミドの合成:
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロブチル)フェニル)-3-メチルベンズアミドの合成:
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロペンチル)フェニル)-3-メチルベンズアミドの合成:
N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)シクロヘキシル)フェニル)-3-メチルベンズアミドの合成:
5-クロロ-3-((5-メトキシ-6-((4-メトキシベンジル)オキシ)ピリジン-3-イル)オキシ)ピリジン-2-アミンの合成:
5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-N-((6-(トリフルオロメチル)ピリジン-3-イル)メチル)ピリジン-2-アミンの合成:
4-((4-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-メトキシフェノキシ)メチル)ベンゾニトリルの合成:
5-クロロ-3-(3-メトキシ-4-((4-トリフルオロメチル)ベンジル)オキシ)フェノキシ)ピリジン-2-アミンの合成:
4-(((5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-3-メトキシピリジン-2-イル)オキシ)メチル)ベンゾニトリルの合成:
5-クロロ-3-((6-((4-クロロベンジル)オキシ)-5-メトキシピリジン-3-イル)オキシ)ピリジン-2-アミンの合成:
化合物302~314の合成は、実施例5の手順と同様である。
N-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-フルオロフェニル)-3-メトキシベンズアミドの合成:
N-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-クロロフェニル)-3-メトキシベンズアミドの合成:
N-(5-((2-アミノ-5-クロロピリジン-3-イル)オキシ)-2-メチルフェニル)-3-メトキシベンズアミドの合成:
N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-2-フルオロフェニル)-3-メトキシベンズアミドの合成:
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)-2-フルオロフェニル)-3-メトキシベンズアミドの合成:
N-(3-(((2-アミノ-5-クロロピリジン-3-イル)オキシ)メチル)-4-フルオロフェニル)-3-メトキシベンズアミドの合成:
(R)-N-(3-(1-((5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミドの合成:
(R)-N-(3-(1-((6-クロロピラジン-2-イル)オキシ)エチル)フェニル)-3-(トリフルオロメチル)ベンズアミド:
(R)-1-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-3-(4-メチルフェニル)尿素の合成:
(R)-1-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-3-(3-メチルフェニル)尿素の合成:
化合物330~347の合成経路は以下のとおりである。
化合物348~356の合成は、実施例7の手順と同様である。
化合物357~366の合成は、実施例7の手順と同様である。
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルフィニル)ベンズアミドの合成:
化合物368~373の合成は、実施例7の手順と同様である。
I.材料と器具:
2104 EnVision(登録商標)マルチラベルリーダー(パーキンエルマー社)
OptiPlate-384、White Opaque 384ウェルマイクロプレート(カタログ番号6007290、パーキンエルマー社)
HTRF kinEASE TKキット(カタログ番号62TKOPEC、シスバイオ社)
CSF-1R(カタログ番号PV3249、インビトロジェン社)
ATP 10mM(カタログ番号PV3227、インビトロジェン社)
DTT 1M(カタログ番号D5545、シグマ社)
MgCl2 1M(カタログ番号M8266、シグマ社)
MnCl2 1M(カタログ番号244589、シグマ社)
1.試薬の調製:
CSF-1Rキナーゼの濃度は表15を参照する。1×キナーゼバッファーを用いて、5×酵素ワーキング溶液を調製する。
Sa-XL665の反応中における濃度は表15を参照する。検出バッファーを用いて、4×Sa-XL665ワーキング溶液を調製する。
検出バッファーでTK-Ab-クリプテートを100倍に希釈したものを、ワーキング溶液とする。
上記の方法に従って全ての試薬を調製した後、酵素を除いて、室温に平衡させ、サンプルをロードする。
1.実験材料:
1.1 細胞株:
マウス骨髄性白血病細胞(NFS-60)
使用直前にDMSOで溶解し、因子フリーの完全培地を用いて、所望の濃度を調製する。
培地:RPMI 1640培地(Gibco社、カタログ番号:31800-022)
ウシ胎児血清:PANSera ES(カタログ番号:2602-P130707)
ペニシリンーストレプトマイシン:TRANS
トリプシン:Gibco社、カタログ番号:25300-062
PBS:ハイクローン社、カタログ番号:SH30258.01
マウス M-CSF/CSF-1タンパク質:Sino Biological Inc. カタログ番号:51112-MNAH
M-CSF:斉魯制薬有限公司提供
対数増殖期のNFS-60細胞(1640培地+10%FBS+40ng/mlのM-CSF+ペニシリンーストレプトマイシン1%)を遠心分離し(1000r/min)、因子フリーの培地に交換して37℃、5%CO2で24時間培養する。遠心分離(1000r/min)し、40ng/mL因子を含む培地に交換して、2×104個/mLで、1ウェル当たり100μLで96ウェルプレートに接種し、16時間後に、1ウェル当たり10μLで、調製された被験化合物を加え、各化合物は3つの重複ウェルを設け、37℃、5%CO2で引き続き72時間培養した後、各ウェルに10μLのCCK試薬を加える。さらに4時間インキュベートした後、波長450nmにて各ウェルの吸光度を測定する。
NFS-60細胞の増殖阻害に関する、代表的な実施例3~52で製造された化合物0.5μMの実験結果は次のとおりである。
本研究では、C57マウスにMC-38細胞株を接種する。
実験動物:C57マウス、雄性、5~6週齢(18~22g)
細胞株:MC38
接種:2×106個/0.1mLとし、3:1の比率でマトリゲルを追加する。
PD1:インビボMAb抗マウスPD-1(CD279)(Bio X Cell社)
群分け:
接種後4日目に、モデル群、抗PD1 2mg/kg群、抗PD1 10mg/kg群、被験化合物のみ群、被験化合物と抗PD1 10mg/kg併用群とランダムに13群に分ける。化合物は毎日30mg/kgの用量で胃内投与し、抗PD1は3日に1回で腹腔内注射する。2週間にわたり継続的に投与する。モデル群では、80%グリセロールと20%の0.5%CMC-Naを毎日胃内投与する。
MC-38移植腫瘍の腫瘍サイズの阻害に関する、代表的な実施例3~52で製造された化合物と抗PD1の併用の実験結果は次のとおりである。
Claims (9)
- 一般式(Ib)
R3は、水素、ハロゲン、C6-C10アリール基、5~10員のヘテロアリール基、C3-C6ヘテロシクロアルキル基から選ばれ、R3の水素のそれぞれは1つ又は複数のR7によって独立して任意に置換されてよく、且つ隣接するR7は5~7員環を形成でき、
Wは、C6-C10アリール基、5~10員のヘテロアリール基から選ばれ、その環上の水素は1つ又は複数のR7によって独立して置換されてよく、
R7は、水素、ハロゲン、ヒドロキシ基、ニトロ基、シアノ基、O(C1-C3)アルキル基、(C1-C5)ヘテロアルキル基、O(C3-C6)シクロアルキル基、O(C3-C6)ヘテロシクロアルキル基、C1-C5アルキル基、C 3-C6シクロアルキル基、C3-C6ヘテロシクロアルキル基、NR5R6、C(O)(C1-C2)アルキル基、C(O)O(C1-C2)アルキル基、P(O)(C1-C2アルキル)2基、SO2シクロプロピル基、S(O)n(C1-C3)アルキル基から選ばれ、
ここで、n=0,1,2であり、且つ2つの隣接するR7は5~7員環を形成でき、
R5及びR6は水素、C1-C3アルキル基、C3-C6シクロアルキル基、C(O)C1-C3アルキル基、S(O)2(C1-C3)アルキル基、S(O)2(C3-C6)シクロアルキル基から独立して選ばれ、又はR5とR6が結合して3~6員環が形成される化合物。 - R3は水素、ハロゲンから選ばれ、Wはベンゼン環、5~10員のヘテロアリール基から選ばれ、その環上の水素は1つ又は複数のR7によって独立して置換されてよく、且つ2つの隣接するR7は5~7員環を形成でき、ここでR7はハロゲン、ヒドロキシ基、ニトロ基、シアノ基、O(C1-C3)アルキル基、(C1-C5)ヘテロアルキル基、O(C3-C6)シクロアルキル基、O(C3-C6)ヘテロシクロアルキル基、C1-C5アルキル基、C 3-C6シクロアルキル基、C3-C6ヘテロシクロアルキル基、N((C1-C2)アルキル)2基、NH(C1-C2)アルキル基、C(O)(C1-C2)アルキル基、C(O)O(C1-C2)アルキル基、P(O)(C1-C2アルキル)2基、SO2シクロプロピル基、S(O)n(C1-C3)アルキル基から選ばれ、ここで、n=0,1,2である請求項1に記載の化合物。
- R3はフェニル基、5~10員のヘテロアリール基、C3-C6ヘテロシクロアルキル基から選ばれ、その環上の水素はハロゲン、ヒドロキシ基、ニトロ基、シアノ基、O(C1-C3)アルキル基、(C1-C5)ヘテロアルキル基、O(C3-C6)シクロアルキル基、O(C3-C6)ヘテロシクロアルキル基、C1-C5アルキル基、C 3-C6シクロアルキル基、C3-C6ヘテロシクロアルキル基、N((C1-C2)アルキル)2基、NH(C1-C2)アルキル基、C(O)(C1-C2)アルキル基、C(O)O(C1-C2)アルキル基、P(O)(C1-C2アルキル)2基、SO2シクロプロピル基、S(O)n(C1-C3)アルキル基によって独立して置換されてよく、ここで、n=0,1,2であり、Wはベンゼン環、5~10員のヘテロアリール基から選ばれ、その環上の水素は1つ又は複数のR7によって独立して置換され、且つ置換基の1つはNH2、N((C1-C2)アルキル)2基、NH(C1-C2)アルキル基、C(O)(C1-C2)アルキル基、C(O)O(C1-C2)アルキル基、P(O)(C1-C2アルキル)2基、SO2シクロプロピル基、S(O)n(C1-C3)アルキル基に限られ、ここで、n=0,1,2であり、且つWで隣接する置換基は5~7員環を形成できる請求項1に記載の化合物。
- R3はフェニル基、ピラゾール、ピリジンから選ばれ、その環上の水素はハロゲン、シアノ基、O(C1-C3)アルキル基、C1-C3アルキル基、C3-C6シクロアルキル基、(C1-C5)ヘテロアルキル基、C3-C6ヘテロシクロアルキル基、N((C1-C2)アルキル)2基、NH(C1-C2)アルキル基によって置換されてよく、且つR3で隣接する置換基は5~7員環を形成できる請求項3に記載の化合物。
- R3はピラゾール、ピリジンから選ばれ、その環上の水素はハロゲン、シアノ基、C1-C3アルキル基、C3-C6シクロアルキル基、(C1-C5)ヘテロアルキル基、C3-C6ヘテロシクロアルキル基によって置換されてよく、且つR3で隣接する置換基は5~7員環を形成できる請求項4に記載の化合物。
- Wはベンゼン環に選ばれ、その環上の水素は1つ又は複数のR7によって独立して置換され、且つ置換基の1つはN((C1-C2)アルキル)2基、C(O)(C1-C2)アルキル基、C(O)O(C1-C2)アルキル基、P(O)(C1-C2アルキル)2基、SO2シクロプロピル基、S(O)n(C1-C3)アルキル基に限られ、ここで、n=0,1,2であり、且つWで隣接する置換基は5~7員環を形成できる請求項3、4又は5に記載の化合物。
- (R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-メトキシベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シアノベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,5-ジクロロベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-エチニルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(イソプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(シクロプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルホスホリル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルニコチンアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-フルオロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-イソプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-イソプロポキシベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(エチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-クロロ-3-メトキシベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-ヒドロキシシクロペンチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-ヒドロキシシクロブチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-4-クロロフェニル)-2-クロロ-3-メチルベンズアミド
N-(3-((R)-1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-((2-ヒドロキシシクロヘキシル)アミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-ヒドロキシシクロヘキシル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-4-((4-メチルピペラジン-1-イル)メチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-3-((4-メチルピペラジン-1-イル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)イル)エチル)フェニル)-4-(4-メチルピペラジン-1-イル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2-メトキシ-5-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-((4-メチルピペラジン-1-イル)メチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(シクロプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(イソプロピルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(シクロペンチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)キノリン-3-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)イソキノリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)キノリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ピロリジン-1-イルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-シクロプロピルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(1-シアノシクロプロピル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロブチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ピロリジン-1-イル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-4-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-5-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[d][1,3]ジオキソール-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-フルオロピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-メチルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-(トリフルオロメチル)ピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-(トリフルオロメチル)ピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-6-(トリフルオロメチル)ピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-6-メチルピリジンカルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-クロロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-4-フルオロ-3-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロ-1H-インデン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-6-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-フルオロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-クロロ-5-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,5-ジメチルベンズアミド
(R)-N-(5-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)-フェニル)-3-(メチルスルホニル)-4-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[b]チオフェン-5-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[b]チオフェン-6-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)-5-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチル-5-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1,5-ジメチル-1H-ピラゾール-3-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-メチルチアゾール-2-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-(tert-ブチル)-1H-ピラゾール-4-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-(イソプロピル)-1H-ピラゾール-4-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1H-インダゾール-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)ベンゾフラン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1H-インドール-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-5-(tert-ブチル)イソキサゾール-3-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-7-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1,2,3,4-テトラヒドロキノリン-7-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチルインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-2-オキソインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-クロロピリジン-3-イル)オキシ)エチル)フェニル)-1,3-ジヒドロイソベンゾフラン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,5-ジメチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾ[b]チオフェン-6-カルボキサミド 1,1-ジオキシド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)-4-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)-5-(トリフルオロメチル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,4-ジメチル-5-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)-4-メチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-メチル-3-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2',3'-ジヒドロスピロ[シクロプロパン-1,1'-インデン]-6'-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-1-メチルインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-クロロ-3-(ジメチルアミノ)ベンズアミド
メチル(R)-3-((3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)カルバモイル)ベンゾエート
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-イソプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロ-1H-インデン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-エチルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-5-イソプロピルニコチンアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-1-メチル-1H-インドール-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)ベンゾ[b]チオフェン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3,3-ジメチル-1,3-ジヒドロイソベンゾフラン-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2H-スピロ[ベンゾフラン-3,1'-シクロプロパン]-5-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-2,3-ジヒドロベンゾフラン-5-カルボキサミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(メチルスルホニル)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-トリフルオロメチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-メチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3,4-ジメチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3,5-ジメチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)-4-メチルベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-1-メチルインドリン-6-カルボキサミド
(R)-N-(3-(1-((2-アミノ-5-(1-(ピペリジン-4-イル)-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シクロプロピルベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-シクロプロピル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-エチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチルピペリジン-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(4-ヒドロキシ-3-メトキシフェニル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-6'-(4-メチルピペラジン-1-イル)-[3,3'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((6-アミノ-[3,4'-ビピリジン]-5-イル)オキシ)エチル)フェニル)-3-(ジメチルアミノ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-5-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-シクロプロピル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-クロロ-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-フルオロ-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-シアノ-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1,3-ジメチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(1-(2-(ジメチルアミノ)-2-オキソエチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N-(3-(1-((2-アミノ-5-(3-メチル-1H-ピラゾール-5-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)ベンズアミド
(R)-N1-(3-(1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-4-(メチルチオ)イソフタルアミド
N-(3-((R)-1-((2-アミノ-5-(1-メチル-1H-ピラゾール-4-イル)ピリジン-3-イル)オキシ)エチル)フェニル)-3-(メチルスルフィニル)ベンズアミド
から選ばれる請求項1に記載の化合物。 - 治療有効量の請求項1~7のいずれか1項に記載の少なくとも1つの化合物と、少なくとも1つの薬学的に許容される添加物とを含むことを特徴とする医薬組成物。
- 医薬品の製造における請求項8に記載の医薬組成物の使用。
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PCT/CN2019/078006 WO2019174601A1 (en) | 2018-03-15 | 2019-03-13 | Heteroaryl compounds as kinase inhibitor |
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PT (1) | PT3749646T (ja) |
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WO2005002673A1 (en) | 2003-07-03 | 2005-01-13 | Astex Therapeutics Limited | Raf kinase inhibitors |
JP2005538975A (ja) | 2002-07-03 | 2005-12-22 | アステックス テクノロジー リミテッド | p38MAPキナーゼ阻害薬としての3−(ヘテロ)アリールメトキシピリジン類およびそれらの類縁体 |
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SI1603570T1 (sl) * | 2003-02-26 | 2013-03-29 | Sugen, Inc. | Spojine aminoheteroarila kot zaviralci proteinkinaze |
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JP2005538975A (ja) | 2002-07-03 | 2005-12-22 | アステックス テクノロジー リミテッド | p38MAPキナーゼ阻害薬としての3−(ヘテロ)アリールメトキシピリジン類およびそれらの類縁体 |
WO2005002673A1 (en) | 2003-07-03 | 2005-01-13 | Astex Therapeutics Limited | Raf kinase inhibitors |
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PT3749646T (pt) | 2022-06-24 |
AU2019233207B2 (en) | 2021-05-27 |
US20220380312A1 (en) | 2022-12-01 |
EP3749646A1 (en) | 2020-12-16 |
KR20200119850A (ko) | 2020-10-20 |
SI3749646T1 (sl) | 2022-09-30 |
CA3093138C (en) | 2023-01-03 |
CA3093138A1 (en) | 2019-09-19 |
AU2019233207A1 (en) | 2020-10-01 |
CN116715625A (zh) | 2023-09-08 |
SG11202008705TA (en) | 2020-10-29 |
KR102556742B1 (ko) | 2023-07-18 |
EP3749646A4 (en) | 2020-12-23 |
CN111601790B (zh) | 2023-03-31 |
PL3749646T3 (pl) | 2022-07-25 |
US11767296B2 (en) | 2023-09-26 |
HUE058998T2 (hu) | 2022-09-28 |
EP3749646B1 (en) | 2022-04-06 |
WO2019174601A1 (en) | 2019-09-19 |
JP2021516250A (ja) | 2021-07-01 |
CN111601790A (zh) | 2020-08-28 |
LT3749646T (lt) | 2022-07-11 |
ES2920702T3 (es) | 2022-08-08 |
DK3749646T3 (da) | 2022-05-02 |
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