ES2658290T3 - Inhibidores de cinasa - Google Patents
Inhibidores de cinasa Download PDFInfo
- Publication number
- ES2658290T3 ES2658290T3 ES10827573.6T ES10827573T ES2658290T3 ES 2658290 T3 ES2658290 T3 ES 2658290T3 ES 10827573 T ES10827573 T ES 10827573T ES 2658290 T3 ES2658290 T3 ES 2658290T3
- Authority
- ES
- Spain
- Prior art keywords
- pyrido
- pyrimidin
- phenylamino
- trifluoromethyl
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
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- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- -1 aryl (C1-C6) alkyl Chemical group 0.000 abstract description 128
- 150000001875 compounds Chemical class 0.000 abstract description 43
- 125000003118 aryl group Chemical group 0.000 abstract description 20
- 229920006395 saturated elastomer Polymers 0.000 abstract description 19
- 125000005842 heteroatom Chemical group 0.000 abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 16
- 125000002950 monocyclic group Chemical group 0.000 abstract description 15
- 125000002619 bicyclic group Chemical group 0.000 abstract description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 13
- 229910052717 sulfur Inorganic materials 0.000 abstract description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 abstract description 11
- 150000003839 salts Chemical class 0.000 abstract description 11
- 239000011593 sulfur Chemical group 0.000 abstract description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 10
- 239000001301 oxygen Chemical group 0.000 abstract description 10
- 150000003457 sulfones Chemical group 0.000 abstract description 10
- 150000003462 sulfoxides Chemical group 0.000 abstract description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 8
- 125000000217 alkyl group Chemical group 0.000 abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 abstract description 4
- 125000005843 halogen group Chemical group 0.000 abstract description 4
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract description 3
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 abstract description 3
- 229940124530 sulfonamide Drugs 0.000 abstract description 3
- 150000003456 sulfonamides Chemical class 0.000 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical class 0.000 abstract description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- CSBPQHGADOHBPJ-UHFFFAOYSA-N 6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1=NC=C2C(=O)NC=CC2=N1 CSBPQHGADOHBPJ-UHFFFAOYSA-N 0.000 description 42
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- 238000000034 method Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 208000008839 Kidney Neoplasms Diseases 0.000 description 8
- 206010038389 Renal cancer Diseases 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 201000010982 kidney cancer Diseases 0.000 description 8
- 201000001441 melanoma Diseases 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- 206010033128 Ovarian cancer Diseases 0.000 description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 description 6
- 201000007455 central nervous system cancer Diseases 0.000 description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- GEOYUPAKWBFMCY-UHFFFAOYSA-N 2-(4-aminopiperidin-1-yl)-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one;hydrochloride Chemical compound Cl.C1CC(N)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 GEOYUPAKWBFMCY-UHFFFAOYSA-N 0.000 description 3
- BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 3
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 3
- 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 3
- RYGGCIBGKFDTSD-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound FC(F)(F)C1=CC=CC(NC=2C=3C(=O)NC=CC=3N=C(N=2)N2CC3=CC=CC=C3CC2)=C1 RYGGCIBGKFDTSD-UHFFFAOYSA-N 0.000 description 2
- XODWAOQPSCMAOU-UHFFFAOYSA-N 2-(4-aminopiperidin-1-yl)-4-[3,5-bis(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one;hydrochloride Chemical compound Cl.C1CC(N)CCN1C1=NC(NC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C2C(=O)NC=CC2=N1 XODWAOQPSCMAOU-UHFFFAOYSA-N 0.000 description 2
- PFXJJNWJPALFKW-UHFFFAOYSA-N 2-(4-hydroxypiperidin-1-yl)-4-[3-methoxy-5-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound FC(F)(F)C1=CC(OC)=CC(NC=2C=3C(=O)NC=CC=3N=C(N=2)N2CCC(O)CC2)=C1 PFXJJNWJPALFKW-UHFFFAOYSA-N 0.000 description 2
- KQMDVPOCKULZAI-UHFFFAOYSA-N 2-(4-hydroxypiperidin-1-yl)-4-[4-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(O)CCN1C1=NC(NC=2C=CC(=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 KQMDVPOCKULZAI-UHFFFAOYSA-N 0.000 description 2
- IDARVBHTOBSLNW-UHFFFAOYSA-N 2-(4-hydroxypiperidin-1-yl)-8-iodo-4-[4-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(O)CCN1C1=NC(NC=2C=CC(=CC=2)C(F)(F)F)=C2C(=O)NC=C(I)C2=N1 IDARVBHTOBSLNW-UHFFFAOYSA-N 0.000 description 2
- PWIFFMFHVJEXQU-UHFFFAOYSA-N 2-(4-oxopiperidin-1-yl)-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound FC(F)(F)C1=CC=CC(NC=2C=3C(=O)NC=CC=3N=C(N=2)N2CCC(=O)CC2)=C1 PWIFFMFHVJEXQU-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- UTJNZILSYJOSJM-UHFFFAOYSA-N 2-[(2-aminophenyl)methylamino]-4-[3,5-bis(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound NC1=CC=CC=C1CNC1=NC(NC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C2C(=O)NC=CC2=N1 UTJNZILSYJOSJM-UHFFFAOYSA-N 0.000 description 2
- JWDVLBRIYMKSPE-HNCPQSOCSA-N 2-[(3r)-3-aminopyrrolidin-1-yl]-8-bromo-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one;hydrochloride Chemical compound Cl.C1[C@H](N)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=C(Br)C2=N1 JWDVLBRIYMKSPE-HNCPQSOCSA-N 0.000 description 2
- NFEMRONPIKCMSD-GFCCVEGCSA-N 2-[(3r)-3-hydroxypyrrolidin-1-yl]-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1[C@H](O)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 NFEMRONPIKCMSD-GFCCVEGCSA-N 0.000 description 2
- MSLUVFDCXLKRLI-MERQFXBCSA-N 2-[(3s)-3-aminopyrrolidin-1-yl]-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one;hydrochloride Chemical compound Cl.C1[C@@H](N)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 MSLUVFDCXLKRLI-MERQFXBCSA-N 0.000 description 2
- NFEMRONPIKCMSD-LBPRGKRZSA-N 2-[(3s)-3-hydroxypyrrolidin-1-yl]-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1[C@@H](O)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 NFEMRONPIKCMSD-LBPRGKRZSA-N 0.000 description 2
- MJZVMIRHKRTFQH-UHFFFAOYSA-N 2-[4-(hydroxymethyl)piperidin-1-yl]-4-[3-methoxy-5-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound FC(F)(F)C1=CC(OC)=CC(NC=2C=3C(=O)NC=CC=3N=C(N=2)N2CCC(CO)CC2)=C1 MJZVMIRHKRTFQH-UHFFFAOYSA-N 0.000 description 2
- XYAAXXARNQURJH-UHFFFAOYSA-N 2-[4-[(dimethylamino)methyl]piperidin-1-yl]-4-[4-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(CN(C)C)CCN1C1=NC(NC=2C=CC(=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 XYAAXXARNQURJH-UHFFFAOYSA-N 0.000 description 2
- SHGLKXHQNKGRJA-QGZVFWFLSA-N 2-[[(2r)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C([C@H](CO)NC=1N=C2C(C(NC=C2)=O)=C(NC=2C=C(C=CC=2)C(F)(F)F)N=1)C1=CC=CC=C1 SHGLKXHQNKGRJA-QGZVFWFLSA-N 0.000 description 2
- SHGLKXHQNKGRJA-KRWDZBQOSA-N 2-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C([C@@H](CO)NC=1N=C2C(C(NC=C2)=O)=C(NC=2C=C(C=CC=2)C(F)(F)F)N=1)C1=CC=CC=C1 SHGLKXHQNKGRJA-KRWDZBQOSA-N 0.000 description 2
- GJQUJKQDZYZNMN-UHFFFAOYSA-N 2-[benzyl(methyl)amino]-4-[4-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound N=1C(NC=2C=CC(=CC=2)C(F)(F)F)=C(C(NC=C2)=O)C2=NC=1N(C)CC1=CC=CC=C1 GJQUJKQDZYZNMN-UHFFFAOYSA-N 0.000 description 2
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 2
- JTDGZXKALXMEHQ-UHFFFAOYSA-N 4-(3-bromoanilino)-2-[4-(dimethylamino)piperidin-1-yl]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(N(C)C)CCN1C1=NC(NC=2C=C(Br)C=CC=2)=C2C(=O)NC=CC2=N1 JTDGZXKALXMEHQ-UHFFFAOYSA-N 0.000 description 2
- ZPJLTKVTAUQPCV-UHFFFAOYSA-N 4-(4-methoxyphenyl)-6-methyl-2-(methylamino)pyrido[4,3-d]pyrimidin-5-one Chemical compound C1=CN(C)C(=O)C=2C1=NC(NC)=NC=2C1=CC=C(OC)C=C1 ZPJLTKVTAUQPCV-UHFFFAOYSA-N 0.000 description 2
- PTKWCXGLEZSJEM-GFCCVEGCSA-N 4-[3,5-bis(trifluoromethyl)anilino]-2-[(3r)-3-hydroxypyrrolidin-1-yl]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1[C@H](O)CCN1C1=NC(NC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C2C(=O)NC=CC2=N1 PTKWCXGLEZSJEM-GFCCVEGCSA-N 0.000 description 2
- WBJOTKFIPMATGB-UHFFFAOYSA-N 4-[3,5-bis(trifluoromethyl)anilino]-2-[4-(dimethylamino)piperidin-1-yl]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(N(C)C)CCN1C1=NC(NC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C2C(=O)NC=CC2=N1 WBJOTKFIPMATGB-UHFFFAOYSA-N 0.000 description 2
- KYWGBJQYXMEPSU-UHFFFAOYSA-N 4-[3,5-bis(trifluoromethyl)anilino]-2-[4-hydroxy-4-(hydroxymethyl)piperidin-1-yl]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(CO)(O)CCN1C1=NC(NC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C2C(=O)NC=CC2=N1 KYWGBJQYXMEPSU-UHFFFAOYSA-N 0.000 description 2
- CPRZMZBPXDPGNC-UHFFFAOYSA-N 4-[4-chloro-3-(trifluoromethyl)anilino]-2-[4-(hydroxymethyl)piperidin-1-yl]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(CO)CCN1C1=NC(NC=2C=C(C(Cl)=CC=2)C(F)(F)F)=C2C(=O)NC=CC2=N1 CPRZMZBPXDPGNC-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- QUCQUTXMTKXZTF-UHFFFAOYSA-N 8-bromo-2-(4-hydroxypiperidin-1-yl)-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(O)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=C(Br)C2=N1 QUCQUTXMTKXZTF-UHFFFAOYSA-N 0.000 description 2
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- ULQQRNIWQOCYCI-UHFFFAOYSA-N 8-chloro-2-(4-hydroxypiperidin-1-yl)-4-[3-(trifluoromethyl)anilino]-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1CC(O)CCN1C1=NC(NC=2C=C(C=CC=2)C(F)(F)F)=C2C(=O)NC=C(Cl)C2=N1 ULQQRNIWQOCYCI-UHFFFAOYSA-N 0.000 description 2
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
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- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
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- CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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| WO2013125543A1 (ja) * | 2012-02-20 | 2013-08-29 | 武田薬品工業株式会社 | 複素環化合物 |
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| WO2014001973A1 (en) | 2012-06-29 | 2014-01-03 | Pfizer Inc. | NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-d]PYRIMIDINES AS LRRK2 INHIBITORS |
| ES2618004T3 (es) * | 2012-08-07 | 2017-06-20 | Merck Patent Gmbh | Derivados de piridopirimidina como inhibidores de proteínas quinasas |
| KR20150042256A (ko) * | 2012-08-13 | 2015-04-20 | 노파르티스 아게 | 비장 티로신 키나제 (syk)의 억제제로서의 비시클릭 헤테로아릴 시클로알킬디아민 유도체 |
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| JP6437452B2 (ja) | 2013-01-14 | 2018-12-12 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｐｉｍキナーゼ阻害剤として有用な二環式芳香族カルボキサミド化合物 |
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| WO2015146928A1 (ja) * | 2014-03-24 | 2015-10-01 | 武田薬品工業株式会社 | 複素環化合物 |
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| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| KR20160035411A (ko) * | 2014-09-23 | 2016-03-31 | 주식회사 오스코텍 | LRRK2 (Leucine Rich Repeat Kinase 2) 키나제 억제제로서의 피리도피리미딘 유도체 화합물 |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| KR101845931B1 (ko) * | 2015-06-18 | 2018-04-05 | 한국화학연구원 | 헤테로아릴 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 pi3 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 |
| WO2016204429A1 (ko) * | 2015-06-18 | 2016-12-22 | 한국화학연구원 | 헤테로아릴 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 pi3 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물. |
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| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| KR102161364B1 (ko) | 2015-09-14 | 2020-09-29 | 화이자 인코포레이티드 | LRRK2 억제제로서 이미다조[4,5-c]퀴놀린 및 이미다조[4,5-c][1,5]나프티리딘 유도체 |
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| AR106830A1 (es) * | 2015-12-04 | 2018-02-21 | Asana Biosciences Llc | Usos de piridazinonas para tratar el cáncer |
| TWI752098B (zh) | 2016-10-10 | 2022-01-11 | 美商亞雷生物製藥股份有限公司 | 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JP7219218B2 (ja) | 2016-12-22 | 2023-02-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規のベンジルアミノ置換キナゾリンおよびｓｏｓ１阻害剤としての誘導体 |
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| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
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| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
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| MX2012004846A (es) | 2012-10-05 |
| IL219447A0 (en) | 2012-06-28 |
| EP2493313A4 (en) | 2013-05-15 |
| CA2779105A1 (en) | 2011-05-05 |
| US20110269739A1 (en) | 2011-11-03 |
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| EP2493313A1 (en) | 2012-09-05 |
| KR101690358B1 (ko) | 2017-01-09 |
| WO2011053861A8 (en) | 2011-10-27 |
| NZ630860A (en) | 2016-03-31 |
| TR201802464T4 (tr) | 2018-03-21 |
| EA029273B1 (ru) | 2018-03-30 |
| AU2010313240A1 (en) | 2012-04-19 |
| WO2011053861A1 (en) | 2011-05-05 |
| US8404677B2 (en) | 2013-03-26 |
| CN102695416A (zh) | 2012-09-26 |
| MY173494A (en) | 2020-01-29 |
| BR112012010085A2 (pt) | 2017-06-20 |
| KR20120140643A (ko) | 2012-12-31 |
| SG10201407012XA (en) | 2014-11-27 |
| EA201290237A1 (ru) | 2013-04-30 |
| ZA201203842B (en) | 2013-01-30 |
| EP2493313B1 (en) | 2017-12-13 |
| NZ599040A (en) | 2014-11-28 |
| CA2779105C (en) | 2016-08-16 |
| CL2012001073A1 (es) | 2012-10-26 |
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