AU2005274390B2 - Substituted hydantoins - Google Patents

Info

Publication number

AU2005274390B2

AU2005274390B2 AU2005274390A AU2005274390A AU2005274390B2 AU 2005274390 B2 AU2005274390 B2 AU 2005274390B2 AU 2005274390 A AU2005274390 A AU 2005274390A AU 2005274390 A AU2005274390 A AU 2005274390A AU 2005274390 B2 AU2005274390 B2 AU 2005274390B2

Authority

AU

Australia

Prior art keywords

phenyl

dioxo

imidazolidin

thiazol

butyramide

Prior art date

2004-08-17

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.)

Ceased

Links

• Espacenet
• Global Dossier
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• 150000001469 hydantoins Chemical class 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 155
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
• 201000010099 disease Diseases 0.000 claims abstract description 18
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
• 201000011510 cancer Diseases 0.000 claims abstract description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 4
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 4
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 4
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 270
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 146
• 239000000203 mixture Substances 0.000 claims description 107
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 72
• 125000000217 alkyl group Chemical group 0.000 claims description 71
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 52
• -1 2,3-Dihydro-benzo[1,4]dioxin-6-yl Chemical group 0.000 claims description 48
• 239000002904 solvent Substances 0.000 claims description 31
• 238000000034 method Methods 0.000 claims description 24
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 23
• 125000003545 alkoxy group Chemical group 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 208000035475 disorder Diseases 0.000 claims description 17
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 16
• 150000002148 esters Chemical class 0.000 claims description 15
• 229940124647 MEK inhibitor Drugs 0.000 claims description 13
• 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 claims description 12
• 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 11
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 239000002253 acid Substances 0.000 claims description 9
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 230000001404 mediated effect Effects 0.000 claims description 7
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
• VKJCLKODXRCZBO-DLPLYFIVSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1=CC(OC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)C(=O)N1 VKJCLKODXRCZBO-DLPLYFIVSA-N 0.000 claims description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 5
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 150000004702 methyl esters Chemical class 0.000 claims description 5
• 230000008569 process Effects 0.000 claims description 5
• UMXZLBLGVVFRBS-AJHZIAPWSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-[4-[2-(2-methoxyethylamino)-2-oxoethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1=CC(OCC(=O)NCCOC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)C(=O)N1 UMXZLBLGVVFRBS-AJHZIAPWSA-N 0.000 claims description 4
• IAYJKKOPYRXHSC-UHFFFAOYSA-N 2-phenyl-N-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound C1(=CC=CC=C1)C(C(=O)NC=1SC=C(N1)C(CC)=O)CC IAYJKKOPYRXHSC-UHFFFAOYSA-N 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• CWBSOUADJQDOSQ-SVIJTADQSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-(4-hydroxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)=CC=C(O)C=C1 CWBSOUADJQDOSQ-SVIJTADQSA-N 0.000 claims description 3
• RKKBPPTYPGTSEA-FNVCAUGXSA-N RO4927350 Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCCO)=CC=2)=O)=N1 RKKBPPTYPGTSEA-FNVCAUGXSA-N 0.000 claims description 3
• RQRLHETVEAMLLF-LYRGGWFBSA-N methyl 2-[[(2s,3r)-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-methylpentanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@H](C)CC)C(=O)NC=2SC=C(N=2)C(=O)OC)=CC=C(OC)C=C1 RQRLHETVEAMLLF-LYRGGWFBSA-N 0.000 claims description 3
• YUHMIVPGCKUVSN-ZMYBRWDISA-N methyl 2-[[(2s,3r)-2-[(4r)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-[(2-methylpropan-2-yl)oxy]butanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1=CC(OCCOC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)OC(C)(C)C)C(=O)NC=2SC=C(N=2)C(=O)OC)C(=O)N1 YUHMIVPGCKUVSN-ZMYBRWDISA-N 0.000 claims description 3
• WGDWYZSBVAQWQN-ZQMYSKGWSA-N methyl 2-[[(2s,3r)-2-[(4r)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylmethoxybutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1=CC(OCCOC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)OCC=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(=O)OC)C(=O)N1 WGDWYZSBVAQWQN-ZQMYSKGWSA-N 0.000 claims description 3
• PGXLBJUAUFKALR-USCONSEESA-N methyl 2-[[(2s,3s)-2-[(4r)-2,5-dioxo-4-(4-propan-2-yloxyphenyl)imidazolidin-1-yl]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OC(C)C)=CC=2)=O)=N1 PGXLBJUAUFKALR-USCONSEESA-N 0.000 claims description 3
• TYOGLUSVTUMCAP-KYNGSXCRSA-N methyl 2-[[(2s,3s)-2-[(4r)-2,5-dioxo-4-phenylimidazolidin-1-yl]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC=CC=2)=O)=N1 TYOGLUSVTUMCAP-KYNGSXCRSA-N 0.000 claims description 3
• RQRLHETVEAMLLF-XZJROXQQSA-N methyl 2-[[(2s,3s)-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-methylpentanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@@H](C)CC)C(=O)NC=2SC=C(N=2)C(=O)OC)=CC=C(OC)C=C1 RQRLHETVEAMLLF-XZJROXQQSA-N 0.000 claims description 3
• XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical group CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 claims description 3
• IMAFKJGJDAVAAF-ARBPTSGCSA-N (2s,3s)-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OC)=CC=2)=O)=N1 IMAFKJGJDAVAAF-ARBPTSGCSA-N 0.000 claims description 2
• BGIUACCETCLDJH-VWMXVWASSA-N (2s,3s)-2-[(4r)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCCOC)=CC=2)=O)=N1 BGIUACCETCLDJH-VWMXVWASSA-N 0.000 claims description 2
• PXJRLPIEUQKKQU-MUEKUWCCSA-N (2s,3s)-2-[(4r)-4-[4-[2-(dimethylamino)ethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCCN(C)C)=CC=2)=O)=N1 PXJRLPIEUQKKQU-MUEKUWCCSA-N 0.000 claims description 2
• MZUVQFITLDJWGN-GHEQTVGYSA-N (2s,3s)-2-[(4r)-4-[4-[2-(methylamino)-2-oxoethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCC(=O)NC)=CC=2)=O)=N1 MZUVQFITLDJWGN-GHEQTVGYSA-N 0.000 claims description 2
• AYTSWSRJBHEGRA-CUJSYCCXSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-[4-(2-amino-2-oxoethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)=CC=C(OCC(N)=O)C=C1 AYTSWSRJBHEGRA-CUJSYCCXSA-N 0.000 claims description 2
• OXTFXLODRCNMPN-FNVCAUGXSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1=CC(OCCOC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)C(=O)N1 OXTFXLODRCNMPN-FNVCAUGXSA-N 0.000 claims description 2
• IVEOUGNWZPSZFV-MUEKUWCCSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-[4-[2-(2-methoxyethoxy)ethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1=CC(OCCOCCOC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)C(=O)N1 IVEOUGNWZPSZFV-MUEKUWCCSA-N 0.000 claims description 2
• XFQXSMXNNQHINY-OPILKIMUSA-N 2-[4-[2,5-dioxo-1-[(2s,3s)-1-oxo-3-phenyl-1-[(4-propanoyl-1,3-thiazol-2-yl)amino]butan-2-yl]imidazolidin-4-yl]phenoxy]acetic acid Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C(C(NC2=O)C=2C=CC(OCC(O)=O)=CC=2)=O)=N1 XFQXSMXNNQHINY-OPILKIMUSA-N 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000001153 fluoro group Chemical group F* 0.000 claims description 2
• YDQDLFQOHXRYFT-GHEQTVGYSA-N methyl 2-[4-[(4r)-2,5-dioxo-1-[(2s,3s)-1-oxo-3-phenyl-1-[(4-propanoyl-1,3-thiazol-2-yl)amino]butan-2-yl]imidazolidin-4-yl]phenoxy]acetate Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCC(=O)OC)=CC=2)=O)=N1 YDQDLFQOHXRYFT-GHEQTVGYSA-N 0.000 claims description 2
• UWQOCAVQZYAIFW-XWIAVFTESA-N methyl 2-[[(2s,3r)-2-[(4r)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-methylpentanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@H](C)CC)C(=O)NC=2SC=C(N=2)C(=O)OC)=CC=C(OCCOC)C=C1 UWQOCAVQZYAIFW-XWIAVFTESA-N 0.000 claims description 2
• HVAHSGWGDBJCHI-FZQKWOKYSA-N methyl 2-[[(2s,3r)-3-hydroxy-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]butanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)O)N2C([C@H](NC2=O)C=2C=CC(OC)=CC=2)=O)=N1 HVAHSGWGDBJCHI-FZQKWOKYSA-N 0.000 claims description 2
• WLQJWIUIHWHAAT-RVHYNSKXSA-N methyl 2-[[(2s,3s)-2-[(4r)-4-(4-methoxy-3-methylphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=C(C)C(OC)=CC=2)=O)=N1 WLQJWIUIHWHAAT-RVHYNSKXSA-N 0.000 claims description 2
• FTSHKUAMSVGXLP-USCONSEESA-N methyl 2-[[(2s,3s)-2-[(4r)-4-[4-(dimethoxyphosphorylmethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCP(=O)(OC)OC)=CC=2)=O)=N1 FTSHKUAMSVGXLP-USCONSEESA-N 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims description 2
• QXZLCHXYDBNFAZ-WUARMDOMSA-N (2S,3S)-N-(4-acetyl-1,3-thiazol-2-yl)-2-[(4R)-4-(4-ethoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide 2,2,2-trifluoroacetic acid Chemical compound C(C)(=O)C=1N=C(SC1)NC([C@H]([C@@H](C)C1=CC=CC=C1)N1C(N[C@@H](C1=O)C1=CC=C(C=C1)OCC)=O)=O.FC(C(=O)O)(F)F QXZLCHXYDBNFAZ-WUARMDOMSA-N 0.000 claims 1
• RTIYENHYKKZGAW-DLPLYFIVSA-N (2s,3s)-2-[(4r)-4-(4-hydroxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(O)=CC=2)=O)=N1 RTIYENHYKKZGAW-DLPLYFIVSA-N 0.000 claims 1
• BVUPTRQCZWWNNV-KSZLIROESA-N (2s,3s)-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylpentanoic acid Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@@H](CC)C=2C=CC=CC=2)C(O)=O)=CC=C(OC)C=C1 BVUPTRQCZWWNNV-KSZLIROESA-N 0.000 claims 1
• IAUOMVZXRVQRFV-IMDCKVJKSA-N (2s,3s)-2-[(4r)-4-[4-[2-(2-methoxyethylamino)-2-oxoethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(OCC(=O)NCCOC)=CC=2)=O)=N1 IAUOMVZXRVQRFV-IMDCKVJKSA-N 0.000 claims 1
• JXHDIDLFXJZARI-ARBPTSGCSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-[4-(2-hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)=CC=C(OCCO)C=C1 JXHDIDLFXJZARI-ARBPTSGCSA-N 0.000 claims 1
• VKHUGIRCRWMSJG-VZVOMBSFSA-N (2s,3s)-n-(4-acetyl-1,3-thiazol-2-yl)-2-[(4r)-4-[4-[2-(diethylamino)ethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(OCCN(CC)CC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)=O)C(=O)N1 VKHUGIRCRWMSJG-VZVOMBSFSA-N 0.000 claims 1
• WZYXLAVDBCMKRS-GHEQTVGYSA-N (2s,3s)-n-[4-(cyclopropanecarbonyl)-1,3-thiazol-2-yl]-2-[(4r)-4-[4-[2-(methylamino)-2-oxoethoxy]phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1=CC(OCC(=O)NC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(=O)C2CC2)C(=O)N1 WZYXLAVDBCMKRS-GHEQTVGYSA-N 0.000 claims 1
• MQJUPCMELUYEDN-UHFFFAOYSA-N 3-phenyl-n-(4-propanoyl-1,3-thiazol-2-yl)butanamide Chemical compound CCC(=O)C1=CSC(NC(=O)CC(C)C=2C=CC=CC=2)=N1 MQJUPCMELUYEDN-UHFFFAOYSA-N 0.000 claims 1
• FYNANZCECDNEPH-RTBURBONSA-N C1=CC=C(C([C@@H](C(=O)NC=2SC=C(N=2)C(=O)O)N2C(=O)[C@@H](C3=CC=C(OC)C=C3)NC2=O)(C)C)C=C1 Chemical compound C1=CC=C(C([C@@H](C(=O)NC=2SC=C(N=2)C(=O)O)N2C(=O)[C@@H](C3=CC=C(OC)C=C3)NC2=O)(C)C)C=C1 FYNANZCECDNEPH-RTBURBONSA-N 0.000 claims 1
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• JJUBLXHBGVUHGS-LYRGGWFBSA-N methyl 2-[[(2s,3r)-3-hydroxy-2-[(4r)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]butanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1=CC(OCCOC)=CC=C1[C@@H]1C(=O)N([C@@H]([C@@H](C)O)C(=O)NC=2SC=C(N=2)C(=O)OC)C(=O)N1 JJUBLXHBGVUHGS-LYRGGWFBSA-N 0.000 description 2
• JDIUNKBCVACKEH-KMUNFCNLSA-N methyl 2-[[(2s,3r)-3-methoxy-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]butanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound C1([C@H]2NC(=O)N(C2=O)[C@@H]([C@@H](C)OC)C(=O)NC=2SC=C(N=2)C(=O)OC)=CC=C(OC)C=C1 JDIUNKBCVACKEH-KMUNFCNLSA-N 0.000 description 2
• GUVRHNNNBJYKSK-BKTGTZMESA-N methyl 2-[[(2s,3s)-2-[(4r)-4-(4-hydroxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C([C@H](NC2=O)C=2C=CC(O)=CC=2)=O)=N1 GUVRHNNNBJYKSK-BKTGTZMESA-N 0.000 description 2
• JBRGGDAMRGNBOI-JUJMCKSGSA-N methyl 2-[[(2s,3s)-2-[4-(4-methylsulfonylphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C=CC=CC=2)N2C(C(NC2=O)C=2C=CC(=CC=2)S(C)(=O)=O)=O)=N1 JBRGGDAMRGNBOI-JUJMCKSGSA-N 0.000 description 2
• GTFTXSAXACOMNB-DLPLYFIVSA-N methyl 2-[[(2s,3s)-2-[[(2r)-2-(4-acetamidophenyl)-2-aminoacetyl]amino]-3-phenylbutanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@@H](NC(=O)[C@H](N)C=2C=CC(NC(C)=O)=CC=2)[C@@H](C)C=2C=CC=CC=2)=N1 GTFTXSAXACOMNB-DLPLYFIVSA-N 0.000 description 2
• AAEDIUPCKIHNOW-YZIZEKMBSA-N methyl 2-[[(2s,3s)-3-(2-methoxyphenyl)-2-[4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]butanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H]([C@@H](C)C=2C(=CC=CC=2)OC)N2C(C(NC2=O)C=2C=CC(OC)=CC=2)=O)=N1 AAEDIUPCKIHNOW-YZIZEKMBSA-N 0.000 description 2
• WYVZZWKIKAKUKV-UHFFFAOYSA-N methyl 2-amino-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(N)=N1 WYVZZWKIKAKUKV-UHFFFAOYSA-N 0.000 description 2
• XWNVDZJUTIQKFF-UHFFFAOYSA-N methyl 3-(2-amino-1,3-thiazol-4-yl)-2-methoxy-3-oxopropanoate Chemical compound COC(=O)C(OC)C(=O)C1=CSC(N)=N1 XWNVDZJUTIQKFF-UHFFFAOYSA-N 0.000 description 2
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• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 2
• 230000002297 mitogenic effect Effects 0.000 description 2
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• CLCDQYYRHRVFEF-VZDHWGDASA-N n-[4-(2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]-2-[(4r)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutanamide Chemical compound C1=CC(OC)=CC=C1[C@@H]1C(=O)N(C(C(C)C=2C=CC=CC=2)C(=O)NC=2SC=C(N=2)C(C)(C)O)C(=O)N1 CLCDQYYRHRVFEF-VZDHWGDASA-N 0.000 description 2
• 208000004296 neuralgia Diseases 0.000 description 2
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• 230000003000 nontoxic effect Effects 0.000 description 2
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• 150000007524 organic acids Chemical class 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000010287 polarization Effects 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 208000023958 prostate neoplasm Diseases 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 108060006633 protein kinase Proteins 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
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• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
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• 239000011780 sodium chloride Substances 0.000 description 2
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• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
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• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
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