NO327817B1 - ``Benzodiazepin-derivater, deres fremstilling, medikament inneholdende slike samt anvendelse av disse for fremstilling av medikament for behandling av sykdom`` - Google Patents
``Benzodiazepin-derivater, deres fremstilling, medikament inneholdende slike samt anvendelse av disse for fremstilling av medikament for behandling av sykdom`` Download PDFInfo
- Publication number
- NO327817B1 NO327817B1 NO20021690A NO20021690A NO327817B1 NO 327817 B1 NO327817 B1 NO 327817B1 NO 20021690 A NO20021690 A NO 20021690A NO 20021690 A NO20021690 A NO 20021690A NO 327817 B1 NO327817 B1 NO 327817B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- mmol
- oxo
- butyl ester
- carbamic acid
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 42
- 239000003814 drug Substances 0.000 title claims description 13
- 229940079593 drug Drugs 0.000 title claims description 8
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title 1
- 238000000034 method Methods 0.000 claims description 545
- 150000001875 compounds Chemical class 0.000 claims description 114
- -1 hydroxyethoxy Chemical group 0.000 claims description 65
- 238000006243 chemical reaction Methods 0.000 claims description 49
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical compound O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- FBPIGKDLQMIHLG-UHFFFAOYSA-N 4-(3-iodophenyl)-7-(2-methoxyethoxy)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COCCOC1=CC=2N=C(C=3C=C(I)C=CC=3)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 FBPIGKDLQMIHLG-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical class C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- QDKZHQGXPVFLHU-UHFFFAOYSA-N 1,5-benzodiazepin-2-one Chemical compound O=C1C=CN=C2C=CC=CC2=N1 QDKZHQGXPVFLHU-UHFFFAOYSA-N 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- OPTKWCKGENRFQA-UHFFFAOYSA-N methyl 2-[[4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]sulfanyl]acetate Chemical compound COC(=O)CSC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 OPTKWCKGENRFQA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical class C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims description 3
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical class C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 3
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical class C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims description 3
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical class C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
- RKIDXLGMZYYSAA-UHFFFAOYSA-N 2-[8-(2-fluorophenyl)-7-hydroxy-2-oxo-1,5-dihydro-1,5-benzodiazepin-4-yl]thiophene-3-carbonitrile Chemical compound OC1=CC=2NC(C3=C(C=CS3)C#N)=CC(=O)NC=2C=C1C1=CC=CC=C1F RKIDXLGMZYYSAA-UHFFFAOYSA-N 0.000 claims description 3
- UVPDZJUTLGSHOW-UHFFFAOYSA-N 3-(7-chloro-2-oxo-8-phenyl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound ClC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1 UVPDZJUTLGSHOW-UHFFFAOYSA-N 0.000 claims description 3
- QRRFEMJQTYRNMN-UHFFFAOYSA-N 3-[7-(4-methylpiperazin-1-yl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1CN(C)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)C#N)=N2 QRRFEMJQTYRNMN-UHFFFAOYSA-N 0.000 claims description 3
- FGIWPVCRHZHHAO-UHFFFAOYSA-N 3-[7-(cyanomethyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC(CC#N)=C1C#CC1=CC=CC=C1 FGIWPVCRHZHHAO-UHFFFAOYSA-N 0.000 claims description 3
- ZVSMESDSZFNDMJ-UHFFFAOYSA-N 3-[7-methoxy-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 ZVSMESDSZFNDMJ-UHFFFAOYSA-N 0.000 claims description 3
- JSFNPUJTYTWCLA-UHFFFAOYSA-N 3-[8-(2,5-difluorophenyl)-7-hydroxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC(F)=CC=C1F JSFNPUJTYTWCLA-UHFFFAOYSA-N 0.000 claims description 3
- MTOSFHOAULLKRN-UHFFFAOYSA-N 4-[8-(2-fluorophenyl)-7-hydroxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound OC1=CC=2N=C(C=3C=C(N=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F MTOSFHOAULLKRN-UHFFFAOYSA-N 0.000 claims description 3
- DXDDOWBFRGJDFS-UHFFFAOYSA-N 4-[8-(2-fluorophenyl)-7-methoxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound COC1=CC=2N=C(C=3C=C(N=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F DXDDOWBFRGJDFS-UHFFFAOYSA-N 0.000 claims description 3
- IWJJFYANLOIUKW-UHFFFAOYSA-N 4-[8-(4-fluorophenyl)-7-hydroxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound OC1=CC=2N=C(C=3C=C(N=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 IWJJFYANLOIUKW-UHFFFAOYSA-N 0.000 claims description 3
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 3
- DFPPYGYDEAPNML-UHFFFAOYSA-N 5-[8-(2-fluorophenyl)-7-methoxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]thiophene-2-carbonitrile Chemical compound COC1=CC=2N=C(C=3SC(=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F DFPPYGYDEAPNML-UHFFFAOYSA-N 0.000 claims description 3
- BAOSWBZMDZMRIY-UHFFFAOYSA-N 8-(2-fluorophenyl)-7-methoxy-4-[3-(2-methylimidazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)N3C(=NC=C3)C)CC(=O)NC=2C=C1C1=CC=CC=C1F BAOSWBZMDZMRIY-UHFFFAOYSA-N 0.000 claims description 3
- FFZSVPXVCARFFX-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-[4-(2-hydroxyethoxy)piperidin-1-yl]-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1CC(OCCO)CCN1C(C(=C1)C=2C=CC(F)=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)N1C=NC=C1)=N2 FFZSVPXVCARFFX-UHFFFAOYSA-N 0.000 claims description 3
- URUMMRWACZFGEQ-UHFFFAOYSA-N 8-[2-(4-fluorophenyl)ethynyl]-7-(hydroxymethyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=C(F)C=C1 URUMMRWACZFGEQ-UHFFFAOYSA-N 0.000 claims description 3
- RFKFAFMEFPSHAN-UHFFFAOYSA-N 8-[2-(4-fluorophenyl)ethynyl]-7-hydroxy-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=C(F)C=C1 RFKFAFMEFPSHAN-UHFFFAOYSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical class C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- HHKGHOHNMXZGJC-UHFFFAOYSA-N chembl404886 Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)N3N=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=C(F)C=C1 HHKGHOHNMXZGJC-UHFFFAOYSA-N 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical class C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 206010027175 memory impairment Diseases 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical class C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- OBKSPYGKOAVWPB-UHFFFAOYSA-N 2-[4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]acetamide Chemical compound NC(=O)CC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 OBKSPYGKOAVWPB-UHFFFAOYSA-N 0.000 claims description 2
- MIKJDYQBHVZYBY-UHFFFAOYSA-N 2-[[4-(3-imidazol-1-ylphenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]oxy]acetonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)N3C=NC=C3)=NC2=CC(OCC#N)=C1C#CC1=CC=CC=C1 MIKJDYQBHVZYBY-UHFFFAOYSA-N 0.000 claims description 2
- RMNNCRGKNMWAII-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-7-(2-methoxyethoxy)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COCCOC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 RMNNCRGKNMWAII-UHFFFAOYSA-N 0.000 claims description 2
- CHFZTXQHQRTDEM-UHFFFAOYSA-N 8-(2-fluorophenyl)-7-hydroxy-4-[3-(triazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)N3N=NC=C3)CC(=O)NC=2C=C1C1=CC=CC=C1F CHFZTXQHQRTDEM-UHFFFAOYSA-N 0.000 claims description 2
- JGIATRRZRPYCNH-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-hydroxy-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 JGIATRRZRPYCNH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 150000002240 furans Chemical class 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
- RMVBDQZEMLMPAJ-UHFFFAOYSA-N 3-[7-chloro-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound ClC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 RMVBDQZEMLMPAJ-UHFFFAOYSA-N 0.000 claims 1
- OPCXKXGFSLZHAI-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-[2-(4-methylimidazol-1-yl)-1,3-thiazol-4-yl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CN1C1=NC(C=2CC(=O)NC3=CC(=CC=C3N=2)C=2C(=CC=CC=2)F)=CS1 OPCXKXGFSLZHAI-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 125000003831 tetrazolyl group Chemical class 0.000 claims 1
- 239000007787 solid Substances 0.000 description 294
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 186
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 118
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
- 239000000460 chlorine Substances 0.000 description 89
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- RAVMZWQUVKTGBS-UHFFFAOYSA-N 3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)benzonitrile Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(C#N)=C1 RAVMZWQUVKTGBS-UHFFFAOYSA-N 0.000 description 68
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 68
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
- OABSXOMYUDYCAN-UHFFFAOYSA-N 6-(3-imidazol-1-ylphenyl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(N2C=NC=C2)=C1 OABSXOMYUDYCAN-UHFFFAOYSA-N 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 235000019439 ethyl acetate Nutrition 0.000 description 50
- 239000000126 substance Substances 0.000 description 48
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 46
- 230000009467 reduction Effects 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 41
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 41
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- PXCREFJJZMYUBE-UHFFFAOYSA-N tert-butyl n-(5-chloro-4-iodo-2-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(I)C=C1[N+]([O-])=O PXCREFJJZMYUBE-UHFFFAOYSA-N 0.000 description 36
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 33
- 239000011734 sodium Substances 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 31
- 239000000243 solution Substances 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 28
- 238000003786 synthesis reaction Methods 0.000 description 27
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- 238000010898 silica gel chromatography Methods 0.000 description 24
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 18
- GEDUXGGQPHDRRS-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C1=CC=CC=C1F GEDUXGGQPHDRRS-UHFFFAOYSA-N 0.000 description 18
- VEAZXGOZDDGHRG-UHFFFAOYSA-N tert-butyl 2-[2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I VEAZXGOZDDGHRG-UHFFFAOYSA-N 0.000 description 17
- ZTCGGBIFOFASKI-UHFFFAOYSA-N tert-butyl acetate;lithium Chemical compound [Li].CC(=O)OC(C)(C)C ZTCGGBIFOFASKI-UHFFFAOYSA-N 0.000 description 17
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- NWHUVKAHKFHVSS-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-fluorophenyl)-5-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=CC=C1F NWHUVKAHKFHVSS-UHFFFAOYSA-N 0.000 description 16
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 16
- KWHURWOGZQWLTK-UHFFFAOYSA-N 5-chloro-4-iodo-2-nitroaniline Chemical compound NC1=CC(Cl)=C(I)C=C1[N+]([O-])=O KWHURWOGZQWLTK-UHFFFAOYSA-N 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- YJHGAFUPACBMDJ-UHFFFAOYSA-N tert-butyl n-(4-iodo-2-nitrophenyl)carbamate Chemical class CC(C)(C)OC(=O)NC1=CC=C(I)C=C1[N+]([O-])=O YJHGAFUPACBMDJ-UHFFFAOYSA-N 0.000 description 14
- 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 14
- 239000000047 product Substances 0.000 description 13
- 235000011149 sulphuric acid Nutrition 0.000 description 13
- 239000013058 crude material Substances 0.000 description 12
- WRZPZLDUJDMQPV-UHFFFAOYSA-N tert-butyl n-(4-iodo-5-methoxy-2-nitrophenyl)carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I WRZPZLDUJDMQPV-UHFFFAOYSA-N 0.000 description 12
- ZVCWEFUWNFPCOF-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C1=CC=C(F)C=C1 ZVCWEFUWNFPCOF-UHFFFAOYSA-N 0.000 description 12
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 11
- ATCKJLDGNXGLAO-UHFFFAOYSA-N bis(trimethylsilyl) propanedioate Chemical compound C[Si](C)(C)OC(=O)CC(=O)O[Si](C)(C)C ATCKJLDGNXGLAO-UHFFFAOYSA-N 0.000 description 11
- 239000006260 foam Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- DFOQTQOOJQTQLK-UHFFFAOYSA-N tert-butyl n-(5-hydroxy-4-iodo-2-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(O)=C(I)C=C1[N+]([O-])=O DFOQTQOOJQTQLK-UHFFFAOYSA-N 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- KUHMJDSOPHMSDX-UHFFFAOYSA-N ethyl 3-oxo-3-[3-(triazol-1-yl)phenyl]propanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 KUHMJDSOPHMSDX-UHFFFAOYSA-N 0.000 description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 10
- SGHMBSAYQBFKCX-UHFFFAOYSA-N tert-butyl n-(2-amino-4-iodo-5-thiomorpholin-4-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1I SGHMBSAYQBFKCX-UHFFFAOYSA-N 0.000 description 10
- JWPDFQPFLOKUES-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-[(2-methylpropan-2-yl)oxy]-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(I)C=C1[N+]([O-])=O JWPDFQPFLOKUES-UHFFFAOYSA-N 0.000 description 10
- MIRCGXDVDSVKQL-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-4-iodo-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CO)=C(I)C=C1[N+]([O-])=O MIRCGXDVDSVKQL-UHFFFAOYSA-N 0.000 description 10
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 9
- 239000012948 isocyanate Substances 0.000 description 9
- 150000002513 isocyanates Chemical class 0.000 description 9
- UPCLTFDFFFRBGN-UHFFFAOYSA-N 2-[[4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]oxy]acetic acid Chemical compound OC(=O)COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 UPCLTFDFFFRBGN-UHFFFAOYSA-N 0.000 description 8
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 8
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- QQJNABOVYNTCRV-UHFFFAOYSA-N tert-butyl 3-(2-cyanopyridin-4-yl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=NC(C#N)=C1 QQJNABOVYNTCRV-UHFFFAOYSA-N 0.000 description 8
- ZMKBGYPEBSWXTI-UHFFFAOYSA-N tert-butyl 3-[3-(2-methylimidazol-1-yl)phenyl]-3-oxopropanoate Chemical compound CC1=NC=CN1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 ZMKBGYPEBSWXTI-UHFFFAOYSA-N 0.000 description 8
- KSVVAPRHVOHHEI-UHFFFAOYSA-N tert-butyl n-(4-iodo-2-nitro-5-thiomorpholin-4-ylphenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1I KSVVAPRHVOHHEI-UHFFFAOYSA-N 0.000 description 8
- MDBPDAZUAOLOCB-UHFFFAOYSA-N tert-butyl n-(4-iodo-5-methyl-2-nitrophenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I MDBPDAZUAOLOCB-UHFFFAOYSA-N 0.000 description 8
- RODXWLBCSMJAHE-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-(2-methoxyethoxy)-2-nitrophenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I RODXWLBCSMJAHE-UHFFFAOYSA-N 0.000 description 8
- XQARXJLLGPJWDV-UHFFFAOYSA-N tert-butyl n-[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCC3(CC2)OCCO3)=C1I XQARXJLLGPJWDV-UHFFFAOYSA-N 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 7
- 235000019502 Orange oil Nutrition 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 230000026045 iodination Effects 0.000 description 7
- 238000006192 iodination reaction Methods 0.000 description 7
- 229910001629 magnesium chloride Inorganic materials 0.000 description 7
- WHLBWPZJFZEKOH-UHFFFAOYSA-N methyl 2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrobenzoate Chemical compound COC(=O)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I WHLBWPZJFZEKOH-UHFFFAOYSA-N 0.000 description 7
- 239000010502 orange oil Substances 0.000 description 7
- JTCQABVWBNJJBB-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(CO)=C1C#CC1=CC=CC=C1 JTCQABVWBNJJBB-UHFFFAOYSA-N 0.000 description 7
- 229910001868 water Inorganic materials 0.000 description 7
- QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- ZBWZEFLYRWANSY-UHFFFAOYSA-N 2-quinoxalin-2-ylsulfanylacetic acid Chemical compound C1=CC=CC2=NC(SCC(=O)O)=CN=C21 ZBWZEFLYRWANSY-UHFFFAOYSA-N 0.000 description 6
- IMCIPAQMQGPLSX-UHFFFAOYSA-N 3-(8-iodo-2-oxo-7-thiomorpholin-4-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound IC1=CC=2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC=2C=C1N1CCSCC1 IMCIPAQMQGPLSX-UHFFFAOYSA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 6
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- IQZVTQILBAIVNH-UHFFFAOYSA-N tert-butyl n-(4-iodo-5-morpholin-4-yl-2-nitrophenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1I IQZVTQILBAIVNH-UHFFFAOYSA-N 0.000 description 6
- YTPZJBPYYVTQHK-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2,5-difluorophenyl)-5-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC(F)=CC=C1F YTPZJBPYYVTQHK-UHFFFAOYSA-N 0.000 description 6
- YOZZIFXZOFPREM-UHFFFAOYSA-N tert-butyl n-[2-amino-4-[2-(4-fluorophenyl)ethynyl]-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C#CC=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 YOZZIFXZOFPREM-UHFFFAOYSA-N 0.000 description 6
- UKRBWRGJTGRVQO-UHFFFAOYSA-N tert-butyl n-[2-amino-4-[2-(4-fluorophenyl)ethynyl]-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C#CC1=CC=C(F)C=C1 UKRBWRGJTGRVQO-UHFFFAOYSA-N 0.000 description 6
- BUGWMAUBKOMZJE-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(2-methoxyethoxy)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 BUGWMAUBKOMZJE-UHFFFAOYSA-N 0.000 description 6
- QGOTZKRSYPTITG-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(4-methoxypiperidin-1-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CC(OC)CCN1C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 QGOTZKRSYPTITG-UHFFFAOYSA-N 0.000 description 6
- JAKTVCUMOGJTLL-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(cyanomethoxy)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(OCC#N)=C1C#CC1=CC=CC=C1 JAKTVCUMOGJTLL-UHFFFAOYSA-N 0.000 description 6
- IKCTXPQRUMWURD-UHFFFAOYSA-N tert-butyl n-[4-iodo-2-nitro-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(COC2OCCCC2)=C1I IKCTXPQRUMWURD-UHFFFAOYSA-N 0.000 description 6
- WBKWUPJXTYQTST-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I WBKWUPJXTYQTST-UHFFFAOYSA-N 0.000 description 6
- JMUWPETYTGXDKM-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethoxy)-4-iodo-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OCC#N)=C(I)C=C1[N+]([O-])=O JMUWPETYTGXDKM-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 150000001502 aryl halides Chemical class 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000008034 disappearance Effects 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- KDEHYSDCHCKIAV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[2-(oxan-2-yloxy)ethoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1OCCOC1CCCCO1 KDEHYSDCHCKIAV-UHFFFAOYSA-N 0.000 description 5
- RKCGDEYBMDJBPO-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-2-nitro-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 RKCGDEYBMDJBPO-UHFFFAOYSA-N 0.000 description 5
- OQQPGLBAZSIFQX-UHFFFAOYSA-N tert-butyl n-[5-[(dimethylamino)methyl]-4-iodo-2-nitrophenyl]carbamate Chemical compound CN(C)CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I OQQPGLBAZSIFQX-UHFFFAOYSA-N 0.000 description 5
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 4
- QXSWHQGIEKUBAS-UHFFFAOYSA-N 1-ethynyl-4-fluorobenzene Chemical group FC1=CC=C(C#C)C=C1 QXSWHQGIEKUBAS-UHFFFAOYSA-N 0.000 description 4
- ZJZAGVOUZXEYLD-UHFFFAOYSA-N 2-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)thiophene-3-carbonitrile Chemical compound O1C(C)(C)OC(=O)C=C1C1=C(C#N)C=CS1 ZJZAGVOUZXEYLD-UHFFFAOYSA-N 0.000 description 4
- IPNMKDWDMHCZBB-UHFFFAOYSA-N 2-[4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]acetic acid Chemical compound OC(=O)CC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 IPNMKDWDMHCZBB-UHFFFAOYSA-N 0.000 description 4
- UOMBZLVDICRZBD-UHFFFAOYSA-N 2-[[8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-7-yl]oxy]acetic acid Chemical compound OC(=O)COC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 UOMBZLVDICRZBD-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- QVCRSYXVWPPBFJ-UHFFFAOYSA-N 4-iodo-2-nitroaniline Chemical class NC1=CC=C(I)C=C1[N+]([O-])=O QVCRSYXVWPPBFJ-UHFFFAOYSA-N 0.000 description 4
- NARYIXHPFAWJKN-UHFFFAOYSA-N 4-iodo-5-(2-methoxyethoxy)-2-nitroaniline Chemical compound COCCOC1=CC(N)=C([N+]([O-])=O)C=C1I NARYIXHPFAWJKN-UHFFFAOYSA-N 0.000 description 4
- LFCGGXMZASAZTE-UHFFFAOYSA-N 4-iodo-5-[(4-methoxyphenyl)methoxy]-2-nitroaniline Chemical compound C1=CC(OC)=CC=C1COC1=CC(N)=C([N+]([O-])=O)C=C1I LFCGGXMZASAZTE-UHFFFAOYSA-N 0.000 description 4
- OLPZPSRSMLZHJA-UHFFFAOYSA-N 4-iodo-5-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-2-nitroaniline Chemical compound COCCOCCOCCOCCOC1=CC(N)=C([N+]([O-])=O)C=C1I OLPZPSRSMLZHJA-UHFFFAOYSA-N 0.000 description 4
- LFEDHUMOJYMWQN-UHFFFAOYSA-N 4-iodo-5-methoxy-2-nitroaniline Chemical compound COC1=CC(N)=C([N+]([O-])=O)C=C1I LFEDHUMOJYMWQN-UHFFFAOYSA-N 0.000 description 4
- DLAZSRKCQDQBPC-UHFFFAOYSA-N 4-iodo-5-methyl-2-nitroaniline Chemical compound CC1=CC(N)=C([N+]([O-])=O)C=C1I DLAZSRKCQDQBPC-UHFFFAOYSA-N 0.000 description 4
- HXBXHVQQFVZFNW-UHFFFAOYSA-N 5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-2-nitro-4-(2-phenylethynyl)aniline Chemical compound O1C(C)(C)OCC1COC1=CC(N)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 HXBXHVQQFVZFNW-UHFFFAOYSA-N 0.000 description 4
- LGMFVZGMVCXNBW-UHFFFAOYSA-N 5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-4-iodo-2-nitroaniline Chemical compound O1C(C)(C)OCC1COC1=CC(N)=C([N+]([O-])=O)C=C1I LGMFVZGMVCXNBW-UHFFFAOYSA-N 0.000 description 4
- IXGGSHYJYYQPGR-UHFFFAOYSA-N 6-(3-iodophenyl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(I)=C1 IXGGSHYJYYQPGR-UHFFFAOYSA-N 0.000 description 4
- LVKISJSUOVZDAL-UHFFFAOYSA-N 7-(2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl)-8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C2OC(C)(C)OC2CN1C1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 LVKISJSUOVZDAL-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 229910004373 HOAc Inorganic materials 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000027089 Parkinsonian disease Diseases 0.000 description 4
- 206010034010 Parkinsonism Diseases 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 4
- OEQIEDAWGSZELP-UHFFFAOYSA-N [1-[4-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]-3-phenylprop-2-ynyl] 2,2-dimethylpropanoate Chemical compound CC(C)(C)OC(=O)NC1=CC(C(OC(=O)C(C)(C)C)C#CC=2C=CC=CC=2)=CC=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 OEQIEDAWGSZELP-UHFFFAOYSA-N 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 150000001543 aryl boronic acids Chemical class 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- XBGDPLROEPFJDG-UHFFFAOYSA-N methyl 2-[2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]sulfanylacetate Chemical compound COC(=O)CSC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I XBGDPLROEPFJDG-UHFFFAOYSA-N 0.000 description 4
- VAZWRTOCBOACHN-UHFFFAOYSA-N methyl 2-[4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]acetate Chemical compound COC(=O)CC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 VAZWRTOCBOACHN-UHFFFAOYSA-N 0.000 description 4
- RAPFRRQKZXDDEJ-UHFFFAOYSA-N methyl 2-[4-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-phenylethynyl)phenyl]acetate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(CC(=O)OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 RAPFRRQKZXDDEJ-UHFFFAOYSA-N 0.000 description 4
- NKGYSGGAEUCELQ-UHFFFAOYSA-N methyl 3-(1,2,4-triazol-1-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2N=CN=C2)=C1 NKGYSGGAEUCELQ-UHFFFAOYSA-N 0.000 description 4
- ZGVYPBINPLNBDH-UHFFFAOYSA-N methyl 3-amino-4-nitrobenzoate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C(N)=C1 ZGVYPBINPLNBDH-UHFFFAOYSA-N 0.000 description 4
- NGXJMMQUTLNUSA-UHFFFAOYSA-N methyl 4-amino-2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]benzoate Chemical compound COC(=O)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1I NGXJMMQUTLNUSA-UHFFFAOYSA-N 0.000 description 4
- XOHRGNCNWBXUHT-UHFFFAOYSA-N methyl 5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitro-2-(2-phenylethynyl)benzoate Chemical compound COC(=O)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 XOHRGNCNWBXUHT-UHFFFAOYSA-N 0.000 description 4
- JHSXRBBTSBWXDY-UHFFFAOYSA-N methyl 5-amino-2-iodo-4-nitrobenzoate Chemical compound COC(=O)C1=CC(N)=C([N+]([O-])=O)C=C1I JHSXRBBTSBWXDY-UHFFFAOYSA-N 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- QVBPZZKELHNMDZ-UHFFFAOYSA-M potassium;3-[(2-methylpropan-2-yl)oxy]-3-oxopropanoate Chemical compound [K+].CC(C)(C)OC(=O)CC([O-])=O QVBPZZKELHNMDZ-UHFFFAOYSA-M 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- DJPLMFDGCAEYNH-UHFFFAOYSA-N tert-butyl 2-[4-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-phenylethynyl)phenoxy]acetate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(OCC(=O)OC(C)(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 DJPLMFDGCAEYNH-UHFFFAOYSA-N 0.000 description 4
- QGBYZMSEIRCPSS-UHFFFAOYSA-N tert-butyl 2-[4-amino-2-(4-fluorophenyl)-5-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1 QGBYZMSEIRCPSS-UHFFFAOYSA-N 0.000 description 4
- XXTKLKFTERLYLO-UHFFFAOYSA-N tert-butyl 2-[4-amino-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-phenylethynyl)phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 XXTKLKFTERLYLO-UHFFFAOYSA-N 0.000 description 4
- OASOWHFXYOHHTL-UHFFFAOYSA-N tert-butyl 3-(2-imidazol-1-ylpyridin-4-yl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=NC(N2C=NC=C2)=C1 OASOWHFXYOHHTL-UHFFFAOYSA-N 0.000 description 4
- NJGOKCQKYUXLSX-UHFFFAOYSA-N tert-butyl 3-(3-cyanophenyl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C#N)=C1 NJGOKCQKYUXLSX-UHFFFAOYSA-N 0.000 description 4
- FEPASYFSULWDNV-UHFFFAOYSA-N tert-butyl 3-(3-imidazol-1-ylphenyl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 FEPASYFSULWDNV-UHFFFAOYSA-N 0.000 description 4
- VTFOIKTXSHSBOV-UHFFFAOYSA-N tert-butyl 3-(5-cyanothiophen-2-yl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=C(C#N)S1 VTFOIKTXSHSBOV-UHFFFAOYSA-N 0.000 description 4
- BSPODPDIDGXFDC-UHFFFAOYSA-N tert-butyl 3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 BSPODPDIDGXFDC-UHFFFAOYSA-N 0.000 description 4
- NBBCEFQYGHPSHM-UHFFFAOYSA-N tert-butyl n-(2-amino-4-iodo-5-morpholin-4-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1I NBBCEFQYGHPSHM-UHFFFAOYSA-N 0.000 description 4
- DGCFEYILWJXXPR-UHFFFAOYSA-N tert-butyl n-(2-amino-5-chloro-4-phenylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(Cl)=C1C1=CC=CC=C1 DGCFEYILWJXXPR-UHFFFAOYSA-N 0.000 description 4
- IUQQARYKMQVTNT-UHFFFAOYSA-N tert-butyl n-(2-amino-5-methyl-4-phenylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=CC=C1 IUQQARYKMQVTNT-UHFFFAOYSA-N 0.000 description 4
- QLAPIWGZGSJNRW-UHFFFAOYSA-N tert-butyl n-(5-methyl-2-nitro-4-phenylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=CC=C1 QLAPIWGZGSJNRW-UHFFFAOYSA-N 0.000 description 4
- YURZHSGDFDWDKL-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2,5-difluorophenyl)-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC=C(F)C=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 YURZHSGDFDWDKL-UHFFFAOYSA-N 0.000 description 4
- ATDREZQXDFLKFB-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=CC=2)F)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 ATDREZQXDFLKFB-UHFFFAOYSA-N 0.000 description 4
- PIESMASXDWSDBV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 PIESMASXDWSDBV-UHFFFAOYSA-N 0.000 description 4
- PBCHSXBXVWATRO-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-iodo-5-morpholin-4-ylphenyl]carbamate Chemical compound IC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 PBCHSXBXVWATRO-UHFFFAOYSA-N 0.000 description 4
- QOQWLTOOEFXJOF-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(2-fluorophenyl)phenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 QOQWLTOOEFXJOF-UHFFFAOYSA-N 0.000 description 4
- SDTUVDKXKMFVOA-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 SDTUVDKXKMFVOA-UHFFFAOYSA-N 0.000 description 4
- FVOFWKDIKICCBS-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(2-methoxyethoxy)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(OCCOC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 FVOFWKDIKICCBS-UHFFFAOYSA-N 0.000 description 4
- KFPQKGGIUMBEMA-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(ethoxymethyl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(COCC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 KFPQKGGIUMBEMA-UHFFFAOYSA-N 0.000 description 4
- XFOXKDSDXMBORO-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1OCC1COC(C)(C)O1 XFOXKDSDXMBORO-UHFFFAOYSA-N 0.000 description 4
- XTCBIBQYBDGAEN-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-[2-(dimethylamino)ethylsulfanyl]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(SCCN(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 XTCBIBQYBDGAEN-UHFFFAOYSA-N 0.000 description 4
- OKAJZINGJHIPBF-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-methoxy-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 OKAJZINGJHIPBF-UHFFFAOYSA-N 0.000 description 4
- KPVIYNHMYGAWKH-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-(oxan-2-yloxymethyl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 KPVIYNHMYGAWKH-UHFFFAOYSA-N 0.000 description 4
- VODIQALLXVZOCX-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2,5-difluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C1=CC(F)=CC=C1F VODIQALLXVZOCX-UHFFFAOYSA-N 0.000 description 4
- DMXMHIAQOPTQSV-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-fluorophenyl)-5-(2-methoxyethoxy)phenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=CC=C1F DMXMHIAQOPTQSV-UHFFFAOYSA-N 0.000 description 4
- YRIZVVRDNOYBPF-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-fluorophenyl)-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 YRIZVVRDNOYBPF-UHFFFAOYSA-N 0.000 description 4
- QMKMTSBNWHYAON-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-fluorophenyl)-5-[(4-methoxyphenyl)methoxy]phenyl]carbamate Chemical compound C1=CC(OC)=CC=C1COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=CC=C1F QMKMTSBNWHYAON-UHFFFAOYSA-N 0.000 description 4
- PDQAAHAJLMSVEV-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluoro-2-methylphenyl)-5-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1C PDQAAHAJLMSVEV-UHFFFAOYSA-N 0.000 description 4
- AJSSFJHWSDLQIY-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-(2-methoxyethoxy)phenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1 AJSSFJHWSDLQIY-UHFFFAOYSA-N 0.000 description 4
- PPAKDRVPHNVIDV-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-(2-oxo-1,3-oxazolidin-3-yl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N1CCOC1=O PPAKDRVPHNVIDV-UHFFFAOYSA-N 0.000 description 4
- GUSFWQGJUVPZAM-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 GUSFWQGJUVPZAM-UHFFFAOYSA-N 0.000 description 4
- CMYHVFPXSHLTAQ-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]phenyl]carbamate Chemical compound CC(C)(C)OCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1 CMYHVFPXSHLTAQ-UHFFFAOYSA-N 0.000 description 4
- SUXKZCKJWUGZON-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-[4-[2-(oxan-2-yloxy)ethoxy]piperidin-1-yl]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC1OCCOC1CCCCO1 SUXKZCKJWUGZON-UHFFFAOYSA-N 0.000 description 4
- LQPIQXBICVUWFB-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1 LQPIQXBICVUWFB-UHFFFAOYSA-N 0.000 description 4
- SKEUSPNYZCKXLG-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-methylphenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1 SKEUSPNYZCKXLG-UHFFFAOYSA-N 0.000 description 4
- UXBIFDXWPSKRPP-UHFFFAOYSA-N tert-butyl n-[2-amino-4-[2-(4-fluorophenyl)ethynyl]-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]phenyl]carbamate Chemical compound CC(C)(C)OCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=C(F)C=C1 UXBIFDXWPSKRPP-UHFFFAOYSA-N 0.000 description 4
- ATLRWSZVYYZKBA-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl)-4-(4-fluorophenyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CC3OC(C)(C)OC3C2)=C1C1=CC=C(F)C=C1 ATLRWSZVYYZKBA-UHFFFAOYSA-N 0.000 description 4
- RKTMIRQEMMSNCD-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(4-methylpiperazin-1-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CN(C)CCN1C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 RKTMIRQEMMSNCD-UHFFFAOYSA-N 0.000 description 4
- NRFXUEQJKRANAB-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(cyanomethoxy)-4-(4-fluorophenyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(OCC#N)=C1C1=CC=C(F)C=C1 NRFXUEQJKRANAB-UHFFFAOYSA-N 0.000 description 4
- ILGIMVQKAJRPSN-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(ethoxymethyl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CCOCC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 ILGIMVQKAJRPSN-UHFFFAOYSA-N 0.000 description 4
- LNVFWYFPSAUUTJ-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(oxan-2-yloxymethyl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 LNVFWYFPSAUUTJ-UHFFFAOYSA-N 0.000 description 4
- IJSWWROTDZSGMC-UHFFFAOYSA-N tert-butyl n-[2-amino-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1OCC1COC(C)(C)O1 IJSWWROTDZSGMC-UHFFFAOYSA-N 0.000 description 4
- KGIDKLOULPJJLI-UHFFFAOYSA-N tert-butyl n-[2-amino-5-[(dimethylamino)methyl]-4-(4-fluorophenyl)phenyl]carbamate Chemical compound CN(C)CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=C(F)C=C1 KGIDKLOULPJJLI-UHFFFAOYSA-N 0.000 description 4
- NWJSISJEHXIXLL-UHFFFAOYSA-N tert-butyl n-[2-amino-5-[2-(dimethylamino)ethylsulfanyl]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CN(C)CCSC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 NWJSISJEHXIXLL-UHFFFAOYSA-N 0.000 description 4
- ODYPYGUWQIUXHQ-UHFFFAOYSA-N tert-butyl n-[2-amino-5-[2-(oxan-2-yloxy)ethoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1OCCOC1CCCCO1 ODYPYGUWQIUXHQ-UHFFFAOYSA-N 0.000 description 4
- IUQRFBVWYMUBIH-UHFFFAOYSA-N tert-butyl n-[2-amino-5-chloro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(Cl)=C1C#CC1=CC=CC=C1 IUQRFBVWYMUBIH-UHFFFAOYSA-N 0.000 description 4
- BWTGZKRUJNMZQG-UHFFFAOYSA-N tert-butyl n-[2-amino-5-chloro-4-(4-fluorophenyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(Cl)=C1C1=CC=C(F)C=C1 BWTGZKRUJNMZQG-UHFFFAOYSA-N 0.000 description 4
- BNTRSSCKMCAICO-UHFFFAOYSA-N tert-butyl n-[2-amino-5-methyl-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 BNTRSSCKMCAICO-UHFFFAOYSA-N 0.000 description 4
- RLWLEFJFBNDVLV-UHFFFAOYSA-N tert-butyl n-[2-amino-5-morpholin-4-yl-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 RLWLEFJFBNDVLV-UHFFFAOYSA-N 0.000 description 4
- UHNYIRKZORAMQO-UHFFFAOYSA-N tert-butyl n-[2-nitro-5-[2-(oxan-2-yloxy)ethoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1OCCOC1CCCCO1 UHNYIRKZORAMQO-UHFFFAOYSA-N 0.000 description 4
- VYRGIQWROXVXAX-UHFFFAOYSA-N tert-butyl n-[4-(2,5-difluorophenyl)-5-[(2-methylpropan-2-yl)oxy]-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C1=CC(F)=CC=C1F VYRGIQWROXVXAX-UHFFFAOYSA-N 0.000 description 4
- QXJITOYINHAQNV-UHFFFAOYSA-N tert-butyl n-[4-(2,5-difluorophenyl)-5-methoxy-2-nitrophenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC(F)=CC=C1F QXJITOYINHAQNV-UHFFFAOYSA-N 0.000 description 4
- ZZEDMZIIUFCQTL-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-(2-methoxyethoxy)-2-nitrophenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=CC=C1F ZZEDMZIIUFCQTL-UHFFFAOYSA-N 0.000 description 4
- DVDRGJZRQLIZNS-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-[(4-methoxyphenyl)methoxy]-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound C1=CC(OC)=CC=C1COC(C(=C1)C=2C(=CC=CC=2)F)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C=2ON=C(C)C=2)=C1 DVDRGJZRQLIZNS-UHFFFAOYSA-N 0.000 description 4
- GNITZRALWNJULW-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-methoxy-2-[[3-oxo-3-[3-(1,2,4-triazol-4-yl)phenyl]propanoyl]amino]phenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=NN=C1 GNITZRALWNJULW-UHFFFAOYSA-N 0.000 description 4
- HMQYDRBAGXYQKR-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-methoxy-2-nitrophenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=CC=C1F HMQYDRBAGXYQKR-UHFFFAOYSA-N 0.000 description 4
- JWKZCAFVRIPLOY-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-(2-oxo-1,3-oxazolidin-3-yl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOC1=O JWKZCAFVRIPLOY-UHFFFAOYSA-N 0.000 description 4
- PQNLYLHLZBKSFN-NDPHRHSWSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]phenyl]carbamate Chemical compound O([C@@H]1CCN(C1)C=1C=C(C(=CC=1C=1C=CC(F)=CC=1)NC(=O)CC(=O)C=1C=C(C=CC=1)N1C=NC=C1)NC(=O)OC(C)(C)C)C1CCCCO1 PQNLYLHLZBKSFN-NDPHRHSWSA-N 0.000 description 4
- IOMUFTDYKKYJOW-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[4-(oxan-2-yloxy)piperidin-1-yl]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC1OC1CCCCO1 IOMUFTDYKKYJOW-UHFFFAOYSA-N 0.000 description 4
- XGDLDXYKJPHFFI-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[4-[2-(oxan-2-yloxy)ethoxy]piperidin-1-yl]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC1OCCOC1CCCCO1 XGDLDXYKJPHFFI-UHFFFAOYSA-N 0.000 description 4
- IZPYIDIRZLCWGQ-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-nitro-5-(2-oxo-1,3-oxazolidin-3-yl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N1CCOC1=O IZPYIDIRZLCWGQ-UHFFFAOYSA-N 0.000 description 4
- RPUOVNZKMHYBCW-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-nitro-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 RPUOVNZKMHYBCW-UHFFFAOYSA-N 0.000 description 4
- TXGWVJWOBBBTQM-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-nitro-5-[4-[2-(oxan-2-yloxy)ethoxy]piperidin-1-yl]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC1OCCOC1CCCCO1 TXGWVJWOBBBTQM-UHFFFAOYSA-N 0.000 description 4
- YYPIOMYGKGXAEO-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-5-(2-methoxyethoxy)-2-nitrophenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1 YYPIOMYGKGXAEO-UHFFFAOYSA-N 0.000 description 4
- DJSVWYOFJNFTLV-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 DJSVWYOFJNFTLV-UHFFFAOYSA-N 0.000 description 4
- JCCAXMAHEKLSMN-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[methyl-[2-(oxan-2-yloxy)ethyl]amino]phenyl]carbamate Chemical compound C=1C(NC(=O)OC(C)(C)C)=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C=C(C#CC=2C=CC(F)=CC=2)C=1N(C)CCOC1CCCCO1 JCCAXMAHEKLSMN-UHFFFAOYSA-N 0.000 description 4
- NJRGMKHSWCCLGV-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-5-(hydroxymethyl)-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(CO)=C1C#CC1=CC=C(F)C=C1 NJRGMKHSWCCLGV-UHFFFAOYSA-N 0.000 description 4
- RVDLHXADZXWTLR-UHFFFAOYSA-N tert-butyl n-[4-iodo-2-nitro-5-[2-(oxan-2-yloxy)ethoxy]phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OCCOC2OCCCC2)=C1I RVDLHXADZXWTLR-UHFFFAOYSA-N 0.000 description 4
- UBZUZHIWSFLKQM-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-(4-methoxypiperidin-1-yl)-2-nitrophenyl]carbamate Chemical compound C1CC(OC)CCN1C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I UBZUZHIWSFLKQM-UHFFFAOYSA-N 0.000 description 4
- WHRQDPYXUJLHIO-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-2-nitrophenyl]carbamate Chemical compound COCCOCCOCCOCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I WHRQDPYXUJLHIO-UHFFFAOYSA-N 0.000 description 4
- ITZVGJLPEHPAFS-UHFFFAOYSA-N tert-butyl n-[5-(1,1-dioxo-1,4-thiazinan-4-yl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N1CCS(=O)(=O)CC1 ITZVGJLPEHPAFS-UHFFFAOYSA-N 0.000 description 4
- QGMLHMVRNCFMJC-UHFFFAOYSA-N tert-butyl n-[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 QGMLHMVRNCFMJC-UHFFFAOYSA-N 0.000 description 4
- ISYMFOUSSDWJEP-UHFFFAOYSA-N tert-butyl n-[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(2-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 ISYMFOUSSDWJEP-UHFFFAOYSA-N 0.000 description 4
- KJAYEARMUQNVTK-UHFFFAOYSA-N tert-butyl n-[5-(2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl)-4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(N2CC3OC(C)(C)OC3C2)=C(C=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 KJAYEARMUQNVTK-UHFFFAOYSA-N 0.000 description 4
- KFWNCGCHKYBFIL-UHFFFAOYSA-N tert-butyl n-[5-(2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl)-4-(4-fluorophenyl)-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CC3OC(C)(C)OC3C2)=C1C1=CC=C(F)C=C1 KFWNCGCHKYBFIL-UHFFFAOYSA-N 0.000 description 4
- FBJWLWAMOCXEDO-UHFFFAOYSA-N tert-butyl n-[5-(2-methoxyethoxy)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 FBJWLWAMOCXEDO-UHFFFAOYSA-N 0.000 description 4
- MBVCRROMYYYMGZ-UHFFFAOYSA-N tert-butyl n-[5-(4-hydroxypiperidin-1-yl)-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCC(O)CC2)=C1I MBVCRROMYYYMGZ-UHFFFAOYSA-N 0.000 description 4
- UEDRGQPRDLHQFK-UHFFFAOYSA-N tert-butyl n-[5-(4-methoxypiperidin-1-yl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CC(OC)CCN1C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 UEDRGQPRDLHQFK-UHFFFAOYSA-N 0.000 description 4
- NZEYJWOHEOTVJS-UHFFFAOYSA-N tert-butyl n-[5-(4-methylpiperazin-1-yl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CN(C)CCN1C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 NZEYJWOHEOTVJS-UHFFFAOYSA-N 0.000 description 4
- JSCUCPPCFXZWEE-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethoxy)-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OCC#N)=C(C#CC=2C=CC=CC=2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 JSCUCPPCFXZWEE-UHFFFAOYSA-N 0.000 description 4
- RKRGBADLKBXODM-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethoxy)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OCC#N)=C(C#CC=2C=CC=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 RKRGBADLKBXODM-UHFFFAOYSA-N 0.000 description 4
- JMKSUQDTKXBWCP-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethoxy)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OCC#N)=C1C#CC1=CC=CC=C1 JMKSUQDTKXBWCP-UHFFFAOYSA-N 0.000 description 4
- VMMJYRHZUDKFNK-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethoxy)-4-(4-fluorophenyl)-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OCC#N)=C1C1=CC=C(F)C=C1 VMMJYRHZUDKFNK-UHFFFAOYSA-N 0.000 description 4
- WSPWSBCKDVPTKD-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethyl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(CC#N)=C1C#CC1=CC=CC=C1 WSPWSBCKDVPTKD-UHFFFAOYSA-N 0.000 description 4
- IYWYBJNGEGWVPH-SECBINFHSA-N tert-butyl n-[5-[(3r)-3-hydroxypyrrolidin-1-yl]-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2C[C@H](O)CC2)=C1I IYWYBJNGEGWVPH-SECBINFHSA-N 0.000 description 4
- IJZOKEVCYZSSFM-UHFFFAOYSA-N tert-butyl n-[5-[(dimethylamino)methyl]-4-(4-fluorophenyl)-2-nitrophenyl]carbamate Chemical compound CN(C)CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1 IJZOKEVCYZSSFM-UHFFFAOYSA-N 0.000 description 4
- DHLSXIHLKCPTQK-UHFFFAOYSA-N tert-butyl n-[5-[2-(dimethylamino)ethylsulfanyl]-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CN(C)CCSC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 DHLSXIHLKCPTQK-UHFFFAOYSA-N 0.000 description 4
- JXXRJXOUAAEXPD-UHFFFAOYSA-N tert-butyl n-[5-[2-(dimethylamino)ethylsulfanyl]-4-iodo-2-nitrophenyl]carbamate Chemical compound CN(C)CCSC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I JXXRJXOUAAEXPD-UHFFFAOYSA-N 0.000 description 4
- DSHHYMTZHRJVHY-UHFFFAOYSA-N tert-butyl n-[5-[2-hydroxyethyl(methyl)amino]-4-iodo-2-nitrophenyl]carbamate Chemical compound OCCN(C)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I DSHHYMTZHRJVHY-UHFFFAOYSA-N 0.000 description 4
- WUJPSFRBMCGSPL-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-phenylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C=2C=CC=CC=2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 WUJPSFRBMCGSPL-UHFFFAOYSA-N 0.000 description 4
- YPMXBAYVVVJLCF-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 YPMXBAYVVVJLCF-UHFFFAOYSA-N 0.000 description 4
- FRANACVKTYIGSU-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 FRANACVKTYIGSU-UHFFFAOYSA-N 0.000 description 4
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 4
- LLPVQGDNKWRPQT-UHFFFAOYSA-N (5-chloro-4-iodo-2-nitrophenyl)carbamic acid Chemical compound OC(=O)NC1=CC(Cl)=C(I)C=C1[N+]([O-])=O LLPVQGDNKWRPQT-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- RBKKYIAGHDZILB-UHFFFAOYSA-N 2,2-dimethyl-6-[3-(2-methylimidazol-1-yl)phenyl]-1,3-dioxin-4-one Chemical compound CC1=NC=CN1C1=CC=CC(C=2OC(C)(C)OC(=O)C=2)=C1 RBKKYIAGHDZILB-UHFFFAOYSA-N 0.000 description 3
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 3
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical class NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 3
- GCPHKTQMABHWPY-UHFFFAOYSA-N 3-chlorothiophene-2-carbonyl chloride Chemical compound ClC(=O)C=1SC=CC=1Cl GCPHKTQMABHWPY-UHFFFAOYSA-N 0.000 description 3
- WXHAKCASYYCJED-UHFFFAOYSA-N 3-imidazol-1-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC(N2C=NC=C2)=C1 WXHAKCASYYCJED-UHFFFAOYSA-N 0.000 description 3
- ZVKOWQCEVFTISF-UHFFFAOYSA-N 4-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)pyridine-2-carbonitrile Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=NC(C#N)=C1 ZVKOWQCEVFTISF-UHFFFAOYSA-N 0.000 description 3
- XCNLZOVZBFSBTM-UHFFFAOYSA-N 4-iodo-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]-2-nitroaniline Chemical compound CC(C)(C)OCCOC1=CC(N)=C([N+]([O-])=O)C=C1I XCNLZOVZBFSBTM-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- MSNLNYAXFVLXPN-UHFFFAOYSA-N [1-[4-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]-3-phenylprop-2-ynyl] 2,2-dimethylpropanoate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(C(OC(=O)C(C)(C)C)C#CC=2C=CC=CC=2)=C1 MSNLNYAXFVLXPN-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- STJDOHVMATYUBD-UHFFFAOYSA-N ethyl 3-(5-cyano-2-fluorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC(C#N)=CC=C1F STJDOHVMATYUBD-UHFFFAOYSA-N 0.000 description 3
- PGNHYEASYXBVHG-UHFFFAOYSA-N ethyl 3-oxo-3-[3-(1,2,4-triazol-4-yl)phenyl]propanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC(N2C=NN=C2)=C1 PGNHYEASYXBVHG-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 229940049906 glutamate Drugs 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- DITWCIRXPIAFGZ-UHFFFAOYSA-N methyl 2-[4-amino-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-phenylethynyl)phenyl]acetate Chemical compound COC(=O)CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 DITWCIRXPIAFGZ-UHFFFAOYSA-N 0.000 description 3
- KVDVCBMELWYHMB-UHFFFAOYSA-N methyl 2-[4-amino-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-phenylethynyl)phenyl]sulfanylacetate Chemical compound COC(=O)CSC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 KVDVCBMELWYHMB-UHFFFAOYSA-N 0.000 description 3
- XXWHILNCWRYXEI-UHFFFAOYSA-N methyl 2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitro-2-(2-phenylethynyl)phenyl]sulfanylacetate Chemical compound COC(=O)CSC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 XXWHILNCWRYXEI-UHFFFAOYSA-N 0.000 description 3
- IJYLGPJXEMBMID-UHFFFAOYSA-N methyl 4-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]benzoate Chemical compound C1=C(I)C(C(=O)OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 IJYLGPJXEMBMID-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- NXEAXHCWGCWWJI-UHFFFAOYSA-N tert-butyl 2-[2-(4-fluorophenyl)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1 NXEAXHCWGCWWJI-UHFFFAOYSA-N 0.000 description 3
- GOOGHKYFBBQHIO-UHFFFAOYSA-N tert-butyl 2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitro-2-(2-phenylethynyl)phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 GOOGHKYFBBQHIO-UHFFFAOYSA-N 0.000 description 3
- IBAOZGUIXMWLRA-UHFFFAOYSA-N tert-butyl 3-[3-(2-methylsulfanylimidazol-1-yl)phenyl]-3-oxopropanoate Chemical compound CSC1=NC=CN1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 IBAOZGUIXMWLRA-UHFFFAOYSA-N 0.000 description 3
- DBCJIHSJIIGDPF-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 DBCJIHSJIIGDPF-UHFFFAOYSA-N 0.000 description 3
- QMJKJTXYPUJSNM-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(4-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 QMJKJTXYPUJSNM-UHFFFAOYSA-N 0.000 description 3
- IBRCWTPWVWOEHV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(4-methoxypiperidin-1-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CC(OC)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 IBRCWTPWVWOEHV-UHFFFAOYSA-N 0.000 description 3
- ZUVFMXFEIQUCEV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-iodophenyl)-3-oxopropanoyl]amino]-5-(2-methoxyethoxy)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(OCCOC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(I)=C1 ZUVFMXFEIQUCEV-UHFFFAOYSA-N 0.000 description 3
- XQADJRRTIUHBRB-PHSANKKPSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]phenyl]carbamate Chemical compound O([C@@H]1CCN(C1)C=1C=C(C(=CC=1C=1C=CC(F)=CC=1)N)NC(=O)OC(C)(C)C)C1CCCCO1 XQADJRRTIUHBRB-PHSANKKPSA-N 0.000 description 3
- HDXVPZGWKLODHA-UHFFFAOYSA-N tert-butyl n-[2-amino-4-[2-(4-fluorophenyl)ethynyl]-5-[methyl-[2-(oxan-2-yloxy)ethyl]amino]phenyl]carbamate Chemical compound C=1C(NC(=O)OC(C)(C)C)=C(N)C=C(C#CC=2C=CC(F)=CC=2)C=1N(C)CCOC1CCCCO1 HDXVPZGWKLODHA-UHFFFAOYSA-N 0.000 description 3
- NXQUWBMRUUVCAI-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 NXQUWBMRUUVCAI-UHFFFAOYSA-N 0.000 description 3
- XEEWPNJLDHDMPN-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(4,4-diethoxypiperidin-1-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CC(OCC)(OCC)CCN1C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 XEEWPNJLDHDMPN-UHFFFAOYSA-N 0.000 description 3
- VUUITKUEKZSHLD-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(cyanomethyl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(CC#N)=C1C#CC1=CC=CC=C1 VUUITKUEKZSHLD-UHFFFAOYSA-N 0.000 description 3
- OOZRCANICQYXKF-UHFFFAOYSA-N tert-butyl n-[2-amino-5-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound COCCOCCOCCOCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 OOZRCANICQYXKF-UHFFFAOYSA-N 0.000 description 3
- VTAUSCHROJXFAG-UHFFFAOYSA-N tert-butyl n-[4-(2,5-difluorophenyl)-5-methoxy-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]phenyl]carbamate Chemical compound C1=C(C=2C(=CC=C(F)C=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 VTAUSCHROJXFAG-UHFFFAOYSA-N 0.000 description 3
- RHFIHBOGBVXYSO-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-2-[[3-[3-(2-methylimidazol-1-yl)phenyl]-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC1=NC=CN1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(OC(C)(C)C)=C(C=2)C=2C(=CC=CC=2)F)NC(=O)OC(C)(C)C)=C1 RHFIHBOGBVXYSO-UHFFFAOYSA-N 0.000 description 3
- KQXCQVFGAHNGON-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]-2-[[3-[3-(2-methylsulfanylimidazol-1-yl)phenyl]-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound CSC1=NC=CN1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(OC(C)(C)C)=C(C=2)C=2C(=CC=CC=2)F)NC(=O)OC(C)(C)C)=C1 KQXCQVFGAHNGON-UHFFFAOYSA-N 0.000 description 3
- SQKJDPQISLMTAM-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=CC=2)F)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 SQKJDPQISLMTAM-UHFFFAOYSA-N 0.000 description 3
- JVNVFRSNXJJKSK-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C1=CC=CC=C1F JVNVFRSNXJJKSK-UHFFFAOYSA-N 0.000 description 3
- HFWMTOZSWSYBMA-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-methoxy-2-[[3-[3-(2-methylimidazol-1-yl)phenyl]-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1C HFWMTOZSWSYBMA-UHFFFAOYSA-N 0.000 description 3
- JBDITQSTTZAZCU-UHFFFAOYSA-N tert-butyl n-[4-(4-fluoro-2-methylphenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC(F)=CC=2)C)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 JBDITQSTTZAZCU-UHFFFAOYSA-N 0.000 description 3
- FAEKJCAASRSAMZ-UHFFFAOYSA-N tert-butyl n-[4-(4-fluoro-2-methylphenyl)-5-methoxy-2-nitrophenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1C FAEKJCAASRSAMZ-UHFFFAOYSA-N 0.000 description 3
- QTJHTFREZPHYHB-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-(2-methoxyethoxy)phenyl]carbamate Chemical compound C1=C(C=2C=CC(F)=CC=2)C(OCCOC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 QTJHTFREZPHYHB-UHFFFAOYSA-N 0.000 description 3
- HLOUQXHORCQDAH-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 HLOUQXHORCQDAH-UHFFFAOYSA-N 0.000 description 3
- OUFBKJNSTWDYLQ-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]phenyl]carbamate Chemical compound C1=C(C=2C=CC(F)=CC=2)C(OCCOC(C)(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 OUFBKJNSTWDYLQ-UHFFFAOYSA-N 0.000 description 3
- VHXYVMYHBFYUFN-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-[3-(2-methylimidazol-1-yl)phenyl]-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC1=NC=CN1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(OC(C)(C)C)=C(C=2)C=2C=CC(F)=CC=2)NC(=O)OC(C)(C)C)=C1 VHXYVMYHBFYUFN-UHFFFAOYSA-N 0.000 description 3
- SSNABXFJQICYTQ-PHSANKKPSA-N tert-butyl n-[4-(4-fluorophenyl)-2-nitro-5-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]phenyl]carbamate Chemical compound O([C@@H]1CCN(C1)C=1C=C(C(=CC=1C=1C=CC(F)=CC=1)[N+]([O-])=O)NC(=O)OC(C)(C)C)C1CCCCO1 SSNABXFJQICYTQ-PHSANKKPSA-N 0.000 description 3
- OPJZZWFYAXWESD-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 OPJZZWFYAXWESD-UHFFFAOYSA-N 0.000 description 3
- YJORJTKHBILPQN-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C1=CC=C(F)C=C1 YJORJTKHBILPQN-UHFFFAOYSA-N 0.000 description 3
- ZWOLXOIFOWKOLL-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-5-methoxy-2-nitrophenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1 ZWOLXOIFOWKOLL-UHFFFAOYSA-N 0.000 description 3
- ADFSMFDAOJWUPK-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC(F)=CC=2)C(OCCOC(C)(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 ADFSMFDAOJWUPK-UHFFFAOYSA-N 0.000 description 3
- XKILBZAKWBXSIS-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-5-[(2-methylpropan-2-yl)oxy]-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C#CC=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 XKILBZAKWBXSIS-UHFFFAOYSA-N 0.000 description 3
- AVTCTCDJYCEQPY-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-5-[(2-methylpropan-2-yl)oxy]-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OC(C)(C)C)=C1C#CC1=CC=C(F)C=C1 AVTCTCDJYCEQPY-UHFFFAOYSA-N 0.000 description 3
- HJGSQOQJNMGPFS-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=C(F)C=C1 HJGSQOQJNMGPFS-UHFFFAOYSA-N 0.000 description 3
- UTGMREKWUVOVSC-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-5-[methyl-[2-(oxan-2-yloxy)ethyl]amino]-2-nitrophenyl]carbamate Chemical compound C=1C(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C(C#CC=2C=CC(F)=CC=2)C=1N(C)CCOC1CCCCO1 UTGMREKWUVOVSC-UHFFFAOYSA-N 0.000 description 3
- MPERVEWUACZMIW-UHFFFAOYSA-N tert-butyl n-[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NC=C2)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 MPERVEWUACZMIW-UHFFFAOYSA-N 0.000 description 3
- SRSYAQSQBYDHIR-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethyl)-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CC#N)=C(C#CC=2C=CC=CC=2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 SRSYAQSQBYDHIR-UHFFFAOYSA-N 0.000 description 3
- LXIKZPJLNNIMSY-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethyl)-4-iodo-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CC#N)=C(I)C=C1[N+]([O-])=O LXIKZPJLNNIMSY-UHFFFAOYSA-N 0.000 description 3
- RZAMUWFFNQFMAE-UHFFFAOYSA-N tert-butyl n-[5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1OCC1COC(C)(C)O1 RZAMUWFFNQFMAE-UHFFFAOYSA-N 0.000 description 3
- YHOSXRYOQALUPK-UHFFFAOYSA-N tert-butyl n-[5-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound COCCOCCOCCOCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 YHOSXRYOQALUPK-UHFFFAOYSA-N 0.000 description 3
- VYSQDXDFSUTURD-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(Cl)=C1C#CC1=CC=CC=C1 VYSQDXDFSUTURD-UHFFFAOYSA-N 0.000 description 3
- AAJVFXMERFMABX-UHFFFAOYSA-N tert-butyl n-[5-chloro-4-(4-fluorophenyl)-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(Cl)=C1C1=CC=C(F)C=C1 AAJVFXMERFMABX-UHFFFAOYSA-N 0.000 description 3
- KTOJGSDLJNUAEP-UHFFFAOYSA-N (2,5-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=CC=C1F KTOJGSDLJNUAEP-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- RNEVREZJAWDXDT-UHFFFAOYSA-N (4-iodo-2-nitrophenyl)carbamic acid Chemical compound OC(=O)NC1=CC=C(I)C=C1[N+]([O-])=O RNEVREZJAWDXDT-UHFFFAOYSA-N 0.000 description 2
- GZOKAVHTSXSLNB-UHFFFAOYSA-N 1,1-dimethoxypropan-2-amine Chemical compound COC(OC)C(C)N GZOKAVHTSXSLNB-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-UHFFFAOYSA-N 0.000 description 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- AIZQKZQVAXDAHQ-UHFFFAOYSA-N 2-(5-amino-2-iodo-4-nitrophenyl)acetonitrile Chemical compound NC1=CC(CC#N)=C(I)C=C1[N+]([O-])=O AIZQKZQVAXDAHQ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- VAIHBHWKPBXNLR-UHFFFAOYSA-N 2-piperidin-4-yloxyethanol Chemical compound OCCOC1CCNCC1 VAIHBHWKPBXNLR-UHFFFAOYSA-N 0.000 description 2
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 2
- UNTMKIYQHROFCP-UHFFFAOYSA-N 3-(tetrazol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(N2N=NN=C2)=C1 UNTMKIYQHROFCP-UHFFFAOYSA-N 0.000 description 2
- ZFBQUMMHYISWNM-UHFFFAOYSA-N 3-[2-(methoxymethylsulfanyl)imidazol-1-yl]benzoic acid Chemical compound COCSC1=NC=CN1C1=CC=CC(C(O)=O)=C1 ZFBQUMMHYISWNM-UHFFFAOYSA-N 0.000 description 2
- JRCPWACHCGGGFU-UHFFFAOYSA-N 3-[2-oxo-8-(2-phenylethynyl)-7-thiomorpholin-4-yl-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C=1C=CC=CC=1C#CC=1C=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=1N1CCSCC1 JRCPWACHCGGGFU-UHFFFAOYSA-N 0.000 description 2
- AIYLGSKMEDZTFH-UHFFFAOYSA-N 4-(3-iodophenyl)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound IC1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)C#CC=2C=CC=CC=2)=C1 AIYLGSKMEDZTFH-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- VLBYHFRQWRWEEI-UHFFFAOYSA-N 7-(2-hydroxyethoxy)-4-(3-imidazol-1-ylphenyl)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCCOC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 VLBYHFRQWRWEEI-UHFFFAOYSA-N 0.000 description 2
- WQYLHDWJUJTSRP-UHFFFAOYSA-N 7-(hydroxymethyl)-4-(3-imidazol-1-ylphenyl)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 WQYLHDWJUJTSRP-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- TXWQDPACEYYHQT-UHFFFAOYSA-N 8-(2-fluorophenyl)-7-hydroxy-4-[3-(2-methylsulfanylimidazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CSC1=NC=CN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(O)C=C3N=2)C=2C(=CC=CC=2)F)=C1 TXWQDPACEYYHQT-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- 208000010496 Heart Arrest Diseases 0.000 description 2
- 101001071429 Homo sapiens Metabotropic glutamate receptor 2 Proteins 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
- 206010057852 Nicotine dependence Diseases 0.000 description 2
- 240000007817 Olea europaea Species 0.000 description 2
- 208000026251 Opioid-Related disease Diseases 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 244000018633 Prunus armeniaca Species 0.000 description 2
- 235000009827 Prunus armeniaca Nutrition 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 229910006124 SOCl2 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 238000006619 Stille reaction Methods 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 208000025569 Tobacco Use disease Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 150000001500 aryl chlorides Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000012973 diazabicyclooctane Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- FLWPKUWQEKIEHQ-UHFFFAOYSA-N dimethyl 2-[2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]propanedioate Chemical compound COC(=O)C(C(=O)OC)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I FLWPKUWQEKIEHQ-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical class FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 2
- KTENZHBTOJGTFH-UHFFFAOYSA-N ethyl 2-(5-amino-2-iodo-4-nitrophenyl)-2-cyanoacetate Chemical compound CCOC(=O)C(C#N)C1=CC(N)=C([N+]([O-])=O)C=C1I KTENZHBTOJGTFH-UHFFFAOYSA-N 0.000 description 2
- HZIKYLAZZZSYKF-UHFFFAOYSA-N ethyl 2-cyanopyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC(C#N)=C1 HZIKYLAZZZSYKF-UHFFFAOYSA-N 0.000 description 2
- DIZFWJVCPSJKGW-UHFFFAOYSA-N ethyl 3-ethynylbenzoate Chemical compound CCOC(=O)C1=CC=CC(C#C)=C1 DIZFWJVCPSJKGW-UHFFFAOYSA-N 0.000 description 2
- PUMNWJHNSFVHQW-UHFFFAOYSA-N ethyl 5-cyanothiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C#N)S1 PUMNWJHNSFVHQW-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 231100000040 eye damage Toxicity 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000003825 glutamate receptor antagonist Substances 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- UDKUIGCVZBERED-UHFFFAOYSA-N methyl 2-[2-iodo-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]acetate Chemical compound COC(=O)CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I UDKUIGCVZBERED-UHFFFAOYSA-N 0.000 description 2
- PRIPMVRLFVYNCN-UHFFFAOYSA-N methyl 2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitro-2-(2-phenylethynyl)phenyl]acetate Chemical compound COC(=O)CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 PRIPMVRLFVYNCN-UHFFFAOYSA-N 0.000 description 2
- BSQWYELDCUXPSJ-UHFFFAOYSA-N methyl 3-azidobenzoate Chemical compound COC(=O)C1=CC=CC(N=[N+]=[N-])=C1 BSQWYELDCUXPSJ-UHFFFAOYSA-N 0.000 description 2
- XPBHWSMZTSSEJE-UHFFFAOYSA-N methyl 3-cyanobenzoate Chemical compound COC(=O)C1=CC=CC(C#N)=C1 XPBHWSMZTSSEJE-UHFFFAOYSA-N 0.000 description 2
- PYPQGJSEANKGFI-UHFFFAOYSA-N methyl 4-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-phenylethynyl)benzoate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(C(=O)OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 PYPQGJSEANKGFI-UHFFFAOYSA-N 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 2
- 201000005040 opiate dependence Diseases 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Substances [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- QJRUGCDPBLUQTE-UHFFFAOYSA-N tert-butyl 3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 QJRUGCDPBLUQTE-UHFFFAOYSA-N 0.000 description 2
- NZPKHKQWEHWTOL-UHFFFAOYSA-N tert-butyl n-(2-nitro-4-tributylstannylphenyl)carbamate Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(NC(=O)OC(C)(C)C)C([N+]([O-])=O)=C1 NZPKHKQWEHWTOL-UHFFFAOYSA-N 0.000 description 2
- JTJFEWDXNKYBOE-UHFFFAOYSA-N tert-butyl n-(2-nitrophenyl)carbamate Chemical class CC(C)(C)OC(=O)NC1=CC=CC=C1[N+]([O-])=O JTJFEWDXNKYBOE-UHFFFAOYSA-N 0.000 description 2
- UURNRDRFUBSLOF-UHFFFAOYSA-N tert-butyl n-(5-chloro-2-nitro-4-phenylphenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(Cl)=C1C1=CC=CC=C1 UURNRDRFUBSLOF-UHFFFAOYSA-N 0.000 description 2
- CVDNQKRXKOJHKD-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 CVDNQKRXKOJHKD-UHFFFAOYSA-N 0.000 description 2
- NSTDGQLOKZPTHN-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(OCCOCCOCCOCCOC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 NSTDGQLOKZPTHN-UHFFFAOYSA-N 0.000 description 2
- AJOLTSCXFBZJAZ-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-morpholin-4-yl-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 AJOLTSCXFBZJAZ-UHFFFAOYSA-N 0.000 description 2
- GFOCXPHSRRVVIU-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-(4-methoxypiperidin-1-yl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CC(OC)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 GFOCXPHSRRVVIU-UHFFFAOYSA-N 0.000 description 2
- ZSTPXOZVUFCZGM-UHFFFAOYSA-N tert-butyl n-[2-[[3-(5-cyano-2-fluorophenyl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC(C#N)=CC=C1F ZSTPXOZVUFCZGM-UHFFFAOYSA-N 0.000 description 2
- ONKCKRLOTHLXEY-UHFFFAOYSA-N tert-butyl n-[2-[[3-(5-cyanothiophen-2-yl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=C(C#N)S1 ONKCKRLOTHLXEY-UHFFFAOYSA-N 0.000 description 2
- MGOQETMZXFNRMR-UHFFFAOYSA-N tert-butyl n-[2-amino-5-methoxy-4-(2-phenylethynyl)phenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C#CC1=CC=CC=C1 MGOQETMZXFNRMR-UHFFFAOYSA-N 0.000 description 2
- XTXAXVBOZPJOFU-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 XTXAXVBOZPJOFU-UHFFFAOYSA-N 0.000 description 2
- YUIAPNVBIMCESJ-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-5-[(4-methoxyphenyl)methoxy]-2-nitrophenyl]carbamate Chemical compound C1=CC(OC)=CC=C1COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=CC=C1F YUIAPNVBIMCESJ-UHFFFAOYSA-N 0.000 description 2
- NURXIOYXCBIQKZ-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-methoxyphenyl]carbamate Chemical compound C1=C(C=2C=CC(F)=CC=2)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 NURXIOYXCBIQKZ-UHFFFAOYSA-N 0.000 description 2
- POVXXJHKOVKMFK-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-methylphenyl]carbamate Chemical compound C1=C(C=2C=CC(F)=CC=2)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 POVXXJHKOVKMFK-UHFFFAOYSA-N 0.000 description 2
- OHPWOTCRICLAOT-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-5-[2-[(2-methylpropan-2-yl)oxy]ethoxy]-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1 OHPWOTCRICLAOT-UHFFFAOYSA-N 0.000 description 2
- UIVCFIKCVDSLLN-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-5-methyl-2-nitrophenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C1=CC=C(F)C=C1 UIVCFIKCVDSLLN-UHFFFAOYSA-N 0.000 description 2
- UKPUJPAESWYRQM-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-(4-methylpiperazin-1-yl)-2-nitrophenyl]carbamate Chemical compound C1CN(C)CCN1C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I UKPUJPAESWYRQM-UHFFFAOYSA-N 0.000 description 2
- BCVHKPQHKPXCNG-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-[(4-methoxyphenyl)methoxy]-2-nitrophenyl]carbamate Chemical compound C1=CC(OC)=CC=C1COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1I BCVHKPQHKPXCNG-UHFFFAOYSA-N 0.000 description 2
- SAWHULLUMSFQFY-UHFFFAOYSA-N tert-butyl n-[5-(2,3-dihydroxypropoxy)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(OCC(O)CO)=C1C#CC1=CC=CC=C1 SAWHULLUMSFQFY-UHFFFAOYSA-N 0.000 description 2
- DILOKKOLHYPPDE-UHFFFAOYSA-N tert-butyl n-[5-(4,4-diethoxypiperidin-1-yl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1CC(OCC)(OCC)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 DILOKKOLHYPPDE-UHFFFAOYSA-N 0.000 description 2
- TVQNDWOCRJBEIU-BETUJISGSA-N tert-butyl n-[5-[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2C[C@@H](O)[C@@H](O)C2)=C1I TVQNDWOCRJBEIU-BETUJISGSA-N 0.000 description 2
- JYNNLNWDVGDWIA-UHFFFAOYSA-N tert-butyl n-[5-methoxy-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C#CC1=CC=CC=C1 JYNNLNWDVGDWIA-UHFFFAOYSA-N 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 1
- QPMSJEFZULFYTB-PGMHMLKASA-N (3r)-pyrrolidin-3-ol;hydrochloride Chemical compound Cl.O[C@@H]1CCNC1 QPMSJEFZULFYTB-PGMHMLKASA-N 0.000 description 1
- IQMLIVUHMSIOQP-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)boronic acid Chemical compound CC1=CC(F)=CC=C1B(O)O IQMLIVUHMSIOQP-UHFFFAOYSA-N 0.000 description 1
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NWHKKDLPTKZXQK-UHFFFAOYSA-N 1,2-dioxin-4-one Chemical compound O=C1COOC=C1 NWHKKDLPTKZXQK-UHFFFAOYSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
- ODRZAZBEQWAOGU-UHFFFAOYSA-N 1,4-dioxin-2-one Chemical compound O=C1COC=CO1 ODRZAZBEQWAOGU-UHFFFAOYSA-N 0.000 description 1
- WMQUKDQWMMOHSA-UHFFFAOYSA-N 1-pyridin-4-ylethanone Chemical compound CC(=O)C1=CC=NC=C1 WMQUKDQWMMOHSA-UHFFFAOYSA-N 0.000 description 1
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 1
- JRNJLIQMCSHIBO-UHFFFAOYSA-N 2,2-dimethyl-6-(3-nitrophenyl)-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC([N+]([O-])=O)=C1 JRNJLIQMCSHIBO-UHFFFAOYSA-N 0.000 description 1
- IQWGVVJCBZCWLE-UHFFFAOYSA-N 2,2-dimethyl-6-[3-(1,2,4-triazol-1-yl)phenyl]-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(N2N=CN=C2)=C1 IQWGVVJCBZCWLE-UHFFFAOYSA-N 0.000 description 1
- IYVABEJIPTUPIW-UHFFFAOYSA-N 2,2-dimethyl-6-[3-(trifluoromethoxy)phenyl]-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(OC(F)(F)F)=C1 IYVABEJIPTUPIW-UHFFFAOYSA-N 0.000 description 1
- OSPULYWIHPRRBJ-UHFFFAOYSA-N 2,2-dimethyl-6-[3-(trifluoromethyl)phenyl]-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(C(F)(F)F)=C1 OSPULYWIHPRRBJ-UHFFFAOYSA-N 0.000 description 1
- AMCNIDHBHUDTBK-UHFFFAOYSA-N 2,2-dimethyl-6-pyridin-4-yl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=NC=C1 AMCNIDHBHUDTBK-UHFFFAOYSA-N 0.000 description 1
- MIVONGSUIOFWRI-UHFFFAOYSA-N 2,2-dimethyl-6-thiophen-2-yl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CS1 MIVONGSUIOFWRI-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- BDLXTDLGTWNUFM-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]ethanol Chemical compound CC(C)(C)OCCO BDLXTDLGTWNUFM-UHFFFAOYSA-N 0.000 description 1
- HHPGQVJTNXTULB-UHFFFAOYSA-N 2-[[4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-7-yl]sulfanyl]acetic acid Chemical compound OC(=O)CSC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 HHPGQVJTNXTULB-UHFFFAOYSA-N 0.000 description 1
- ZSUKTXUPUHTSCG-UHFFFAOYSA-N 2-[[8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-7-yl]oxy]-n-hydroxyacetamide Chemical compound ONC(=O)COC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 ZSUKTXUPUHTSCG-UHFFFAOYSA-N 0.000 description 1
- CQQVPWVPKHCWGC-UHFFFAOYSA-N 2-[[8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-7-yl]oxy]acetonitrile Chemical compound C1=CC(F)=CC=C1C(C(=C1)OCC#N)=CC2=C1N=C(C=1C=C(C=CC=1)N1C=NC=C1)CC(=O)N2 CQQVPWVPKHCWGC-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- IRKAKCMCUJXUNX-UHFFFAOYSA-N 2-imidazol-1-ylpyridine-4-carbonyl chloride;hydrochloride Chemical compound Cl.ClC(=O)C1=CC=NC(N2C=NC=C2)=C1 IRKAKCMCUJXUNX-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- HDAKKFUBVLXOCP-UHFFFAOYSA-N 3-(3-chlorophenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(Cl)=C1 HDAKKFUBVLXOCP-UHFFFAOYSA-N 0.000 description 1
- FPCNNSUAUZFMIL-UHFFFAOYSA-N 3-(3-chlorothiophen-2-yl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C=1SC=CC=1Cl FPCNNSUAUZFMIL-UHFFFAOYSA-N 0.000 description 1
- XFODIAHSXPAKCW-UHFFFAOYSA-N 3-(3-cyanophenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(C#N)=C1 XFODIAHSXPAKCW-UHFFFAOYSA-N 0.000 description 1
- XXHUWCQDTHEDHI-UHFFFAOYSA-N 3-(3-cyanothiophen-2-yl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C=1SC=CC=1C#N XXHUWCQDTHEDHI-UHFFFAOYSA-N 0.000 description 1
- QSIJJFJVURXYMN-UHFFFAOYSA-N 3-(3-imidazol-1-ylphenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 QSIJJFJVURXYMN-UHFFFAOYSA-N 0.000 description 1
- MDHICEGQTXCLTJ-UHFFFAOYSA-N 3-(3-iodophenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(I)=C1 MDHICEGQTXCLTJ-UHFFFAOYSA-N 0.000 description 1
- JOQVOMFQLAREKJ-UHFFFAOYSA-N 3-(3-methoxyphenyl)-3-oxopropanoic acid Chemical compound COC1=CC=CC(C(=O)CC(O)=O)=C1 JOQVOMFQLAREKJ-UHFFFAOYSA-N 0.000 description 1
- DSXBYJRDCMAELK-UHFFFAOYSA-N 3-(7-methyl-2-oxo-8-phenyl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound CC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1 DSXBYJRDCMAELK-UHFFFAOYSA-N 0.000 description 1
- WADMLEPOHOQAAZ-UHFFFAOYSA-N 3-(8-iodo-7-morpholin-4-yl-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound IC1=CC=2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC=2C=C1N1CCOCC1 WADMLEPOHOQAAZ-UHFFFAOYSA-N 0.000 description 1
- NDILQXVACSSLIV-UHFFFAOYSA-N 3-(triazol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(N2N=NC=C2)=C1 NDILQXVACSSLIV-UHFFFAOYSA-N 0.000 description 1
- MGKIOAXLPYJSMU-UHFFFAOYSA-N 3-(trifluoromethoxy)benzoyl chloride Chemical compound FC(F)(F)OC1=CC=CC(C(Cl)=O)=C1 MGKIOAXLPYJSMU-UHFFFAOYSA-N 0.000 description 1
- RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-N 0.000 description 1
- FTWHMDBXCRYRPI-UHFFFAOYSA-N 3-[7-(1,1-dioxo-1,4-thiazinan-4-yl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C=1C=CC=CC=1C#CC=1C=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=1N1CCS(=O)(=O)CC1 FTWHMDBXCRYRPI-UHFFFAOYSA-N 0.000 description 1
- YSWUJXOSXIVHNX-UHFFFAOYSA-N 3-[7-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C=1C=CC=CC=1C#CC=1C=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=1N(CC1)CCC21OCCO2 YSWUJXOSXIVHNX-UHFFFAOYSA-N 0.000 description 1
- IRZCSKVBQBNCPL-UHFFFAOYSA-N 3-[7-(2,3-dihydroxypropoxy)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound OCC(O)COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 IRZCSKVBQBNCPL-UHFFFAOYSA-N 0.000 description 1
- OQAGJVCQYAGMNB-UHFFFAOYSA-N 3-[7-(2-methoxyethoxy)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzamide Chemical compound COCCOC1=CC=2N=C(C=3C=C(C=CC=3)C(N)=O)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 OQAGJVCQYAGMNB-UHFFFAOYSA-N 0.000 description 1
- XOMMFNLLVVFUCJ-UHFFFAOYSA-N 3-[7-(2-methoxyethoxy)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COCCOC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 XOMMFNLLVVFUCJ-UHFFFAOYSA-N 0.000 description 1
- UQTVJVBFZCOSHH-UHFFFAOYSA-N 3-[7-(4-methoxypiperidin-1-yl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1CC(OC)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)C#N)=N2 UQTVJVBFZCOSHH-UHFFFAOYSA-N 0.000 description 1
- NMVLUUKGEXUMHK-UHFFFAOYSA-N 3-[7-(cyanomethoxy)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC(OCC#N)=C1C#CC1=CC=CC=C1 NMVLUUKGEXUMHK-UHFFFAOYSA-N 0.000 description 1
- JWVWVYBGABFDKK-UHFFFAOYSA-N 3-[7-(ethoxymethyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound CCOCC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 JWVWVYBGABFDKK-UHFFFAOYSA-N 0.000 description 1
- YXIDAYRYJQZYFW-UHFFFAOYSA-N 3-[7-(hydroxymethyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound OCC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 YXIDAYRYJQZYFW-UHFFFAOYSA-N 0.000 description 1
- CAQROSAQYGOASE-UHFFFAOYSA-N 3-[7-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COCCOCCOCCOCCOC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 CAQROSAQYGOASE-UHFFFAOYSA-N 0.000 description 1
- ROSMXWAAURHMJH-UHFFFAOYSA-N 3-[7-methyl-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound CC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 ROSMXWAAURHMJH-UHFFFAOYSA-N 0.000 description 1
- FGNZXALQOFFQIB-UHFFFAOYSA-N 3-[7-morpholin-4-yl-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C=1C=CC=CC=1C#CC=1C=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=1N1CCOCC1 FGNZXALQOFFQIB-UHFFFAOYSA-N 0.000 description 1
- YIXOBRAXXYDBDE-UHFFFAOYSA-N 3-[8-(2,5-difluorophenyl)-7-methoxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC(F)=CC=C1F YIXOBRAXXYDBDE-UHFFFAOYSA-N 0.000 description 1
- AJACGLKFNBAASP-UHFFFAOYSA-N 3-[8-(2-fluorophenyl)-7-(2-methoxyethoxy)-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COCCOC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F AJACGLKFNBAASP-UHFFFAOYSA-N 0.000 description 1
- AKBMBQXVISSBFQ-UHFFFAOYSA-N 3-[8-(2-fluorophenyl)-7-(hydroxymethyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound OCC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F AKBMBQXVISSBFQ-UHFFFAOYSA-N 0.000 description 1
- KZNHRXCKLQWQIR-UHFFFAOYSA-N 3-[8-(2-fluorophenyl)-7-hydroxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F KZNHRXCKLQWQIR-UHFFFAOYSA-N 0.000 description 1
- WZMPXYDSQLTJDG-UHFFFAOYSA-N 3-[8-(2-fluorophenyl)-7-methoxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F WZMPXYDSQLTJDG-UHFFFAOYSA-N 0.000 description 1
- AOZLSLHPWQREFB-UHFFFAOYSA-N 3-[8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-7-yl]-1,3-oxazolidin-2-one Chemical compound C1=CC(F)=CC=C1C(C(=C1)N2C(OCC2)=O)=CC2=C1N=C(C=1C=C(C=CC=1)N1C=NC=C1)CC(=O)N2 AOZLSLHPWQREFB-UHFFFAOYSA-N 0.000 description 1
- YVSDGSDHNGQHIX-UHFFFAOYSA-N 3-[8-(4-fluorophenyl)-7-hydroxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 YVSDGSDHNGQHIX-UHFFFAOYSA-N 0.000 description 1
- LYCCVBLUKJRDOF-UHFFFAOYSA-N 3-amino-4-nitrobenzoic acid Chemical compound NC1=CC(C(O)=O)=CC=C1[N+]([O-])=O LYCCVBLUKJRDOF-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 description 1
- RPESZQVUWMFBEO-UHFFFAOYSA-N 3-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C#N)=C1 RPESZQVUWMFBEO-UHFFFAOYSA-N 0.000 description 1
- DTMUVPXCTSEHRY-UHFFFAOYSA-N 3-cyanothiophene-2-carbonyl chloride Chemical compound ClC(=O)C=1SC=CC=1C#N DTMUVPXCTSEHRY-UHFFFAOYSA-N 0.000 description 1
- XLDLRRGZWIEEHT-UHFFFAOYSA-N 3-hydroxy-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C(O)=C1 XLDLRRGZWIEEHT-UHFFFAOYSA-N 0.000 description 1
- VKJZLGSUMISODO-UHFFFAOYSA-N 3-imidazol-1-ylbenzoyl chloride;hydrochloride Chemical compound Cl.ClC(=O)C1=CC=CC(N2C=NC=C2)=C1 VKJZLGSUMISODO-UHFFFAOYSA-N 0.000 description 1
- DTELTOREECFDBC-UHFFFAOYSA-N 3-iodobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(I)=C1 DTELTOREECFDBC-UHFFFAOYSA-N 0.000 description 1
- PJRBPKOOGLKPFB-UHFFFAOYSA-N 3-isothiocyanatobenzoic acid Chemical compound OC(=O)C1=CC=CC(N=C=S)=C1 PJRBPKOOGLKPFB-UHFFFAOYSA-N 0.000 description 1
- RUQIUASLAXJZIE-UHFFFAOYSA-N 3-methoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1 RUQIUASLAXJZIE-UHFFFAOYSA-N 0.000 description 1
- NXTNASSYJUXJDV-UHFFFAOYSA-N 3-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(C(Cl)=O)=C1 NXTNASSYJUXJDV-UHFFFAOYSA-N 0.000 description 1
- SRMVKGOSKXKRPN-UHFFFAOYSA-N 3-oxo-3-[3-(trifluoromethoxy)phenyl]propanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(OC(F)(F)F)=C1 SRMVKGOSKXKRPN-UHFFFAOYSA-N 0.000 description 1
- ODTVKMNSRRLGQP-UHFFFAOYSA-N 3-oxo-3-[3-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(C(F)(F)F)=C1 ODTVKMNSRRLGQP-UHFFFAOYSA-N 0.000 description 1
- XGBWQOBKCNZNFE-UHFFFAOYSA-N 3-oxo-3-pyridin-4-ylpropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=NC=C1 XGBWQOBKCNZNFE-UHFFFAOYSA-N 0.000 description 1
- KIWNJRYYJXFCNE-UHFFFAOYSA-N 3-oxo-3-thiophen-2-ylpropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CS1 KIWNJRYYJXFCNE-UHFFFAOYSA-N 0.000 description 1
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- RKWNCLHXDFUNDF-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-7-(4-methoxypiperidin-1-yl)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1CC(OC)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)N1C=NC=C1)=N2 RKWNCLHXDFUNDF-UHFFFAOYSA-N 0.000 description 1
- NXDQSYYEQJJESV-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-7-(4-oxopiperidin-1-yl)-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1CC(=O)CCN1C(C(=C1)C#CC=2C=CC=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)N1C=NC=C1)=N2 NXDQSYYEQJJESV-UHFFFAOYSA-N 0.000 description 1
- XIFRYNVTAVPWGO-UHFFFAOYSA-N 4-fluoro-3-[8-(2-fluorophenyl)-7-methoxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COC1=CC=2N=C(C=3C(=CC=C(C=3)C#N)F)CC(=O)NC=2C=C1C1=CC=CC=C1F XIFRYNVTAVPWGO-UHFFFAOYSA-N 0.000 description 1
- VOIBCYUAXZMBBX-UHFFFAOYSA-N 4-iodo-1-isocyanato-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(I)=CC=C1N=C=O VOIBCYUAXZMBBX-UHFFFAOYSA-N 0.000 description 1
- ZEYSHALLPAKUHG-UHFFFAOYSA-N 4-methoxypiperidine Chemical compound COC1CCNCC1 ZEYSHALLPAKUHG-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- HECQLSKVDRQPKX-UHFFFAOYSA-N 5-[8-(2-fluorophenyl)-7-hydroxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]thiophene-2-carbonitrile Chemical compound OC1=CC=2N=C(C=3SC(=CC=3)C#N)CC(=O)NC=2C=C1C1=CC=CC=C1F HECQLSKVDRQPKX-UHFFFAOYSA-N 0.000 description 1
- ZCWXYZBQDNFULS-UHFFFAOYSA-N 5-chloro-2-nitroaniline Chemical compound NC1=CC(Cl)=CC=C1[N+]([O-])=O ZCWXYZBQDNFULS-UHFFFAOYSA-N 0.000 description 1
- YXMKDOXPHLWTFR-UHFFFAOYSA-N 5-cyano-2-fluorobenzoyl chloride Chemical compound FC1=CC=C(C#N)C=C1C(Cl)=O YXMKDOXPHLWTFR-UHFFFAOYSA-N 0.000 description 1
- IGDYNWKWXUCIJB-UHFFFAOYSA-N 5-methyl-2-nitroaniline Chemical compound CC1=CC=C([N+]([O-])=O)C(N)=C1 IGDYNWKWXUCIJB-UHFFFAOYSA-N 0.000 description 1
- SOSGXWUECGZGGB-UHFFFAOYSA-N 6-(2-imidazol-1-ylpyridin-4-yl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=NC(N2C=NC=C2)=C1 SOSGXWUECGZGGB-UHFFFAOYSA-N 0.000 description 1
- PAULRSCADPEICA-UHFFFAOYSA-N 6-(3-chlorophenyl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(Cl)=C1 PAULRSCADPEICA-UHFFFAOYSA-N 0.000 description 1
- HLSUVVXAVDJQSU-UHFFFAOYSA-N 6-(3-chlorothiophen-2-yl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=C(Cl)C=CS1 HLSUVVXAVDJQSU-UHFFFAOYSA-N 0.000 description 1
- XDUZGGAZMNSUJZ-UHFFFAOYSA-N 6-(3-methoxyphenyl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound COC1=CC=CC(C=2OC(C)(C)OC(=O)C=2)=C1 XDUZGGAZMNSUJZ-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- RKPYJQQHWXFXFO-UHFFFAOYSA-N 7-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-8-(2-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC1=CC=CC=C1C(C(=C1)N2CCC3(CC2)OCCO3)=CC2=C1N=C(C=1C=C(C=CC=1)N1C=NC=C1)CC(=O)N2 RKPYJQQHWXFXFO-UHFFFAOYSA-N 0.000 description 1
- BIOBWBDPORNMBS-MKPDMIMOSA-N 7-[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]-8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1[C@@H](O)[C@@H](O)CN1C(C(=C1)C=2C=CC(F)=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)N1C=NC=C1)=N2 BIOBWBDPORNMBS-MKPDMIMOSA-N 0.000 description 1
- OZULQSSDVTWZHM-UHFFFAOYSA-N 7-[(dimethylamino)methyl]-8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CN(C)CC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 OZULQSSDVTWZHM-UHFFFAOYSA-N 0.000 description 1
- WKYWXLBMXMIUNK-UHFFFAOYSA-N 7-chloro-8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=CC(F)=CC=C1C(C(=C1)Cl)=CC2=C1N=C(C=1C=C(C=CC=1)N1C=NC=C1)CC(=O)N2 WKYWXLBMXMIUNK-UHFFFAOYSA-N 0.000 description 1
- CWPDJOWAVFIBLT-UHFFFAOYSA-N 8-(2,5-difluorophenyl)-7-methoxy-4-[3-(triazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)N3N=NC=C3)CC(=O)NC=2C=C1C1=CC(F)=CC=C1F CWPDJOWAVFIBLT-UHFFFAOYSA-N 0.000 description 1
- GONNIDOPONIHEI-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-7-(4-oxopiperidin-1-yl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC1=CC=CC=C1C(C(=C1)N2CCC(=O)CC2)=CC2=C1N=C(C=1C=C(C=CC=1)N1C=NC=C1)CC(=O)N2 GONNIDOPONIHEI-UHFFFAOYSA-N 0.000 description 1
- QAHRAMRBOSBMEQ-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-7-methoxy-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=CC=C1F QAHRAMRBOSBMEQ-UHFFFAOYSA-N 0.000 description 1
- CETJSTBZOJQTPJ-UHFFFAOYSA-N 8-(2-fluorophenyl)-7-hydroxy-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=CC=C1F CETJSTBZOJQTPJ-UHFFFAOYSA-N 0.000 description 1
- QXZBVTKOJYTLBF-UHFFFAOYSA-N 8-(2-fluorophenyl)-7-hydroxy-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(O)C=C3N=2)C=2C(=CC=CC=2)F)=C1 QXZBVTKOJYTLBF-UHFFFAOYSA-N 0.000 description 1
- VXQXQLIXIFGISZ-UHFFFAOYSA-N 8-(2-fluorophenyl)-7-methoxy-4-[3-(1,2,4-triazol-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NN=C3)CC(=O)NC=2C=C1C1=CC=CC=C1F VXQXQLIXIFGISZ-UHFFFAOYSA-N 0.000 description 1
- ZYZFUFVUMWGTPE-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-4-(3-imidazol-1-ylphenyl)-7-methoxy-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1C ZYZFUFVUMWGTPE-UHFFFAOYSA-N 0.000 description 1
- XTDDMMHIIVVWHZ-UHFFFAOYSA-N 8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-7-(2-methoxyethoxy)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COCCOC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 XTDDMMHIIVVWHZ-UHFFFAOYSA-N 0.000 description 1
- DJFGAAQGTGOWOY-UHFFFAOYSA-N 8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-7-(4-oxopiperidin-1-yl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=CC(F)=CC=C1C(C(=C1)N2CCC(=O)CC2)=CC2=C1N=C(C=1C=C(C=CC=1)N1C=NC=C1)CC(=O)N2 DJFGAAQGTGOWOY-UHFFFAOYSA-N 0.000 description 1
- OKTTYJTWZKARAB-UHFFFAOYSA-N 8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-7-methoxy-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 OKTTYJTWZKARAB-UHFFFAOYSA-N 0.000 description 1
- KAZPOQXHYWBQRU-UHFFFAOYSA-N 8-(4-fluorophenyl)-4-(3-imidazol-1-ylphenyl)-7-methyl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 KAZPOQXHYWBQRU-UHFFFAOYSA-N 0.000 description 1
- DVZCRUBYONIWFW-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-(2-hydroxyethoxy)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCCOC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 DVZCRUBYONIWFW-UHFFFAOYSA-N 0.000 description 1
- NPUGROPSHBNBCI-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-(4-hydroxypiperidin-1-yl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1CC(O)CCN1C(C(=C1)C=2C=CC(F)=CC=2)=CC2=C1NC(=O)CC(C=1C=C(C=CC=1)N1C=NC=C1)=N2 NPUGROPSHBNBCI-UHFFFAOYSA-N 0.000 description 1
- JPMCJZKFOMMSGW-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-(hydroxymethyl)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 JPMCJZKFOMMSGW-UHFFFAOYSA-N 0.000 description 1
- JSDAKITVXJQGOK-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-hydroxy-4-[3-(2-methylimidazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC=CN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(O)C=C3N=2)C=2C=CC(F)=CC=2)=C1 JSDAKITVXJQGOK-UHFFFAOYSA-N 0.000 description 1
- UOEAWMXWNHEPLC-UHFFFAOYSA-N 8-(4-fluorophenyl)-7-hydroxy-4-[3-(triazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OC1=CC=2N=C(C=3C=C(C=CC=3)N3N=NC=C3)CC(=O)NC=2C=C1C1=CC=C(F)C=C1 UOEAWMXWNHEPLC-UHFFFAOYSA-N 0.000 description 1
- MYEKYFUWNWDWRH-UHFFFAOYSA-N 8-[2-(4-fluorophenyl)ethynyl]-7-(2-hydroxyethoxy)-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCCOC1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=C(F)C=C1 MYEKYFUWNWDWRH-UHFFFAOYSA-N 0.000 description 1
- CHIPHPDGPBIINM-UHFFFAOYSA-N 8-[2-(4-fluorophenyl)ethynyl]-7-[2-hydroxyethyl(methyl)amino]-4-(3-imidazol-1-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCCN(C)C1=CC=2N=C(C=3C=C(C=CC=3)N3C=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=C(F)C=C1 CHIPHPDGPBIINM-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000007848 Bronsted acid Substances 0.000 description 1
- KPOSNCHQVIAWFF-UHFFFAOYSA-N C1=C([N+]([O-])=O)C(NC(=O)O)=CC(N2CCC(CC2)OCCOC2OCCCC2)=C1I Chemical compound C1=C([N+]([O-])=O)C(NC(=O)O)=CC(N2CCC(CC2)OCCOC2OCCCC2)=C1I KPOSNCHQVIAWFF-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
- 102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
- 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 1
- 102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 1
- 102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
- 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- PPFCVAIOHXHTCZ-UHFFFAOYSA-N OCCNC1=CC(NC(O)=O)=C([N+]([O-])=O)C=C1I Chemical compound OCCNC1=CC(NC(O)=O)=C([N+]([O-])=O)C=C1I PPFCVAIOHXHTCZ-UHFFFAOYSA-N 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JUKZWMBQUZVCFT-UHFFFAOYSA-N [1-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]-3-phenylprop-2-ynyl] 2,2-dimethylpropanoate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(C(OC(=O)C(C)(C)C)C#CC=2C=CC=CC=2)=C1 JUKZWMBQUZVCFT-UHFFFAOYSA-N 0.000 description 1
- OBDSITLACDGNMC-UHFFFAOYSA-N [Rh+] Chemical class [Rh+] OBDSITLACDGNMC-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- PZAGQUOSOTUKEC-UHFFFAOYSA-N acetic acid;sulfuric acid Chemical compound CC(O)=O.OS(O)(=O)=O PZAGQUOSOTUKEC-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- MATPZHBYOVDBLI-JJYYJPOSSA-N dcg-iv Chemical compound OC(=O)[C@@H](N)C1[C@@H](C(O)=O)[C@@H]1C(O)=O MATPZHBYOVDBLI-JJYYJPOSSA-N 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- XHFUVBWCMLLKOZ-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N)=N1 XHFUVBWCMLLKOZ-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- OGVAOONRHSVSBS-UHFFFAOYSA-N ethyl 2-imidazol-1-yl-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N2C=NC=C2)=N1 OGVAOONRHSVSBS-UHFFFAOYSA-N 0.000 description 1
- IXPIZLFZHBVZCN-UHFFFAOYSA-N ethyl 3-(1-methylimidazol-2-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2N(C=CN=2)C)=C1 IXPIZLFZHBVZCN-UHFFFAOYSA-N 0.000 description 1
- UEGSATJBTPSVSB-UHFFFAOYSA-N ethyl 3-(2,4-dimethylimidazol-1-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(N2C(=NC(C)=C2)C)=C1 UEGSATJBTPSVSB-UHFFFAOYSA-N 0.000 description 1
- VLLMQFBOCPBXFU-UHFFFAOYSA-N ethyl 3-(2-methylimidazol-1-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(N2C(=NC=C2)C)=C1 VLLMQFBOCPBXFU-UHFFFAOYSA-N 0.000 description 1
- DOMASSRNCAIGBA-UHFFFAOYSA-N ethyl 3-(2-methylsulfanylimidazol-1-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(N2C(=NC=C2)SC)=C1 DOMASSRNCAIGBA-UHFFFAOYSA-N 0.000 description 1
- PHNJTBAZKIUEOQ-UHFFFAOYSA-N ethyl 3-(3-chlorothiophen-2-yl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C=1SC=CC=1Cl PHNJTBAZKIUEOQ-UHFFFAOYSA-N 0.000 description 1
- RDYVOLQRIFEJAZ-UHFFFAOYSA-N ethyl 3-(3-methyl-1,2-oxazol-5-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2ON=C(C)C=2)=C1 RDYVOLQRIFEJAZ-UHFFFAOYSA-N 0.000 description 1
- UCKLESSQOQNAOT-UHFFFAOYSA-N ethyl 3-[2-(methoxymethylsulfanyl)imidazol-1-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(N2C(=NC=C2)SCOC)=C1 UCKLESSQOQNAOT-UHFFFAOYSA-N 0.000 description 1
- YWULJOLZBRTPLF-UHFFFAOYSA-N ethyl 3-oxo-3-[3-(tetrazol-1-yl)phenyl]propanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC(N2N=NN=C2)=C1 YWULJOLZBRTPLF-UHFFFAOYSA-N 0.000 description 1
- TUEYHEWXYWCDHA-UHFFFAOYSA-N ethyl 5-methylthiadiazole-4-carboxylate Chemical compound CCOC(=O)C=1N=NSC=1C TUEYHEWXYWCDHA-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- MCRFCFOUSBRLFA-UHFFFAOYSA-J lead;propanoate Chemical compound [Pb].CCC([O-])=O.CCC([O-])=O.CCC([O-])=O.CCC([O-])=O MCRFCFOUSBRLFA-UHFFFAOYSA-J 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- CHKVEDLTACTUAS-UHFFFAOYSA-L magnesium;methyl carbonate Chemical compound [Mg+2].COC([O-])=O.COC([O-])=O CHKVEDLTACTUAS-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
- 108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
- 108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
- 108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
- 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- DHOBJSAITBISCF-UHFFFAOYSA-N methyl 3-(1,2,4-triazol-4-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2C=NN=C2)=C1 DHOBJSAITBISCF-UHFFFAOYSA-N 0.000 description 1
- XADHIERRCYKPBO-UHFFFAOYSA-N methyl 3-(4-methylimidazol-1-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2C=C(C)N=C2)=C1 XADHIERRCYKPBO-UHFFFAOYSA-N 0.000 description 1
- CWINGXPWIXWOBS-UHFFFAOYSA-N methyl 3-imidazol-1-ylbenzoate Chemical compound COC(=O)C1=CC=CC(N2C=NC=C2)=C1 CWINGXPWIXWOBS-UHFFFAOYSA-N 0.000 description 1
- JFAUDSIHYBPGMH-UHFFFAOYSA-N methyl 4-(3-cyanophenyl)-2-oxo-8-(2-phenylethynyl)-1,3-dihydro-1,5-benzodiazepine-7-carboxylate Chemical compound COC(=O)C1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 JFAUDSIHYBPGMH-UHFFFAOYSA-N 0.000 description 1
- WPKASCVASRPKNY-UHFFFAOYSA-N methyl 4-(3-cyanophenyl)-8-iodo-2-oxo-1,3-dihydro-1,5-benzodiazepine-7-carboxylate Chemical compound C1C(=O)NC=2C=C(I)C(C(=O)OC)=CC=2N=C1C1=CC=CC(C#N)=C1 WPKASCVASRPKNY-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- NZFHJBSDSXDUAO-UHFFFAOYSA-N o-tritylhydroxylamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(ON)C1=CC=CC=C1 NZFHJBSDSXDUAO-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- WVUCPRGADMCTBN-UHFFFAOYSA-M potassium;3-ethoxy-3-oxopropanoate Chemical compound [K+].CCOC(=O)CC([O-])=O WVUCPRGADMCTBN-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- PZYCCRUCWBBJPV-UHFFFAOYSA-N tert-butyl 2-[2-(4-fluorophenyl)-4-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]acetate Chemical compound C1=C(C=2C=CC(F)=CC=2)C(OCC(=O)OC(C)(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 PZYCCRUCWBBJPV-UHFFFAOYSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- FPUSSPQEUANTGI-UHFFFAOYSA-N tert-butyl 2-chloropyridine-4-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=NC(Cl)=C1 FPUSSPQEUANTGI-UHFFFAOYSA-N 0.000 description 1
- PQBVKHDYYNWOGU-UHFFFAOYSA-N tert-butyl 3-(2-imidazol-1-yl-1,3-thiazol-4-yl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CSC(N2C=NC=C2)=N1 PQBVKHDYYNWOGU-UHFFFAOYSA-N 0.000 description 1
- KOKMBMHWRHIBJO-UHFFFAOYSA-N tert-butyl 3-(3-nitrophenyl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC([N+]([O-])=O)=C1 KOKMBMHWRHIBJO-UHFFFAOYSA-N 0.000 description 1
- FXYUUJOVJMZZRL-UHFFFAOYSA-N tert-butyl 3-[2-(4-methylimidazol-1-yl)-1,3-thiazol-4-yl]-3-oxopropanoate Chemical compound C1=NC(C)=CN1C1=NC(C(=O)CC(=O)OC(C)(C)C)=CS1 FXYUUJOVJMZZRL-UHFFFAOYSA-N 0.000 description 1
- TXRIKUXEGHKRNE-UHFFFAOYSA-N tert-butyl 3-[3-(1-methylimidazol-2-yl)phenyl]-3-oxopropanoate Chemical compound CN1C=CN=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 TXRIKUXEGHKRNE-UHFFFAOYSA-N 0.000 description 1
- QPODRURMCNUBJK-UHFFFAOYSA-N tert-butyl 3-[3-(2,4-dimethylimidazol-1-yl)phenyl]-3-oxopropanoate Chemical compound CC1=NC(C)=CN1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 QPODRURMCNUBJK-UHFFFAOYSA-N 0.000 description 1
- KIEBEYIEYUTILO-UHFFFAOYSA-N tert-butyl 3-[3-(4-methylimidazol-1-yl)phenyl]-3-oxopropanoate Chemical compound C1=NC(C)=CN1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 KIEBEYIEYUTILO-UHFFFAOYSA-N 0.000 description 1
- KVTIMDDCYIYKAQ-UHFFFAOYSA-N tert-butyl 3-[3-[2-(methoxymethylsulfanyl)imidazol-1-yl]phenyl]-3-oxopropanoate Chemical compound COCSC1=NC=CN1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 KVTIMDDCYIYKAQ-UHFFFAOYSA-N 0.000 description 1
- HKEQDRWVAMTWJO-UHFFFAOYSA-N tert-butyl 3-oxo-3-[3-(1,2,4-triazol-4-yl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2C=NN=C2)=C1 HKEQDRWVAMTWJO-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- KCZFBLNQOSFGSH-UHFFFAOYSA-N tert-butyl n-(2-aminophenyl)carbamate Chemical class CC(C)(C)OC(=O)NC1=CC=CC=C1N KCZFBLNQOSFGSH-UHFFFAOYSA-N 0.000 description 1
- XMYXDMJZHVRYKZ-UHFFFAOYSA-N tert-butyl n-(4-ethynyl-2-nitrophenyl)carbamate Chemical class CC(C)(C)OC(=O)NC1=CC=C(C#C)C=C1[N+]([O-])=O XMYXDMJZHVRYKZ-UHFFFAOYSA-N 0.000 description 1
- DNNALGJPVCZTJY-UHFFFAOYSA-N tert-butyl n-(4-iodo-2-nitro-5-pyrrolidin-1-ylphenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCCC2)=C1I DNNALGJPVCZTJY-UHFFFAOYSA-N 0.000 description 1
- LBYWOOGCOYSUOC-UHFFFAOYSA-N tert-butyl n-(5-hydroxy-2-nitrophenyl)carbamate Chemical class CC(C)(C)OC(=O)NC1=CC(O)=CC=C1[N+]([O-])=O LBYWOOGCOYSUOC-UHFFFAOYSA-N 0.000 description 1
- CIYHTQGIMRVCII-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=CC=2)F)C=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 CIYHTQGIMRVCII-UHFFFAOYSA-N 0.000 description 1
- BJDJQLXJTMFUHM-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2,5-difluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=C(F)C=2)F)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 BJDJQLXJTMFUHM-UHFFFAOYSA-N 0.000 description 1
- AIWSGGPEOOGIOC-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-(2-methoxyethoxy)phenyl]carbamate Chemical compound C1=C(C=2C(=CC=CC=2)F)C(OCCOC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 AIWSGGPEOOGIOC-UHFFFAOYSA-N 0.000 description 1
- PACGXFKSGSIMQA-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-iodo-5-thiomorpholin-4-ylphenyl]carbamate Chemical compound IC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCSCC1 PACGXFKSGSIMQA-UHFFFAOYSA-N 0.000 description 1
- IIBLRUHSCJFXSR-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanothiophen-2-yl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=CC=2)F)C=C1NC(=O)CC(=O)C=1SC=CC=1C#N IIBLRUHSCJFXSR-UHFFFAOYSA-N 0.000 description 1
- SUEHEZJDLWZWSR-UHFFFAOYSA-N tert-butyl n-[2-[[3-(5-cyanothiophen-2-yl)-3-oxopropanoyl]amino]-4-(2-fluorophenyl)-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=CC=2)F)C=C1NC(=O)CC(=O)C1=CC=C(C#N)S1 SUEHEZJDLWZWSR-UHFFFAOYSA-N 0.000 description 1
- LDQXPBKYVTUMFN-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(4-fluorophenyl)-5-[4-(oxan-2-yloxy)piperidin-1-yl]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC1OC1CCCCO1 LDQXPBKYVTUMFN-UHFFFAOYSA-N 0.000 description 1
- LHNJEKCZBAKCSX-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(2-fluorophenyl)phenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 LHNJEKCZBAKCSX-UHFFFAOYSA-N 0.000 description 1
- CHXZKWLMKXHUCI-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(4-fluorophenyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C(N)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 CHXZKWLMKXHUCI-UHFFFAOYSA-N 0.000 description 1
- XGPYBZCXADCJBD-UHFFFAOYSA-N tert-butyl n-[2-nitro-4-(2-phenylethynyl)-5-thiomorpholin-4-ylphenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N1CCSCC1 XGPYBZCXADCJBD-UHFFFAOYSA-N 0.000 description 1
- IXQQTXASXPOKKL-UHFFFAOYSA-N tert-butyl n-[2-nitro-5-(oxan-2-yloxymethyl)-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C=1C=CC=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 IXQQTXASXPOKKL-UHFFFAOYSA-N 0.000 description 1
- QYBLEUJTYNHBIE-UHFFFAOYSA-N tert-butyl n-[4-(2-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C(=CC=CC=2)F)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 QYBLEUJTYNHBIE-UHFFFAOYSA-N 0.000 description 1
- ODLIVVCFLQRYLM-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OC(C)(C)C)=C(C=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 ODLIVVCFLQRYLM-UHFFFAOYSA-N 0.000 description 1
- IFEUVABEKCGLJC-UHFFFAOYSA-N tert-butyl n-[4-(4-fluorophenyl)-2-nitro-5-[4-(oxan-2-yloxy)piperidin-1-yl]phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC1OC1CCCCO1 IFEUVABEKCGLJC-UHFFFAOYSA-N 0.000 description 1
- DPHHKVJOAWWWPW-UHFFFAOYSA-N tert-butyl n-[4-[2-(4-fluorophenyl)ethynyl]-2-nitro-5-(oxan-2-yloxymethyl)phenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C#CC=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1COC1CCCCO1 DPHHKVJOAWWWPW-UHFFFAOYSA-N 0.000 description 1
- IYDWJAYDJTVPIQ-UHFFFAOYSA-N tert-butyl n-[4-iodo-2-nitro-5-(2-oxo-1,3-oxazolidin-3-yl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2C(OCC2)=O)=C1I IYDWJAYDJTVPIQ-UHFFFAOYSA-N 0.000 description 1
- WELAETIILLBYBH-YJJYDOSJSA-N tert-butyl n-[4-iodo-2-nitro-5-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2C[C@@H](CC2)OC2OCCCC2)=C1I WELAETIILLBYBH-YJJYDOSJSA-N 0.000 description 1
- YPUHYOHHVAKLFI-UHFFFAOYSA-N tert-butyl n-[4-iodo-2-nitro-5-[4-(oxan-2-yloxy)piperidin-1-yl]phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCC(CC2)OC2OCCCC2)=C1I YPUHYOHHVAKLFI-UHFFFAOYSA-N 0.000 description 1
- XESPICUIDDDAFA-UHFFFAOYSA-N tert-butyl n-[4-iodo-5-[methyl-[2-(oxan-2-yloxy)ethyl]amino]-2-nitrophenyl]carbamate Chemical compound C=1C(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C(I)C=1N(C)CCOC1CCCCO1 XESPICUIDDDAFA-UHFFFAOYSA-N 0.000 description 1
- XFZVNMMEAMYQAE-UHFFFAOYSA-N tert-butyl n-[5-(1,1-dioxo-1,4-thiazinan-4-yl)-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCS(=O)(=O)CC2)=C1I XFZVNMMEAMYQAE-UHFFFAOYSA-N 0.000 description 1
- NAQNGEDYQDGLEN-UHFFFAOYSA-N tert-butyl n-[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(2-fluorophenyl)-2-nitrophenyl]carbamate Chemical compound C=1C=CC=C(F)C=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 NAQNGEDYQDGLEN-UHFFFAOYSA-N 0.000 description 1
- BVQPNXUZFDWHSU-UHFFFAOYSA-N tert-butyl n-[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-(4-fluorophenyl)-2-nitrophenyl]carbamate Chemical compound C=1C=C(F)C=CC=1C=1C=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=1N(CC1)CCC21OCCO2 BVQPNXUZFDWHSU-UHFFFAOYSA-N 0.000 description 1
- YASZPGYUCZHJSZ-UHFFFAOYSA-N tert-butyl n-[5-(2,3-dihydroxypropoxy)-4-iodo-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OCC(O)CO)=C(I)C=C1[N+]([O-])=O YASZPGYUCZHJSZ-UHFFFAOYSA-N 0.000 description 1
- JVBAPDRJZQDPBR-UHFFFAOYSA-N tert-butyl n-[5-(2,5-dihydropyrrol-1-yl)-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CC=CC2)=C1I JVBAPDRJZQDPBR-UHFFFAOYSA-N 0.000 description 1
- CGUYKIYUZWXELL-UHFFFAOYSA-N tert-butyl n-[5-(2-hydroxyethylamino)-4-iodo-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(NCCO)=C(I)C=C1[N+]([O-])=O CGUYKIYUZWXELL-UHFFFAOYSA-N 0.000 description 1
- WHJOLISQLQBDTO-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethoxy)-4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OCC#N)=C(C=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 WHJOLISQLQBDTO-UHFFFAOYSA-N 0.000 description 1
- UMMOLDKPRFIQKL-GASCZTMLSA-N tert-butyl n-[5-[(3ar,6as)-2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl]-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2C[C@@H]3OC(C)(C)O[C@@H]3C2)=C1I UMMOLDKPRFIQKL-GASCZTMLSA-N 0.000 description 1
- AUOJEGKKAWFGNW-UHFFFAOYSA-N tert-butyl n-[5-[(dimethylamino)methyl]-4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound C1=C(C=2C=CC(F)=CC=2)C(CN(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 AUOJEGKKAWFGNW-UHFFFAOYSA-N 0.000 description 1
- YRPQXMLUULQKPB-UHFFFAOYSA-N tert-butyl n-[5-[4-(2-hydroxyethoxy)piperidin-1-yl]-4-iodo-2-nitrophenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCC(CC2)OCCO)=C1I YRPQXMLUULQKPB-UHFFFAOYSA-N 0.000 description 1
- AARXCEBPINROGX-UHFFFAOYSA-N tert-butyl n-[5-chloro-4-(4-fluorophenyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C=2C=CC(F)=CC=2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 AARXCEBPINROGX-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
- UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Otolaryngology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99120520 | 1999-10-15 | ||
PCT/EP2000/009553 WO2001029011A2 (en) | 1999-10-15 | 2000-09-29 | Benzodiazepine derivatives as metabotropic glutamate receptor antagonists |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20021690L NO20021690L (no) | 2002-04-10 |
NO20021690D0 NO20021690D0 (no) | 2002-04-10 |
NO327817B1 true NO327817B1 (no) | 2009-09-28 |
Family
ID=8239207
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20021690A NO327817B1 (no) | 1999-10-15 | 2002-04-10 | ``Benzodiazepin-derivater, deres fremstilling, medikament inneholdende slike samt anvendelse av disse for fremstilling av medikament for behandling av sykdom`` |
Country Status (35)
Country | Link |
---|---|
US (1) | US6407094B1 (ru) |
EP (1) | EP1224174B1 (ru) |
JP (1) | JP3857138B2 (ru) |
KR (1) | KR100480320B1 (ru) |
CN (1) | CN1195522C (ru) |
AR (1) | AR026029A1 (ru) |
AT (1) | ATE250039T1 (ru) |
AU (1) | AU774451B2 (ru) |
BR (1) | BR0014859A (ru) |
CA (1) | CA2386974C (ru) |
CO (1) | CO5261604A1 (ru) |
CZ (1) | CZ20021653A3 (ru) |
DE (1) | DE60005386T2 (ru) |
DK (1) | DK1224174T3 (ru) |
EG (1) | EG24079A (ru) |
ES (1) | ES2204704T3 (ru) |
GC (1) | GC0000263A (ru) |
HK (1) | HK1051038A1 (ru) |
HR (1) | HRP20020259A2 (ru) |
HU (1) | HUP0203142A3 (ru) |
IL (2) | IL148816A0 (ru) |
JO (1) | JO2262B1 (ru) |
MA (1) | MA26831A1 (ru) |
MY (1) | MY125540A (ru) |
NO (1) | NO327817B1 (ru) |
NZ (1) | NZ517999A (ru) |
PE (1) | PE20010681A1 (ru) |
PL (1) | PL357418A1 (ru) |
PT (1) | PT1224174E (ru) |
RU (1) | RU2259360C2 (ru) |
SI (1) | SI1224174T1 (ru) |
TR (1) | TR200201023T2 (ru) |
WO (1) | WO2001029011A2 (ru) |
YU (1) | YU26202A (ru) |
ZA (1) | ZA200202544B (ru) |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR0014761A (pt) | 1999-10-15 | 2002-07-02 | Hoffmann La Roche | Derivados de benzodiazepina |
SK13692003A3 (sk) * | 2001-04-12 | 2004-05-04 | F. Hoffmann-La Roche Ag | Deriváty dihydrobenzo[b][4,1]diazepín-2-ónu ako antagonisty mGluR2 |
MXPA03009311A (es) * | 2001-04-12 | 2004-02-12 | Hoffmann La Roche | Derivados de dihidro-benzo[b][1,4]diazepin-2-ona como antagonistas ii del receptor metabotropico de glutamato (mglur2). |
US7766013B2 (en) | 2001-06-05 | 2010-08-03 | Alexza Pharmaceuticals, Inc. | Aerosol generating method and device |
US20070122353A1 (en) | 2001-05-24 | 2007-05-31 | Hale Ron L | Drug condensation aerosols and kits |
US6949542B2 (en) * | 2002-02-06 | 2005-09-27 | Hoffman-La Roche Inc. | Dihydro-benzo[b][1,4]diazepin-2-one derivatives |
JP2006501265A (ja) * | 2002-09-10 | 2006-01-12 | ノバルティス アクチエンゲゼルシャフト | 嗜癖および鬱病を含むmgluレセプターに関連する疾患を処置するためのmgluレセプターアンタゴニスト |
WO2004104490A1 (en) | 2003-05-21 | 2004-12-02 | Alexza Pharmaceuticals, Inc. | Self-contained heating unit and drug-supply unit employing same |
WO2005014002A1 (en) * | 2003-07-25 | 2005-02-17 | F. Hoffmann-La Roche Ag | Combination of mglur2 antagonist and ache inhibitor for treatment of acute and/or chronic neurological disorders |
FR2862969A1 (fr) | 2003-11-28 | 2005-06-03 | Oreal | Procede de preparation de derives paraphenylenediamine a groupement pyrrolidinyle, substitue par un radical azote, et composes intermediaires |
DE102004010893A1 (de) * | 2004-03-06 | 2005-09-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue ß-Ketoamid-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
DE602005008095D1 (de) | 2004-11-05 | 2008-08-21 | Hoffmann La Roche | Verfahren zur herstellung von isonikotinsäurederivaten |
AP2007004047A0 (en) | 2005-01-20 | 2007-06-30 | Pfizer Ltd | Substituted triazole derivatives as oxtocin antagonists |
TWI417095B (zh) * | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | 1,4-二取代之3-氰基-吡啶酮衍生物及其作為mGluR2-受體之正向異位性調節劑之用途 |
TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
ES2594867T3 (es) | 2007-03-09 | 2016-12-23 | Alexza Pharmaceuticals, Inc. | Unidad de calentamiento para usar en un dispositivo de administración de fármaco |
ES2369866T3 (es) * | 2007-04-19 | 2011-12-07 | F. Hoffmann-La Roche Ag | Derivados de dihidro-benzo[b][1,4]diazepin-2-ona-sulfonamida. |
JP5366269B2 (ja) | 2007-09-14 | 2013-12-11 | ジャンセン ファーマシューティカルズ, インコーポレイテッド. | 1,3−二置換4−(アリル−x−フェニル)−1h−ピリジン−2−オン |
ES2356032T3 (es) | 2007-09-14 | 2011-04-04 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | 4-fenil-3,4,5,6-tetrahidro-2h,1'h-[1,4']bipiridinil-2'-onas 1,3'-disustituidas. |
KR20100080597A (ko) * | 2007-09-14 | 2010-07-09 | 오르토-맥닐-얀센 파마슈티칼스 인코포레이티드 | 1,3-이치환된-4-페닐-1h-피리딘-2-온 |
CN101815437A (zh) * | 2007-09-26 | 2010-08-25 | 辛乃山医学院 | 氮杂胞苷类似物和其应用 |
CN101861316B (zh) * | 2007-11-14 | 2013-08-21 | 奥梅-杨森制药有限公司 | 咪唑并[1,2-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
CN102143955B (zh) | 2008-09-02 | 2013-08-14 | Omj制药公司 | 作为代谢型谷氨酸受体调节剂的3-氮杂二环[3.1.0]己烷衍生物 |
WO2010043396A1 (en) | 2008-10-16 | 2010-04-22 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors |
EP2373649B1 (en) | 2008-11-28 | 2013-01-23 | Janssen Pharmaceuticals, Inc. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
JP5707390B2 (ja) | 2009-05-12 | 2015-04-30 | ジャンセン ファーマシューティカルズ, インコーポレイテッド | 1,2,4−トリアゾロ[4,3−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
SG10201402250TA (en) | 2009-05-12 | 2014-07-30 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo [4,3-a] pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders |
CN101891706B (zh) * | 2010-04-09 | 2013-05-29 | 复旦大学 | 3,4-二氢苯并[f][1,4]噻氮杂*类化合物或其盐及其药物用途 |
EP2599775A4 (en) | 2010-07-29 | 2014-04-30 | Taisho Pharmaceutical Co Ltd | ETHINYLPYRAZOLDERIVAT |
EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
ES2536433T3 (es) | 2010-11-08 | 2015-05-25 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
CA2814996C (en) | 2010-11-08 | 2019-10-01 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
JP2012153674A (ja) * | 2011-01-28 | 2012-08-16 | Astellas Pharma Inc | ジ(アリールアミノ)アリール化合物の製造方法及びその合成中間体 |
EP2925292A1 (en) | 2012-10-23 | 2015-10-07 | F. Hoffmann-La Roche AG | Mglu2/3 antagonists for the treatment of autistic disorders |
JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
CN109999025A (zh) | 2014-01-21 | 2019-07-12 | 詹森药业有限公司 | 包括代谢型谷氨酸能受体亚型2的正别构调节物或正位激动剂的组合及其用途 |
NZ722385A (en) | 2014-01-21 | 2019-11-29 | Janssen Pharmaceutica Nv | Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use |
US9895324B2 (en) | 2014-03-26 | 2018-02-20 | University Of Kentucky Research Foundation | Halogenated diarylacetylenes and methods of treating cancer |
WO2015162076A2 (en) | 2014-04-23 | 2015-10-29 | F. Hoffmann-La Roche Ag | Mglu2/3 antagonists for the treatment of intellectual disabilities |
JP6552061B2 (ja) | 2014-06-10 | 2019-07-31 | サンフォード−バーンハム メディカル リサーチ インスティテュート | 代謝型グルタミン酸受容体の負のアロステリックモジュレーター(nams)とその使用 |
CN106243050B (zh) * | 2016-08-10 | 2019-09-06 | 安徽恒星制药有限公司 | 一种适合工业化生产氯巴占的方法 |
CN109836356B (zh) * | 2017-11-24 | 2022-03-08 | 沈阳化工研究院有限公司 | 一种芳甲醚衍生物及其应用 |
RU2702358C1 (ru) * | 2019-06-04 | 2019-10-08 | Федеральное государственное бюджетное научное учреждение Уфимский федеральный исследовательский центр Российской академии наук | Способ получения 2,2,4-триалкил-2,3-дигидро-1Н-1,5-бензодиазепинов |
CN114349779B (zh) * | 2021-12-29 | 2023-09-26 | 智仑超纯环氧树脂(西安)有限公司 | 一种改性二氧化硅颗粒除氯剂及其制备方法及应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0843660A1 (en) * | 1995-07-31 | 1998-05-27 | Novo Nordisk A/S | Heterocyclic compounds, their preparation and use |
EP1037878A2 (en) * | 1997-11-21 | 2000-09-27 | Nps Pharmaceuticals, Inc. | Metabotropic glutamate receptor antagonists for treating central nervous system diseases |
-
2000
- 2000-09-29 AT AT00969347T patent/ATE250039T1/de not_active IP Right Cessation
- 2000-09-29 WO PCT/EP2000/009553 patent/WO2001029011A2/en active IP Right Grant
- 2000-09-29 PL PL00357418A patent/PL357418A1/xx unknown
- 2000-09-29 NZ NZ517999A patent/NZ517999A/en unknown
- 2000-09-29 JP JP2001531811A patent/JP3857138B2/ja not_active Expired - Fee Related
- 2000-09-29 DE DE60005386T patent/DE60005386T2/de not_active Expired - Lifetime
- 2000-09-29 PT PT00969347T patent/PT1224174E/pt unknown
- 2000-09-29 RU RU2002110104/04A patent/RU2259360C2/ru not_active IP Right Cessation
- 2000-09-29 IL IL14881600A patent/IL148816A0/xx active IP Right Grant
- 2000-09-29 AU AU79102/00A patent/AU774451B2/en not_active Ceased
- 2000-09-29 CA CA002386974A patent/CA2386974C/en not_active Expired - Fee Related
- 2000-09-29 DK DK00969347T patent/DK1224174T3/da active
- 2000-09-29 BR BR0014859-8A patent/BR0014859A/pt not_active Application Discontinuation
- 2000-09-29 KR KR10-2002-7004838A patent/KR100480320B1/ko not_active IP Right Cessation
- 2000-09-29 SI SI200030210T patent/SI1224174T1/xx unknown
- 2000-09-29 TR TR2002/01023T patent/TR200201023T2/xx unknown
- 2000-09-29 CN CNB008142742A patent/CN1195522C/zh not_active Expired - Fee Related
- 2000-09-29 EP EP00969347A patent/EP1224174B1/en not_active Expired - Lifetime
- 2000-09-29 HU HU0203142A patent/HUP0203142A3/hu unknown
- 2000-09-29 YU YU26202A patent/YU26202A/sh unknown
- 2000-09-29 CZ CZ20021653A patent/CZ20021653A3/cs unknown
- 2000-09-29 ES ES00969347T patent/ES2204704T3/es not_active Expired - Lifetime
- 2000-10-10 PE PE2000001083A patent/PE20010681A1/es not_active Application Discontinuation
- 2000-10-10 JO JO2000169A patent/JO2262B1/en active
- 2000-10-11 GC GCP2000950 patent/GC0000263A/en active
- 2000-10-12 CO CO00077957A patent/CO5261604A1/es not_active Application Discontinuation
- 2000-10-13 MY MYPI20004817A patent/MY125540A/en unknown
- 2000-10-13 AR ARP000105386A patent/AR026029A1/es unknown
- 2000-10-13 US US09/687,240 patent/US6407094B1/en not_active Expired - Fee Related
- 2000-10-14 EG EG20001310A patent/EG24079A/xx active
-
2002
- 2002-03-21 IL IL148816A patent/IL148816A/en not_active IP Right Cessation
- 2002-03-27 HR HR20020259A patent/HRP20020259A2/xx not_active Application Discontinuation
- 2002-03-28 ZA ZA200202544A patent/ZA200202544B/xx unknown
- 2002-04-10 NO NO20021690A patent/NO327817B1/no not_active IP Right Cessation
- 2002-04-15 MA MA26601A patent/MA26831A1/fr unknown
-
2003
- 2003-04-17 HK HK03102802A patent/HK1051038A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO327817B1 (no) | ``Benzodiazepin-derivater, deres fremstilling, medikament inneholdende slike samt anvendelse av disse for fremstilling av medikament for behandling av sykdom`` | |
EP1379522B1 (en) | DIHYDRO-BENZO(b)(1,4)DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS I | |
EP1379511B1 (en) | DIHYDRO-BENZO (b) (1, 4) DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS II | |
US6509328B1 (en) | Glutamate receptor antagonists | |
AU2002310912A1 (en) | Dihydro-benzo[b][1,4]diazepin-2-one derivatives as mGluR2 antagonists I | |
EP2137167A1 (en) | Dihydro-benzo[b][1,4]diazepin-2-one sulfonamide derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |