DE69811360T2 - Diazepinoindolone als phophodiesterase 4 inhibitoren - Google Patents

Info

Publication number

DE69811360T2

DE69811360T2 DE69811360T DE69811360T DE69811360T2 DE 69811360 T2 DE69811360 T2 DE 69811360T2 DE 69811360 T DE69811360 T DE 69811360T DE 69811360 T DE69811360 T DE 69811360T DE 69811360 T2 DE69811360 T2 DE 69811360T2

Authority

DE

Germany

Prior art keywords

oxo

methyl

diazepino

phenyl

indol

Prior art date

1997-04-30

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• ZWOMUDQWODQGQH-UHFFFAOYSA-N 1H-pyrrolo[2,3-g][1,2]benzodiazepin-2-one Chemical compound C1=CC2=NN=CC=CC2=C2C1=CC(=O)N2 ZWOMUDQWODQGQH-UHFFFAOYSA-N 0.000 title claims description 9
• 239000003112 inhibitor Substances 0.000 title description 3
• 238000000034 method Methods 0.000 claims abstract description 139
• 150000001875 compounds Chemical class 0.000 claims abstract description 114
• 208000006673 asthma Diseases 0.000 claims abstract description 9
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 9
• 206010065687 Bone loss Diseases 0.000 claims abstract description 5
• 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 5
• 206010067125 Liver injury Diseases 0.000 claims abstract description 5
• 206010040070 Septic Shock Diseases 0.000 claims abstract description 5
• 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 5
• 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 230000036303 septic shock Effects 0.000 claims abstract description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 129
• 239000000203 mixture Substances 0.000 claims description 103
• 239000000543 intermediate Substances 0.000 claims description 77
• 239000002904 solvent Substances 0.000 claims description 57
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 44
• 230000008569 process Effects 0.000 claims description 44
• -1 -(CH2)n-OR3 Chemical class 0.000 claims description 42
• 239000002253 acid Substances 0.000 claims description 38
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 31
• 150000002431 hydrogen Chemical group 0.000 claims description 26
• 239000002609 medium Substances 0.000 claims description 20
• 150000001412 amines Chemical class 0.000 claims description 19
• 150000002148 esters Chemical class 0.000 claims description 19
• 150000003839 salts Chemical class 0.000 claims description 17
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• 238000002360 preparation method Methods 0.000 claims description 14
• 238000006243 chemical reaction Methods 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 11
• 239000000460 chlorine Substances 0.000 claims description 11
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 11
• HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• NWCMLDFYUXRUPL-UHFFFAOYSA-N 2-methyl-3-(9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-3-yl)-4-oxo-3,4-dihydroquinazoline-7-carboxylic acid Chemical compound CC1=CC=2CCC=C(C(N(C=3)N4C(C5=CC=C(C=C5N=C4C)C(O)=O)=O)=O)C=2N1C=3C1=CC=CC=C1 NWCMLDFYUXRUPL-UHFFFAOYSA-N 0.000 claims description 9
• 230000009435 amidation Effects 0.000 claims description 9
• 238000007112 amidation reaction Methods 0.000 claims description 9
• 150000001408 amides Chemical class 0.000 claims description 9
• 239000003054 catalyst Substances 0.000 claims description 9
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 150000001721 carbon Chemical group 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 150000004678 hydrides Chemical class 0.000 claims description 8
• RTDDGJVVKVRATF-UHFFFAOYSA-N 1,10-diazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7,9-pentaen-12-one Chemical group O=C1CN=Cc2cccc3ccn1c23 RTDDGJVVKVRATF-UHFFFAOYSA-N 0.000 claims description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 230000006181 N-acylation Effects 0.000 claims description 7
• 229910052794 bromium Inorganic materials 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
• 230000002378 acidificating effect Effects 0.000 claims description 6
• 230000032050 esterification Effects 0.000 claims description 6
• 238000005886 esterification reaction Methods 0.000 claims description 6
• 150000002466 imines Chemical class 0.000 claims description 6
• KCKIKSJECTZLJA-UHFFFAOYSA-N indol-4-one Chemical compound O=C1C=CC=C2N=CC=C12 KCKIKSJECTZLJA-UHFFFAOYSA-N 0.000 claims description 6
• 230000007935 neutral effect Effects 0.000 claims description 6
• IVKNUIVDQMARCO-UHFFFAOYSA-N oxazin-4-one Chemical compound O=C1C=CON=C1 IVKNUIVDQMARCO-UHFFFAOYSA-N 0.000 claims description 6
• GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 6
• 208000011231 Crohn disease Diseases 0.000 claims description 5
• 125000003118 aryl group Chemical group 0.000 claims description 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• PUWFKEVSIACIBJ-UHFFFAOYSA-N methyl 3-(6-methoxy-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-2-methyl-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C(=O)OC)=CC=C(C2=O)C=1N=C(C)N2C(C(N1CCC=2C=C(OC)C=C3C1=2)=O)N=C3C1=CC=CC=C1 PUWFKEVSIACIBJ-UHFFFAOYSA-N 0.000 claims description 5
• DAJBLWXUFLHGGH-DEOSSOPVSA-N (11S)-11-(2-methyl-4-oxoquinazolin-3-yl)-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound N([C@H](C(N1CCC=2C=CC=C3C1=2)=O)N1C(=O)C2=CC=CC=C2N=C1C)=C3C1=CC=CC=C1 DAJBLWXUFLHGGH-DEOSSOPVSA-N 0.000 claims description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
• GSXVPNLAOHBBKA-VWLOTQADSA-N 2-methyl-3-[(11S)-6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl]-4-oxoquinazoline-7-carboxylic acid Chemical compound C=1C(C)=CC=2CCN(C([C@@H](N=3)N4C(C5=CC=C(C=C5N=C4C)C(O)=O)=O)=O)C=2C=1C=3C1=CC=CC=C1 GSXVPNLAOHBBKA-VWLOTQADSA-N 0.000 claims description 4
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
• 239000004472 Lysine Substances 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 4
• 235000008206 alpha-amino acids Nutrition 0.000 claims description 4
• 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 4
• 239000004220 glutamic acid Substances 0.000 claims description 4
• 231100000234 hepatic damage Toxicity 0.000 claims description 4
• 230000003301 hydrolyzing effect Effects 0.000 claims description 4
• 230000008818 liver damage Effects 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
• 239000000376 reactant Substances 0.000 claims description 4
• 238000005809 transesterification reaction Methods 0.000 claims description 4
• RHAUFQSERALOMZ-SANMLTNESA-N (11S)-11-(2,5-dimethyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C([C@@H](N=3)N4C(C5=C(C)C=CC=C5N=C4C)=O)=O)C=2C=1C=3C1=CC=CC=C1 RHAUFQSERALOMZ-SANMLTNESA-N 0.000 claims description 3
• HVUUBQWZWIBQGA-SANMLTNESA-N (11S)-11-(2,6-dimethyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound N([C@H](C(N1CCC=2C=C(C)C=C3C1=2)=O)N1C(C)=NC2=CC=C(C=C2C1=O)C)=C3C1=CC=CC=C1 HVUUBQWZWIBQGA-SANMLTNESA-N 0.000 claims description 3
• MOEXNCSUAQSQAX-SANMLTNESA-N (11S)-11-(2,8-dimethyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C([C@@H](N=3)N4C(C5=CC=CC(C)=C5N=C4C)=O)=O)C=2C=1C=3C1=CC=CC=C1 MOEXNCSUAQSQAX-SANMLTNESA-N 0.000 claims description 3
• PKVZSJLYYVGXRM-QHCPKHFHSA-N (11S)-11-(2-methyl-4-oxopyrido[3,4-d]pyrimidin-3-yl)-6-nitro-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound N([C@H](C(N1CCC=2C=C(C=C3C1=2)[N+]([O-])=O)=O)N1C(=O)C2=CC=NC=C2N=C1C)=C3C1=CC=CC=C1 PKVZSJLYYVGXRM-QHCPKHFHSA-N 0.000 claims description 3
• GCQYMZYZLNYUSY-VWLOTQADSA-N (11S)-11-(5-fluoro-2-methyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C([C@@H](N=3)N4C(C5=C(F)C=CC=C5N=C4C)=O)=O)C=2C=1C=3C1=CC=CC=C1 GCQYMZYZLNYUSY-VWLOTQADSA-N 0.000 claims description 3
• YJLSARIGMMOOGK-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 2-methyl-3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C)=CC=2CCN(C3=O)C=2C=1C(C=1C=CC=CC=1)=NC3N(C(C1=CC=2)=O)C(C)=NC1=CC=2C(=O)OC1=C(F)C(F)=C(F)C(F)=C1F YJLSARIGMMOOGK-UHFFFAOYSA-N 0.000 claims description 3
• SIMTYOMWZNXSJJ-UHFFFAOYSA-N (2-hydroxy-3-morpholin-4-ylpropyl) 2-methyl-3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C)=CC=2CCN(C3=O)C=2C=1C(C=1C=CC=CC=1)=NC3N(C(C1=CC=2)=O)C(C)=NC1=CC=2C(=O)OCC(O)CN1CCOCC1 SIMTYOMWZNXSJJ-UHFFFAOYSA-N 0.000 claims description 3
• UQPGREVGZRHTAK-UHFFFAOYSA-N 11-(2,5-dimethyl-4-oxoquinazolin-3-yl)-6-nitro-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound CC1=NC2=CC=CC(C)=C2C(=O)N1C(C(N1CCC=2C=C(C=C3C1=2)[N+]([O-])=O)=O)N=C3C1=CC=CC=C1 UQPGREVGZRHTAK-UHFFFAOYSA-N 0.000 claims description 3
• FKMLEKVIYSANCY-UHFFFAOYSA-N 11-(2,6-dimethyl-4-oxoquinazolin-3-yl)-6-nitro-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound O=C1C2=CC(C)=CC=C2N=C(C)N1C(C(N1CCC=2C=C(C=C3C1=2)[N+]([O-])=O)=O)N=C3C1=CC=CC=C1 FKMLEKVIYSANCY-UHFFFAOYSA-N 0.000 claims description 3
• LUQNQFIQFJBKRV-UHFFFAOYSA-N 11-(2,8-dimethyl-4-oxoquinazolin-3-yl)-6-nitro-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound CC1=NC2=C(C)C=CC=C2C(=O)N1C(C(N1CCC=2C=C(C=C3C1=2)[N+]([O-])=O)=O)N=C3C1=CC=CC=C1 LUQNQFIQFJBKRV-UHFFFAOYSA-N 0.000 claims description 3
• AZQNANWJQLZKCT-UHFFFAOYSA-N 11-(5-chloro-2-methyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C(C(N=3)N4C(C5=C(Cl)C=CC=C5N=C4C)=O)=O)C=2C=1C=3C1=CC=CC=C1 AZQNANWJQLZKCT-UHFFFAOYSA-N 0.000 claims description 3
• HXSPYSYFRCKEPX-UHFFFAOYSA-N 11-(5-chloro-2-methyl-4-oxoquinazolin-3-yl)-6-nitro-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound CC1=NC2=CC=CC(Cl)=C2C(=O)N1C(C(N1CCC=2C=C(C=C3C1=2)[N+]([O-])=O)=O)N=C3C1=CC=CC=C1 HXSPYSYFRCKEPX-UHFFFAOYSA-N 0.000 claims description 3
• RMPDEUYKGHVHHO-UHFFFAOYSA-N 11-(5-methoxy-2-methyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound O=C1C=2C(OC)=CC=CC=2N=C(C)N1C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 RMPDEUYKGHVHHO-UHFFFAOYSA-N 0.000 claims description 3
• LMUOPFLPXGNHCL-UHFFFAOYSA-N 11-(6-methoxy-2-methyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound O=C1C2=CC(OC)=CC=C2N=C(C)N1C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 LMUOPFLPXGNHCL-UHFFFAOYSA-N 0.000 claims description 3
• HVQANRLCVWQRKC-UHFFFAOYSA-N 11-(7-methoxy-2-methyl-4-oxoquinazolin-3-yl)-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(OC)=CC=C(C2=O)C=1N=C(C)N2C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 HVQANRLCVWQRKC-UHFFFAOYSA-N 0.000 claims description 3
• JYEQMGWEPKWGDQ-UHFFFAOYSA-N 11-(8-bromo-2,6-dimethyl-4-oxoquinazolin-3-yl)-6-nitro-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound O=C1C2=CC(C)=CC(Br)=C2N=C(C)N1C(C(N1CCC=2C=C(C=C3C1=2)[N+]([O-])=O)=O)N=C3C1=CC=CC=C1 JYEQMGWEPKWGDQ-UHFFFAOYSA-N 0.000 claims description 3
• FGVLFFGUYNXWKT-UHFFFAOYSA-N 11-[2-(methoxymethyl)-4-oxoquinazolin-3-yl]-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound COCC1=NC2=CC=CC=C2C(=O)N1C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 FGVLFFGUYNXWKT-UHFFFAOYSA-N 0.000 claims description 3
• REKBDMOCNVHHBI-UHFFFAOYSA-N 11-[5-(hydroxymethyl)-2-methyl-4-oxoquinazolin-3-yl]-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C(C(N=3)N4C(C5=C(CO)C=CC=C5N=C4C)=O)=O)C=2C=1C=3C1=CC=CC=C1 REKBDMOCNVHHBI-UHFFFAOYSA-N 0.000 claims description 3
• GBHSNPOCVNFENX-UHFFFAOYSA-N 11-[7-(hydroxymethyl)-2-methyl-4-oxoquinazolin-3-yl]-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C(C(N=3)N4C(C5=CC=C(CO)C=C5N=C4C)=O)=O)C=2C=1C=3C1=CC=CC=C1 GBHSNPOCVNFENX-UHFFFAOYSA-N 0.000 claims description 3
• SEDAFPIGTLFWEA-UHFFFAOYSA-N 11-[7-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-2-methyl-4-oxoquinazolin-3-yl]-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one Chemical compound C=1C(C)=CC=2CCN(C3=O)C=2C=1C(C=1C=CC=CC=1)=NC3N(C(C1=CC=2)=O)C(C)=NC1=CC=2C(=O)N1CCN(CCO)CC1 SEDAFPIGTLFWEA-UHFFFAOYSA-N 0.000 claims description 3
• WGNHXSYCJCLOJO-UHFFFAOYSA-N 2-[[4-[[3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazolin-2-yl]methoxy]-4-oxobutanoyl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C=1C(C)=CC=2CCN(C(C(N=3)N4C(C5=CC=CC=C5N=C4COC(=O)CCC(=O)NC(CCCCNC(=O)OC(C)(C)C)C(O)=O)=O)=O)C=2C=1C=3C1=CC=CC=C1 WGNHXSYCJCLOJO-UHFFFAOYSA-N 0.000 claims description 3
• MEULVEMAASHPAZ-UHFFFAOYSA-N 2-acetyloxyethyl 2-methyl-3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C(=O)OCCOC(=O)C)=CC=C(C2=O)C=1N=C(C)N2C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 MEULVEMAASHPAZ-UHFFFAOYSA-N 0.000 claims description 3
• VAUTUGGBWWRHIY-UHFFFAOYSA-N 2-hydroxyethyl 2-methyl-3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C)=CC=2CCN(C(C(N=3)N4C(C5=CC=C(C=C5N=C4C)C(=O)OCCO)=O)=O)C=2C=1C=3C1=CC=CC=C1 VAUTUGGBWWRHIY-UHFFFAOYSA-N 0.000 claims description 3
• IFMSCYUQRZNAFK-UHFFFAOYSA-N 2-methoxyethyl 2-methyl-3-(6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl)-4-oxoquinazoline-7-carboxylate Chemical compound C=1C(C(=O)OCCOC)=CC=C(C2=O)C=1N=C(C)N2C(C(N1CCC=2C=C(C)C=C3C1=2)=O)N=C3C1=CC=CC=C1 IFMSCYUQRZNAFK-UHFFFAOYSA-N 0.000 claims description 3
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• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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• VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
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