KR20070113225A - 히스타민 ｈ３ 수용체에 대해 친화성을 갖는 융합된 티아졸유도체 - Google Patents

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Publication number

KR20070113225A

KR20070113225A KR1020077020994A KR20077020994A KR20070113225A KR 20070113225 A KR20070113225 A KR 20070113225A KR 1020077020994 A KR1020077020994 A KR 1020077020994A KR 20077020994 A KR20077020994 A KR 20077020994A KR 20070113225 A KR20070113225 A KR 20070113225A

Authority

KR

South Korea

Prior art keywords

alkyl

mmol

tetrahydro

thiazolo

cyclobutyl

Prior art date

2005-03-14

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.)

Withdrawn

Links

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• 150000007979 thiazole derivatives Chemical class 0.000 title abstract description 3
• 102000004384 Histamine H3 receptors Human genes 0.000 title description 9
• 108090000981 Histamine H3 receptors Proteins 0.000 title description 9
• 238000000034 method Methods 0.000 claims abstract description 115
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 8
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 8
• 125000000217 alkyl group Chemical group 0.000 claims description 217
• 150000001875 compounds Chemical class 0.000 claims description 96
• -1 -C 3-8 cycloalkyl Chemical group 0.000 claims description 77
• 125000001072 heteroaryl group Chemical group 0.000 claims description 69
• 125000003118 aryl group Chemical group 0.000 claims description 65
• 125000000623 heterocyclic group Chemical group 0.000 claims description 47
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
• 229910052736 halogen Inorganic materials 0.000 claims description 42
• 150000002367 halogens Chemical class 0.000 claims description 41
• 239000001257 hydrogen Substances 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
• 125000001424 substituent group Chemical group 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 29
• 238000006243 chemical reaction Methods 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
• 239000012453 solvate Substances 0.000 claims description 22
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 150000002431 hydrogen Chemical class 0.000 claims description 14
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
• 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 description 4
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 150000002902 organometallic compounds Chemical class 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
• 150000003018 phosphorus compounds Chemical class 0.000 claims 1
• LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 259
• 238000002360 preparation method Methods 0.000 abstract description 7
• 230000000144 pharmacologic effect Effects 0.000 abstract description 3
• 208000020016 psychiatric disease Diseases 0.000 abstract description 3
• 230000000926 neurological effect Effects 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 675
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 279
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 218
• 239000000243 solution Substances 0.000 description 132
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 116
• 239000000047 product Substances 0.000 description 111
• 229910021529 ammonia Inorganic materials 0.000 description 109
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
• 238000010992 reflux Methods 0.000 description 82
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 78
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
• 238000012799 strong cation exchange Methods 0.000 description 75
• 238000005342 ion exchange Methods 0.000 description 69
• 229910052786 argon Inorganic materials 0.000 description 58
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 42
• 230000002829 reductive effect Effects 0.000 description 41
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• 238000010898 silica gel chromatography Methods 0.000 description 40
• 239000002904 solvent Substances 0.000 description 39
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
• 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 33
• 239000011541 reaction mixture Substances 0.000 description 32
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 30
• 238000004440 column chromatography Methods 0.000 description 30
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
• 210000004027 cell Anatomy 0.000 description 23
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 20
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 19
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 19
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 18
• 229910000027 potassium carbonate Inorganic materials 0.000 description 17
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 17
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 16
• VFHJFPGGWIXTMI-UHFFFAOYSA-N 6-cyclobutyl-2-piperidin-4-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C3CCNCC3)=C2CC1 VFHJFPGGWIXTMI-UHFFFAOYSA-N 0.000 description 16
• VLTPTYUTFLPHFK-UHFFFAOYSA-N 2,2,2-trifluoro-1-(2-iodo-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl)ethanone Chemical compound C1CN(C(=O)C(F)(F)F)CCC2=C1SC(I)=N2 VLTPTYUTFLPHFK-UHFFFAOYSA-N 0.000 description 15
• 229960001340 histamine Drugs 0.000 description 15
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 15
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [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 14
• SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 14
• IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 13
• 239000005557 antagonist Substances 0.000 description 13
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• 229910052794 bromium Inorganic materials 0.000 description 12
• 229910000029 sodium carbonate Inorganic materials 0.000 description 12
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
• 239000004793 Polystyrene Substances 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 239000002609 medium Substances 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• 229920002223 polystyrene Polymers 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 125000002950 monocyclic group Chemical group 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
• YXCBMVKTMYRQHH-UHFFFAOYSA-N 2-(4-bromophenyl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=CC(Br)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 YXCBMVKTMYRQHH-UHFFFAOYSA-N 0.000 description 8
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
• MQEVKGXAHHFTOC-UHFFFAOYSA-N 6-cyclobutyl-2-iodo-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CC=2SC(I)=NC=2CCN1C1CCC1 MQEVKGXAHHFTOC-UHFFFAOYSA-N 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• GYBIVLSDYIABQH-UHFFFAOYSA-N (6-chloropyridin-3-yl)-trimethylstannane Chemical compound C[Sn](C)(C)C1=CC=C(Cl)N=C1 GYBIVLSDYIABQH-UHFFFAOYSA-N 0.000 description 7
• SOSZRSSOEUVNSJ-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 SOSZRSSOEUVNSJ-UHFFFAOYSA-N 0.000 description 7
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
• PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
• 125000002619 bicyclic group Chemical group 0.000 description 6
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
• BSEBWOQMJFGBDM-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=CC=C1C(S1)=NC2=C1CCNCC2 BSEBWOQMJFGBDM-UHFFFAOYSA-N 0.000 description 5
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
• 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 5
• 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 description 5
• NQULAAUVWPUYMT-UHFFFAOYSA-N 6-cyclobutyl-2-pyrrolidin-3-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C3CNCC3)=C2CC1 NQULAAUVWPUYMT-UHFFFAOYSA-N 0.000 description 5
• 239000004229 Alkannin Substances 0.000 description 5
• 239000004230 Fast Yellow AB Substances 0.000 description 5
• UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 125000005843 halogen group Chemical group 0.000 description 5
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 5
• 239000013612 plasmid Substances 0.000 description 5
• 230000008569 process Effects 0.000 description 5
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