TW201706263A - 化合物 - Google Patents

Info

Publication number

TW201706263A

TW201706263A TW105115842A TW105115842A TW201706263A TW 201706263 A TW201706263 A TW 201706263A TW 105115842 A TW105115842 A TW 105115842A TW 105115842 A TW105115842 A TW 105115842A TW 201706263 A TW201706263 A TW 201706263A

Authority

TW

Taiwan

Prior art keywords

alkyl

methyl

indol

compound

ethyl

Prior art date

2015-05-21

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 243
• 150000003839 salts Chemical class 0.000 claims abstract description 142
• 101100406797 Arabidopsis thaliana PAD4 gene Proteins 0.000 claims abstract description 43
• 101150094373 Padi4 gene Proteins 0.000 claims abstract description 43
• 102100035731 Protein-arginine deiminase type-4 Human genes 0.000 claims abstract description 43
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 25
• 206010047115 Vasculitis Diseases 0.000 claims abstract description 19
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 18
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
• 201000011510 cancer Diseases 0.000 claims abstract description 15
• 208000004921 cutaneous lupus erythematosus Diseases 0.000 claims abstract description 14
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 14
• 208000006673 asthma Diseases 0.000 claims abstract description 13
• 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 12
• 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 12
• 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 11
• 238000000034 method Methods 0.000 claims description 246
• -1 -OH Chemical group 0.000 claims description 241
• 125000000217 alkyl group Chemical group 0.000 claims description 116
• 229910052757 nitrogen Inorganic materials 0.000 claims description 82
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 32
• 239000003814 drug Substances 0.000 claims description 28
• 239000008194 pharmaceutical composition Substances 0.000 claims description 28
• 125000001475 halogen functional group Chemical group 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 230000000694 effects Effects 0.000 claims description 20
• 238000004519 manufacturing process Methods 0.000 claims description 20
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 18
• 230000001404 mediated effect Effects 0.000 claims description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 7
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 7
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 125000001188 haloalkyl group Chemical group 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 239000005711 Benzoic acid Substances 0.000 claims description 5
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000006413 ring segment Chemical group 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
• 206010009887 colitis Diseases 0.000 claims description 3
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 229910052740 iodine Inorganic materials 0.000 claims description 3
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• 208000025865 Ulcer Diseases 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 231100000397 ulcer Toxicity 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 14
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 501
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 315
• 235000019439 ethyl acetate Nutrition 0.000 description 239
• 239000000543 intermediate Substances 0.000 description 220
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 210
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 174
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
• 239000000203 mixture Substances 0.000 description 150
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 150
• 239000011541 reaction mixture Substances 0.000 description 137
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 122
• 239000000243 solution Substances 0.000 description 120
• 238000006243 chemical reaction Methods 0.000 description 113
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 111
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 108
• 239000002904 solvent Substances 0.000 description 103
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 95
• 239000000047 product Substances 0.000 description 94
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 85
• 239000010410 layer Substances 0.000 description 74
• 239000007787 solid Substances 0.000 description 70
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 62
• 239000012043 crude product Substances 0.000 description 61
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 61
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 60
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 46
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 46
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 44
• 238000000746 purification Methods 0.000 description 41
• 239000011734 sodium Substances 0.000 description 41
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 40
• 239000000725 suspension Substances 0.000 description 39
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• 150000002148 esters Chemical class 0.000 description 36
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 33
• 238000009472 formulation Methods 0.000 description 33
• 239000012044 organic layer Substances 0.000 description 33
• 238000002360 preparation method Methods 0.000 description 33
• 230000002829 reductive effect Effects 0.000 description 33
• 239000003921 oil Substances 0.000 description 30
• 235000019198 oils Nutrition 0.000 description 29
• 238000003756 stirring Methods 0.000 description 29
• 238000004458 analytical method Methods 0.000 description 27
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 27
• 239000007821 HATU Substances 0.000 description 25
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
• 239000002585 base Substances 0.000 description 25
• 239000000843 powder Substances 0.000 description 24
• 230000002209 hydrophobic effect Effects 0.000 description 23
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 23
• 239000013078 crystal Substances 0.000 description 21
• 239000011521 glass Substances 0.000 description 21
• 238000004128 high performance liquid chromatography Methods 0.000 description 20
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 19
• 239000000443 aerosol Substances 0.000 description 19
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 239000002253 acid Substances 0.000 description 18
• 238000002347 injection Methods 0.000 description 18
• 239000007924 injection Substances 0.000 description 18
• 125000004429 atom Chemical group 0.000 description 17
• 239000000523 sample Substances 0.000 description 17
• 229910000104 sodium hydride Inorganic materials 0.000 description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 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
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 229960000583 acetic acid Drugs 0.000 description 15
• 229910052796 boron Inorganic materials 0.000 description 15
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 15
• BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 15
• 239000012312 sodium hydride Substances 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 14
• 238000004296 chiral HPLC Methods 0.000 description 14
• 201000010099 disease Diseases 0.000 description 14
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 14
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 14
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• 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 13
• 150000001412 amines Chemical class 0.000 description 13
• 239000003054 catalyst Substances 0.000 description 13
• 229910000420 cerium oxide Inorganic materials 0.000 description 13
• 239000012530 fluid Substances 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 13
• 230000008569 process Effects 0.000 description 13
• 239000002552 dosage form Substances 0.000 description 12
• 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 11
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 238000004587 chromatography analysis Methods 0.000 description 11
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 11
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 238000010828 elution Methods 0.000 description 10
• 235000019253 formic acid Nutrition 0.000 description 10
• 206010025135 lupus erythematosus Diseases 0.000 description 10
• 229940071648 metered dose inhaler Drugs 0.000 description 10
• 239000003380 propellant Substances 0.000 description 10
• 108090000623 proteins and genes Proteins 0.000 description 10
• 239000012488 sample solution Substances 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
• 229910021529 ammonia Inorganic materials 0.000 description 9
• 239000000460 chlorine Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 239000006071 cream Substances 0.000 description 9
• 229910052739 hydrogen Inorganic materials 0.000 description 9
• 239000001257 hydrogen Substances 0.000 description 9
• 238000001727 in vivo Methods 0.000 description 9
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 9
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 9
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 9
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 8
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• 150000001299 aldehydes Chemical class 0.000 description 8
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 238000005984 hydrogenation reaction Methods 0.000 description 8
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 8
• 239000002480 mineral oil Substances 0.000 description 8
• 235000010446 mineral oil Nutrition 0.000 description 8
• 150000002828 nitro derivatives Chemical class 0.000 description 8
• 235000018102 proteins Nutrition 0.000 description 8
• 102000004169 proteins and genes Human genes 0.000 description 8
• 210000001519 tissue Anatomy 0.000 description 8
• 238000000825 ultraviolet detection Methods 0.000 description 8
• USMKPCZKQNSUFQ-UHFFFAOYSA-N 2-(1-ethylindol-2-yl)-1-methylbenzimidazole Chemical compound C(C)N1C(=CC2=CC=CC=C12)C1=NC2=C(N1C)C=CC=C2 USMKPCZKQNSUFQ-UHFFFAOYSA-N 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• 239000002775 capsule Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• RUJMPEWZLDVEAV-UHFFFAOYSA-N methyl 4-(methylamino)-3-nitrobenzoate Chemical compound CNC1=CC=C(C(=O)OC)C=C1[N+]([O-])=O RUJMPEWZLDVEAV-UHFFFAOYSA-N 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 229920003023 plastic Polymers 0.000 description 7
• 239000004033 plastic Substances 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 239000012453 solvate Substances 0.000 description 7
• RSPBMMVLDZQYKH-UHFFFAOYSA-N 1-ethylindole-2-carbaldehyde Chemical compound C1=CC=C2N(CC)C(C=O)=CC2=C1 RSPBMMVLDZQYKH-UHFFFAOYSA-N 0.000 description 6
• SBNOTUDDIXOFSN-UHFFFAOYSA-N 1h-indole-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=CC2=C1 SBNOTUDDIXOFSN-UHFFFAOYSA-N 0.000 description 6
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• CETPSERCERDGAM-UHFFFAOYSA-N ceric oxide Chemical compound O=[Ce]=O CETPSERCERDGAM-UHFFFAOYSA-N 0.000 description 6
• 229910000422 cerium(IV) oxide Inorganic materials 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 6
• 150000002576 ketones Chemical class 0.000 description 6
• 238000001819 mass spectrum Methods 0.000 description 6
• TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 6
• 210000001331 nose Anatomy 0.000 description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
• WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 6
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 230000009885 systemic effect Effects 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 239000003643 water by type Substances 0.000 description 6
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 5
• NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 5
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 5
• 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 5
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