IL96486A

IL96486A - Tricyclic compounds, their preparation and pharmaceutical compositions containing them

Tricyclic compounds, their preparation and pharmaceutical compositions containing them

Info

Publication number: IL96486A
Authority: IL; Israel
Prior art keywords: azabicyclo; compound; oct; formula; methyl
Prior art date: 1989-11-28

Application number

IL9648690A

Other languages

English (en)

Other versions

IL96486A0 (en

Original Assignee

Syntex Inc

Priority date

1989-11-28

Filing date

1990-11-27

Publication date

1995-03-30

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23755479&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL96486(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1990-11-27 Application filed by Syntex Inc filed Critical Syntex Inc

1990-11-27 Priority to IL11062290A priority Critical patent/IL110622A/en

1991-08-16 Publication of IL96486A0 publication Critical patent/IL96486A0/xx

1995-03-30 Publication of IL96486A publication Critical patent/IL96486A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 317
238000002360 preparation method Methods 0.000 title claims description 24
239000008194 pharmaceutical composition Substances 0.000 title claims description 13
-1 nitro, amino, amino carbonyl Chemical group 0.000 claims abstract description 88
125000000217 alkyl group Chemical group 0.000 claims abstract description 41
125000001424 substituent group Chemical group 0.000 claims abstract description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 22
125000003545 alkoxy group Chemical group 0.000 claims abstract description 21
229910052736 halogen Inorganic materials 0.000 claims abstract description 21
150000002367 halogens Chemical class 0.000 claims abstract description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
125000002541 furyl group Chemical group 0.000 claims abstract description 4
125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 4
125000001544 thienyl group Chemical group 0.000 claims abstract description 4
125000000753 cycloalkyl group Chemical group 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 100
239000000203 mixture Substances 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 43
VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 34
238000011282 treatment Methods 0.000 claims description 32
241001465754 Metazoa Species 0.000 claims description 31
206010047700 Vomiting Diseases 0.000 claims description 27
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
239000012458 free base Substances 0.000 claims description 20
239000000546 pharmaceutical excipient Substances 0.000 claims description 16
239000002585 base Substances 0.000 claims description 15
230000008569 process Effects 0.000 claims description 14
102000035037 5-HT3 receptors Human genes 0.000 claims description 13
108091005477 5-HT3 receptors Proteins 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 13
238000005984 hydrogenation reaction Methods 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
150000001204 N-oxides Chemical class 0.000 claims description 11
150000001412 amines Chemical class 0.000 claims description 10
238000001727 in vivo Methods 0.000 claims description 10
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 9
DIDFYSQVOPVZQB-QGZVFWFLSA-N 2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5,6-dihydro-4h-benzo[de]isoquinolin-1-one Chemical compound C1N(CC2)CCC2[C@@H]1N1C(=O)C(C=CC=C2CCC3)=C2C3=C1 DIDFYSQVOPVZQB-QGZVFWFLSA-N 0.000 claims description 8
208000002193 Pain Diseases 0.000 claims description 8
208000015114 central nervous system disease Diseases 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 8
230000036407 pain Effects 0.000 claims description 8
208000024172 Cardiovascular disease Diseases 0.000 claims description 7
208000018522 Gastrointestinal disease Diseases 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
PUJYERFTXHTQQE-UHFFFAOYSA-N 2h-isoquinolin-1-one;hydrochloride Chemical compound Cl.C1=CC=C2C(=O)NC=CC2=C1 PUJYERFTXHTQQE-UHFFFAOYSA-N 0.000 claims description 5
230000002152 alkylating effect Effects 0.000 claims description 5
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 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 3
230000001590 oxidative effect Effects 0.000 claims description 3
239000000376 reactant Substances 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
208000010643 digestive system disease Diseases 0.000 claims description 2
208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
PBFPVQBBVRHUHM-UHFFFAOYSA-N 6-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-6-azatricyclo[6.3.1.04,12]dodeca-1(12),4,8,10-tetraen-7-one Chemical compound C1CC2=CC=CC(C3=O)=C2C1=CN3C(C1)CC2CCC1N2C PBFPVQBBVRHUHM-UHFFFAOYSA-N 0.000 claims 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 40
239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 abstract description 8
229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 abstract description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
238000012360 testing method Methods 0.000 description 48
239000000243 solution Substances 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 40
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
241000700159 Rattus Species 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
239000002253 acid Substances 0.000 description 29
229940093499 ethyl acetate Drugs 0.000 description 29
235000019439 ethyl acetate Nutrition 0.000 description 29
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
229910001868 water Inorganic materials 0.000 description 25
239000003981 vehicle Substances 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
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 description 17
230000002829 reductive effect Effects 0.000 description 17
235000012054 meals Nutrition 0.000 description 16
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 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
235000019441 ethanol Nutrition 0.000 description 15
239000010410 layer Substances 0.000 description 15
241000699670 Mus sp. Species 0.000 description 14
150000001408 amides Chemical group 0.000 description 14
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
201000010099 disease Diseases 0.000 description 13
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 12
229960004316 cisplatin Drugs 0.000 description 12
239000003814 drug Substances 0.000 description 12
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
229940079593 drug Drugs 0.000 description 11
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 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
238000003556 assay Methods 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 10
239000013078 crystal Substances 0.000 description 10
238000002425 crystallisation Methods 0.000 description 10
230000008025 crystallization Effects 0.000 description 10
239000007787 solid Substances 0.000 description 10
210000002784 stomach Anatomy 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
WYWNEDARFVJQSG-UHFFFAOYSA-N 2-methylserotonin Chemical compound C1=C(O)C=C2C(CCN)=C(C)NC2=C1 WYWNEDARFVJQSG-UHFFFAOYSA-N 0.000 description 9
208000019901 Anxiety disease Diseases 0.000 description 9
241000282472 Canis lupus familiaris Species 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
230000036506 anxiety Effects 0.000 description 9
239000002904 solvent Substances 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
235000011114 ammonium hydroxide Nutrition 0.000 description 8
230000003474 anti-emetic effect Effects 0.000 description 8
230000000949 anxiolytic effect Effects 0.000 description 8
150000001721 carbon Chemical group 0.000 description 8
239000007788 liquid Substances 0.000 description 8
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
238000000926 separation method Methods 0.000 description 8
230000008673 vomiting Effects 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
206010038776 Retching Diseases 0.000 description 7
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 7
230000009467 reduction Effects 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
241000699666 Mus <mouse, genus> Species 0.000 description 6
239000003513 alkali Substances 0.000 description 6
230000029936 alkylation Effects 0.000 description 6
238000005804 alkylation reaction Methods 0.000 description 6
239000000908 ammonium hydroxide Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000002895 emetic Substances 0.000 description 6
235000013305 food Nutrition 0.000 description 6
229910000042 hydrogen bromide Inorganic materials 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
230000003287 optical effect Effects 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000010992 reflux Methods 0.000 description 6
230000004044 response Effects 0.000 description 6
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
229960003920 cocaine Drugs 0.000 description 5
230000003931 cognitive performance Effects 0.000 description 5
DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000001990 intravenous administration Methods 0.000 description 5
229960002715 nicotine Drugs 0.000 description 5
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
239000000047 product Substances 0.000 description 5
CPZBLNMUGSZIPR-RDJZCZTQSA-N (3ar)-2-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3h-benzo[de]isoquinolin-1-one Chemical compound C1N(CC2)CCC2[C@H]1N1C(=O)C(C=CC=C2CCC3)=C2[C@@H]3C1 CPZBLNMUGSZIPR-RDJZCZTQSA-N 0.000 description 4
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
241000282339 Mustela Species 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
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210000003710 cerebral cortex Anatomy 0.000 description 4
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229910052739 hydrogen Inorganic materials 0.000 description 4
239000007924 injection Substances 0.000 description 4
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239000007928 intraperitoneal injection Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000005259 measurement Methods 0.000 description 4
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
229910052697 platinum Inorganic materials 0.000 description 4
XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 description 4
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REUAXQZIRFXQML-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-amine Chemical compound C1CC2C(N)CN1CC2 REUAXQZIRFXQML-UHFFFAOYSA-N 0.000 description 3
DBPHZCRAKOJSMX-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-4-amine Chemical compound C1CN2CCC1(N)CC2 DBPHZCRAKOJSMX-UHFFFAOYSA-N 0.000 description 3
GCFQXKYHWFWGSB-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalene-1-carboxylic acid Chemical compound C1CCCC2=C1C=CC=C2C(=O)O GCFQXKYHWFWGSB-UHFFFAOYSA-N 0.000 description 3
101100225042 Arabidopsis thaliana ECI3 gene Proteins 0.000 description 3
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229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
206010012735 Diarrhoea Diseases 0.000 description 3
102100028565 Epimerase family protein SDR39U1 Human genes 0.000 description 3
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 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
101000915432 Homo sapiens Epimerase family protein SDR39U1 Proteins 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
238000000692 Student's t-test Methods 0.000 description 3
239000002168 alkylating agent Substances 0.000 description 3
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