TW200403233A

TW200403233A - Chemical compounds

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Info

Publication number: TW200403233A
Authority: TW; Taiwan
Prior art keywords: alkyl; group; keto; chloro; carboxamide
Prior art date: 2002-03-06

Application number

TW092104667A

Other languages

English (en)

Chinese (zh)

Inventor

Alan Martin Birch

Andrew David Morley

Original Assignee

Astrazeneca Ab

Priority date

2002-03-06

Filing date

2003-03-05

Publication date

2004-03-01

2003-03-05 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-03-01 Publication of TW200403233A publication Critical patent/TW200403233A/zh

Links

150000001875 compounds Chemical class 0.000 title claims description 177
-1 Heterocyclic amides Chemical class 0.000 claims abstract description 416
239000001257 hydrogen Substances 0.000 claims abstract description 82
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 82
238000000034 method Methods 0.000 claims abstract description 70
150000003839 salts Chemical class 0.000 claims abstract description 67
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 64
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 53
125000003118 aryl group Chemical group 0.000 claims abstract description 30
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 28
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 20
238000011282 treatment Methods 0.000 claims abstract description 20
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 16
229940002612 prodrug Drugs 0.000 claims abstract description 14
239000000651 prodrug Substances 0.000 claims abstract description 14
238000004519 manufacturing process Methods 0.000 claims abstract description 11
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 3
125000000217 alkyl group Chemical group 0.000 claims description 209
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 114
125000003545 alkoxy group Chemical group 0.000 claims description 68
150000002148 esters Chemical class 0.000 claims description 64
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 61
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
125000001424 substituent group Chemical group 0.000 claims description 52
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 50
238000001727 in vivo Methods 0.000 claims description 49
229910052757 nitrogen Inorganic materials 0.000 claims description 48
229910052799 carbon Inorganic materials 0.000 claims description 34
125000005843 halogen group Chemical group 0.000 claims description 34
239000002253 acid Substances 0.000 claims description 30
150000001412 amines Chemical class 0.000 claims description 30
125000004093 cyano group Chemical group *C#N 0.000 claims description 30
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
241001465754 Metazoa Species 0.000 claims description 21
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 21
VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 claims description 19
125000004429 atom Chemical group 0.000 claims description 19
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 19
125000001072 heteroaryl group Chemical group 0.000 claims description 18
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 claims description 17
239000008103 glucose Substances 0.000 claims description 17
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 17
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
125000006239 protecting group Chemical group 0.000 claims description 14
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 13
210000004369 blood Anatomy 0.000 claims description 13
239000008280 blood Substances 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 13
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
239000000460 chlorine Substances 0.000 claims description 11
229910052801 chlorine Inorganic materials 0.000 claims description 11
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
241000282412 Homo Species 0.000 claims description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
229910052796 boron Inorganic materials 0.000 claims description 8
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
238000006467 substitution reaction Methods 0.000 claims description 8
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 8
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 7
208000008589 Obesity Diseases 0.000 claims description 7
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000000468 ketone group Chemical group 0.000 claims description 7
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
235000020824 obesity Nutrition 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims description 6
102000004877 Insulin Human genes 0.000 claims description 6
108090001061 Insulin Proteins 0.000 claims description 6
206010022489 Insulin Resistance Diseases 0.000 claims description 6
229930194542 Keto Natural products 0.000 claims description 6
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
230000015572 biosynthetic process Effects 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
229940125396 insulin Drugs 0.000 claims description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
208000011580 syndromic disease Diseases 0.000 claims description 6
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
239000004593 Epoxy Substances 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
125000002883 imidazolyl group Chemical group 0.000 claims description 5
125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 5
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
150000003857 carboxamides Chemical class 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
150000001241 acetals Chemical class 0.000 claims description 3
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
201000001421 hyperglycemia Diseases 0.000 claims description 3
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
SIJBDWPVNAYVGY-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxolane Chemical group CC1(C)OCCO1 SIJBDWPVNAYVGY-UHFFFAOYSA-N 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
ZPUQJJGFUQRGKR-UHFFFAOYSA-N 5-chloro-n-[2-oxo-1-[2-oxo-2-(2h-tetrazol-5-ylamino)ethyl]-3,4-dihydroquinolin-3-yl]-1h-indole-2-carboxamide Chemical compound C=1C2=CC(Cl)=CC=C2NC=1C(=O)NC(C1=O)CC2=CC=CC=C2N1CC(=O)NC=1N=NNN=1 ZPUQJJGFUQRGKR-UHFFFAOYSA-N 0.000 claims description 2
206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
DATMASHOXJGXOE-UHFFFAOYSA-N N1C(=CC2=CC=CC=C12)C(=O)N.C1=CC=CC=2C3=CC=CC=C3CC12 Chemical compound N1C(=CC2=CC=CC=C12)C(=O)N.C1=CC=CC=2C3=CC=CC=C3CC12 DATMASHOXJGXOE-UHFFFAOYSA-N 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
230000003451 hyperinsulinaemic effect Effects 0.000 claims description 2
201000008980 hyperinsulinism Diseases 0.000 claims description 2
125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 2
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 2
ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
FCUZQICLMRWBQN-UHFFFAOYSA-N 4-chloro-9h-fluorene Chemical compound C1C2=CC=CC=C2C2=C1C=CC=C2Cl FCUZQICLMRWBQN-UHFFFAOYSA-N 0.000 claims 1
KQTGCJMBUBYSLL-UHFFFAOYSA-N 4-piperidin-1-ylmorpholine Chemical compound C1CCCCN1N1CCOCC1 KQTGCJMBUBYSLL-UHFFFAOYSA-N 0.000 claims 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
239000013256 coordination polymer Chemical group 0.000 claims 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims 1
125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
ZYXWYDDFNXBTFO-UHFFFAOYSA-N tetrazolidine Chemical compound C1NNNN1 ZYXWYDDFNXBTFO-UHFFFAOYSA-N 0.000 claims 1
125000000335 thiazolyl group Chemical group 0.000 claims 1
108010046163 Glycogen Phosphorylase Proteins 0.000 abstract description 15
102000007390 Glycogen Phosphorylase Human genes 0.000 abstract description 15
230000000694 effects Effects 0.000 abstract description 14
230000002401 inhibitory effect Effects 0.000 abstract description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 4
201000010099 disease Diseases 0.000 abstract description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
230000008569 process Effects 0.000 abstract description 2
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 5
125000001475 halogen functional group Chemical group 0.000 abstract 3
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
125000005549 heteroarylene group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
238000006243 chemical reaction Methods 0.000 description 57
239000002585 base Substances 0.000 description 54
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
239000007787 solid Substances 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
150000002431 hydrogen Chemical group 0.000 description 35
239000000243 solution Substances 0.000 description 33
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
239000000203 mixture Substances 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
235000019439 ethyl acetate Nutrition 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
229960001031 glucose Drugs 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
229920002527 Glycogen Polymers 0.000 description 15
229940096919 glycogen Drugs 0.000 description 15
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000011734 sodium Substances 0.000 description 13
239000000725 suspension Substances 0.000 description 13
238000012360 testing method Methods 0.000 description 13
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
238000003556 assay Methods 0.000 description 11
230000002829 reductive effect Effects 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
238000004440 column chromatography Methods 0.000 description 10
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 10
239000003112 inhibitor Substances 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
206010012601 diabetes mellitus Diseases 0.000 description 9
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 9
210000004185 liver Anatomy 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-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
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
125000003277 amino group Chemical group 0.000 description 8
239000012131 assay buffer Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
CYSPWCARDHRYJX-UHFFFAOYSA-N 9h-fluoren-1-amine Chemical compound C12=CC=CC=C2CC2=C1C=CC=C2N CYSPWCARDHRYJX-UHFFFAOYSA-N 0.000 description 7
125000000304 alkynyl group Chemical group 0.000 description 7
239000007859 condensation product Substances 0.000 description 7
238000010168 coupling process Methods 0.000 description 7
238000005859 coupling reaction Methods 0.000 description 7
229910052731 fluorine Inorganic materials 0.000 description 7
239000011737 fluorine Substances 0.000 description 7
235000003599 food sweetener Nutrition 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
238000010992 reflux Methods 0.000 description 7
239000003765 sweetening agent Substances 0.000 description 7
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 6
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical group CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
230000008878 coupling Effects 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
239000003755 preservative agent Substances 0.000 description 6
239000007921 spray Substances 0.000 description 6
239000003039 volatile agent Substances 0.000 description 6
239000004606 Fillers/Extenders Substances 0.000 description 5
229910019142 PO4 Inorganic materials 0.000 description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
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