TW200305412A - Chemical compounds - Google Patents

Info

Publication number

TW200305412A

TW200305412A TW092104650A TW92104650A TW200305412A TW 200305412 A TW200305412 A TW 200305412A TW 092104650 A TW092104650 A TW 092104650A TW 92104650 A TW92104650 A TW 92104650A TW 200305412 A TW200305412 A TW 200305412A

Authority

TW

Taiwan

Prior art keywords

pyrrole

alkyl

group

chloro

keto

Prior art date

2002-03-06

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims description 257
• -1 Heterocyclic amides Chemical class 0.000 claims abstract description 529
• 238000000034 method Methods 0.000 claims abstract description 133
• 239000001257 hydrogen Substances 0.000 claims abstract description 122
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 122
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 85
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 81
• 150000003839 salts Chemical class 0.000 claims abstract description 79
• 125000003118 aryl group Chemical group 0.000 claims abstract description 37
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 30
• 238000011282 treatment Methods 0.000 claims abstract description 23
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 20
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
• 229940002612 prodrug Drugs 0.000 claims abstract description 15
• 239000000651 prodrug Substances 0.000 claims abstract description 15
• 238000004519 manufacturing process Methods 0.000 claims abstract description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 3
• 125000000217 alkyl group Chemical group 0.000 claims description 275
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 140
• 125000003545 alkoxy group Chemical group 0.000 claims description 86
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 79
• 150000002148 esters Chemical class 0.000 claims description 76
• 229910052757 nitrogen Inorganic materials 0.000 claims description 74
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 60
• 125000001424 substituent group Chemical group 0.000 claims description 60
• 238000001727 in vivo Methods 0.000 claims description 59
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 56
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 51
• FSUPKDUNLKQBCN-UHFFFAOYSA-N 1H-pyrrole-2-carboximidamide Chemical compound NC(=N)C1=CC=CN1 FSUPKDUNLKQBCN-UHFFFAOYSA-N 0.000 claims description 50
• 125000005843 halogen group Chemical group 0.000 claims description 47
• 239000002253 acid Substances 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 44
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 44
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 43
• RLOQBKJCOAXOLR-UHFFFAOYSA-N 1h-pyrrole-2-carboxamide Chemical compound NC(=O)C1=CC=CN1 RLOQBKJCOAXOLR-UHFFFAOYSA-N 0.000 claims description 40
• 150000001412 amines Chemical class 0.000 claims description 40
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 38
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 28
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 26
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
• 241001465754 Metazoa Species 0.000 claims description 20
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 18
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 17
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
• 125000006239 protecting group Chemical group 0.000 claims description 17
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 16
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 14
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 14
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 13
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 13
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
• 239000000126 substance Substances 0.000 claims description 11
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
• 125000001425 triazolyl group Chemical group 0.000 claims description 11
• 241000282412 Homo Species 0.000 claims description 10
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
• 125000000304 alkynyl group Chemical group 0.000 claims description 10
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 8
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 7
• 239000004593 Epoxy Substances 0.000 claims description 7
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
• 229910052796 boron Inorganic materials 0.000 claims description 7
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 6
• 208000008589 Obesity Diseases 0.000 claims description 6
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 201000001421 hyperglycemia Diseases 0.000 claims description 6
• 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 6
• 201000008980 hyperinsulinism Diseases 0.000 claims description 6
• 125000000468 ketone group Chemical group 0.000 claims description 6
• 235000020824 obesity Nutrition 0.000 claims description 6
• 208000011580 syndromic disease Diseases 0.000 claims description 6
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 6
• 208000028867 ischemia Diseases 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 4
• 229930194542 Keto Natural products 0.000 claims description 4
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims description 4
• 150000001721 carbon Chemical group 0.000 claims description 4
• 239000010949 copper Substances 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 229930192474 thiophene Natural products 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• GQMYQEAXTITUAE-UHFFFAOYSA-N 1H-indole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=CC2=C1 GQMYQEAXTITUAE-UHFFFAOYSA-N 0.000 claims description 3
• SIJBDWPVNAYVGY-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OCCO1 SIJBDWPVNAYVGY-UHFFFAOYSA-N 0.000 claims description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
• 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 3
• 206010022489 Insulin Resistance Diseases 0.000 claims description 3
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• 238000010586 diagram Methods 0.000 claims description 3
• 239000011733 molybdenum Substances 0.000 claims description 3
• 229910052750 molybdenum Inorganic materials 0.000 claims description 3
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 3
• 239000011593 sulfur Substances 0.000 claims description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 2
• HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical group CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 claims 2
• 125000003342 alkenyl group Chemical group 0.000 claims 2
• 229940127004 drugs for type 2 diabetes Drugs 0.000 claims 2
• BNMNQUBPZZSXQU-UHFFFAOYSA-N 1,3-dioxole-4-carboxylic acid Chemical compound OC(=O)C1=COCO1 BNMNQUBPZZSXQU-UHFFFAOYSA-N 0.000 claims 1
• WTNQYKWYCKCADH-UHFFFAOYSA-N 2-chloro-n-[1-[3-(dimethylamino)-2-hydroxypropyl]-2-oxo-3,4-dihydroquinolin-3-yl]-6h-thieno[2,3-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2N(CC(O)CN(C)C)C(=O)C(NC(=O)C=3NC=4SC(Cl)=CC=4C=3)CC2=C1 WTNQYKWYCKCADH-UHFFFAOYSA-N 0.000 claims 1
• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims 1
• JVIDNYYUINLENN-UHFFFAOYSA-N C(=O)(O)C1=C2C=3C=CC=C(C3CC2=CC=C1)N.N1C=CC=C1 Chemical compound C(=O)(O)C1=C2C=3C=CC=C(C3CC2=CC=C1)N.N1C=CC=C1 JVIDNYYUINLENN-UHFFFAOYSA-N 0.000 claims 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 1
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims 1
• 230000005494 condensation Effects 0.000 claims 1
• 238000009833 condensation Methods 0.000 claims 1
• 229910052802 copper Inorganic materials 0.000 claims 1
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims 1
• 229940088597 hormone Drugs 0.000 claims 1
• 239000005556 hormone Substances 0.000 claims 1
• 210000004153 islets of langerhan Anatomy 0.000 claims 1
• 208000031225 myocardial ischemia Diseases 0.000 claims 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 abstract description 17
• 102000007390 Glycogen Phosphorylase Human genes 0.000 abstract description 17
• 230000000694 effects Effects 0.000 abstract description 15
• 230000002401 inhibitory effect Effects 0.000 abstract description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 5
• 201000010099 disease Diseases 0.000 abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
• 230000008569 process Effects 0.000 abstract description 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 5
• 125000001475 halogen functional group Chemical group 0.000 abstract 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
• 125000005549 heteroarylene group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
• 238000006243 chemical reaction Methods 0.000 description 83
• 238000005481 NMR spectroscopy Methods 0.000 description 74
• 239000007787 solid Substances 0.000 description 69
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
• 150000002431 hydrogen Chemical class 0.000 description 47
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 41
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• 239000000203 mixture Substances 0.000 description 39
• 239000000460 chlorine Substances 0.000 description 38
• 239000000243 solution Substances 0.000 description 37
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
• 235000019439 ethyl acetate Nutrition 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 28
• 229910052801 chlorine Inorganic materials 0.000 description 27
• 239000002585 base Substances 0.000 description 25
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
• 235000019341 magnesium sulphate Nutrition 0.000 description 20
• 238000004440 column chromatography Methods 0.000 description 19
• 230000002829 reductive effect Effects 0.000 description 19
• 229920006395 saturated elastomer Polymers 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• 238000010992 reflux Methods 0.000 description 17
• 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 16
• 125000004429 atom Chemical group 0.000 description 16
• 239000008103 glucose Substances 0.000 description 16
• 229960001031 glucose Drugs 0.000 description 16
• 238000012360 testing method Methods 0.000 description 16
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 15
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
• 125000003277 amino group Chemical group 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• 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 13
• 238000003556 assay Methods 0.000 description 13
• 229920002527 Glycogen Polymers 0.000 description 12
• 239000004480 active ingredient Substances 0.000 description 12
• 125000001309 chloro group Chemical group Cl* 0.000 description 12
• 229940096919 glycogen Drugs 0.000 description 12
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 238000001914 filtration Methods 0.000 description 11
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• 238000001704 evaporation Methods 0.000 description 10
• 230000008020 evaporation Effects 0.000 description 10
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• 210000004185 liver Anatomy 0.000 description 10
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 125000002883 imidazolyl group Chemical group 0.000 description 9
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
• 239000007858 starting material Substances 0.000 description 9
• 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
• 238000004458 analytical method Methods 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 238000005859 coupling reaction Methods 0.000 description 8
• 206010012601 diabetes mellitus Diseases 0.000 description 8
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 239000007859 condensation product Substances 0.000 description 7
• 239000011737 fluorine Substances 0.000 description 7
• 229910052731 fluorine Inorganic materials 0.000 description 7
• 235000003599 food sweetener Nutrition 0.000 description 7
• 239000007789 gas Substances 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 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 description 7
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 7
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