NZ526623A

NZ526623A - Carbazole derivatives and their use as neuropeptide Y5 receptor ligands

Carbazole derivatives and their use as neuropeptide Y5 receptor ligands

Info

Publication number: NZ526623A
Authority: NZ; New Zealand
Prior art keywords: compound; formula; 4alkyl; optionally substituted; carbamoyl
Prior art date: 2000-12-22

Application number

NZ526623A

Other languages

English (en)

Inventor

Michael Howard Block

Kevin Michael Foote

Craig Samuel Donald

Paul Schofield

Original Assignee

Astrazeneca Ab

Priority date

2000-12-22

Filing date

2001-12-17

Publication date

2004-11-26

2000-12-22 Priority claimed from GBGB0031382.5A external-priority patent/GB0031382D0/en

2001-09-11 Priority claimed from GBGB0121919.5A external-priority patent/GB0121919D0/en

2001-12-17 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-11-26 Publication of NZ526623A publication Critical patent/NZ526623A/en

Links

102000028582 Neuropeptide Y5 receptor Human genes 0.000 title claims description 26
108010046593 Neuropeptide Y5 receptor Proteins 0.000 title claims description 26
239000003446 ligand Substances 0.000 title description 2
125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 225
238000000034 method Methods 0.000 claims abstract description 160
230000008569 process Effects 0.000 claims abstract description 33
208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 15
208000030814 Eating disease Diseases 0.000 claims abstract description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
235000014632 disordered eating Nutrition 0.000 claims abstract description 14
238000004519 manufacturing process Methods 0.000 claims abstract description 12
230000001404 mediated effect Effects 0.000 claims abstract description 7
-1 cyano, hydroxy Chemical group 0.000 claims description 417
125000000623 heterocyclic group Chemical group 0.000 claims description 79
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 61
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 60
239000000243 solution Substances 0.000 claims description 59
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 55
229910052799 carbon Inorganic materials 0.000 claims description 55
229910052757 nitrogen Inorganic materials 0.000 claims description 54
150000003839 salts Chemical class 0.000 claims description 52
239000000203 mixture Substances 0.000 claims description 45
239000012453 solvate Substances 0.000 claims description 44
150000002148 esters Chemical class 0.000 claims description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 39
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
125000004452 carbocyclyl group Chemical group 0.000 claims description 27
238000001727 in vivo Methods 0.000 claims description 27
238000011282 treatment Methods 0.000 claims description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
241001465754 Metazoa Species 0.000 claims description 18
150000001412 amines Chemical class 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 17
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 claims description 16
239000003814 drug Substances 0.000 claims description 14
125000006239 protecting group Chemical group 0.000 claims description 14
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 13
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
208000035475 disorder Diseases 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
239000003085 diluting agent Substances 0.000 claims description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 8
125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 7
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 claims description 6
239000008101 lactose Substances 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
238000009472 formulation Methods 0.000 claims description 5
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
238000002347 injection Methods 0.000 claims description 5
239000007924 injection Substances 0.000 claims description 5
235000019359 magnesium stearate Nutrition 0.000 claims description 5
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
239000002775 capsule Substances 0.000 claims description 3
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
125000004468 heterocyclylthio group Chemical group 0.000 claims description 3
OWFBVZBGOIYECX-UHFFFAOYSA-N 1-n-(2,4-dimethyl-9-propan-2-ylcarbazol-3-yl)piperidine-1,3-dicarboxamide Chemical compound CC=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)N1CCCC(C(N)=O)C1 OWFBVZBGOIYECX-UHFFFAOYSA-N 0.000 claims description 2
LVVQMWROURBWIV-UHFFFAOYSA-N 1-n-(4-methyl-9-propan-2-ylcarbazol-3-yl)piperidine-1,3-dicarboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)N1CCCC(C(N)=O)C1 LVVQMWROURBWIV-UHFFFAOYSA-N 0.000 claims description 2
HMXROEBLPFGRRC-UHFFFAOYSA-N 4-hydroxy-n-(2-methyl-9-propan-2-ylcarbazol-3-yl)piperidine-1-carboxamide Chemical compound CC=1C=C2N(C(C)C)C3=CC=CC=C3C2=CC=1NC(=O)N1CCC(O)CC1 HMXROEBLPFGRRC-UHFFFAOYSA-N 0.000 claims description 2
239000011248 coating agent Substances 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
ZNFMHLDBJPAFEQ-UHFFFAOYSA-N n-(4-methyl-9-propan-2-ylcarbazol-3-yl)morpholine-4-carboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)N1CCOCC1 ZNFMHLDBJPAFEQ-UHFFFAOYSA-N 0.000 claims description 2
VRBFOCCJIARKLA-UHFFFAOYSA-N n-(6-fluoro-4-methyl-9-propan-2-ylcarbazol-3-yl)-4-hydroxypiperidine-1-carboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=C(F)C=C3C2=C(C)C=1NC(=O)N1CCC(O)CC1 VRBFOCCJIARKLA-UHFFFAOYSA-N 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 9
239000008215 water for injection Substances 0.000 claims 3
229940068918 polyethylene glycol 400 Drugs 0.000 claims 2
239000001488 sodium phosphate Substances 0.000 claims 2
229910000162 sodium phosphate Inorganic materials 0.000 claims 2
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 2
229920000623 Cellulose acetate phthalate Polymers 0.000 claims 1
229940081734 cellulose acetate phthalate Drugs 0.000 claims 1
238000000576 coating method Methods 0.000 claims 1
CVCCDFPEKAUSBB-UHFFFAOYSA-N n-(6-fluoro-4-methyl-9-propan-2-ylcarbazol-3-yl)morpholine-4-carboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=C(F)C=C3C2=C(C)C=1NC(=O)N1CCOCC1 CVCCDFPEKAUSBB-UHFFFAOYSA-N 0.000 claims 1
108090000189 Neuropeptides Proteins 0.000 abstract description 5
102000003797 Neuropeptides Human genes 0.000 abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 146
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
238000005481 NMR spectroscopy Methods 0.000 description 77
235000019439 ethyl acetate Nutrition 0.000 description 68
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 55
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 50
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
239000007787 solid Substances 0.000 description 35
239000002904 solvent Substances 0.000 description 31
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
239000007858 starting material Substances 0.000 description 29
239000000651 prodrug Substances 0.000 description 28
229940002612 prodrug Drugs 0.000 description 28
239000011541 reaction mixture Substances 0.000 description 27
101150041968 CDC13 gene Proteins 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
125000005843 halogen group Chemical group 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 19
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
238000004587 chromatography analysis Methods 0.000 description 18
239000003480 eluent Substances 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
239000002253 acid Substances 0.000 description 14
239000004480 active ingredient Substances 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
101710151321 Melanostatin Proteins 0.000 description 13
102400000064 Neuropeptide Y Human genes 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 12
239000000047 product Substances 0.000 description 12
241000282414 Homo sapiens Species 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 10
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 10
238000002360 preparation method Methods 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000007788 liquid Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
125000002252 acyl group Chemical group 0.000 description 8
239000012267 brine Substances 0.000 description 8
239000012528 membrane Substances 0.000 description 8
125000003386 piperidinyl group Chemical group 0.000 description 8
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 8
238000010992 reflux Methods 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
208000008589 Obesity Diseases 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
239000003795 chemical substances by application 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
235000020824 obesity Nutrition 0.000 description 7
239000000546 pharmaceutical excipient Substances 0.000 description 7
239000000843 powder Substances 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
125000000217 alkyl group Chemical group 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
230000027455 binding Effects 0.000 description 6
125000001246 bromo group Chemical group Br* 0.000 description 6
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000001816 cooling Methods 0.000 description 6
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 6
239000003755 preservative agent Substances 0.000 description 6
230000001737 promoting effect Effects 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
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VRPPTWROMMUVEU-UHFFFAOYSA-N 2,4-dimethyl-9-propan-2-ylcarbazol-3-amine Chemical compound NC1=C(C)C=C2N(C(C)C)C3=CC=CC=C3C2=C1C VRPPTWROMMUVEU-UHFFFAOYSA-N 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
241000238631 Hexapoda Species 0.000 description 5
101000983116 Homo sapiens Pancreatic prohormone Proteins 0.000 description 5
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230000007062 hydrolysis Effects 0.000 description 5
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229910000104 sodium hydride Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
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229920002261 Corn starch Polymers 0.000 description 4
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230000037396 body weight Effects 0.000 description 4
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JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
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