SK15372000A3 - Spôsob prípravy 4-substituovaných-1h-indol-3-glyoxamidov - Google Patents

Spôsob prípravy 4-substituovaných-1h-indol-3-glyoxamidov Download PDF

Info

Publication number: SK15372000A3
Authority: SK; Slovakia
Prior art keywords: alkyl; formula; compound; group; halogen
Prior art date: 1998-04-17

Application number

SK1537-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Benjamin Alan Anderson

Nancy Kay Harn

Original Assignee

Eli Lilly And Company

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-04-17

Filing date

1999-04-15

Publication date

2001-08-06

1999-04-15 Application filed by Eli Lilly And Company filed Critical Eli Lilly And Company

2001-08-06 Publication of SK15372000A3 publication Critical patent/SK15372000A3/sk

Links

238000004519 manufacturing process Methods 0.000 title abstract description 6
150000001875 compounds Chemical class 0.000 claims abstract description 91
238000002360 preparation method Methods 0.000 claims abstract description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 61
125000000217 alkyl group Chemical group 0.000 claims description 35
-1 bromo, chloro, fluoro, iodo Chemical group 0.000 claims description 30
238000000034 method Methods 0.000 claims description 30
229910052736 halogen Inorganic materials 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 17
239000002904 solvent Substances 0.000 claims description 16
229940002612 prodrug Drugs 0.000 claims description 15
239000000651 prodrug Substances 0.000 claims description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 13
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 12
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000003795 chemical substances by application Substances 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
239000002168 alkylating agent Substances 0.000 claims description 8
229940100198 alkylating agent Drugs 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 claims description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 6
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
229910021529 ammonia Inorganic materials 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
238000010438 heat treatment Methods 0.000 claims description 6
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 6
230000002152 alkylating effect Effects 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
238000005185 salting out Methods 0.000 claims description 5
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
230000003301 hydrolyzing effect Effects 0.000 claims description 4
230000001590 oxidative effect Effects 0.000 claims description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
238000005576 amination reaction Methods 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
230000000911 decarboxylating effect Effects 0.000 claims description 2
230000018044 dehydration Effects 0.000 claims description 2
238000006297 dehydration reaction Methods 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 4
150000008064 anhydrides Chemical class 0.000 claims 1
OGBAQIDQMBHMAQ-UHFFFAOYSA-N bromo-chloro-fluoro-lambda3-iodane Chemical compound FI(Cl)Br OGBAQIDQMBHMAQ-UHFFFAOYSA-N 0.000 claims 1
LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 17
230000002401 inhibitory effect Effects 0.000 abstract description 3
229960000583 acetic acid Drugs 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
235000011054 acetic acid Nutrition 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 24
239000000243 solution Substances 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
239000007858 starting material Substances 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
239000000203 mixture Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
150000002148 esters Chemical class 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
AMANDCZTVNQSNB-UHFFFAOYSA-N glyoxamide Chemical group NC(=O)C=O AMANDCZTVNQSNB-UHFFFAOYSA-N 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000003921 oil 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
239000000047 product Substances 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
NLMQHXUGJIAKTH-UHFFFAOYSA-N 4-hydroxyindole Chemical compound OC1=CC=CC2=C1C=CN2 NLMQHXUGJIAKTH-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
AWMLDBKLOPNOAR-UHFFFAOYSA-N 2-(1h-indol-3-yl)-2-oxoacetamide Chemical class C1=CC=C2C(C(=O)C(=O)N)=CNC2=C1 AWMLDBKLOPNOAR-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
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 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
238000009835 boiling Methods 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
206010039073 rheumatoid arthritis Diseases 0.000 description 3
239000002002 slurry Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 2
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
FHSUFDYFOHSYHI-UHFFFAOYSA-N 3-oxopentanoic acid Chemical class CCC(=O)CC(O)=O FHSUFDYFOHSYHI-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
206010040070 Septic Shock Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
230000005587 bubbling Effects 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical class O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000003814 drug Substances 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
150000002475 indoles Chemical class 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
FGOBZQSGNGDLJO-UHFFFAOYSA-N methyl 2-(1-benzyl-2-ethylindol-4-yl)oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)C=CC=C2N1CC1=CC=CC=C1 FGOBZQSGNGDLJO-UHFFFAOYSA-N 0.000 description 2
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical group COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
235000011118 potassium hydroxide Nutrition 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
230000036303 septic shock Effects 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
230000009466 transformation Effects 0.000 description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
WAZKIRPFJTZRDA-UHFFFAOYSA-N 1-benzyl-2-ethyl-6,7-dihydro-5h-indol-4-one Chemical compound CCC1=CC(C(CCC2)=O)=C2N1CC1=CC=CC=C1 WAZKIRPFJTZRDA-UHFFFAOYSA-N 0.000 description 1
NOJRMCOLPORPBZ-UHFFFAOYSA-N 1-benzyl-2-ethylindol-4-ol Chemical compound CCC1=CC2=C(O)C=CC=C2N1CC1=CC=CC=C1 NOJRMCOLPORPBZ-UHFFFAOYSA-N 0.000 description 1
BNBDCONJJYXXEV-UHFFFAOYSA-N 1-benzyl-2-ethylindole Chemical compound CCC1=CC2=CC=CC=C2N1CC1=CC=CC=C1 BNBDCONJJYXXEV-UHFFFAOYSA-N 0.000 description 1
NJZQOCCEDXRQJM-UHFFFAOYSA-N 1-benzylindole Chemical class C1=CC2=CC=CC=C2N1CC1=CC=CC=C1 NJZQOCCEDXRQJM-UHFFFAOYSA-N 0.000 description 1
JHFAEUICJHBVHB-UHFFFAOYSA-N 1h-indol-2-ol Chemical class C1=CC=C2NC(O)=CC2=C1 JHFAEUICJHBVHB-UHFFFAOYSA-N 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
MUCJWQDVQFONMN-UHFFFAOYSA-N 2-(2-oxobutyl)cyclohexane-1,3-dione Chemical compound CCC(=O)CC1C(=O)CCCC1=O MUCJWQDVQFONMN-UHFFFAOYSA-N 0.000 description 1
QFHVHZJGQWMBTE-UHFFFAOYSA-N 2-(trifluoromethyl)-1h-indole Chemical class C1=CC=C2NC(C(F)(F)F)=CC2=C1 QFHVHZJGQWMBTE-UHFFFAOYSA-N 0.000 description 1
UMDWJYHTZUWTET-UHFFFAOYSA-N 2-amino-1-(1h-indol-3-yl)ethanol Chemical class C1=CC=C2C(C(O)CN)=CNC2=C1 UMDWJYHTZUWTET-UHFFFAOYSA-N 0.000 description 1
IQZBVCPFGDQAOW-UHFFFAOYSA-N 2-ethyl-2-(2-morpholin-4-ylethylperoxy)butanamide Chemical compound CCC(CC)(C(N)=O)OOCCN1CCOCC1 IQZBVCPFGDQAOW-UHFFFAOYSA-N 0.000 description 1
ZUESEQKVMJPYSG-UHFFFAOYSA-N 2-ethyl-3-[2-oxo-2-(propylamino)acetyl]-4-(1-phenylethyl)-1H-indole-6-carboxylic acid Chemical compound C1(=CC=CC=C1)C(C)C1=C2C(=C(NC2=CC(=C1)C(=O)O)CC)C(C(=O)NCCC)=O ZUESEQKVMJPYSG-UHFFFAOYSA-N 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
QRAFJHXNLQTXQW-UHFFFAOYSA-N 2-methylpropyl hydrogen carbonate Chemical compound CC(C)COC(O)=O QRAFJHXNLQTXQW-UHFFFAOYSA-N 0.000 description 1
XYHQIDFNVLQRME-UHFFFAOYSA-N 3-(1,2-oxazol-3-yl)-1H-indol-2-amine Chemical class NC=1NC2=CC=CC=C2C=1C=1C=CON=1 XYHQIDFNVLQRME-UHFFFAOYSA-N 0.000 description 1
LUNOXNMCFPFPMO-UHFFFAOYSA-N 4-methoxy-1h-indole Chemical class COC1=CC=CC2=C1C=CN2 LUNOXNMCFPFPMO-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
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 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
206010039085 Rhinitis allergic Diseases 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
239000003513 alkali Substances 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
201000010105 allergic rhinitis Diseases 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
229930007927 cymene Natural products 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
108010061433 diazepam-binding inhibitor receptor Proteins 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
238000013467 fragmentation Methods 0.000 description 1
238000006062 fragmentation reaction Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
231100001261 hazardous Toxicity 0.000 description 1
DDTGNKBZWQHIEH-UHFFFAOYSA-N heptalene Chemical compound C1=CC=CC=C2C=CC=CC=C21 DDTGNKBZWQHIEH-UHFFFAOYSA-N 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
KCKIKSJECTZLJA-UHFFFAOYSA-N indol-4-one Chemical compound O=C1C=CC=C2N=CC=C12 KCKIKSJECTZLJA-UHFFFAOYSA-N 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
208000014674 injury Diseases 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
MGPLBSPZSIFUQX-UHFFFAOYSA-N methyl 4-methylbenzenesulfinate Chemical compound COS(=O)C1=CC=C(C)C=C1 MGPLBSPZSIFUQX-UHFFFAOYSA-N 0.000 description 1
PSNSVDSRLUYDKF-UHFFFAOYSA-N methyl benzenesulfinate Chemical compound COS(=O)C1=CC=CC=C1 PSNSVDSRLUYDKF-UHFFFAOYSA-N 0.000 description 1
YZFRMTIOGUDRCS-UHFFFAOYSA-N methyl phenylmethanesulfinate Chemical compound COS(=O)CC1=CC=CC=C1 YZFRMTIOGUDRCS-UHFFFAOYSA-N 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
230000002438 mitochondrial effect Effects 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
GUVXZFRDPCKWEM-UHFFFAOYSA-N pentalene Chemical compound C1=CC2=CC=CC2=C1 GUVXZFRDPCKWEM-UHFFFAOYSA-N 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000010970 precious metal Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
KVCGISUBCHHTDD-UHFFFAOYSA-M sodium;4-methylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1 KVCGISUBCHHTDD-UHFFFAOYSA-M 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000000725 suspension Substances 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
230000008733 trauma Effects 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK1537-2000A 1998-04-17 1999-04-15 Spôsob prípravy 4-substituovaných-1h-indol-3-glyoxamidov SK15372000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8211098P	1998-04-17	1998-04-17
PCT/US1999/008332 WO1999054300A1 (fr)	1998-04-17	1999-04-15	Procede de fabrication de 1h-indole-3-glyoxamides 4-substitues

Publications (1)

Publication Number	Publication Date
SK15372000A3 true SK15372000A3 (sk)	2001-08-06

Family

ID=22169126

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1537-2000A SK15372000A3 (sk)	1998-04-17	1999-04-15	Spôsob prípravy 4-substituovaných-1h-indol-3-glyoxamidov

Country Status (27)

Country	Link
US (1)	US6265591B1 (fr)
EP (1)	EP1071663A4 (fr)
JP (1)	JP2002512225A (fr)
KR (1)	KR20010042741A (fr)
CN (1)	CN1305459A (fr)
AR (1)	AR015767A1 (fr)
AU (1)	AU750368B2 (fr)
BR (1)	BR9909697A (fr)
CA (1)	CA2326515A1 (fr)
CO (1)	CO5080803A1 (fr)
DZ (1)	DZ2770A1 (fr)
EA (1)	EA003582B1 (fr)
EG (1)	EG22139A (fr)
HK (1)	HK1039120A1 (fr)
HR (1)	HRP20000685A2 (fr)
HU (1)	HUP0101344A3 (fr)
ID (1)	ID26021A (fr)
IL (1)	IL138827A0 (fr)
NO (1)	NO20005148L (fr)
NZ (1)	NZ507175A (fr)
PE (1)	PE20000430A1 (fr)
PL (1)	PL343487A1 (fr)
SK (1)	SK15372000A3 (fr)
SV (1)	SV1999000043A (fr)
TR (1)	TR200002999T2 (fr)
WO (1)	WO1999054300A1 (fr)
ZA (1)	ZA200005294B (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6407261B1 (en)	1998-04-17	2002-06-18	Eli Lilly And Company	Process for preparing 4-hdyroxy indole, indazole and carbazole compounds
JP2002512222A (ja) *	1998-04-17	2002-04-23	イーライ・リリー・アンド・カンパニー	４−ヒドロキシインドール、インダゾール、及び、カルバゾール化合物の製造方法
DE19962300A1 (de) *	1999-12-23	2001-06-28	Asta Medica Ag	Substituierte N-Benzyl-Indol-3-yl-glyoxylsäure-Derivate mit Antitumorwirkung
US20030225149A1 (en) *	2002-04-30	2003-12-04	Blazecka Peter G.	Process for preparing highly functionalized gamma-butyrolactams and gamma-amino acids
CN107233337A (zh)	2009-04-29	2017-10-10	阿马里纳药物爱尔兰有限公司	含有epa和心血管剂的药物组合物以及使用其的方法
AR088377A1 (es)	2011-10-20	2014-05-28	Siena Biotech Spa	Proceso para la preparacion de 6-cloro-2,3,4,9-tetrahidro-1h-carbazol-1-carboxamida y compuestos intermedios de esta

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX9501608A (es)	1994-04-01	1997-02-28	Lilly Co Eli	1h-indol-3-glioxilamidas inhibidoras de spla2.
JP2002512222A (ja) *	1998-04-17	2002-04-23	イーライ・リリー・アンド・カンパニー	４−ヒドロキシインドール、インダゾール、及び、カルバゾール化合物の製造方法

1999
- 1999-04-14 DZ DZ990070A patent/DZ2770A1/fr active
- 1999-04-15 AU AU35648/99A patent/AU750368B2/en not_active Ceased
- 1999-04-15 US US09/647,471 patent/US6265591B1/en not_active Expired - Fee Related
- 1999-04-15 HU HU0101344A patent/HUP0101344A3/hu unknown
- 1999-04-15 EG EG104099D patent/EG22139A/xx active
- 1999-04-15 EP EP99917556A patent/EP1071663A4/fr not_active Withdrawn
- 1999-04-15 PE PE1999000312A patent/PE20000430A1/es not_active Application Discontinuation
- 1999-04-15 SV SV1999000043A patent/SV1999000043A/es not_active Application Discontinuation
- 1999-04-15 HK HK02100522.5A patent/HK1039120A1/zh unknown
- 1999-04-15 KR KR1020007011468A patent/KR20010042741A/ko not_active Withdrawn
- 1999-04-15 AR ARP990101753A patent/AR015767A1/es not_active Application Discontinuation
- 1999-04-15 CA CA002326515A patent/CA2326515A1/fr not_active Abandoned
- 1999-04-15 BR BR9909697-8A patent/BR9909697A/pt not_active IP Right Cessation
- 1999-04-15 ID IDW20002058A patent/ID26021A/id unknown
- 1999-04-15 PL PL99343487A patent/PL343487A1/xx not_active Application Discontinuation
- 1999-04-15 TR TR2000/02999T patent/TR200002999T2/xx unknown
- 1999-04-15 IL IL13882799A patent/IL138827A0/xx unknown
- 1999-04-15 JP JP2000544641A patent/JP2002512225A/ja not_active Withdrawn
- 1999-04-15 HR HR20000685A patent/HRP20000685A2/hr not_active Application Discontinuation
- 1999-04-15 EA EA200001076A patent/EA003582B1/ru not_active IP Right Cessation
- 1999-04-15 CN CN99807248A patent/CN1305459A/zh active Pending
- 1999-04-15 NZ NZ507175A patent/NZ507175A/xx unknown
- 1999-04-15 WO PCT/US1999/008332 patent/WO1999054300A1/fr not_active Ceased
- 1999-04-15 SK SK1537-2000A patent/SK15372000A3/sk unknown
- 1999-04-16 CO CO99022895A patent/CO5080803A1/es unknown
2000
- 2000-09-29 ZA ZA200005294A patent/ZA200005294B/en unknown
- 2000-10-13 NO NO20005148A patent/NO20005148L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
HRP20000685A2 (en)	2001-10-31
ZA200005294B (en)	2001-10-01
TR200002999T2 (tr)	2001-01-22
NO20005148D0 (no)	2000-10-13
AU750368B2 (en)	2002-07-18
EP1071663A4 (fr)	2002-06-19
PL343487A1 (en)	2001-08-27
EP1071663A1 (fr)	2001-01-31
CA2326515A1 (fr)	1999-10-28
CO5080803A1 (es)	2001-09-25
BR9909697A (pt)	2000-12-19
JP2002512225A (ja)	2002-04-23
WO1999054300A1 (fr)	1999-10-28
NZ507175A (en)	2002-12-20
EG22139A (en)	2002-08-30
HK1039120A1 (zh)	2002-04-12
HUP0101344A2 (hu)	2001-09-28
NO20005148L (no)	2000-11-09
KR20010042741A (ko)	2001-05-25
AU3564899A (en)	1999-11-08
US6265591B1 (en)	2001-07-24
AR015767A1 (es)	2001-05-16
SV1999000043A (es)	2000-05-02
HUP0101344A3 (en)	2002-12-28
EA003582B1 (ru)	2003-06-26
ID26021A (id)	2000-11-16
PE20000430A1 (es)	2000-05-24
EA200001076A1 (ru)	2001-04-23
CN1305459A (zh)	2001-07-25
IL138827A0 (en)	2001-10-31
DZ2770A1 (fr)	2003-12-01

Publication	Publication Date	Title
SK15372000A3 (sk)	2001-08-06	Spôsob prípravy 4-substituovaných-1h-indol-3-glyoxamidov
KR20010014167A (ko)	2001-02-26	4-치환-1ｈ-인돌-3-글리옥스아미드의 제조 방법
US7582771B2 (en)	2009-09-01	Process for the synthesis of cPLA2 inhibitors
US6407261B1 (en)	2002-06-18	Process for preparing 4-hdyroxy indole, indazole and carbazole compounds
US6380397B1 (en)	2002-04-30	Process for preparing 4-substituted-1H-indole-3-glyoxamides
US6617460B1 (en)	2003-09-09	Process for preparing toluenesulfinates
WO2015181507A1 (fr)	2015-12-03	Nouveaux composes de type 5-acylsulfanyl-histidine en tant que precurseurs des 5-sulfanylhistidines correspondantes et de leurs disulfures
CZ20003824A3 (cs)	2001-01-17	Způsob přípravy 4-substituovaných-lH-indol-3- glyoxamidů
US6570023B1 (en)	2003-05-27	Process for preparing toluenesulfinates
JP2002512222A (ja)	2002-04-23	４−ヒドロキシインドール、インダゾール、及び、カルバゾール化合物の製造方法
MXPA00009955A (en)	2001-07-31	Process for preparing 4-substituted-1h-indole-3-glyoxamides
CA2347718A1 (fr)	2000-04-20	Procede de preparation de 4-1h-indole-3-glyoxamides substituees
CZ466499A3 (cs)	2000-09-13	Způsob přípravy v poloze 4-substituovaného derivátu ΙΗ-indol glyoxamidu a meziprodukt pro tuto přípravu
MXPA99011973A (en)	2000-09-04	Process for preparing 4-substituted-1h-indole-3-glyoxamides