NO901082L

NO901082L - Fremgangsmaate for fremstilling av tetrahydrokinolin-derivater.

Fremgangsmaate for fremstilling av tetrahydrokinolin-derivater.

Info

Publication number: NO901082L
Authority: NO; Norway
Prior art keywords: tetrahydroquinoline; dichloro; carboxy; methoxycarbonyl; benzylcarbonylamino
Prior art date: 1989-03-08

Application number

NO90901082A

Other languages

English (en)

Norwegian (no)

Other versions

NO901082D0 (no

Inventor

Raymond Baker

William R Carling

Paul D Leeson

Julian D Smith

Original Assignee

Merck Sharp & Dohme

Priority date

1989-03-08

Filing date

1990-03-07

Publication date

1990-09-10

1989-03-08 Priority claimed from GB898905334A external-priority patent/GB8905334D0/en

1989-11-22 Priority claimed from GB898926431A external-priority patent/GB8926431D0/en

1990-03-07 Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme

1990-03-07 Publication of NO901082D0 publication Critical patent/NO901082D0/no

1990-09-10 Publication of NO901082L publication Critical patent/NO901082L/no

Links

238000000034 method Methods 0.000 title claims description 150
238000002360 preparation method Methods 0.000 title claims description 20
238000001727 in vivo Methods 0.000 claims abstract description 10
150000001875 compounds Chemical class 0.000 claims description 412
229910052739 hydrogen Inorganic materials 0.000 claims description 80
239000001257 hydrogen Substances 0.000 claims description 56
125000000217 alkyl group Chemical group 0.000 claims description 42
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
150000003839 salts Chemical class 0.000 claims description 28
150000002431 hydrogen Chemical class 0.000 claims description 25
229910052799 carbon Inorganic materials 0.000 claims description 20
150000002430 hydrocarbons Chemical class 0.000 claims description 20
239000007858 starting material Substances 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 19
239000004215 Carbon black (E152) Substances 0.000 claims description 18
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
229930195733 hydrocarbon Natural products 0.000 claims description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
125000001072 heteroaryl group Chemical group 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
239000011593 sulfur Chemical group 0.000 claims description 6
SJRYDRWHNWQNOU-UHFFFAOYSA-N 5,7-dichloro-4-oxo-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound C1=C(Cl)C=C2NC(C(=O)O)CC(=O)C2=C1Cl SJRYDRWHNWQNOU-UHFFFAOYSA-N 0.000 claims description 5
239000003638 chemical reducing agent Substances 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
CHLCLKBLWDXZBK-UHFFFAOYSA-N 5,7-dichloro-4-(naphthalene-1-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=CC2=CC=CC=C12 CHLCLKBLWDXZBK-UHFFFAOYSA-N 0.000 claims description 4
BAHGYLRVRXQLQF-UHFFFAOYSA-N 5,7-dichloro-4-[(2-chlorobenzoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=CC=C1Cl BAHGYLRVRXQLQF-UHFFFAOYSA-N 0.000 claims description 4
KGWFKYGFVABCPZ-UHFFFAOYSA-N 5,7-dichloro-4-[(4-chlorobenzoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=C(Cl)C=C1 KGWFKYGFVABCPZ-UHFFFAOYSA-N 0.000 claims description 4
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000006575 electron-withdrawing group Chemical group 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
229910052698 phosphorus Chemical group 0.000 claims description 4
239000011574 phosphorus Chemical group 0.000 claims description 4
DXLDOHDNZZDNMF-UHFFFAOYSA-N 5,7-dichloro-4-(2,5-dioxoimidazolidin-1-yl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1N1C(=O)CNC1=O DXLDOHDNZZDNMF-UHFFFAOYSA-N 0.000 claims description 3
WTMXBEBFNDJTPK-UHFFFAOYSA-N 5,7-dichloro-4-(3,5-dichloroanilino)-4-ethoxycarbonyl-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound C1C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C2C1(C(=O)OCC)NC1=CC(Cl)=CC(Cl)=C1 WTMXBEBFNDJTPK-UHFFFAOYSA-N 0.000 claims description 3
239000005864 Sulphur Substances 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
125000005646 oximino group Chemical group 0.000 claims description 3
230000002829 reductive effect Effects 0.000 claims description 3
IGGKTIIZGDTYRR-UHFFFAOYSA-N 1-amino-4-(2-anilino-2-oxoethyl)-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2N(N)C(C(O)=O)CC1CC(=O)NC1=CC=CC=C1 IGGKTIIZGDTYRR-UHFFFAOYSA-N 0.000 claims description 2
XXROTNVKFKTTGS-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCOC(=O)C(C)(C)C)CC1NC(=O)CC1=CC=CC=C1 XXROTNVKFKTTGS-UHFFFAOYSA-N 0.000 claims description 2
HCXILQPWGBCLQF-UHFFFAOYSA-N 2-(dimethylamino)ethyl 5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCCN(C)C)CC1NC(=O)CC1=CC=CC=C1 HCXILQPWGBCLQF-UHFFFAOYSA-N 0.000 claims description 2
HJLQJEWCEURCJI-UHFFFAOYSA-N 2-hydroxyethyl 5,7-dichloro-4-(1,3-dioxolan-2-yl)-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCCO)CC1C1OCCO1 HJLQJEWCEURCJI-UHFFFAOYSA-N 0.000 claims description 2
RXIJESYGXYMNGH-UHFFFAOYSA-N 3,5,7-trimethyl-4-oxo-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound CC1=CC(C)=C2C(=O)C(C)C(C(O)=O)NC2=C1 RXIJESYGXYMNGH-UHFFFAOYSA-N 0.000 claims description 2
XUUAFMPPQSFWPJ-UHFFFAOYSA-N 3-(dimethylamino)propyl 5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCCCN(C)C)CC1NC(=O)CC1=CC=CC=C1 XUUAFMPPQSFWPJ-UHFFFAOYSA-N 0.000 claims description 2
OYIWRENTXLJIPF-UHFFFAOYSA-N 4-(2-anilino-2-oxoethyl)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1CC(=O)NC1=CC=CC=C1 OYIWRENTXLJIPF-UHFFFAOYSA-N 0.000 claims description 2
CGSMJDKJNUDZPS-UHFFFAOYSA-N 4-(4-aminobutanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NC(=O)CCCN)CC(C(O)=O)NC2=C1 CGSMJDKJNUDZPS-UHFFFAOYSA-N 0.000 claims description 2
KYKZFXSYXFCJNB-UHFFFAOYSA-N 4-(5-aminopentanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NC(=O)CCCCN)CC(C(O)=O)NC2=C1 KYKZFXSYXFCJNB-UHFFFAOYSA-N 0.000 claims description 2
IHFOCHGLNDPRAQ-UHFFFAOYSA-N 4-(benzylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NCC1=CC=CC=C1 IHFOCHGLNDPRAQ-UHFFFAOYSA-N 0.000 claims description 2
KBKZVGPXCPXUCR-UHFFFAOYSA-N 4-(butanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NC(=O)CCC)CC(C(O)=O)NC2=C1 KBKZVGPXCPXUCR-UHFFFAOYSA-N 0.000 claims description 2
CHHZLBUNRQPRRK-UHFFFAOYSA-N 4-(carboxymethyl)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(CC(=O)O)CC(C(O)=O)NC2=C1 CHHZLBUNRQPRRK-UHFFFAOYSA-N 0.000 claims description 2
GLVOLCOUVYQFSL-UHFFFAOYSA-N 4-[(2-carboxybenzoyl)amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=CC=C1C(O)=O GLVOLCOUVYQFSL-UHFFFAOYSA-N 0.000 claims description 2
FICHULGDUXSFQK-UHFFFAOYSA-N 4-[3-[4-(aminomethyl)phenyl]propanoylamino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CN)=CC=C1CCC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 FICHULGDUXSFQK-UHFFFAOYSA-N 0.000 claims description 2
QSKNBTSORJLLKP-UHFFFAOYSA-N 4-[[2-(4-acetylphenyl)acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(C(=O)C)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 QSKNBTSORJLLKP-UHFFFAOYSA-N 0.000 claims description 2
ACCMQYNBAWCWPP-UHFFFAOYSA-N 4-[[2-(4-aminophenyl)acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(N)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 ACCMQYNBAWCWPP-UHFFFAOYSA-N 0.000 claims description 2
YCZJKJFPLKWYGS-UHFFFAOYSA-N 4-[[2-[2-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound NCC1=CC=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 YCZJKJFPLKWYGS-UHFFFAOYSA-N 0.000 claims description 2
HSICVGBLAAAVTI-UHFFFAOYSA-N 4-[[2-[3-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound NCC1=CC=CC(CC(=O)NC2C3=C(Cl)C=C(Cl)C=C3NC(C2)C(O)=O)=C1 HSICVGBLAAAVTI-UHFFFAOYSA-N 0.000 claims description 2
NDQJACUPOSVRNA-UHFFFAOYSA-N 4-[[2-[4-(2-aminoethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CCN)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 NDQJACUPOSVRNA-UHFFFAOYSA-N 0.000 claims description 2
FLVXMOMZZXOYMY-UHFFFAOYSA-N 4-[[2-[4-(3-aminoprop-2-ynyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CC#CN)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 FLVXMOMZZXOYMY-UHFFFAOYSA-N 0.000 claims description 2
SIWXBAWLEMNSHV-UHFFFAOYSA-N 4-[[2-[4-(3-aminopropyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CCCN)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 SIWXBAWLEMNSHV-UHFFFAOYSA-N 0.000 claims description 2
FSACUBNWOHAJPG-UHFFFAOYSA-N 4-[[2-[4-(4-aminobut-2-ynyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CC#CCN)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 FSACUBNWOHAJPG-UHFFFAOYSA-N 0.000 claims description 2
LYVODCHKWZOJKH-UHFFFAOYSA-N 4-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CN)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 LYVODCHKWZOJKH-UHFFFAOYSA-N 0.000 claims description 2
OUCNSRPGPLLUIC-UHFFFAOYSA-N 4-[[4-(2-aminoethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CCN)=CC=C1C(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 OUCNSRPGPLLUIC-UHFFFAOYSA-N 0.000 claims description 2
GJONEQUISMPIEM-UHFFFAOYSA-N 4-[[4-(aminomethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CN)=CC=C1C(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 GJONEQUISMPIEM-UHFFFAOYSA-N 0.000 claims description 2
UCKHICKHGAOGAP-UHFFFAOYSA-N 4-[[anilino(oxo)methyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)NC1=CC=CC=C1 UCKHICKHGAOGAP-UHFFFAOYSA-N 0.000 claims description 2
MRSNQAYYAZMIFI-UHFFFAOYSA-N 4-acetamido-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NC(=O)C)CC(C(O)=O)NC2=C1 MRSNQAYYAZMIFI-UHFFFAOYSA-N 0.000 claims description 2
OKHDZBONRBUIKZ-UHFFFAOYSA-N 4-amino-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(N)CC(C(O)=O)NC2=C1 OKHDZBONRBUIKZ-UHFFFAOYSA-N 0.000 claims description 2
SIFKDUJBOXTKPK-UHFFFAOYSA-N 4-benzamido-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=CC=C1 SIFKDUJBOXTKPK-UHFFFAOYSA-N 0.000 claims description 2
PUDDGGNDHQKNSV-UHFFFAOYSA-N 4-carbamoyl-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(C(=O)N)CC(C(O)=O)NC2=C1 PUDDGGNDHQKNSV-UHFFFAOYSA-N 0.000 claims description 2
PIMWZLLINMBBLN-UHFFFAOYSA-N 4-methoxycarbonyl-5,7-dimethyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound CC1=CC(C)=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 PIMWZLLINMBBLN-UHFFFAOYSA-N 0.000 claims description 2
LYDCDGFKBCEJSI-UHFFFAOYSA-N 5,6,7-trichloro-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=C(Cl)C(Cl)=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 LYDCDGFKBCEJSI-UHFFFAOYSA-N 0.000 claims description 2
VOCVRWBLHFNXGP-UHFFFAOYSA-N 5,7-dibromo-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound BrC1=CC(Br)=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 VOCVRWBLHFNXGP-UHFFFAOYSA-N 0.000 claims description 2
GAPAAVKVDPEXLK-UHFFFAOYSA-N 5,7-dichloro-1,2,3,4-tetrahydroquinoline-2,4-dicarboxylic acid Chemical compound C1=C(Cl)C=C2NC(C(=O)O)CC(C(O)=O)C2=C1Cl GAPAAVKVDPEXLK-UHFFFAOYSA-N 0.000 claims description 2
DRJNABNEPWXXNF-UHFFFAOYSA-N 5,7-dichloro-4-(1,2,3,4-tetrahydroisoquinoline-3-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1NCC2=CC=CC=C2C1 DRJNABNEPWXXNF-UHFFFAOYSA-N 0.000 claims description 2
DVRSJXGXYYNCGL-UHFFFAOYSA-N 5,7-dichloro-4-(2,3-dihydroindole-1-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)N1C2=CC=CC=C2CC1 DVRSJXGXYYNCGL-UHFFFAOYSA-N 0.000 claims description 2
SLPMRAQUZIESLS-UHFFFAOYSA-N 5,7-dichloro-4-(2-methoxy-2-oxoethyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(CC(=O)OC)CC(C(O)=O)NC2=C1 SLPMRAQUZIESLS-UHFFFAOYSA-N 0.000 claims description 2
QANDVJACMBCRND-UHFFFAOYSA-N 5,7-dichloro-4-(2-methylpropanoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NC(=O)C(C)C)CC(C(O)=O)NC2=C1 QANDVJACMBCRND-UHFFFAOYSA-N 0.000 claims description 2
WEANZEQVYJHPIV-UHFFFAOYSA-N 5,7-dichloro-4-(3-phenylprop-2-enoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C=CC1=CC=CC=C1 WEANZEQVYJHPIV-UHFFFAOYSA-N 0.000 claims description 2
MYQLWUQXVQMOCY-UHFFFAOYSA-N 5,7-dichloro-4-(3-phenylpropanoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CCC1=CC=CC=C1 MYQLWUQXVQMOCY-UHFFFAOYSA-N 0.000 claims description 2
DBAWGZLWFPLLGA-UHFFFAOYSA-N 5,7-dichloro-4-(4-phenylbutanoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CCCC1=CC=CC=C1 DBAWGZLWFPLLGA-UHFFFAOYSA-N 0.000 claims description 2
QYPYDRIJPVJFPY-UHFFFAOYSA-N 5,7-dichloro-4-(9h-fluorene-9-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1C2=CC=CC=C2C2=CC=CC=C21 QYPYDRIJPVJFPY-UHFFFAOYSA-N 0.000 claims description 2
AHLDJXGDYFXSIX-UHFFFAOYSA-N 5,7-dichloro-4-(cyclohexanecarbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1CCCCC1 AHLDJXGDYFXSIX-UHFFFAOYSA-N 0.000 claims description 2
OAJRZAZPPHZOAF-UHFFFAOYSA-N 5,7-dichloro-4-(diphenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 OAJRZAZPPHZOAF-UHFFFAOYSA-N 0.000 claims description 2
SUPITBJPZHKMJH-UHFFFAOYSA-N 5,7-dichloro-4-(methanesulfonamido)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NS(=O)(=O)C)CC(C(O)=O)NC2=C1 SUPITBJPZHKMJH-UHFFFAOYSA-N 0.000 claims description 2
VAPNFIVZIJNPFO-UHFFFAOYSA-N 5,7-dichloro-4-(naphthalen-1-ylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)NC1=CC=CC2=CC=CC=C12 VAPNFIVZIJNPFO-UHFFFAOYSA-N 0.000 claims description 2
SZIULTCUKDLKIH-UHFFFAOYSA-N 5,7-dichloro-4-(naphthalene-2-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=C(C=CC=C2)C2=C1 SZIULTCUKDLKIH-UHFFFAOYSA-N 0.000 claims description 2
FVDAKKSMPCAEBA-UHFFFAOYSA-N 5,7-dichloro-4-(phenylmethoxycarbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)OCC1=CC=CC=C1 FVDAKKSMPCAEBA-UHFFFAOYSA-N 0.000 claims description 2
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BPVVRUFBQBOTMI-UHFFFAOYSA-N 5,7-dichloro-4-[(4-methoxyphenyl)carbamoylamino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 BPVVRUFBQBOTMI-UHFFFAOYSA-N 0.000 claims description 2
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MJOMZPLXUBQVRR-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(2-chlorophenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CC1=CC=CC=C1Cl MJOMZPLXUBQVRR-UHFFFAOYSA-N 0.000 claims description 2
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PGDZCDJDFSBESB-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(4-hydroxy-3-nitrophenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 PGDZCDJDFSBESB-UHFFFAOYSA-N 0.000 claims description 2
LWUVTCGISHTDRW-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(4-hydroxyphenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CC1=CC=C(O)C=C1 LWUVTCGISHTDRW-UHFFFAOYSA-N 0.000 claims description 2
CBQIALPYICPTEX-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(4-methoxyphenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 CBQIALPYICPTEX-UHFFFAOYSA-N 0.000 claims description 2
HDKVRCMROTVGSY-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(4-methylphenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 HDKVRCMROTVGSY-UHFFFAOYSA-N 0.000 claims description 2
ZJLDULLDWVFYGB-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(4-nitrophenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CC1=CC=C([N+]([O-])=O)C=C1 ZJLDULLDWVFYGB-UHFFFAOYSA-N 0.000 claims description 2
ODSQEDRZMGMHQH-UHFFFAOYSA-N 5,7-dichloro-4-[[2-[4-(methylaminomethyl)phenyl]acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CNC)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 ODSQEDRZMGMHQH-UHFFFAOYSA-N 0.000 claims description 2
JDAWRPNTZBCEEF-UHFFFAOYSA-N 5,7-dichloro-4-[[2-[4-[(dimethylamino)methyl]phenyl]acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CN(C)C)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 JDAWRPNTZBCEEF-UHFFFAOYSA-N 0.000 claims description 2
QERAQWAALXLNLZ-UHFFFAOYSA-N 5,7-dichloro-4-[[methyl-(4-methylphenyl)carbamoyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C2C1NC(=O)N(C)C1=CC=C(C)C=C1 QERAQWAALXLNLZ-UHFFFAOYSA-N 0.000 claims description 2
OVLNNOFDEZTVSQ-UHFFFAOYSA-N 5,7-dichloro-4-[methyl(phenylcarbamoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C2C1N(C)C(=O)NC1=CC=CC=C1 OVLNNOFDEZTVSQ-UHFFFAOYSA-N 0.000 claims description 2
FRNPTFLJWOHWNH-UHFFFAOYSA-N 5,7-dichloro-4-ethoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(C(=O)OCC)CC(C(O)=O)NC2=C1 FRNPTFLJWOHWNH-UHFFFAOYSA-N 0.000 claims description 2
DMRUXWXAEJRYBZ-UHFFFAOYSA-N 5,7-dichloro-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 DMRUXWXAEJRYBZ-UHFFFAOYSA-N 0.000 claims description 2
BOCRIMBCASJYAV-UHFFFAOYSA-N 5,7-dichloro-4-phenylmethoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1C(=O)OCC1=CC=CC=C1 BOCRIMBCASJYAV-UHFFFAOYSA-N 0.000 claims description 2
LFVBYLFMIGAHPX-UHFFFAOYSA-N 5,7-dichloro-n-[2-(dimethylamino)ethyl]-4-(phenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxamide Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)NCCN(C)C)CC1NC(=O)NC1=CC=CC=C1 LFVBYLFMIGAHPX-UHFFFAOYSA-N 0.000 claims description 2
XUAJGEXPOHCPSQ-UHFFFAOYSA-N 5,7-dichloro-n-[2-(dimethylamino)ethyl]-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxamide Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)NCCN(C)C)CC1NC(=O)CC1=CC=CC=C1 XUAJGEXPOHCPSQ-UHFFFAOYSA-N 0.000 claims description 2
MBRKOXFWEOPFCO-UHFFFAOYSA-N 5,7-dimethyl-4-oxo-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound O=C1CC(C(O)=O)NC2=CC(C)=CC(C)=C21 MBRKOXFWEOPFCO-UHFFFAOYSA-N 0.000 claims description 2
GNMBVSHTVYXPQF-UHFFFAOYSA-N 7-chloro-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 GNMBVSHTVYXPQF-UHFFFAOYSA-N 0.000 claims description 2
FBBUJQUXLXQMFM-UHFFFAOYSA-N 7-chloro-5-iodo-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(I)=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 FBBUJQUXLXQMFM-UHFFFAOYSA-N 0.000 claims description 2
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
RCZPUOGIBBDGHL-UHFFFAOYSA-N [2-(methylamino)-2-oxoethyl] 4-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCC(=O)NC)CC1NC(=O)CC1=CC=C(CN)C=C1 RCZPUOGIBBDGHL-UHFFFAOYSA-N 0.000 claims description 2
DMKCBPMFJHQBTL-UHFFFAOYSA-N [2-(methylamino)-2-oxoethyl] 5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCC(=O)NC)CC1NC(=O)CC1=CC=CC=C1 DMKCBPMFJHQBTL-UHFFFAOYSA-N 0.000 claims description 2
PLYPTTWVQVAUCL-UHFFFAOYSA-N [2-[2-(dimethylamino)ethylamino]-2-oxoethyl] 5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCC(=O)NCCN(C)C)CC1NC(=O)CC1=CC=CC=C1 PLYPTTWVQVAUCL-UHFFFAOYSA-N 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
125000006598 aminocarbonylamino group Chemical group 0.000 claims description 2
239000001099 ammonium carbonate Substances 0.000 claims description 2
235000012501 ammonium carbonate Nutrition 0.000 claims description 2
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
DFBGXLFBBUGWBK-UHFFFAOYSA-N hexyl 4-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OCCCCCC)CC1NC(=O)CC1=CC=C(CN)C=C1 DFBGXLFBBUGWBK-UHFFFAOYSA-N 0.000 claims description 2
150000002443 hydroxylamines Chemical class 0.000 claims description 2
125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
VYMXBOMYLIDBFY-UHFFFAOYSA-N methyl 4-[3-[4-(aminomethyl)phenyl]propanoylamino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CCC1=CC=C(CN)C=C1 VYMXBOMYLIDBFY-UHFFFAOYSA-N 0.000 claims description 2
XGSZSNWFHTWPFU-UHFFFAOYSA-N methyl 4-[[2-[2-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=CC=C1CN XGSZSNWFHTWPFU-UHFFFAOYSA-N 0.000 claims description 2
VCELGJWMXHGKSU-UHFFFAOYSA-N methyl 4-[[2-[3-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=CC(CN)=C1 VCELGJWMXHGKSU-UHFFFAOYSA-N 0.000 claims description 2
QMDTXYARJZRYPT-UHFFFAOYSA-N methyl 4-[[2-[4-(2-aminoethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CCN)C=C1 QMDTXYARJZRYPT-UHFFFAOYSA-N 0.000 claims description 2
XNARQXKJBMJWEP-UHFFFAOYSA-N methyl 4-[[2-[4-(3-aminopropyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CCCN)C=C1 XNARQXKJBMJWEP-UHFFFAOYSA-N 0.000 claims description 2
KITLMZBBASZXTL-UHFFFAOYSA-N methyl 4-[[2-[4-(4-aminobut-2-ynyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CC#CCN)C=C1 KITLMZBBASZXTL-UHFFFAOYSA-N 0.000 claims description 2
LVDCMNTYUAQZMT-UHFFFAOYSA-N methyl 4-[[2-[4-(4-aminobutyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CCCCN)C=C1 LVDCMNTYUAQZMT-UHFFFAOYSA-N 0.000 claims description 2
GELUCNBJKPSMDG-UHFFFAOYSA-N methyl 4-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CN)C=C1 GELUCNBJKPSMDG-UHFFFAOYSA-N 0.000 claims description 2
YBYDAOBFFABQAO-UHFFFAOYSA-N methyl 4-[[3-(aminomethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)C1=CC=CC(CN)=C1 YBYDAOBFFABQAO-UHFFFAOYSA-N 0.000 claims description 2
APZBXNIUKXJSLL-UHFFFAOYSA-N methyl 4-[[4-(2-aminoethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)C1=CC=C(CCN)C=C1 APZBXNIUKXJSLL-UHFFFAOYSA-N 0.000 claims description 2
NQHSSFRIZMBWIP-UHFFFAOYSA-N methyl 4-[[4-(aminomethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)C1=CC=C(CN)C=C1 NQHSSFRIZMBWIP-UHFFFAOYSA-N 0.000 claims description 2
JITHISWNQGRDTO-UHFFFAOYSA-N methyl 5,7-dichloro-4-[[2-[4-(methylaminomethyl)phenyl]acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C1=CC(CNC)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)C1 JITHISWNQGRDTO-UHFFFAOYSA-N 0.000 claims description 2
UYAISWHALNGCDE-UHFFFAOYSA-N methyl 5,7-dichloro-4-[[2-[4-[(dimethylamino)methyl]phenyl]acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CN(C)C)C=C1 UYAISWHALNGCDE-UHFFFAOYSA-N 0.000 claims description 2
150000003248 quinolines Chemical class 0.000 claims description 2
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims 4
DGYQNXJFAHZNAQ-UHFFFAOYSA-N 4-(3-aminopropanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(NC(=O)CCN)CC(C(O)=O)NC2=C1 DGYQNXJFAHZNAQ-UHFFFAOYSA-N 0.000 claims 1
VOFSYTJPDIFPCK-UHFFFAOYSA-N 4-(benzylcarbamoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)NCC1=CC=CC=C1 VOFSYTJPDIFPCK-UHFFFAOYSA-N 0.000 claims 1
MHEJITOIEDOABW-UHFFFAOYSA-N 4-[[2-[4-(4-aminobutyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(CCCCN)=CC=C1CC(=O)NC1C2=C(Cl)C=C(Cl)C=C2NC(C(O)=O)C1 MHEJITOIEDOABW-UHFFFAOYSA-N 0.000 claims 1
VTALXGDDMCOLTF-UHFFFAOYSA-N 4-[[3-(aminomethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound NCC1=CC=CC(C(=O)NC2C3=C(Cl)C=C(Cl)C=C3NC(C2)C(O)=O)=C1 VTALXGDDMCOLTF-UHFFFAOYSA-N 0.000 claims 1
LDDAZYZVBAUMGJ-UHFFFAOYSA-N 5,7-dichloro-4-(2-phenylpropanoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C2C1NC(=O)C(C)C1=CC=CC=C1 LDDAZYZVBAUMGJ-UHFFFAOYSA-N 0.000 claims 1
DMEWYMCVSFTHHU-UHFFFAOYSA-N 5,7-dichloro-4-(3-methyl-1,2,4-oxadiazol-5-yl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound CC1=NOC(C2C3=C(Cl)C=C(Cl)C=C3NC(C2)C(O)=O)=N1 DMEWYMCVSFTHHU-UHFFFAOYSA-N 0.000 claims 1
NSEIGQYUSFJQQX-UHFFFAOYSA-N 5,7-dichloro-4-(cyclohexylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)NC1CCCCC1 NSEIGQYUSFJQQX-UHFFFAOYSA-N 0.000 claims 1
DPJYWYRNTXJFCU-UHFFFAOYSA-N 5,7-dichloro-4-(furan-2-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=CO1 DPJYWYRNTXJFCU-UHFFFAOYSA-N 0.000 claims 1
NXURUXHHGGAABF-UHFFFAOYSA-N 5,7-dichloro-4-(phenylcarbamothioylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=S)NC1=CC=CC=C1 NXURUXHHGGAABF-UHFFFAOYSA-N 0.000 claims 1
BXVWOHOVVWOTQZ-UHFFFAOYSA-N 5,7-dichloro-4-[(3-chlorobenzoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)C1=CC=CC(Cl)=C1 BXVWOHOVVWOTQZ-UHFFFAOYSA-N 0.000 claims 1
QCBYWVGANQEHBX-UHFFFAOYSA-N 5,7-dichloro-4-[(3-nitrophenyl)carbamoylamino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)NC1=CC=CC([N+]([O-])=O)=C1 QCBYWVGANQEHBX-UHFFFAOYSA-N 0.000 claims 1
JJZPCHQQJVUSCG-UHFFFAOYSA-N 5,7-dichloro-4-[[2-(2-nitrophenyl)acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1NC(=O)CC1=CC=CC=C1[N+]([O-])=O JJZPCHQQJVUSCG-UHFFFAOYSA-N 0.000 claims 1
ATHHJRDDJOWENP-UHFFFAOYSA-N 5-chloro-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(Cl)=C2C(C(=O)OC)CC(C(O)=O)NC2=C1 ATHHJRDDJOWENP-UHFFFAOYSA-N 0.000 claims 1
BKLDNOTZGAYLCN-UHFFFAOYSA-N methyl 4-[[2-[4-(3-aminoprop-2-ynyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)OC)CC1NC(=O)CC1=CC=C(CC#CN)C=C1 BKLDNOTZGAYLCN-UHFFFAOYSA-N 0.000 claims 1
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical class C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 abstract description 38
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 abstract description 10
239000005557 antagonist Substances 0.000 abstract description 5
230000002378 acidificating effect Effects 0.000 abstract description 4
208000015122 neurodegenerative disease Diseases 0.000 abstract description 3
230000002265 prevention Effects 0.000 abstract description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 543
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 440
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 248
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 204
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
239000000243 solution Substances 0.000 description 184
235000019439 ethyl acetate Nutrition 0.000 description 147
239000013078 crystal Substances 0.000 description 136
239000000203 mixture Substances 0.000 description 127
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 124
-1 4-substituted 1,2,3,4-tetrahydroquinolines Chemical class 0.000 description 115
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 114
239000007787 solid Substances 0.000 description 99
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 96
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 93
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
229910001868 water Inorganic materials 0.000 description 66
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 62
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 61
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 60
239000002904 solvent Substances 0.000 description 59
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
239000011541 reaction mixture Substances 0.000 description 54
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 52
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 42
239000012267 brine Substances 0.000 description 42
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 41
239000012044 organic layer Substances 0.000 description 41
239000003921 oil Substances 0.000 description 38
235000019198 oils Nutrition 0.000 description 38
239000000463 material Substances 0.000 description 37
229910002091 carbon monoxide Inorganic materials 0.000 description 36
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 35
239000003480 eluent Substances 0.000 description 34
239000011734 sodium Substances 0.000 description 33
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
238000001914 filtration Methods 0.000 description 29
239000012299 nitrogen atmosphere Substances 0.000 description 29
239000000741 silica gel Substances 0.000 description 28
229910002027 silica gel Inorganic materials 0.000 description 28
238000003776 cleavage reaction Methods 0.000 description 27
230000007017 scission Effects 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 25
238000003756 stirring Methods 0.000 description 25
229960000583 acetic acid Drugs 0.000 description 24
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
239000000284 extract Substances 0.000 description 24
238000004587 chromatography analysis Methods 0.000 description 23
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
229910000041 hydrogen chloride Inorganic materials 0.000 description 23
238000010992 reflux Methods 0.000 description 23
239000000725 suspension Substances 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 20
239000000047 product Substances 0.000 description 20
239000003208 petroleum Substances 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 18
229910000069 nitrogen hydride Inorganic materials 0.000 description 18
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
239000003960 organic solvent Substances 0.000 description 16
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
238000000354 decomposition reaction Methods 0.000 description 15
239000010410 layer Substances 0.000 description 15
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 15
239000000460 chlorine Substances 0.000 description 14
239000012043 crude product Substances 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 13
VBPIHYKTAGVZAP-DKXTVVGFSA-N methyl (2r,4s)-4-amino-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate;hydrochloride Chemical compound Cl.C1=C(Cl)C=C2N[C@@H](C(=O)OC)C[C@H](N)C2=C1Cl VBPIHYKTAGVZAP-DKXTVVGFSA-N 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
239000011343 solid material Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
101150041968 CDC13 gene Proteins 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
239000007864 aqueous solution Substances 0.000 description 11
238000001953 recrystallisation Methods 0.000 description 11
XQVBCMVMASBDCK-LDXVYITESA-N (2r,4s)-4-[[3-(aminomethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.NCC1=CC=CC(C(=O)N[C@@H]2C3=C(Cl)C=C(Cl)C=C3N[C@H](C2)C(O)=O)=C1 XQVBCMVMASBDCK-LDXVYITESA-N 0.000 description 10
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
NYBZRUOSBRYIDG-LSDHHAIUSA-N (2r,4s)-5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)CC1=CC=CC=C1 NYBZRUOSBRYIDG-LSDHHAIUSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000009835 boiling Methods 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
229910000029 sodium carbonate Inorganic materials 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
238000001035 drying Methods 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 8
239000012362 glacial acetic acid Substances 0.000 description 8
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 8
230000000717 retained effect Effects 0.000 description 8
239000003826 tablet Substances 0.000 description 8
125000003368 amide group Chemical group 0.000 description 7
239000012230 colorless oil Substances 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000012153 distilled water Substances 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
OZWJFLQRRBWNIV-JKSUJKDBSA-N methyl (2r,4s)-5,7-dichloro-4-[(2-phenylacetyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC)C(=O)CC1=CC=CC=C1 OZWJFLQRRBWNIV-JKSUJKDBSA-N 0.000 description 7
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 7
MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 6
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical group NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
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 6
238000004090 dissolution Methods 0.000 description 6
239000006260 foam Substances 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
FFNBFMYPRNXLDU-LEWJYISDSA-N methyl (2r,4s)-5,7-dichloro-4-[[2-[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]phenyl]acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC)C(=O)CC1=CC=C(CCNC(=O)OC(C)(C)C)C=C1 FFNBFMYPRNXLDU-LEWJYISDSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
SLPMRAQUZIESLS-LHLIQPBNSA-N (2r,4r)-5,7-dichloro-4-(2-methoxy-2-oxoethyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](CC(=O)OC)C[C@H](C(O)=O)NC2=C1 SLPMRAQUZIESLS-LHLIQPBNSA-N 0.000 description 5
HIDJWBGOQFTDLU-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC(O)=O HIDJWBGOQFTDLU-UHFFFAOYSA-N 0.000 description 5
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 5
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 5
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
125000001931 aliphatic group Chemical group 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
FVVVQSONOSMTOP-LSDHHAIUSA-N methyl (2r,4s)-5,7-dichloro-4-(phenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC)C(=O)NC1=CC=CC=C1 FVVVQSONOSMTOP-LSDHHAIUSA-N 0.000 description 5
XZLULHHAJUFQRR-UHFFFAOYSA-N methyl 2-[4-(3-azidoprop-2-ynyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CC#CN=[N+]=[N-])C=C1 XZLULHHAJUFQRR-UHFFFAOYSA-N 0.000 description 5
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical group [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 5
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
229910003446 platinum oxide Inorganic materials 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
CXTVGVSMPFINEK-UHFFFAOYSA-N 1-isocyanato-3,4-dihydro-2h-quinoline Chemical compound C1=CC=C2N(N=C=O)CCCC2=C1 CXTVGVSMPFINEK-UHFFFAOYSA-N 0.000 description 4
MQNHKLMHRZYTBZ-UHFFFAOYSA-N 3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoic acid Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(C(O)=O)=C1 MQNHKLMHRZYTBZ-UHFFFAOYSA-N 0.000 description 4
PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
QCEBSMVCKDUXPF-ZWKOTPCHSA-N C1=CC(NC(=O)OC(C)(C)C)=CC=C1CC(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1CC(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 QCEBSMVCKDUXPF-ZWKOTPCHSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
239000004471 Glycine Substances 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
239000012346 acetyl chloride Substances 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000027455 binding Effects 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
RHSLCDLHQUOHKP-SIKLNZKXSA-N dibenzyl (2r,4s)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2,4-dicarboxylate Chemical compound O=C([C@H]1C[C@@H](C2=C(Cl)C=C(C=C2N1)Cl)C(=O)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 RHSLCDLHQUOHKP-SIKLNZKXSA-N 0.000 description 4
CGXFMIUPJAMEKN-UHFFFAOYSA-N dimethyl 5,7-dichloroquinoline-2,4-dicarboxylate Chemical compound ClC1=CC(Cl)=CC2=NC(C(=O)OC)=CC(C(=O)OC)=C21 CGXFMIUPJAMEKN-UHFFFAOYSA-N 0.000 description 4
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
229960003692 gamma aminobutyric acid Drugs 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
FIAZUJNOAMQPAN-IMTBSYHQSA-N methyl (2r,4s)-4-carbamoyl-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C1=C(Cl)C=C2N[C@@H](C(=O)OC)C[C@H](C(N)=O)C2=C1Cl FIAZUJNOAMQPAN-IMTBSYHQSA-N 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
239000006187 pill Substances 0.000 description 4
239000012047 saturated solution Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
UCKHICKHGAOGAP-UONOGXRCSA-N (2R,4S)-4-[[anilino(oxo)methyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)NC1=CC=CC=C1 UCKHICKHGAOGAP-UONOGXRCSA-N 0.000 description 3
ATJSYAFAXDEYRV-IDVLALEDSA-N (2r,4s)-4-[[4-(2-aminoethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC(CCN)=CC=C1C(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 ATJSYAFAXDEYRV-IDVLALEDSA-N 0.000 description 3
SIFKDUJBOXTKPK-UONOGXRCSA-N (2r,4s)-4-benzamido-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)C1=CC=CC=C1 SIFKDUJBOXTKPK-UONOGXRCSA-N 0.000 description 3
DMRUXWXAEJRYBZ-IMTBSYHQSA-N (2r,4s)-5,7-dichloro-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](C(=O)OC)C[C@H](C(O)=O)NC2=C1 DMRUXWXAEJRYBZ-IMTBSYHQSA-N 0.000 description 3
VBPIHYKTAGVZAP-UHFFFAOYSA-N (5,7-dichloro-2-methoxycarbonyl-1,2,3,4-tetrahydroquinolin-4-yl)azanium;chloride Chemical compound Cl.C1=C(Cl)C=C2NC(C(=O)OC)CC(N)C2=C1Cl VBPIHYKTAGVZAP-UHFFFAOYSA-N 0.000 description 3
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 3
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 3
CYFSDBDAECVIBK-UHFFFAOYSA-N 3,4-dihydro-2h-quinolin-1-ylurea Chemical compound C1=CC=C2N(NC(=O)N)CCCC2=C1 CYFSDBDAECVIBK-UHFFFAOYSA-N 0.000 description 3
UQRLKWGPEVNVHT-UHFFFAOYSA-N 3,5-dichloroaniline Chemical compound NC1=CC(Cl)=CC(Cl)=C1 UQRLKWGPEVNVHT-UHFFFAOYSA-N 0.000 description 3
OKIXNBMMYLPUJB-UHFFFAOYSA-N 5,7-dichloro-4-ethoxycarbonylquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2C(C(=O)OCC)=CC(C(O)=O)=NC2=C1 OKIXNBMMYLPUJB-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
239000007832 Na2SO4 Substances 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
125000003282 alkyl amino group Chemical group 0.000 description 3
125000000304 alkynyl group Chemical group 0.000 description 3
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
229940024606 amino acid Drugs 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
SBYVSXWAKJZJJU-UHFFFAOYSA-N diethyl 5,7-dichloroquinoline-2,4-dicarboxylate Chemical compound ClC1=CC(Cl)=CC2=NC(C(=O)OCC)=CC(C(=O)OCC)=C21 SBYVSXWAKJZJJU-UHFFFAOYSA-N 0.000 description 3
QVEAXLLMFQIYGD-OIBJUYFYSA-N dimethyl (2r,4s)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2,4-dicarboxylate Chemical compound C1=C(Cl)C=C2N[C@@H](C(=O)OC)C[C@H](C(=O)OC)C2=C1Cl QVEAXLLMFQIYGD-OIBJUYFYSA-N 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
125000002541 furyl group Chemical group 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
CQRCMMGZXBLGPW-RDDDGLTNSA-N methyl (2r,4r)-5,7-dichloro-4-(2-methoxy-2-oxoethyl)-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound ClC1=CC(Cl)=C2[C@@H](CC(=O)OC)C[C@H](C(=O)OC)NC2=C1 CQRCMMGZXBLGPW-RDDDGLTNSA-N 0.000 description 3
DKJHANWVFCPODY-NWDGAFQWSA-N methyl (2r,4s)-5,7-dichloro-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C1=C(Cl)C=C2N[C@@H](C(=O)OC)C[C@H](NC(=O)OC(C)(C)C)C2=C1Cl DKJHANWVFCPODY-NWDGAFQWSA-N 0.000 description 3
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
230000004770 neurodegeneration Effects 0.000 description 3
230000036963 noncompetitive effect Effects 0.000 description 3
125000001715 oxadiazolyl group Chemical group 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
FWLKYEAOOIPJRL-UHFFFAOYSA-N prop-1-yn-1-ol Chemical compound CC#CO FWLKYEAOOIPJRL-UHFFFAOYSA-N 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
230000009467 reduction Effects 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
238000002390 rotary evaporation Methods 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 3
229930192474 thiophene Natural products 0.000 description 3
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
QOKWZGNWNMSSMQ-LJLRIERRSA-N (2r,4r)-1-acetamido-4-[4-(3-aminopropyl)phenyl]-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)C)C(O)=O)=CC=C(CCCN)C=C1 QOKWZGNWNMSSMQ-LJLRIERRSA-N 0.000 description 2
OYIWRENTXLJIPF-MEBBXXQBSA-N (2r,4r)-4-(2-anilino-2-oxoethyl)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)NC1=CC=CC=C1 OYIWRENTXLJIPF-MEBBXXQBSA-N 0.000 description 2
RWRVLIGGFDNNOD-CZUORRHYSA-N (2r,4r)-5,7-dichloro-1-[(2-methoxyacetyl)amino]-4-phenyl-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)COC)C(O)=O)=CC=CC=C1 RWRVLIGGFDNNOD-CZUORRHYSA-N 0.000 description 2
JDWVGDBGCSDWNP-VZXYPILPSA-N (2r,4s)-4-(4-aminobutanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.ClC1=CC(Cl)=C2[C@@H](NC(=O)CCCN)C[C@H](C(O)=O)NC2=C1 JDWVGDBGCSDWNP-VZXYPILPSA-N 0.000 description 2
IHFOCHGLNDPRAQ-DZGCQCFKSA-N (2r,4s)-4-(benzylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)CC1=CC=CC=C1 IHFOCHGLNDPRAQ-DZGCQCFKSA-N 0.000 description 2
KBKZVGPXCPXUCR-WDEREUQCSA-N (2r,4s)-4-(butanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](NC(=O)CCC)C[C@H](C(O)=O)NC2=C1 KBKZVGPXCPXUCR-WDEREUQCSA-N 0.000 description 2
GLVOLCOUVYQFSL-UONOGXRCSA-N (2r,4s)-4-[(2-carboxybenzoyl)amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)C1=CC=CC=C1C(O)=O GLVOLCOUVYQFSL-UONOGXRCSA-N 0.000 description 2
CZGIGSINOQKILO-MCJVGQIASA-N (2r,4s)-4-[3-[4-(aminomethyl)phenyl]propanoylamino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1CCC(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 CZGIGSINOQKILO-MCJVGQIASA-N 0.000 description 2
AHLDJXGDYFXSIX-UONOGXRCSA-N (2r,4s)-5,7-dichloro-4-(cyclohexanecarbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)C1CCCCC1 AHLDJXGDYFXSIX-UONOGXRCSA-N 0.000 description 2
OAJRZAZPPHZOAF-VQTJNVASSA-N (2r,4s)-5,7-dichloro-4-(diphenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 OAJRZAZPPHZOAF-VQTJNVASSA-N 0.000 description 2
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208000012601 choreatic disease Diseases 0.000 description 2
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230000001054 cortical effect Effects 0.000 description 2
NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
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KPIIYTXTXNVJFI-UHFFFAOYSA-N dimethyl 2-(3,5-dichloroanilino)butanedioate Chemical compound COC(=O)CC(C(=O)OC)NC1=CC(Cl)=CC(Cl)=C1 KPIIYTXTXNVJFI-UHFFFAOYSA-N 0.000 description 2
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 2
239000012055 enteric layer Substances 0.000 description 2
ZPSJKCHZJFRHJD-UHFFFAOYSA-N ethyl 2-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(CNC(=O)OC(C)(C)C)C=C1 ZPSJKCHZJFRHJD-UHFFFAOYSA-N 0.000 description 2
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
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239000007789 gas Substances 0.000 description 2
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BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
239000003456 ion exchange resin Substances 0.000 description 2
229920003303 ion-exchange polymer Polymers 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
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239000011968 lewis acid catalyst Substances 0.000 description 2
229910003002 lithium salt Inorganic materials 0.000 description 2
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
ZTCWRDFGBJYEBT-LEWJYISDSA-N methyl (2R,4S)-5,7-dichloro-4-[[2-[2-ethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]acetyl]amino]-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C(C)(C)(C)OC(=O)NC1=CC(=C(C=C1)CC(=O)N[C@H]1C[C@@H](NC2=CC(=CC(=C12)Cl)Cl)C(=O)OC)CC ZTCWRDFGBJYEBT-LEWJYISDSA-N 0.000 description 2
AACTUWKRERILCH-KQKCUOLZSA-N methyl (2r,4r)-1-acetamido-4-[4-(aminomethyl)phenyl]-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylate;hydrochloride Chemical compound Cl.C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(C)=O)C(=O)OC)=CC=C(CN)C=C1 AACTUWKRERILCH-KQKCUOLZSA-N 0.000 description 2
TVMGSZGDHJNRGD-RHSMWYFYSA-N methyl (2r,4r)-5,7-dichloro-1-[(2-methoxyacetyl)amino]-4-phenyl-3,4-dihydro-2h-quinoline-2-carboxylate Chemical compound C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)COC)C(=O)OC)=CC=CC=C1 TVMGSZGDHJNRGD-RHSMWYFYSA-N 0.000 description 2
ZRJPBQSGYIVWIY-SMDDNHRTSA-N methyl (2r,4s)-1-amino-5,7-dichloro-4-(pyridine-4-carbonyl)-3,4-dihydro-2h-quinoline-2-carboxylate Chemical compound O=C([C@H]1C[C@@H](N(C2=CC(Cl)=CC(Cl)=C21)N)C(=O)OC)C1=CC=NC=C1 ZRJPBQSGYIVWIY-SMDDNHRTSA-N 0.000 description 2
RPIWBODCVDLIPA-NWDGAFQWSA-N methyl (2r,4s)-4-(butanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound ClC1=CC(Cl)=C2[C@@H](NC(=O)CCC)C[C@H](C(=O)OC)NC2=C1 RPIWBODCVDLIPA-NWDGAFQWSA-N 0.000 description 2
AEBMCPNCWATGQM-DLBZAZTESA-N methyl (2r,4s)-4-[[2-[2-(azidomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC)C(=O)CC1=CC=CC=C1CN=[N+]=[N-] AEBMCPNCWATGQM-DLBZAZTESA-N 0.000 description 2
MNLXHCNINRDJLH-LSDHHAIUSA-N methyl (2r,4s)-4-benzamido-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC)C(=O)C1=CC=CC=C1 MNLXHCNINRDJLH-LSDHHAIUSA-N 0.000 description 2
HVMGTYPDQLDKNG-LEWJYISDSA-N methyl (2r,4s)-5,7-dichloro-4-(diphenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC)C(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 HVMGTYPDQLDKNG-LEWJYISDSA-N 0.000 description 2
CDVSQCQXGDPUJE-UHFFFAOYSA-N methyl 2-[3-(azidomethyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(CN=[N+]=[N-])=C1 CDVSQCQXGDPUJE-UHFFFAOYSA-N 0.000 description 2
YPHYEUAIDAUFAH-UHFFFAOYSA-N methyl 2-[3-(bromomethyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(CBr)=C1 YPHYEUAIDAUFAH-UHFFFAOYSA-N 0.000 description 2
UMLCXALUSHYMHG-UHFFFAOYSA-N methyl 2-[3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(CNC(=O)OC(C)(C)C)=C1 UMLCXALUSHYMHG-UHFFFAOYSA-N 0.000 description 2
ZFCJPTKEPBGKCI-UHFFFAOYSA-N methyl 2-[4-(3-chloroprop-2-ynyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CC#CCl)C=C1 ZFCJPTKEPBGKCI-UHFFFAOYSA-N 0.000 description 2
QYQWIMMCPURQMW-UHFFFAOYSA-N methyl 2-[4-(3-hydroxyprop-2-ynyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CC#CO)C=C1 QYQWIMMCPURQMW-UHFFFAOYSA-N 0.000 description 2
DPVGTQZICUYCJS-UHFFFAOYSA-N methyl 2-[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CCNC(=O)OC(C)(C)C)C=C1 DPVGTQZICUYCJS-UHFFFAOYSA-N 0.000 description 2
SHDAGOCCNMNEAG-UHFFFAOYSA-N methyl 2-[4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CCCNC(=O)OC(C)(C)C)C=C1 SHDAGOCCNMNEAG-UHFFFAOYSA-N 0.000 description 2
YKZYDUABWXPWAS-UHFFFAOYSA-N methyl 3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)CCCC2=C1 YKZYDUABWXPWAS-UHFFFAOYSA-N 0.000 description 2
QWSSNDTZJLKHPN-UHFFFAOYSA-N methyl 4-carbonochloridoyl-5,7-dichloroquinoline-2-carboxylate Chemical compound ClC1=CC(Cl)=CC2=NC(C(=O)OC)=CC(C(Cl)=O)=C21 QWSSNDTZJLKHPN-UHFFFAOYSA-N 0.000 description 2
ZJLIFEUQYJXNQZ-UHFFFAOYSA-N methyl 5,7-dichloro-1-[(2-phenylacetyl)amino]-3,4-dihydro-2H-quinoline-2-carboxylate Chemical compound COC(=O)C1CCc2c(Cl)cc(Cl)cc2N1NC(=O)Cc1ccccc1 ZJLIFEUQYJXNQZ-UHFFFAOYSA-N 0.000 description 2
JFLHSAWGYFMAQQ-UHFFFAOYSA-N methyl 5,7-dichloro-4-hydroxyimino-2,3-dihydro-1H-quinoline-2-carboxylate Chemical compound C1=C(Cl)C=C2NC(C(=O)OC)CC(=NO)C2=C1Cl JFLHSAWGYFMAQQ-UHFFFAOYSA-N 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
229960003424 phenylacetic acid Drugs 0.000 description 2
239000003279 phenylacetic acid Substances 0.000 description 2
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
230000004044 response Effects 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
125000003003 spiro group Chemical group 0.000 description 2
229940014800 succinic anhydride Drugs 0.000 description 2
DGTUFLYMRODGLT-FZKQIMNGSA-N tert-butyl (2r,4r)-4-(2-anilino-2-oxoethyl)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound C([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)OC(C)(C)C)C(=O)NC1=CC=CC=C1 DGTUFLYMRODGLT-FZKQIMNGSA-N 0.000 description 2
WMTBIMVVSXCNRO-NOZJJQNGSA-N tert-butyl (2r,4r)-5,7-dichloro-4-(2-methoxy-2-oxoethyl)-1,2,3,4-tetrahydroquinoline-2-carboxylate Chemical compound ClC1=CC(Cl)=C2[C@@H](CC(=O)OC)C[C@H](C(=O)OC(C)(C)C)NC2=C1 WMTBIMVVSXCNRO-NOZJJQNGSA-N 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
WMUZDBZPDLHUMW-UHFFFAOYSA-N (2-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1[N+]([O-])=O WMUZDBZPDLHUMW-UHFFFAOYSA-N 0.000 description 1
CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 description 1
RXIJESYGXYMNGH-LDYMZIIASA-N (2r,3r)-3,5,7-trimethyl-4-oxo-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound CC1=CC(C)=C2C(=O)[C@H](C)[C@H](C(O)=O)NC2=C1 RXIJESYGXYMNGH-LDYMZIIASA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
IBKUEYXUAZQDTK-IUODEOHRSA-N (2r,4r)-1-(carbamoylamino)-5,7-dichloro-4-(4-methylphenyl)-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1[C@@H]1C2=C(Cl)C=C(Cl)C=C2N(NC(N)=O)[C@@H](C(O)=O)C1 IBKUEYXUAZQDTK-IUODEOHRSA-N 0.000 description 1
PNQIDCVLJDGXQQ-BXUZGUMPSA-N (2r,4r)-1-(carbamoylamino)-5,7-dichloro-4-cyclohexyl-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)N)C(O)=O)CCCCC1 PNQIDCVLJDGXQQ-BXUZGUMPSA-N 0.000 description 1
ZXSHKZZRICNPDR-OGPPPPIKSA-N (2r,4r)-1-acetamido-4-[4-(4-aminobutyl)phenyl]-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)C)C(O)=O)=CC=C(CCCCN)C=C1 ZXSHKZZRICNPDR-OGPPPPIKSA-N 0.000 description 1
KBOSAOWEZQJPGL-SATBOSKTSA-N (2r,4r)-1-acetamido-4-[4-(aminomethyl)phenyl]-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)C)C(O)=O)=CC=C(CN)C=C1 KBOSAOWEZQJPGL-SATBOSKTSA-N 0.000 description 1
MZCWZCHLSGNURW-BDJLRTHQSA-N (2r,4r)-1-acetamido-5,7-dichloro-4-(4-chloro-3-nitrophenyl)-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C1([C@H]2C[C@@H](N(C3=CC(Cl)=CC(Cl)=C32)NC(=O)C)C(O)=O)=CC=C(Cl)C([N+]([O-])=O)=C1 MZCWZCHLSGNURW-BDJLRTHQSA-N 0.000 description 1
CHHZLBUNRQPRRK-MLUIRONXSA-N (2r,4r)-4-(carboxymethyl)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](CC(=O)O)C[C@H](C(O)=O)NC2=C1 CHHZLBUNRQPRRK-MLUIRONXSA-N 0.000 description 1
QSPHJSYDRTUERE-GHMZBOCLSA-N (2r,4r)-5,7-dichloro-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@H](NC(=O)OC(C)(C)C)C[C@H](C(O)=O)NC2=C1 QSPHJSYDRTUERE-GHMZBOCLSA-N 0.000 description 1
OGYNXFUGHPCFIH-IUODEOHRSA-N (2r,4s)-1-amino-5,7-dichloro-4-(2-cyclohexylacetyl)-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound O=C([C@H]1C[C@@H](N(C2=CC(Cl)=CC(Cl)=C21)N)C(O)=O)CC1CCCCC1 OGYNXFUGHPCFIH-IUODEOHRSA-N 0.000 description 1
LDTQDEAAOJAYTI-IUODEOHRSA-N (2r,4s)-1-amino-5,7-dichloro-4-[2-(3-chlorophenyl)acetyl]-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound O=C([C@H]1C[C@@H](N(C2=CC(Cl)=CC(Cl)=C21)N)C(O)=O)CC1=CC=CC(Cl)=C1 LDTQDEAAOJAYTI-IUODEOHRSA-N 0.000 description 1
YTOODMLFISWPQI-VHSXEESVSA-N (2r,4s)-4-(3-carboxypropanoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](NC(=O)CCC(=O)O)C[C@H](C(O)=O)NC2=C1 YTOODMLFISWPQI-VHSXEESVSA-N 0.000 description 1
VOFSYTJPDIFPCK-LSDHHAIUSA-N (2r,4s)-4-(benzylcarbamoylamino)-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)NCC1=CC=CC=C1 VOFSYTJPDIFPCK-LSDHHAIUSA-N 0.000 description 1
QJNUERHDWFBTTL-RHSMWYFYSA-N (2r,4s)-4-[2-(4-acetamidophenyl)acetyl]-1-amino-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C1=CC(NC(=O)C)=CC=C1CC(=O)[C@@H]1C2=C(Cl)C=C(Cl)C=C2N(N)[C@@H](C(O)=O)C1 QJNUERHDWFBTTL-RHSMWYFYSA-N 0.000 description 1
FLRNWARLADNMNT-RHSMWYFYSA-N (2r,4s)-4-[2-(4-acetylphenyl)acetyl]-1-amino-5,7-dichloro-3,4-dihydro-2h-quinoline-2-carboxylic acid Chemical compound C1=CC(C(=O)C)=CC=C1CC(=O)[C@@H]1C2=C(Cl)C=C(Cl)C=C2N(N)[C@@H](C(O)=O)C1 FLRNWARLADNMNT-RHSMWYFYSA-N 0.000 description 1
GFBNWSYBCDBNTL-IDVLALEDSA-N (2r,4s)-4-[[2-[2-(aminomethyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.NCC1=CC=CC=C1CC(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 GFBNWSYBCDBNTL-IDVLALEDSA-N 0.000 description 1
JAXLLCNKYJGYJX-CJRXIRLBSA-N (2r,4s)-4-[[2-[4-(3-aminoprop-2-ynyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC(CC#CN)=CC=C1CC(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 JAXLLCNKYJGYJX-CJRXIRLBSA-N 0.000 description 1
PTYRXXBXSYSREO-GRTNUQQKSA-N (2r,4s)-4-[[2-[4-(4-aminobut-2-ynyl)phenyl]acetyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC(CC#CCN)=CC=C1CC(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 PTYRXXBXSYSREO-GRTNUQQKSA-N 0.000 description 1
ACXHJKZGBHIDNJ-LDXVYITESA-N (2r,4s)-4-[[4-(aminomethyl)benzoyl]amino]-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1C(=O)N[C@@H]1C2=C(Cl)C=C(Cl)C=C2N[C@@H](C(O)=O)C1 ACXHJKZGBHIDNJ-LDXVYITESA-N 0.000 description 1
MRSNQAYYAZMIFI-VHSXEESVSA-N (2r,4s)-4-acetamido-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](NC(=O)C)C[C@H](C(O)=O)NC2=C1 MRSNQAYYAZMIFI-VHSXEESVSA-N 0.000 description 1
OKHDZBONRBUIKZ-POYBYMJQSA-N (2r,4s)-4-amino-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](N)C[C@H](C(O)=O)NC2=C1 OKHDZBONRBUIKZ-POYBYMJQSA-N 0.000 description 1
CYXZXQVFXFYTRR-QDOHZIMISA-N (2r,4s)-4-amino-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.ClC1=CC(Cl)=C2[C@@H](N)C[C@H](C(O)=O)NC2=C1 CYXZXQVFXFYTRR-QDOHZIMISA-N 0.000 description 1
PUDDGGNDHQKNSV-YLWLKBPMSA-N (2r,4s)-4-carbamoyl-5,7-dichloro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](C(=O)N)C[C@H](C(O)=O)NC2=C1 PUDDGGNDHQKNSV-YLWLKBPMSA-N 0.000 description 1
VOCVRWBLHFNXGP-IMTBSYHQSA-N (2r,4s)-5,7-dibromo-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound BrC1=CC(Br)=C2[C@@H](C(=O)OC)C[C@H](C(O)=O)NC2=C1 VOCVRWBLHFNXGP-IMTBSYHQSA-N 0.000 description 1
QANDVJACMBCRND-WDEREUQCSA-N (2r,4s)-5,7-dichloro-4-(2-methylpropanoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=C2[C@@H](NC(=O)C(C)C)C[C@H](C(O)=O)NC2=C1 QANDVJACMBCRND-WDEREUQCSA-N 0.000 description 1
QYPYDRIJPVJFPY-VQTJNVASSA-N (2r,4s)-5,7-dichloro-4-(9h-fluorene-9-carbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2N[C@@H](C(=O)O)C[C@@H]1NC(=O)C1C2=CC=CC=C2C2=CC=CC=C21 QYPYDRIJPVJFPY-VQTJNVASSA-N 0.000 description 1
VAPNFIVZIJNPFO-ZWKOTPCHSA-N (2r,4s)-5,7-dichloro-4-(naphthalen-1-ylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2N[C@@H](C(=O)O)C[C@@H]1NC(=O)NC1=CC=CC2=CC=CC=C12 VAPNFIVZIJNPFO-ZWKOTPCHSA-N 0.000 description 1
NXURUXHHGGAABF-UONOGXRCSA-N (2r,4s)-5,7-dichloro-4-(phenylcarbamothioylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=S)NC1=CC=CC=C1 NXURUXHHGGAABF-UONOGXRCSA-N 0.000 description 1
FVDAKKSMPCAEBA-LSDHHAIUSA-N (2r,4s)-5,7-dichloro-4-(phenylmethoxycarbonylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)OCC1=CC=CC=C1 FVDAKKSMPCAEBA-LSDHHAIUSA-N 0.000 description 1
BAHGYLRVRXQLQF-UONOGXRCSA-N (2r,4s)-5,7-dichloro-4-[(2-chlorobenzoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@H]1C[C@@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)C1=CC=CC=C1Cl BAHGYLRVRXQLQF-UONOGXRCSA-N 0.000 description 1
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ATHHJRDDJOWENP-IMTBSYHQSA-N (2r,4s)-5-chloro-4-methoxycarbonyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC(Cl)=C2[C@@H](C(=O)OC)C[C@H](C(O)=O)NC2=C1 ATHHJRDDJOWENP-IMTBSYHQSA-N 0.000 description 1
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QBHBHOSRLDPIHG-UHFFFAOYSA-N (4-hydroxy-3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 QBHBHOSRLDPIHG-UHFFFAOYSA-N 0.000 description 1
YBADLXQNJCMBKR-UHFFFAOYSA-N (4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-N 0.000 description 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
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