ES2315875T3 - Heterociclos biciclicos como inhibidores de integrasa del vih. - Google Patents

Info

Publication number

ES2315875T3

ES2315875T3 ES05750075T ES05750075T ES2315875T3 ES 2315875 T3 ES2315875 T3 ES 2315875T3 ES 05750075 T ES05750075 T ES 05750075T ES 05750075 T ES05750075 T ES 05750075T ES 2315875 T3 ES2315875 T3 ES 2315875T3

Authority

ES

Spain

Prior art keywords

oxo

methyl

oxazin

hydroxy

dimethyl

Prior art date

2004-05-28

Legal status (The legal status 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 status listed.)

Expired - Lifetime

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• 239000003112 inhibitor Substances 0.000 title claims description 48
• 150000001875 compounds Chemical class 0.000 claims abstract description 363
• -1 dioxothiazinyl Chemical group 0.000 claims abstract description 137
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 65
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 55
• 239000001257 hydrogen Substances 0.000 claims abstract description 51
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 38
• 150000003839 salts Chemical class 0.000 claims abstract description 38
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 32
• 239000012453 solvate Substances 0.000 claims abstract description 28
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 24
• 125000001475 halogen functional group Chemical group 0.000 claims abstract description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
• 125000001424 substituent group Chemical group 0.000 claims abstract description 15
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 10
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims abstract description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 8
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims abstract description 6
• 125000005059 halophenyl group Chemical group 0.000 claims abstract description 4
• 125000005429 oxyalkyl group Chemical group 0.000 claims abstract description 4
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims abstract description 3
• 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 3
• 125000002541 furyl group Chemical group 0.000 claims abstract description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims abstract description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 claims abstract description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 3
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 3
• 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 3
• 125000001113 thiadiazolyl group Chemical group 0.000 claims abstract description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 3
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 3
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims abstract description 3
• 125000001425 triazolyl group Chemical group 0.000 claims abstract description 3
• 239000000203 mixture Substances 0.000 claims description 185
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
• 239000003795 chemical substances by application Substances 0.000 claims description 25
• LDSKYBVNIGKJHA-UHFFFAOYSA-N 2h-1,4-oxazine-2-carboxamide Chemical compound NC(=O)C1OC=CN=C1 LDSKYBVNIGKJHA-UHFFFAOYSA-N 0.000 claims description 23
• 208000030507 AIDS Diseases 0.000 claims description 20
• 150000002148 esters Chemical class 0.000 claims description 16
• 239000002777 nucleoside Substances 0.000 claims description 16
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 15
• 238000011282 treatment Methods 0.000 claims description 15
• 208000031886 HIV Infections Diseases 0.000 claims description 14
• 208000037357 HIV infectious disease Diseases 0.000 claims description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 14
• 150000003833 nucleoside derivatives Chemical class 0.000 claims description 14
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
• HFHGVIBGEFYIFU-UHFFFAOYSA-N 3h-oxazepine-2-carboxamide Chemical compound NC(=O)N1CC=CC=CO1 HFHGVIBGEFYIFU-UHFFFAOYSA-N 0.000 claims description 11
• 230000005764 inhibitory process Effects 0.000 claims description 9
• 108010002459 HIV Integrase Proteins 0.000 claims description 8
• 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 8
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 7
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 7
• 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 7
• 229940099797 HIV integrase inhibitor Drugs 0.000 claims description 7
• 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 7
• 239000003084 hiv integrase inhibitor Substances 0.000 claims description 7
• 208000015181 infectious disease Diseases 0.000 claims description 7
• 230000035800 maturation Effects 0.000 claims description 7
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
• 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 5
• 230000004927 fusion Effects 0.000 claims description 5
• 239000004030 hiv protease inhibitor Substances 0.000 claims description 5
• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 5
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 claims description 5
• 230000034303 cell budding Effects 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 108010010369 HIV Protease Proteins 0.000 claims description 3
• DWLVWMUCHSLGSU-UHFFFAOYSA-N dimethylcarbamic acid Chemical compound CN(C)C(O)=O DWLVWMUCHSLGSU-UHFFFAOYSA-N 0.000 claims description 3
• 125000001188 haloalkyl group Chemical group 0.000 claims description 3
• 239000002835 hiv fusion inhibitor Substances 0.000 claims description 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
• COEOZBBXBIAOHC-UHFFFAOYSA-N pyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound O1C=CN2C=CC(C(=O)N)=NC2=C1 COEOZBBXBIAOHC-UHFFFAOYSA-N 0.000 claims description 3
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 2
• KATSFXHQLOKKKZ-UHFFFAOYSA-N 3-hydroxy-9,9-dimethyl-n-[(2-methylsulfonylphenyl)methyl]-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=CC=C1S(C)(=O)=O KATSFXHQLOKKKZ-UHFFFAOYSA-N 0.000 claims description 2
• CKUVWMOMSIPZMI-UHFFFAOYSA-N 9,9-diethyl-n-[(4-fluoro-2-methylsulfonylphenyl)methyl]-3-hydroxy-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CCC1(CC)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1S(C)(=O)=O CKUVWMOMSIPZMI-UHFFFAOYSA-N 0.000 claims description 2
• ZFGUMKBFKVQRLF-UHFFFAOYSA-N 9,9-diethyl-n-[[4-fluoro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-3-hydroxy-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CCC1(CC)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1C=NC=N1 ZFGUMKBFKVQRLF-UHFFFAOYSA-N 0.000 claims description 2
• UCULMFRTTVDHQW-UHFFFAOYSA-N 9,9-diethyl-n-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-3-hydroxy-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CCC1(CC)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1C(=O)NC UCULMFRTTVDHQW-UHFFFAOYSA-N 0.000 claims description 2
• 125000000304 alkynyl group Chemical group 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
• ZHSFPAHDEUORJZ-UHFFFAOYSA-N n-[(2-acetamido-4-fluorophenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC(=O)NC1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 ZHSFPAHDEUORJZ-UHFFFAOYSA-N 0.000 claims description 2
• YHWFNVSJZVKCNP-UHFFFAOYSA-N n-[(4-fluoro-2-methylsulfonylphenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1S(C)(=O)=O YHWFNVSJZVKCNP-UHFFFAOYSA-N 0.000 claims description 2
• XGMAGKLMXYOTEJ-UHFFFAOYSA-N n-[(4-fluoro-2-morpholin-4-ylphenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1CCOCC1 XGMAGKLMXYOTEJ-UHFFFAOYSA-N 0.000 claims description 2
• GOEURYJGZXLMPA-UHFFFAOYSA-N n-[(4-fluoro-2-sulfamoylphenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1S(N)(=O)=O GOEURYJGZXLMPA-UHFFFAOYSA-N 0.000 claims description 2
• LYTKZEQMSYFEPI-UHFFFAOYSA-N n-[[2-(dimethylsulfamoyl)-4-fluorophenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CN(C)S(=O)(=O)C1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 LYTKZEQMSYFEPI-UHFFFAOYSA-N 0.000 claims description 2
• STAJYGBIAZYIRP-UHFFFAOYSA-N n-[[2-(dimethylsulfamoyl)-4-fluorophenyl]methyl]-9,9-diethyl-3-hydroxy-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CCC1(CC)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1S(=O)(=O)N(C)C STAJYGBIAZYIRP-UHFFFAOYSA-N 0.000 claims description 2
• LISWJAIKDPKEJR-UHFFFAOYSA-N n-[[2-[3-(dimethylcarbamoyl)-1,2,4-triazol-1-yl]-4-fluorophenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound N1=C(C(=O)N(C)C)N=CN1C1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 LISWJAIKDPKEJR-UHFFFAOYSA-N 0.000 claims description 2
• CSSGZDUICVWCPW-UHFFFAOYSA-N n-[[4-fluoro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1C=NC=N1 CSSGZDUICVWCPW-UHFFFAOYSA-N 0.000 claims description 2
• FONCPLRXMYTFAG-UHFFFAOYSA-N n-[[4-fluoro-2-(1-methyltetrazol-5-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CN1N=NN=C1C1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 FONCPLRXMYTFAG-UHFFFAOYSA-N 0.000 claims description 2
• ZAQPIFMYOBOZNA-UHFFFAOYSA-N n-[[4-fluoro-2-(1h-pyrazol-5-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1C1=CC=NN1 ZAQPIFMYOBOZNA-UHFFFAOYSA-N 0.000 claims description 2
• NTQJGIZIRNLSRZ-UHFFFAOYSA-N n-[[4-fluoro-2-(2-hydroxyethylcarbamoyl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1C(=O)NCCO NTQJGIZIRNLSRZ-UHFFFAOYSA-N 0.000 claims description 2
• IDNNBICIBQJMKQ-UHFFFAOYSA-N n-[[4-fluoro-2-(2-oxo-1,3-oxazolidin-3-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1CCOC1=O IDNNBICIBQJMKQ-UHFFFAOYSA-N 0.000 claims description 2
• ZAYNAGILDTUKKA-UHFFFAOYSA-N n-[[4-fluoro-2-(2-oxoazetidin-1-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1CCC1=O ZAYNAGILDTUKKA-UHFFFAOYSA-N 0.000 claims description 2
• MWXPELHYKUPTBS-UHFFFAOYSA-N n-[[4-fluoro-2-(2-oxopiperidin-1-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1CCCCC1=O MWXPELHYKUPTBS-UHFFFAOYSA-N 0.000 claims description 2
• YPGPHKYNAXOSJE-UHFFFAOYSA-N n-[[4-fluoro-2-(2-oxopyrrolidin-1-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1CCCC1=O YPGPHKYNAXOSJE-UHFFFAOYSA-N 0.000 claims description 2
• ZGOIAZNKBHHQNV-UHFFFAOYSA-N n-[[4-fluoro-2-(3-methyl-1,2,4-triazol-1-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound N1=C(C)N=CN1C1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 ZGOIAZNKBHHQNV-UHFFFAOYSA-N 0.000 claims description 2
• QOZUICSVLJMIDW-UHFFFAOYSA-N n-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CNC(=O)C1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 QOZUICSVLJMIDW-UHFFFAOYSA-N 0.000 claims description 2
• PLWNJEHHXBQCHO-UHFFFAOYSA-N n-[[4-fluoro-2-(methylsulfamoyl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CNS(=O)(=O)C1=CC(F)=CC=C1CNC(=O)C1=C(O)C(=O)N(CCOC2(C)C)C2=N1 PLWNJEHHXBQCHO-UHFFFAOYSA-N 0.000 claims description 2
• RQOGKHGPSHFOKR-UHFFFAOYSA-N n-[[4-fluoro-2-(morpholine-4-carbonyl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1C(=O)N1CCOCC1 RQOGKHGPSHFOKR-UHFFFAOYSA-N 0.000 claims description 2
• XBNFBNRVYGOFOX-UHFFFAOYSA-N n-[[4-fluoro-2-(thiadiazol-4-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1C1=CSN=N1 XBNFBNRVYGOFOX-UHFFFAOYSA-N 0.000 claims description 2
• BTXFIDOCDUUPLO-UHFFFAOYSA-N n-[[4-fluoro-2-[3-(4-methylpiperazine-1-carbonyl)-1,2,4-triazol-1-yl]phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound C1CN(C)CCN1C(=O)C1=NN(C=2C(=CC=C(F)C=2)CNC(=O)C2=C(C(=O)N3C(C(OCC3)(C)C)=N2)O)C=N1 BTXFIDOCDUUPLO-UHFFFAOYSA-N 0.000 claims description 2
• QOIZCKSYIIKGTA-UHFFFAOYSA-N n-[[4-fluoro-2-[3-(morpholine-4-carbonyl)-1,2,4-triazol-1-yl]phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N(N=1)C=NC=1C(=O)N1CCOCC1 QOIZCKSYIIKGTA-UHFFFAOYSA-N 0.000 claims description 2
• 125000003835 nucleoside group Chemical group 0.000 claims description 2
• JROPBYGZSRBHDV-UHFFFAOYSA-N oxazine-2-carboxamide Chemical compound NC(=O)N1OC=CC=C1 JROPBYGZSRBHDV-UHFFFAOYSA-N 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
• PYYHHGCMPCSNFK-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 PYYHHGCMPCSNFK-UHFFFAOYSA-N 0.000 claims 4
• 239000003937 drug carrier Substances 0.000 claims 3
• NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 abstract 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 abstract 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 1
• 101100134925 Gallus gallus COR6 gene Proteins 0.000 abstract 1
• 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 abstract 1
• 239000000543 intermediate Substances 0.000 description 359
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 358
• 125000003118 aryl group Chemical group 0.000 description 258
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 158
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 145
• 239000007787 solid Substances 0.000 description 142
• 239000000243 solution Substances 0.000 description 142
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 127
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 108
• 238000000034 method Methods 0.000 description 104
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 98
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
• 239000011541 reaction mixture Substances 0.000 description 67
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
• 235000019441 ethanol Nutrition 0.000 description 53
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 53
• 239000002904 solvent Substances 0.000 description 48
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