CA2726742A1 - Hiv integrase inhibitors from pyridoxine - Google Patents

Info

Publication number

CA2726742A1

CA2726742A1 CA2726742A CA2726742A CA2726742A1 CA 2726742 A1 CA2726742 A1 CA 2726742A1 CA 2726742 A CA2726742 A CA 2726742A CA 2726742 A CA2726742 A CA 2726742A CA 2726742 A1 CA2726742 A1 CA 2726742A1

Authority

CA

Canada

Prior art keywords

pyridine

hydroxymethyl

methyl

hydroxy

fluoro

Prior art date

2008-06-04

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 title abstract description 32
• 229940011671 vitamin b6 Drugs 0.000 title abstract description 16
• 235000008160 pyridoxine Nutrition 0.000 title abstract description 12
• 239000011677 pyridoxine Substances 0.000 title abstract description 12
• 229940099797 HIV integrase inhibitor Drugs 0.000 title description 6
• 239000003084 hiv integrase inhibitor Substances 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 289
• 208000030507 AIDS Diseases 0.000 claims abstract description 94
• 208000031886 HIV Infections Diseases 0.000 claims abstract description 70
• 150000003839 salts Chemical class 0.000 claims abstract description 65
• 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 63
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 63
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
• 238000000034 method Methods 0.000 claims description 84
• -1 cyclic acetal Chemical class 0.000 claims description 68
• 206010001513 AIDS related complex Diseases 0.000 claims description 56
• 241000124008 Mammalia Species 0.000 claims description 54
• 239000003795 chemical substances by application Substances 0.000 claims description 53
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 41
• 125000000623 heterocyclic group Chemical group 0.000 claims description 40
• 125000000217 alkyl group Chemical group 0.000 claims description 38
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 38
• 230000002401 inhibitory effect Effects 0.000 claims description 35
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
• 238000011282 treatment Methods 0.000 claims description 30
• 230000010076 replication Effects 0.000 claims description 27
• 239000003112 inhibitor Substances 0.000 claims description 26
• JKEJZMBNSCISGJ-UHFFFAOYSA-N 3-hydroxy-4-(hydroxymethyl)pyridine-2,5-dicarboxylic acid Chemical compound OCC1=C(O)C(C(O)=O)=NC=C1C(O)=O JKEJZMBNSCISGJ-UHFFFAOYSA-N 0.000 claims description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 23
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 22
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 15
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
• 229940124524 integrase inhibitor Drugs 0.000 claims description 15
• 239000002850 integrase inhibitor Substances 0.000 claims description 15
• 125000002837 carbocyclic group Chemical group 0.000 claims description 14
• CQKZEYRKXBYWMH-UHFFFAOYSA-N methyl 5-[(4-fluoroanilino)methyl]-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxylate Chemical compound C1=2COC(C)(C)OC=2C(C(=O)OC)=NC=C1CNC1=CC=C(F)C=C1 CQKZEYRKXBYWMH-UHFFFAOYSA-N 0.000 claims description 14
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 13
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 13
• GLDIURMIXDXSMN-UHFFFAOYSA-N methyl 5-[[2-(4-fluorophenyl)ethylamino]methyl]-3-hydroxy-4-(hydroxymethyl)pyridine-2-carboxylate Chemical compound OCC1=C(O)C(C(=O)OC)=NC=C1CNCCC1=CC=C(F)C=C1 GLDIURMIXDXSMN-UHFFFAOYSA-N 0.000 claims description 12
• PMYIEUBVAWDQRS-UHFFFAOYSA-N 8-methoxycarbonyl-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-5-carboxylic acid Chemical compound C1OC(C)(C)OC2=C1C(C(O)=O)=CN=C2C(=O)OC PMYIEUBVAWDQRS-UHFFFAOYSA-N 0.000 claims description 11
• 229940079593 drug Drugs 0.000 claims description 11
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
• ZSCCDMBVYRIVNB-UHFFFAOYSA-N 5-[[(3,5-difluorophenyl)methylamino]methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CNCC1=CC(F)=CC(F)=C1 ZSCCDMBVYRIVNB-UHFFFAOYSA-N 0.000 claims description 10
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 10
• ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 10
• WBJDHFGIDYKBFY-UHFFFAOYSA-N ethyl 5-[(4-methoxyphenyl)methoxymethyl]-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxylate Chemical compound C1=2COC(C)(C)OC=2C(C(=O)OCC)=NC=C1COCC1=CC=C(OC)C=C1 WBJDHFGIDYKBFY-UHFFFAOYSA-N 0.000 claims description 10
• 229910052740 iodine Inorganic materials 0.000 claims description 10
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 10
• CTNFPGBWTDBYEL-UHFFFAOYSA-N 2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-5,8-dicarboxylic acid Chemical compound C1=NC(C(O)=O)=C2OC(C)(C)OCC2=C1C(O)=O CTNFPGBWTDBYEL-UHFFFAOYSA-N 0.000 claims description 9
• ITOYFMIYLYCBAY-UHFFFAOYSA-N 5-n-[(4-fluorophenyl)methyl]-4-(hydroxymethyl)-2-n,3-bis(phenylmethoxy)pyridine-2,5-dicarboxamide Chemical compound C=1C=CC=CC=1COC=1C(CO)=C(C(=O)NCC=2C=CC(F)=CC=2)C=NC=1C(=O)NOCC1=CC=CC=C1 ITOYFMIYLYCBAY-UHFFFAOYSA-N 0.000 claims description 9
• BWQCVSXBXPZTDM-UHFFFAOYSA-N methyl 5-[[2-(4-fluorophenyl)ethyl-(2-phenylmethoxyethyl)amino]methyl]-3-hydroxy-4-(hydroxymethyl)pyridine-2-carboxylate Chemical compound OCC1=C(O)C(C(=O)OC)=NC=C1CN(CCC=1C=CC(F)=CC=1)CCOCC1=CC=CC=C1 BWQCVSXBXPZTDM-UHFFFAOYSA-N 0.000 claims description 9
• WONPGURDNWNHHQ-UHFFFAOYSA-N 5-n-[(4-fluorophenyl)methyl]-2-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2,5-dicarboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1C(=O)NCC1=CC=C(F)C=C1 WONPGURDNWNHHQ-UHFFFAOYSA-N 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• IQPRDAUAWXZCAP-UHFFFAOYSA-N 5-n-[(4-fluorophenyl)methyl]-2-n,3-dihydroxy-4-(methoxymethyl)-5-n-methylpyridine-2,5-dicarboxamide Chemical compound COCC1=C(O)C(C(=O)NO)=NC=C1C(=O)N(C)CC1=CC=C(F)C=C1 IQPRDAUAWXZCAP-UHFFFAOYSA-N 0.000 claims description 7
• 229910052794 bromium Inorganic materials 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• RNWFZPIKVZUZNV-UHFFFAOYSA-N methyl 5-[(4-fluorophenoxy)methyl]-3-hydroxy-4-(hydroxymethyl)pyridine-2-carboxylate Chemical compound OCC1=C(O)C(C(=O)OC)=NC=C1COC1=CC=C(F)C=C1 RNWFZPIKVZUZNV-UHFFFAOYSA-N 0.000 claims description 7
• OKJNSJDZIWMLFB-UHFFFAOYSA-N n,3-dihydroxy-4-(hydroxymethyl)-5-(phenylmethoxymethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(CO)=C1COCC1=CC=CC=C1 OKJNSJDZIWMLFB-UHFFFAOYSA-N 0.000 claims description 7
• XHLCFPQRJWMQRV-UHFFFAOYSA-N n-hydroxy-5-[(4-methoxyphenyl)methoxymethyl]-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxamide Chemical compound C1=CC(OC)=CC=C1COCC1=CN=C(C(=O)NO)C2=C1COC(C)(C)O2 XHLCFPQRJWMQRV-UHFFFAOYSA-N 0.000 claims description 7
• 230000002265 prevention Effects 0.000 claims description 7
• PVSYQIXIJHOLTC-UHFFFAOYSA-N 3-oxo-n,7-bis(phenylmethoxy)-1h-furo[3,4-c]pyridine-6-carboxamide Chemical compound N=1C=C2C(=O)OCC2=C(OCC=2C=CC=CC=2)C=1C(=O)NOCC1=CC=CC=C1 PVSYQIXIJHOLTC-UHFFFAOYSA-N 0.000 claims description 6
• QUNIRSQMCBAOSZ-UHFFFAOYSA-N 5-[(4-fluorophenoxy)methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1COC1=CC=C(F)C=C1 QUNIRSQMCBAOSZ-UHFFFAOYSA-N 0.000 claims description 6
• ZVWFTPUOKIBHQI-UHFFFAOYSA-N 5-[(4-fluorophenyl)methoxymethyl]-3-hydroxy-4-(hydroxymethyl)-n-methoxypyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NOC)=NC=C1COCC1=CC=C(F)C=C1 ZVWFTPUOKIBHQI-UHFFFAOYSA-N 0.000 claims description 6
• VYGXRZBKAJVIJW-UHFFFAOYSA-N 5-[[(4-fluorophenyl)methylamino]methyl]-n,3-dihydroxy-4-(methoxymethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(COC)=C1CNCC1=CC=C(F)C=C1 VYGXRZBKAJVIJW-UHFFFAOYSA-N 0.000 claims description 6
• UKDLDONJZMSTEV-UHFFFAOYSA-N 5-[[2-(4-fluorophenyl)ethyl-(2-phenylmethoxyethyl)amino]methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(CO)=C1CN(CCC=1C=CC(F)=CC=1)CCOCC1=CC=CC=C1 UKDLDONJZMSTEV-UHFFFAOYSA-N 0.000 claims description 6
• RTKGPACNBFFCJY-UHFFFAOYSA-N 5-n-[(3,4-dichlorophenyl)methyl]-2-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2,5-dicarboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1C(=O)NCC1=CC=C(Cl)C(Cl)=C1 RTKGPACNBFFCJY-UHFFFAOYSA-N 0.000 claims description 6
• FHSCDBHUYRRVJD-UHFFFAOYSA-N 5-n-[(3-chloro-4-fluorophenyl)methyl]-2-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2,5-dicarboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1C(=O)NCC1=CC=C(F)C(Cl)=C1 FHSCDBHUYRRVJD-UHFFFAOYSA-N 0.000 claims description 6
• IEXOFQPWSZJDRB-UHFFFAOYSA-N 6-(cyclohexylmethylcarbamoyl)-5-hydroxy-4-(hydroxymethyl)pyridine-3-carboxylic acid Chemical compound C1CCCC(C1)CNC(=O)C1=NC=C(C(=C1O)CO)C(=O)O IEXOFQPWSZJDRB-UHFFFAOYSA-N 0.000 claims description 6
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 6
• FBRWTGLPJDETON-UHFFFAOYSA-N methyl 5-[(4-fluorobenzoyl)amino]-3-hydroxy-4-(hydroxymethyl)pyridine-2-carboxylate Chemical compound OCC1=C(O)C(C(=O)OC)=NC=C1NC(=O)C1=CC=C(F)C=C1 FBRWTGLPJDETON-UHFFFAOYSA-N 0.000 claims description 6
• NTLZFMFCOJRHET-UHFFFAOYSA-N n,3-dihydroxy-4-(hydroxymethyl)-5-[(4-methoxyphenyl)methoxymethyl]pyridine-2-carboxamide Chemical compound C1=CC(OC)=CC=C1COCC1=CN=C(C(=O)NO)C(O)=C1CO NTLZFMFCOJRHET-UHFFFAOYSA-N 0.000 claims description 6
• FFZSWIQSHFCKNH-UHFFFAOYSA-N 2-n,3-dihydroxy-4-(hydroxymethyl)-5-n-[(4-methoxyphenyl)methyl]pyridine-2,5-dicarboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CN=C(C(=O)NO)C(O)=C1CO FFZSWIQSHFCKNH-UHFFFAOYSA-N 0.000 claims description 5
• VJJKFCKXTKKZSQ-UHFFFAOYSA-N 3,3-dimethyl-n,9-bis(phenylmethoxy)-1,5-dihydro-[1,3]dioxepino[5,6-c]pyridine-8-carboxamide Chemical compound C=1C=CC=CC=1COC1=C2COC(C)(C)OCC2=CN=C1C(=O)NOCC1=CC=CC=C1 VJJKFCKXTKKZSQ-UHFFFAOYSA-N 0.000 claims description 5
• OTDKXUSSYKLJGA-UHFFFAOYSA-N 4-(hydroxymethyl)-5-n-[(4-methoxyphenyl)methyl]-2-n,3-bis(phenylmethoxy)pyridine-2,5-dicarboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C(C(=C1OCC=2C=CC=CC=2)CO)=CN=C1C(=O)NOCC1=CC=CC=C1 OTDKXUSSYKLJGA-UHFFFAOYSA-N 0.000 claims description 5
• IFMUKTJCKCYWED-UHFFFAOYSA-N 5-[(1,3-benzodioxol-5-ylmethylamino)methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(CO)=C1CNCC1=CC=C(OCO2)C2=C1 IFMUKTJCKCYWED-UHFFFAOYSA-N 0.000 claims description 5
• OPEPLKQILVRERB-UHFFFAOYSA-N 5-n-(1,3-benzodioxol-5-ylmethyl)-4-(hydroxymethyl)-2-n,3-bis(phenylmethoxy)pyridine-2,5-dicarboxamide Chemical compound C=1C=CC=CC=1CONC(=O)C1=NC=C(C(=O)NCC=2C=C3OCOC3=CC=2)C(CO)=C1OCC1=CC=CC=C1 OPEPLKQILVRERB-UHFFFAOYSA-N 0.000 claims description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• VYPJXHXXYSIJJQ-UHFFFAOYSA-N methyl 5-[(n-benzyl-4-fluoroanilino)methyl]-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxylate Chemical compound C1=2COC(C)(C)OC=2C(C(=O)OC)=NC=C1CN(C=1C=CC(F)=CC=1)CC1=CC=CC=C1 VYPJXHXXYSIJJQ-UHFFFAOYSA-N 0.000 claims description 5
• 125000001424 substituent group Chemical group 0.000 claims description 5
• IBTVYFOLKUZFLD-UHFFFAOYSA-N 3-hydroxy-4-methylpyridine-2,5-dicarboxylic acid Chemical compound CC1=C(O)C(C(O)=O)=NC=C1C(O)=O IBTVYFOLKUZFLD-UHFFFAOYSA-N 0.000 claims description 4
• HGTZGAMRDSGHMI-UHFFFAOYSA-N 5-[(4-fluoroanilino)methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CNC1=CC=C(F)C=C1 HGTZGAMRDSGHMI-UHFFFAOYSA-N 0.000 claims description 4
• GCKFPURLKGQKOY-UHFFFAOYSA-N 5-[(4-fluorobenzoyl)amino]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1NC(=O)C1=CC=C(F)C=C1 GCKFPURLKGQKOY-UHFFFAOYSA-N 0.000 claims description 4
• JQIKOEPLEWEKEB-UHFFFAOYSA-N 5-[(4-fluorophenyl)carbamoylamino]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1NC(=O)NC1=CC=C(F)C=C1 JQIKOEPLEWEKEB-UHFFFAOYSA-N 0.000 claims description 4
• XFQCLAQMOBBEHN-UHFFFAOYSA-N 5-[[(4-fluorophenyl)methylamino]methyl]-4-(hydroxymethyl)-n,3-bis(phenylmethoxy)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NOCC=2C=CC=CC=2)=C(OCC=2C=CC=CC=2)C(CO)=C1CNCC1=CC=C(F)C=C1 XFQCLAQMOBBEHN-UHFFFAOYSA-N 0.000 claims description 4
• QMCBMFZENXCGDG-UHFFFAOYSA-N 5-n-(1,3-benzodioxol-5-ylmethyl)-2-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2,5-dicarboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1C(=O)NCC1=CC=C(OCO2)C2=C1 QMCBMFZENXCGDG-UHFFFAOYSA-N 0.000 claims description 4
• WNKSQLOELQBBNL-UHFFFAOYSA-N 5-n-[(3,4-dichlorophenyl)methyl]-4-(hydroxymethyl)-2-n,3-bis(phenylmethoxy)pyridine-2,5-dicarboxamide Chemical compound C=1C=CC=CC=1COC=1C(CO)=C(C(=O)NCC=2C=C(Cl)C(Cl)=CC=2)C=NC=1C(=O)NOCC1=CC=CC=C1 WNKSQLOELQBBNL-UHFFFAOYSA-N 0.000 claims description 4
• SGVBVQOXYAPALR-UHFFFAOYSA-N ethyl 3-hydroxy-4-(hydroxymethyl)-5-[(4-methoxyphenyl)methoxymethyl]pyridine-2-carboxylate Chemical compound OCC1=C(O)C(C(=O)OCC)=NC=C1COCC1=CC=C(OC)C=C1 SGVBVQOXYAPALR-UHFFFAOYSA-N 0.000 claims description 4
• 229940125777 fusion inhibitor Drugs 0.000 claims description 4
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
• DOAQXGHYQMKBOY-UHFFFAOYSA-N methyl 5-[(3-chloro-4-fluorophenoxy)methyl]-3-hydroxy-4-methylpyridine-2-carboxylate Chemical compound CC1=C(O)C(C(=O)OC)=NC=C1COC1=CC=C(F)C(Cl)=C1 DOAQXGHYQMKBOY-UHFFFAOYSA-N 0.000 claims description 4
• QTDDXBMFVGYZCO-UHFFFAOYSA-N methyl 5-[(4-fluorobenzoyl)amino]-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxylate Chemical compound C1=2COC(C)(C)OC=2C(C(=O)OC)=NC=C1NC(=O)C1=CC=C(F)C=C1 QTDDXBMFVGYZCO-UHFFFAOYSA-N 0.000 claims description 4
• AFQXWIGENBFDDH-UHFFFAOYSA-N methyl 5-[(4-fluorophenyl)carbamoylamino]-3-hydroxy-4-(hydroxymethyl)pyridine-2-carboxylate Chemical compound OCC1=C(O)C(C(=O)OC)=NC=C1NC(=O)NC1=CC=C(F)C=C1 AFQXWIGENBFDDH-UHFFFAOYSA-N 0.000 claims description 4
• CVWLRFVNKILCMQ-UHFFFAOYSA-N methyl 5-[(4-fluorophenyl)methyl-methylcarbamoyl]-4-(methoxymethyl)-3-phenylmethoxypyridine-2-carboxylate Chemical compound COCC1=C(C(=O)N(C)CC=2C=CC(F)=CC=2)C=NC(C(=O)OC)=C1OCC1=CC=CC=C1 CVWLRFVNKILCMQ-UHFFFAOYSA-N 0.000 claims description 4
• RWOKJWJCJHASCE-UHFFFAOYSA-N methyl 5-amino-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxylate Chemical compound C1OC(C)(C)OC2=C1C(N)=CN=C2C(=O)OC RWOKJWJCJHASCE-UHFFFAOYSA-N 0.000 claims description 4
• UVCLMUJRGGBZMC-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-6-(hydroxymethyl)-4-(methoxymethyl)-n-methyl-5-phenylmethoxypyridine-3-carboxamide Chemical compound OCC1=NC=C(C(=O)N(C)CC=2C=CC(F)=CC=2)C(COC)=C1OCC1=CC=CC=C1 UVCLMUJRGGBZMC-UHFFFAOYSA-N 0.000 claims description 4
• LEIAZUKOBVWTEH-UHFFFAOYSA-N pyridine-2,5-dicarboxamide Chemical compound NC(=O)C1=CC=C(C(N)=O)N=C1 LEIAZUKOBVWTEH-UHFFFAOYSA-N 0.000 claims description 4
• HAOFXADKEVRTHW-UHFFFAOYSA-N 4-(hydroxymethyl)-3-methoxypyridine-2,5-dicarboxylic acid Chemical compound COC1=C(CO)C(C(O)=O)=CN=C1C(O)=O HAOFXADKEVRTHW-UHFFFAOYSA-N 0.000 claims description 3
• GIDJZLATDOQHJV-UHFFFAOYSA-N 5-[(2,4-difluorophenyl)methoxymethyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1COCC1=CC=C(F)C=C1F GIDJZLATDOQHJV-UHFFFAOYSA-N 0.000 claims description 3
• LHSPHCQJJRQLBG-UHFFFAOYSA-N 5-[(2,4-difluorophenyl)methoxymethyl]-n,3-dihydroxy-4-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(C)=C1COCC1=CC=C(F)C=C1F LHSPHCQJJRQLBG-UHFFFAOYSA-N 0.000 claims description 3
• YQQZZELJPWZZGF-UHFFFAOYSA-N 5-[(3,4-difluorophenyl)methoxymethyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1COCC1=CC=C(F)C(F)=C1 YQQZZELJPWZZGF-UHFFFAOYSA-N 0.000 claims description 3
• NMWOCFQCEBZNNZ-UHFFFAOYSA-N 5-[(3,4-difluorophenyl)methoxymethyl]-n,3-dihydroxy-4-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(C)=C1COCC1=CC=C(F)C(F)=C1 NMWOCFQCEBZNNZ-UHFFFAOYSA-N 0.000 claims description 3
• FEJVUNZIBZSMGY-UHFFFAOYSA-N 5-[(3-chloro-4-fluorophenoxy)methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1COC1=CC=C(F)C(Cl)=C1 FEJVUNZIBZSMGY-UHFFFAOYSA-N 0.000 claims description 3
• GDNUYSNPENMCFT-UHFFFAOYSA-N 5-[(3-chloro-4-fluorophenoxy)methyl]-n,3-dihydroxy-4-methylpyridine-2-carboxamide Chemical compound CC1=C(O)C(C(=O)NO)=NC=C1COC1=CC=C(F)C(Cl)=C1 GDNUYSNPENMCFT-UHFFFAOYSA-N 0.000 claims description 3
• WPQWKTUJUVNCSU-UHFFFAOYSA-N 5-[(3-chloro-4-fluorophenyl)methoxymethyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1COCC1=CC=C(F)C(Cl)=C1 WPQWKTUJUVNCSU-UHFFFAOYSA-N 0.000 claims description 3
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