JP5514810B2 - ピリドキシンに由来するhivインテグラーゼ阻害剤 - Google Patents
ピリドキシンに由来するhivインテグラーゼ阻害剤 Download PDFInfo
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- JP5514810B2 JP5514810B2 JP2011511948A JP2011511948A JP5514810B2 JP 5514810 B2 JP5514810 B2 JP 5514810B2 JP 2011511948 A JP2011511948 A JP 2011511948A JP 2011511948 A JP2011511948 A JP 2011511948A JP 5514810 B2 JP5514810 B2 JP 5514810B2
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- JP
- Japan
- Prior art keywords
- pyridine
- hydroxymethyl
- hydroxy
- methyl
- fluoro
- Prior art date
- 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 - Fee Related
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- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 title description 20
- 235000008160 pyridoxine Nutrition 0.000 title description 10
- 239000011677 pyridoxine Substances 0.000 title description 10
- 229940011671 vitamin b6 Drugs 0.000 title description 10
- 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 description 296
- 238000000034 method Methods 0.000 claims description 95
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 71
- -1 cyclic acetal Chemical class 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 241000124008 Mammalia Species 0.000 claims description 56
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 229910052799 carbon Inorganic materials 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 208000030507 AIDS Diseases 0.000 claims description 36
- 239000003112 inhibitor Substances 0.000 claims description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 208000031886 HIV Infections Diseases 0.000 claims description 33
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 33
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 30
- 230000010076 replication Effects 0.000 claims description 29
- 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 27
- 208000037357 HIV infectious disease Diseases 0.000 claims description 23
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 23
- 230000002401 inhibitory effect Effects 0.000 claims description 23
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 19
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 18
- 239000002850 integrase inhibitor Substances 0.000 claims description 15
- 229940124524 integrase inhibitor Drugs 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 11
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
- 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
- 239000003085 diluting agent Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 208000011580 syndromic disease Diseases 0.000 claims description 10
- 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 9
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 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 9
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 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 8
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 8
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 8
- 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 8
- 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 7
- 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 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 6
- 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 6
- 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 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
- 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 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
- 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 6
- 125000001424 substituent group Chemical group 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 5
- 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 5
- GVMFTSKCVWVIEU-UHFFFAOYSA-N 5-n-[(3,5-difluorophenyl)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(F)=CC(F)=C1 GVMFTSKCVWVIEU-UHFFFAOYSA-N 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 230000004927 fusion Effects 0.000 claims description 5
- QDZZDVQGBKTLHV-UHFFFAOYSA-N (2,4-difluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1F QDZZDVQGBKTLHV-UHFFFAOYSA-N 0.000 claims description 4
- HMTSWYPNXFHGEP-UHFFFAOYSA-N (4-methylphenyl)methanamine Chemical compound CC1=CC=C(CN)C=C1 HMTSWYPNXFHGEP-UHFFFAOYSA-N 0.000 claims description 4
- DVOHZSVOEPGUCR-UHFFFAOYSA-N 2-(aminomethyl)-5-fluoro-n-methylbenzamide Chemical compound CNC(=O)C1=CC(F)=CC=C1CN DVOHZSVOEPGUCR-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- KLUWZKUNSNZLQN-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-2-N,3-dihydroxy-4-(methoxymethyl)-5-N-methyl-4H-pyridine-2,5-dicarboxamide Chemical compound FC1=CC=C(CC2(C(C(=C(N=C2)C(=O)NO)O)COC)C(=O)NC)C=C1 KLUWZKUNSNZLQN-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 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 3
- 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
- FPUFEHAERIWFGW-UHFFFAOYSA-N 5-(benzenesulfonylmethyl)-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(CO)=C1CS(=O)(=O)C1=CC=CC=C1 FPUFEHAERIWFGW-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
- 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 3
- 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 3
- 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 3
- PCWUCFJREVXPDR-UHFFFAOYSA-N 5-[(4-fluorophenoxy)methyl]-n,3-dihydroxy-4-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(C)=C1COC1=CC=C(F)C=C1 PCWUCFJREVXPDR-UHFFFAOYSA-N 0.000 claims description 3
- AUWUXJLJRXNOOP-UHFFFAOYSA-N 5-[(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=C1 AUWUXJLJRXNOOP-UHFFFAOYSA-N 0.000 claims description 3
- HIRRETCAGVJAOY-UHFFFAOYSA-N 5-[(4-fluorophenyl)methoxymethyl]-n,3-dihydroxy-4-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(C)=C1COCC1=CC=C(F)C=C1 HIRRETCAGVJAOY-UHFFFAOYSA-N 0.000 claims description 3
- FJLYYNOZVRLFSJ-UHFFFAOYSA-N 5-[(4-fluorophenyl)methylsulfonylmethyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CS(=O)(=O)CC1=CC=C(F)C=C1 FJLYYNOZVRLFSJ-UHFFFAOYSA-N 0.000 claims description 3
- GBFDKHXFIGIKJI-UHFFFAOYSA-N 5-[(4-fluorophenyl)methylsulfonylmethyl]-n-hydroxy-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridine-8-carboxamide Chemical compound C1=NC(C(=O)NO)=C2OC(C)(C)OCC2=C1CS(=O)(=O)CC1=CC=C(F)C=C1 GBFDKHXFIGIKJI-UHFFFAOYSA-N 0.000 claims description 3
- OGIQXAWRYHWHLV-UHFFFAOYSA-N 5-[(n-benzyl-4-fluoroanilino)methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(CO)=C1CN(C=1C=CC(F)=CC=1)CC1=CC=CC=C1 OGIQXAWRYHWHLV-UHFFFAOYSA-N 0.000 claims description 3
- IOQZJNXCWMQCQT-UHFFFAOYSA-N 5-[2-(4-fluorophenyl)ethoxymethyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1COCCC1=CC=C(F)C=C1 IOQZJNXCWMQCQT-UHFFFAOYSA-N 0.000 claims description 3
- OUCRCIGGGOIDGL-UHFFFAOYSA-N 5-[2-(4-fluorophenyl)ethyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CCC1=CC=C(F)C=C1 OUCRCIGGGOIDGL-UHFFFAOYSA-N 0.000 claims description 3
- LKWPCCKVLOJHGM-UHFFFAOYSA-N 5-[[2-(4-fluorophenyl)ethylamino]methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CNCCC1=CC=C(F)C=C1 LKWPCCKVLOJHGM-UHFFFAOYSA-N 0.000 claims description 3
- BERJEDGQFJTHSB-UHFFFAOYSA-N 5-[[[1-(4-fluorophenyl)cyclopropyl]amino]methyl]-n,3-dihydroxy-4-(hydroxymethyl)pyridine-2-carboxamide Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CNC1(C=2C=CC(F)=CC=2)CC1 BERJEDGQFJTHSB-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
- GNTCVIRTMBKALL-UHFFFAOYSA-N benzyl n-[(3-chloro-4-fluorophenyl)methyl]-n-[[5-hydroxy-6-(hydroxycarbamoyl)-4-(hydroxymethyl)pyridin-3-yl]methyl]carbamate Chemical compound OCC1=C(O)C(C(=O)NO)=NC=C1CN(C(=O)OCC=1C=CC=CC=1)CC1=CC=C(F)C(Cl)=C1 GNTCVIRTMBKALL-UHFFFAOYSA-N 0.000 claims description 3
- ZSLJRMUVUPIGSF-UHFFFAOYSA-N benzyl n-[(4-fluorophenyl)methyl]-n-[[5-hydroxy-6-(hydroxycarbamoyl)-4-methylpyridin-3-yl]methyl]carbamate Chemical compound C1=NC(C(=O)NO)=C(O)C(C)=C1CN(C(=O)OCC=1C=CC=CC=1)CC1=CC=C(F)C=C1 ZSLJRMUVUPIGSF-UHFFFAOYSA-N 0.000 claims description 3
- SMAZAYYPTCCMNN-UHFFFAOYSA-N benzyl n-[8-(hydroxycarbamoyl)-2,2-dimethyl-4h-[1,3]dioxino[4,5-c]pyridin-5-yl]carbamate Chemical compound C1=NC(C(=O)NO)=C2OC(C)(C)OCC2=C1NC(=O)OCC1=CC=CC=C1 SMAZAYYPTCCMNN-UHFFFAOYSA-N 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- LVPMIMZXDYBCDF-UHFFFAOYSA-N isocinchomeronic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)N=C1 LVPMIMZXDYBCDF-UHFFFAOYSA-N 0.000 claims description 3
- SULNVRMLCGEGOP-UHFFFAOYSA-N n,3-dihydroxy-4-(hydroxymethyl)-5-(3-phenylpropyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NO)=C(O)C(CO)=C1CCCC1=CC=CC=C1 SULNVRMLCGEGOP-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- AIDS & HIV (AREA)
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- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13087408P | 2008-06-04 | 2008-06-04 | |
| US61/130,874 | 2008-06-06 | ||
| PCT/CA2009/000787 WO2009146555A1 (en) | 2008-06-04 | 2009-06-04 | Hiv integrase inhibitors from pyridoxine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011521979A JP2011521979A (ja) | 2011-07-28 |
| JP2011521979A5 JP2011521979A5 (enExample) | 2012-01-05 |
| JP5514810B2 true JP5514810B2 (ja) | 2014-06-04 |
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| CN102209541B (zh) | 2008-09-08 | 2016-05-18 | 小利兰·斯坦福大学托管委员会 | 醛脱氢酶活性调节剂和其使用方法 |
| JP2012506856A (ja) | 2008-10-28 | 2012-03-22 | ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティ | アルデヒドデヒドロゲナーゼのモジュレーターおよびその使用方法 |
| US8283366B2 (en) * | 2010-01-22 | 2012-10-09 | Ambrilia Biopharma, Inc. | Derivatives of pyridoxine for inhibiting HIV integrase |
| US10457659B2 (en) | 2011-04-29 | 2019-10-29 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for increasing proliferation of adult salivary stem cells |
| WO2013102145A1 (en) | 2011-12-28 | 2013-07-04 | Global Blood Therapeutics, Inc. | Substituted heteroaryl aldehyde compounds and methods for their use in increasing tissue oxygenation |
| JP6242810B2 (ja) | 2011-12-28 | 2017-12-06 | グローバル・ブラッド・セラピューティクス・インコーポレイテッドGlobal Blood Therapeutics,Inc. | 置換ベンズアルデヒド化合物および組織酸素化の増加におけるそれらの使用方法 |
| KR20150135332A (ko) * | 2013-03-14 | 2015-12-02 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 | 미토콘드리아 알데히드 탈수소효소-2 조절인자들 및 이들의 사용 방법 |
| SG11201507320QA (en) | 2013-03-15 | 2015-10-29 | Global Blood Therapeutics Inc | Compounds and uses thereof for the modulation of hemoglobin |
| US8952171B2 (en) | 2013-03-15 | 2015-02-10 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| ES2993155T3 (en) | 2013-03-15 | 2024-12-23 | Global Blood Therapeutics Inc | Compounds and uses thereof for the modulation of hemoglobin |
| US9422279B2 (en) | 2013-03-15 | 2016-08-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9458139B2 (en) | 2013-03-15 | 2016-10-04 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9604999B2 (en) | 2013-03-15 | 2017-03-28 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US10100043B2 (en) | 2013-03-15 | 2018-10-16 | Global Blood Therapeutics, Inc. | Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation |
| US20140274961A1 (en) | 2013-03-15 | 2014-09-18 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US10266551B2 (en) | 2013-03-15 | 2019-04-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9802900B2 (en) | 2013-03-15 | 2017-10-31 | Global Blood Therapeutics, Inc. | Bicyclic heteroaryl compounds and uses thereof for the modulation of hemoglobin |
| SG11201507453VA (en) | 2013-03-15 | 2015-10-29 | Global Blood Therapeutics Inc | Compounds and uses thereof for the modulation of hemoglobin |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| PL3102208T5 (pl) | 2014-02-07 | 2024-10-14 | Global Blood Therapeutics, Inc. | Krystaliczny polimorf wolnej zasady 2-hydroksy-6-((2-(1-izopropylo-1h-pirazol-5-ilo)pirydyn-3-ylo)metoksy)benzaldehydu |
| MA41841A (fr) | 2015-03-30 | 2018-02-06 | Global Blood Therapeutics Inc | Composés aldéhyde pour le traitement de la fibrose pulmonaire, de l'hypoxie, et de maladies auto-immunes et des tissus conjonctifs |
| ES3039236T3 (en) | 2015-12-04 | 2025-10-20 | Global Blood Therapeutics Inc | Dosing regimens for 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde |
| TW202246215A (zh) | 2015-12-18 | 2022-12-01 | 美商亞德利克斯公司 | 作為非全身tgr5促效劑之經取代之4-苯基吡啶化合物 |
| US12084472B2 (en) | 2015-12-18 | 2024-09-10 | Ardelyx, Inc. | Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists |
| TWI752307B (zh) | 2016-05-12 | 2022-01-11 | 美商全球血液治療公司 | 新穎化合物及製造化合物之方法 |
| TW202332423A (zh) | 2016-10-12 | 2023-08-16 | 美商全球血液治療公司 | 包含2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)吡啶-3-基)甲氧基)-苯甲醛之片劑 |
| CN108203439B (zh) * | 2016-12-20 | 2020-04-14 | 四川大学 | 苯乙烯吡啶类化合物、其制备方法和用途 |
| RU2641309C1 (ru) * | 2017-07-24 | 2018-01-17 | федеральное государственное автономное образовательное учреждение высшего образования "Казанский (Приволжский) федеральный университет" (ФГАОУ ВО КФУ) | Антисептическое лекарственное средство |
| EP3687538B1 (en) * | 2017-10-30 | 2024-04-17 | Montreal Heart Institute | Methods of treating elevated plasma cholesterol |
| US11014884B2 (en) | 2018-10-01 | 2021-05-25 | Global Blood Therapeutics, Inc. | Modulators of hemoglobin |
| US12404260B2 (en) * | 2019-04-11 | 2025-09-02 | Janssen Pharmaceutica Nv | Pyridine rings containing derivatives as MALT1 inhibitors |
| WO2020237374A1 (en) * | 2019-05-28 | 2020-12-03 | Montreal Heart Institute | Picolinic acid derivatives and use thereof for treating diseases associated with elevated cholesterol |
| CN113116890B (zh) * | 2021-04-25 | 2022-06-03 | 西南大学 | 5-Pyridoxolactone用于制备抑制家蚕核型多角体病毒的药物中的应用 |
| CN117343006B (zh) * | 2023-10-08 | 2024-07-09 | 河南科技大学 | 一种arb-272572的制备方法 |
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| US6107291A (en) | 1997-12-19 | 2000-08-22 | Amgen Inc. | Azepine or larger medium ring derivatives and methods of use |
| ATE260255T1 (de) * | 1998-11-05 | 2004-03-15 | Pfizer Prod Inc | 5-oxo-pyrrolidine-2-carbonsäure- hydroxamidderivate |
| PA8586801A1 (es) | 2002-10-31 | 2005-02-04 | Pfizer | Inhibidores de hiv-integrasa, composiciones farmaceuticas y metodos para su uso |
| EP1656348B1 (en) * | 2003-08-20 | 2007-02-07 | Axys Pharmaceuticals, Inc. | Acetylene derivatives as inhibitors of histone deacetylase |
| CA2564356A1 (en) * | 2004-04-26 | 2005-11-03 | Pfizer Inc. | Pyrrolopyridine derivatives and their use as hiv-integrase inhibitors |
| US8114886B2 (en) * | 2005-04-08 | 2012-02-14 | Daiichi Sankyo Company, Limited | Pyridylmethylsulfone derivative |
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2009
- 2009-06-04 WO PCT/CA2009/000787 patent/WO2009146555A1/en not_active Ceased
- 2009-06-04 CN CN2009801304571A patent/CN102112447B/zh not_active Expired - Fee Related
- 2009-06-04 AU AU2009253812A patent/AU2009253812A1/en not_active Abandoned
- 2009-06-04 RU RU2010153656/04A patent/RU2010153656A/ru unknown
- 2009-06-04 CA CA2726742A patent/CA2726742A1/en not_active Abandoned
- 2009-06-04 JP JP2011511948A patent/JP5514810B2/ja not_active Expired - Fee Related
- 2009-06-04 EP EP09757017A patent/EP2300433A4/en not_active Withdrawn
- 2009-06-04 US US12/995,890 patent/US8742123B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
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| WO2009146555A8 (en) | 2010-12-23 |
| US8742123B2 (en) | 2014-06-03 |
| EP2300433A1 (en) | 2011-03-30 |
| RU2010153656A (ru) | 2012-07-20 |
| EP2300433A4 (en) | 2012-03-07 |
| CA2726742A1 (en) | 2009-12-10 |
| AU2009253812A1 (en) | 2009-12-10 |
| CN102112447A (zh) | 2011-06-29 |
| WO2009146555A1 (en) | 2009-12-10 |
| CN102112447B (zh) | 2013-06-26 |
| US20110178120A1 (en) | 2011-07-21 |
| JP2011521979A (ja) | 2011-07-28 |
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