RU2745269C2 - Новые соединения и производные сульфонимидоилпуринона для лечения и профилактики вирусной инфекции - Google Patents

Info

Publication number

RU2745269C2

RU2745269C2 RU2017142577A RU2017142577A RU2745269C2 RU 2745269 C2 RU2745269 C2 RU 2745269C2 RU 2017142577 A RU2017142577 A RU 2017142577A RU 2017142577 A RU2017142577 A RU 2017142577A RU 2745269 C2 RU2745269 C2 RU 2745269C2

Authority

RU

Russia

Prior art keywords

purin

methyl

amino

compound

propylsulfonimidoyl

Prior art date

2015-05-08

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 812
• 238000011282 treatment Methods 0.000 title claims abstract description 28
• 238000011321 prophylaxis Methods 0.000 title abstract description 3
• 208000036142 Viral infection Diseases 0.000 title description 4
• 230000009385 viral infection Effects 0.000 title description 4
• -1 cyano, carboxy, carbamoyl Chemical group 0.000 claims abstract description 234
• 238000000034 method Methods 0.000 claims abstract description 20
• 230000000694 effects Effects 0.000 claims abstract description 13
• 125000005843 halogen group Chemical group 0.000 claims abstract description 13
• 208000002672 hepatitis B Diseases 0.000 claims abstract description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 9
• 238000002360 preparation method Methods 0.000 claims abstract description 8
• 108010060825 Toll-Like Receptor 7 Proteins 0.000 claims abstract description 5
• 102000008236 Toll-Like Receptor 7 Human genes 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 170
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
• KFDGFNQIYSAVAY-UHFFFAOYSA-N 6-amino-9-benzyl-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=CC=C1)=O KFDGFNQIYSAVAY-UHFFFAOYSA-N 0.000 claims description 23
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 18
• 125000004803 chlorobenzyl group Chemical group 0.000 claims description 18
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 16
• 125000006178 methyl benzyl group Chemical group 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 229940044616 toll-like receptor 7 agonist Drugs 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 12
• GJZZDPHTUXZRDP-UHFFFAOYSA-N 6-amino-9-benzyl-2-(methylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)C)CC1=CC=CC=C1)=O GJZZDPHTUXZRDP-UHFFFAOYSA-N 0.000 claims description 11
• 125000004175 fluorobenzyl group Chemical group 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 11
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• BRSQFEYCEJEYCJ-UHFFFAOYSA-N 6-amino-2-(ethylsulfonimidoyl)-9-[(4-methylphenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CC)CC1=CC=C(C=C1)C)=O BRSQFEYCEJEYCJ-UHFFFAOYSA-N 0.000 claims description 9
• UTHROXJUYVNHHL-DEOSSOPVSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-(ethylsulfonimidoyl)-7H-purin-8-one Chemical compound CC[S@](=N)(=O)C1=NC(N)=C2NC(=O)N(CC3=CC=C(Cl)C=C3)C2=N1 UTHROXJUYVNHHL-DEOSSOPVSA-N 0.000 claims description 9
• 125000006287 difluorobenzyl group Chemical group 0.000 claims description 9
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
• MSSXPOADQWRGGF-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-2,2-dimethylpropanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(C)(C)C)=O)S(=O)(=N)CCC MSSXPOADQWRGGF-UHFFFAOYSA-N 0.000 claims description 8
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000002946 cyanobenzyl group Chemical group 0.000 claims description 8
• GJWKQSSMTVBHRA-UHFFFAOYSA-N methyl 4-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]benzoate Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C(=O)OC)C=C1)=O GJWKQSSMTVBHRA-UHFFFAOYSA-N 0.000 claims description 8
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 8
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
• GVKDJOFFPHLPOW-UHFFFAOYSA-N 6-amino-9-[(4-bromophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)Br)=O GVKDJOFFPHLPOW-UHFFFAOYSA-N 0.000 claims description 7
• WLAWDJREXFPHPH-VWLOTQADSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound C(C1=CC=C(Cl)C=C1)N1C2=C(C(=NC([S@](=O)(=N)CCC)=N2)N)NC1=O WLAWDJREXFPHPH-VWLOTQADSA-N 0.000 claims description 7
• OMOVBYAITFNLQV-UHFFFAOYSA-N 6-amino-9-[(6-chloropyridin-3-yl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC(=CC=1)Cl)=O OMOVBYAITFNLQV-UHFFFAOYSA-N 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 7
• LUXRVHGJZAYSCL-UHFFFAOYSA-N 4-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]benzoic acid Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C(=O)O)C=C1)=O LUXRVHGJZAYSCL-UHFFFAOYSA-N 0.000 claims description 6
• GMEXKXFTVMLTOL-UHFFFAOYSA-N 6-amino-2-(methylsulfonimidoyl)-9-(pyridin-4-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)C)CC1=CC=NC=C1)=O GMEXKXFTVMLTOL-UHFFFAOYSA-N 0.000 claims description 6
• APBICSQRGKTYKB-UHFFFAOYSA-N 6-amino-2-(propylsulfonimidoyl)-9-[[4-(trifluoromethyl)phenyl]methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)C(F)(F)F)=O APBICSQRGKTYKB-UHFFFAOYSA-N 0.000 claims description 6
• OZGLMHHFCJLROC-UHFFFAOYSA-N 6-amino-9-[(4-fluorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)F)=O OZGLMHHFCJLROC-UHFFFAOYSA-N 0.000 claims description 6
• YXFJJQUVGAPZKB-UHFFFAOYSA-N 6-amino-9-[(4-methylphenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)C)=O YXFJJQUVGAPZKB-UHFFFAOYSA-N 0.000 claims description 6
• BQGJLGCRAYYVSZ-UHFFFAOYSA-N 6-amino-9-[(6-methylpyridin-3-yl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC(=CC=1)C)=O BQGJLGCRAYYVSZ-UHFFFAOYSA-N 0.000 claims description 6
• XVAXOGSGLHCPMT-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2-methoxyethylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCOC)CC1=CC=CC=C1)=O XVAXOGSGLHCPMT-UHFFFAOYSA-N 0.000 claims description 6
• 102000006992 Interferon-alpha Human genes 0.000 claims description 6
• 108010047761 Interferon-alpha Proteins 0.000 claims description 6
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• LHRAYRPXCNIOOH-UHFFFAOYSA-N 1-[6-amino-9-benzyl-8-oxo-2-(propylsulfonimidoyl)purin-7-yl]ethyl acetate Chemical compound C(C)(=O)OC(C)N1C(N(C2=NC(=NC(=C12)N)S(=O)(=N)CCC)CC1=CC=CC=C1)=O LHRAYRPXCNIOOH-UHFFFAOYSA-N 0.000 claims description 5
• MRIWBJKYLHNMRZ-UHFFFAOYSA-N 3-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]benzamide Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=C(C(=O)N)C=CC=1)=O MRIWBJKYLHNMRZ-UHFFFAOYSA-N 0.000 claims description 5
• HMLYDPXOOQGKTP-UHFFFAOYSA-N 3-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]benzonitrile Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=C(C#N)C=CC=1)=O HMLYDPXOOQGKTP-UHFFFAOYSA-N 0.000 claims description 5
• OOTVBBLVGZVFGS-UHFFFAOYSA-N 4-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]benzonitrile Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C#N)C=C1)=O OOTVBBLVGZVFGS-UHFFFAOYSA-N 0.000 claims description 5
• MJRDPVUQHOCHAV-UHFFFAOYSA-N 6-amino-2-(3-chloropropylsulfonimidoyl)-9-[(4-methoxyphenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCCCl)CC1=CC=C(C=C1)OC)=O MJRDPVUQHOCHAV-UHFFFAOYSA-N 0.000 claims description 5
• WJVVXYFIAALPNG-UHFFFAOYSA-N 6-amino-2-(methylsulfonimidoyl)-9-(pyridin-2-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)C)CC1=NC=CC=C1)=O WJVVXYFIAALPNG-UHFFFAOYSA-N 0.000 claims description 5
• MSSWBOIWSSIBHI-UHFFFAOYSA-N 6-amino-2-(methylsulfonimidoyl)-9-(pyridin-3-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)C)CC=1C=NC=CC=1)=O MSSWBOIWSSIBHI-UHFFFAOYSA-N 0.000 claims description 5
• KZXZEGLHTOJPOP-UHFFFAOYSA-N 6-amino-9-[(2-chlorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=C(C=CC=C1)Cl)=O KZXZEGLHTOJPOP-UHFFFAOYSA-N 0.000 claims description 5
• MBQBYGUMANOLRF-UHFFFAOYSA-N 6-amino-9-[(3,4-dichlorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=C(C=C1)Cl)Cl)=O MBQBYGUMANOLRF-UHFFFAOYSA-N 0.000 claims description 5
• YNGIHTJQHZVVFN-UHFFFAOYSA-N 6-amino-9-[(3-chloro-4-methylphenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=C(C=C1)C)Cl)=O YNGIHTJQHZVVFN-UHFFFAOYSA-N 0.000 claims description 5
• FQRMTGZFXMHCSC-UHFFFAOYSA-N 6-amino-9-[(3-chlorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=CC=C1)Cl)=O FQRMTGZFXMHCSC-UHFFFAOYSA-N 0.000 claims description 5
• WVHPAEYDRFCAKO-UHFFFAOYSA-N 6-amino-9-[(4-methoxyphenyl)methyl]-2-(methylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)C)CC1=CC=C(C=C1)OC)=O WVHPAEYDRFCAKO-UHFFFAOYSA-N 0.000 claims description 5
• MXYRBJOFSGLHBL-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2,2,2-trifluoroethylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CC(F)(F)F)CC1=CC=CC=C1)=O MXYRBJOFSGLHBL-UHFFFAOYSA-N 0.000 claims description 5
• HXSLBQAQKGKHPJ-UHFFFAOYSA-N 6-amino-9-benzyl-2-(cyclohexylmethylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CC1CCCCC1)CC1=CC=CC=C1)=O HXSLBQAQKGKHPJ-UHFFFAOYSA-N 0.000 claims description 5
• XFDVJIPIVPRMJX-UHFFFAOYSA-N 6-amino-9-benzyl-2-(ethylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CC)CC1=CC=CC=C1)=O XFDVJIPIVPRMJX-UHFFFAOYSA-N 0.000 claims description 5
• AWEYWRZATBLERV-UHFFFAOYSA-N 9-[(4-chlorophenyl)methyl]-6-(ethylamino)-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC)S(=O)(=N)CCC AWEYWRZATBLERV-UHFFFAOYSA-N 0.000 claims description 5
• XYCHAVDXFFLWQJ-UHFFFAOYSA-N 9-benzyl-6-(cyclopropylamino)-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC1CC1)S(=O)(=N)CCC XYCHAVDXFFLWQJ-UHFFFAOYSA-N 0.000 claims description 5
• QNJDNDBLKCNKGH-UHFFFAOYSA-N 9-benzyl-6-(ethylamino)-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NCC)S(=O)(=N)CCC QNJDNDBLKCNKGH-UHFFFAOYSA-N 0.000 claims description 5
• YSCLHWJXXFOWHI-UHFFFAOYSA-N 9-benzyl-6-(propan-2-ylamino)-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(C)C)S(=O)(=N)CCC YSCLHWJXXFOWHI-UHFFFAOYSA-N 0.000 claims description 5
• QXOBPBVKQCQQAI-UHFFFAOYSA-N 9-benzyl-6-(propylamino)-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NCCC)S(=O)(=N)CCC QXOBPBVKQCQQAI-UHFFFAOYSA-N 0.000 claims description 5
• OCLKTSCMYMCMJQ-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-2-ethylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CC)CC)=O)S(=O)(=N)CCC OCLKTSCMYMCMJQ-UHFFFAOYSA-N 0.000 claims description 5
• ZKJRMYURRTVASS-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-2-methylpentanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CCC)C)=O)S(=O)(=N)CCC ZKJRMYURRTVASS-UHFFFAOYSA-N 0.000 claims description 5
• GBEBBMFAEQUXKE-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-2-propylpentanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CCC)CCC)=O)S(=O)(=N)CCC GBEBBMFAEQUXKE-UHFFFAOYSA-N 0.000 claims description 5
• OSSHGUPKKOUUGT-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]acetamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C)=O)S(=O)(=N)CCC OSSHGUPKKOUUGT-UHFFFAOYSA-N 0.000 claims description 5
• PQNPXVINORKDLR-UHFFFAOYSA-N N-[9-benzyl-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-2-propylpentanamide Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(C(CCC)CCC)=O)S(=O)(=N)CCC PQNPXVINORKDLR-UHFFFAOYSA-N 0.000 claims description 5
• BCXKQQHBMBXTLH-UHFFFAOYSA-N N-[9-benzyl-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]pentanamide Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(CCCC)=O)S(=O)(=N)CCC BCXKQQHBMBXTLH-UHFFFAOYSA-N 0.000 claims description 5
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
• 125000006278 bromobenzyl group Chemical group 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000006286 dichlorobenzyl group Chemical group 0.000 claims description 5
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
• XEIFQSWWZYZIMI-UHFFFAOYSA-N 4-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]-N-(2-methoxyethyl)benzamide Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C(=O)NCCOC)C=C1)=O XEIFQSWWZYZIMI-UHFFFAOYSA-N 0.000 claims description 4
• UOCHSLAWCBRFAO-UHFFFAOYSA-N 6-amino-2-(ethylsulfonimidoyl)-9-[(4-fluorophenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CC)CC1=CC=C(C=C1)F)=O UOCHSLAWCBRFAO-UHFFFAOYSA-N 0.000 claims description 4
• YEPVOOTXMQFLJF-UHFFFAOYSA-N 6-amino-9-(2-methylpropyl)-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC(C)C)=O YEPVOOTXMQFLJF-UHFFFAOYSA-N 0.000 claims description 4
• ZMNFFJHJNOPQLT-UHFFFAOYSA-N 6-amino-9-[(2-methylpyrimidin-5-yl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC(=NC=1)C)=O ZMNFFJHJNOPQLT-UHFFFAOYSA-N 0.000 claims description 4
• JXBUDGCMKVLNEW-UHFFFAOYSA-N 6-amino-9-[(3,4-difluorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=C(C=C1)F)F)=O JXBUDGCMKVLNEW-UHFFFAOYSA-N 0.000 claims description 4
• IYZZWMCSHFSKJC-UHFFFAOYSA-N 6-amino-9-[(4-chloro-3-methylphenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=C(C=C1)Cl)C)=O IYZZWMCSHFSKJC-UHFFFAOYSA-N 0.000 claims description 4
• YOKSITUASXLPJK-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-(methylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)C)CC1=CC=C(C=C1)Cl)=O YOKSITUASXLPJK-UHFFFAOYSA-N 0.000 claims description 4
• CGOHLAKYSFQURM-UHFFFAOYSA-N 6-amino-9-[(4-methoxyphenyl)methyl]-2-(3-pyrrolidin-1-ylpropylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCCN1CCCC1)CC1=CC=C(C=C1)OC)=O CGOHLAKYSFQURM-UHFFFAOYSA-N 0.000 claims description 4
• WVXMROKBYNVSDX-UHFFFAOYSA-N 6-amino-9-[(4-methylsulfonylphenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)S(=O)(=O)C)=O WVXMROKBYNVSDX-UHFFFAOYSA-N 0.000 claims description 4
• MSMGQARGIFSWGQ-UHFFFAOYSA-N 6-amino-9-[[4-(piperidine-1-carbonyl)phenyl]methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)C(=O)N1CCCCC1)=O MSMGQARGIFSWGQ-UHFFFAOYSA-N 0.000 claims description 4
• CDMVZHHOTBQWJC-UHFFFAOYSA-N 6-amino-9-benzyl-2-(3-methoxypropylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCCOC)CC1=CC=CC=C1)=O CDMVZHHOTBQWJC-UHFFFAOYSA-N 0.000 claims description 4
• CARHRXYETPUULC-UHFFFAOYSA-N 6-methyl-9-[(2-methylpyrimidin-5-yl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound CC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC(=NC=1)C)=O CARHRXYETPUULC-UHFFFAOYSA-N 0.000 claims description 4
• YJXYKDUWIFDOMI-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-3-methylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(CC(C)C)=O)S(=O)(=N)CCC YJXYKDUWIFDOMI-UHFFFAOYSA-N 0.000 claims description 4
• VWICUQQUYQWFGE-UHFFFAOYSA-N [6-amino-9-benzyl-2-(methylsulfonimidoyl)-8-oxopurin-7-yl]methyl acetate Chemical compound C(C)(=O)OCN1C(N(C2=NC(=NC(=C12)N)S(=O)(=N)C)CC1=CC=CC=C1)=O VWICUQQUYQWFGE-UHFFFAOYSA-N 0.000 claims description 4
• JITYDGRQWOQCGT-UHFFFAOYSA-N [6-amino-9-benzyl-8-oxo-2-(propylsulfonimidoyl)purin-7-yl]methyl 2,2-dimethylpropanoate Chemical compound CC(C(=O)OCN1C(N(C2=NC(=NC(=C12)N)S(=O)(=N)CCC)CC1=CC=CC=C1)=O)(C)C JITYDGRQWOQCGT-UHFFFAOYSA-N 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• YUCCBADIVGNCIC-UHFFFAOYSA-N 4-[[6-amino-8-oxo-2-(propylsulfonimidoyl)-7H-purin-9-yl]methyl]benzamide Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C(=O)N)C=C1)=O YUCCBADIVGNCIC-UHFFFAOYSA-N 0.000 claims description 3
• RXVPTJHAOBJTOO-UHFFFAOYSA-N 6-amino-9-[(4-chloro-3-fluorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=C(C=C1)Cl)F)=O RXVPTJHAOBJTOO-UHFFFAOYSA-N 0.000 claims description 3
• OEOSDGACEVTXNN-UHFFFAOYSA-N [6-amino-9-benzyl-8-oxo-2-(propylsulfonimidoyl)purin-7-yl]methyl acetate Chemical compound C(C)(=O)OCN1C(N(C2=NC(=NC(=C12)N)S(=O)(=N)CCC)CC1=CC=CC=C1)=O OEOSDGACEVTXNN-UHFFFAOYSA-N 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000006493 trifluoromethyl benzyl group Chemical group 0.000 claims description 3
• WJLOTTAIZSVTCY-UHFFFAOYSA-N 6-methyl-2-(propylsulfonimidoyl)-9-(pyrimidin-5-ylmethyl)-7H-purin-8-one Chemical compound CC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC=NC=1)=O WJLOTTAIZSVTCY-UHFFFAOYSA-N 0.000 claims description 2
• IGRNQJZRQYXIFY-UHFFFAOYSA-N NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=C(C=C(C=C1)Cl)Cl)=O Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=C(C=C(C=C1)Cl)Cl)=O IGRNQJZRQYXIFY-UHFFFAOYSA-N 0.000 claims description 2
• 239000013543 active substance Substances 0.000 claims description 2
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 229940044601 receptor agonist Drugs 0.000 claims 2
• 239000000018 receptor agonist Substances 0.000 claims 2
• XEMSWCLTGRTCJX-UHFFFAOYSA-N 2-(propylsulfonimidoyl)-7,9-dihydropurin-8-one Chemical compound C(CC)S(=O)(=N)C1=NC=C2NC(NC2=N1)=O XEMSWCLTGRTCJX-UHFFFAOYSA-N 0.000 claims 1
• 229940126601 medicinal product Drugs 0.000 claims 1
• 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
• 241000700721 Hepatitis B virus Species 0.000 abstract description 18
• 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 abstract description 17
• 102100039390 Toll-like receptor 7 Human genes 0.000 abstract description 15
• 239000000556 agonist Substances 0.000 abstract description 9
• 239000000126 substance Substances 0.000 abstract description 9
• 208000015181 infectious disease Diseases 0.000 abstract description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 3
• 230000001939 inductive effect Effects 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 7
• 230000011488 interferon-alpha production Effects 0.000 abstract 1
• 238000001819 mass spectrum Methods 0.000 description 317
• 239000007787 solid Substances 0.000 description 297
• 238000005481 NMR spectroscopy Methods 0.000 description 101
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
• 239000000243 solution Substances 0.000 description 55
• 150000003839 salts Chemical class 0.000 description 53
• 239000000203 mixture Substances 0.000 description 49
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 239000011541 reaction mixture Substances 0.000 description 42
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
• GTYRLXXHXBTNQV-UHFFFAOYSA-N 6-amino-9-[(2-chlorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=C(C=CC=C1)Cl)=O GTYRLXXHXBTNQV-UHFFFAOYSA-N 0.000 description 33
• 238000012360 testing method Methods 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
• 210000004027 cell Anatomy 0.000 description 29
• UTKOWHRNPQDYNX-UHFFFAOYSA-N 6-amino-9-[(2-chlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=C(C=CC=C1)Cl)=O UTKOWHRNPQDYNX-UHFFFAOYSA-N 0.000 description 28
• XTZYFTXASKYXGM-UHFFFAOYSA-N 6-chloro-N-[(2-chlorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=C(C=CC=C1)Cl)[N+](=O)[O-] XTZYFTXASKYXGM-UHFFFAOYSA-N 0.000 description 28
• KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 27
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 27
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 26
• 238000010828 elution Methods 0.000 description 25
• DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 25
• RYWCQJDEHXJHRI-XJMXIVSISA-N 2-[3-[5-[6-[3-[3-(carboxymethyl)phenyl]-4-[(2r,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]hexyl]-2-[(2r,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]phenyl]acetic acid Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC(C(=C1)C=2C=C(CC(O)=O)C=CC=2)=CC=C1CCCCCCC(C=C1C=2C=C(CC(O)=O)C=CC=2)=CC=C1O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 RYWCQJDEHXJHRI-XJMXIVSISA-N 0.000 description 24
• GNMOFFHKLDZUBH-UHFFFAOYSA-N 6-chloro-9-[(2-chlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=C(C=CC=C1)Cl)=O GNMOFFHKLDZUBH-UHFFFAOYSA-N 0.000 description 24
• WPYNEOHJXNKMSR-UHFFFAOYSA-N 9-[(2-chlorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C(C=CC=C1)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC WPYNEOHJXNKMSR-UHFFFAOYSA-N 0.000 description 24
• 238000000926 separation method Methods 0.000 description 24
• 239000000651 prodrug Substances 0.000 description 23
• 229940002612 prodrug Drugs 0.000 description 23
• 235000019439 ethyl acetate Nutrition 0.000 description 22
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• SRMFHHGQKBMKFJ-UHFFFAOYSA-N 6-chloro-4-N-[(2-chlorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=C(C=CC=C1)Cl)N SRMFHHGQKBMKFJ-UHFFFAOYSA-N 0.000 description 18
• 239000003814 drug Substances 0.000 description 18
• PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 17
• HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 17
• UJMGBGIFVTZJHH-UHFFFAOYSA-N 6-amino-9-benzyl-2-methylsulfanyl-7h-purin-8-one Chemical compound C12=NC(SC)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 UJMGBGIFVTZJHH-UHFFFAOYSA-N 0.000 description 17
• 239000003153 chemical reaction reagent Substances 0.000 description 17
• 239000002253 acid Substances 0.000 description 16
• 230000006698 induction Effects 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• 229940079593 drug Drugs 0.000 description 15
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 14
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 14
• TYOKNHSCNCBJSB-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]-2-propylpentanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CCC)CCC)=O)S(=O)CCC TYOKNHSCNCBJSB-UHFFFAOYSA-N 0.000 description 13
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
• 229960003180 glutathione Drugs 0.000 description 13
• 238000007866 imination reaction Methods 0.000 description 13
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• HONIKIYFGCHQSJ-UHFFFAOYSA-N 6-amino-9-benzyl-2-methylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C)CC1=CC=CC=C1)=O HONIKIYFGCHQSJ-UHFFFAOYSA-N 0.000 description 12
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 238000004296 chiral HPLC Methods 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
• 238000002560 therapeutic procedure Methods 0.000 description 11
• YVHWMATXRMXZJI-UHFFFAOYSA-N 6-amino-9-benzyl-2-sulfanylidene-1,7-dihydropurin-8-one Chemical compound OC1=NC=2C(N)=NC(S)=NC=2N1CC1=CC=CC=C1 YVHWMATXRMXZJI-UHFFFAOYSA-N 0.000 description 10
• SZOLEYUWCQFUIF-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]-2-propylpentanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CCC)CCC)=O)SCCC SZOLEYUWCQFUIF-UHFFFAOYSA-N 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 150000002500 ions Chemical class 0.000 description 10
• 239000000523 sample Substances 0.000 description 10
• HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 9
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
• WNIFXTZUXYGFQT-UHFFFAOYSA-N 6-chloro-9-[(6-methylpyridin-3-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=CC=1)C)=O WNIFXTZUXYGFQT-UHFFFAOYSA-N 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
• WHPIOZVTTVHXBK-UHFFFAOYSA-N 9-[(3-chloro-4-methylphenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC=1C=C(C=CC=1C)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC WHPIOZVTTVHXBK-UHFFFAOYSA-N 0.000 description 8
• 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 8
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
• 108010057466 NF-kappa B Proteins 0.000 description 8
• 102000003945 NF-kappa B Human genes 0.000 description 8
• 108700008625 Reporter Genes Proteins 0.000 description 8
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 210000001853 liver microsome Anatomy 0.000 description 8
• 229920000137 polyphosphoric acid Polymers 0.000 description 8
• 238000002953 preparative HPLC Methods 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• GYIUDLLQLVWKPP-UHFFFAOYSA-N 2-propylpentanoyl 2-propylpentanoate Chemical compound CCCC(CCC)C(=O)OC(=O)C(CCC)CCC GYIUDLLQLVWKPP-UHFFFAOYSA-N 0.000 description 7
• JHNLZOVBAQWGQU-UHFFFAOYSA-N 380814_sial Chemical compound CS(O)(=O)=O.O=P(=O)OP(=O)=O JHNLZOVBAQWGQU-UHFFFAOYSA-N 0.000 description 7
• SAZGJPXEDWRWQT-UHFFFAOYSA-N 4-amino-3-[(4-chlorophenyl)methyl]-2-oxo-1H-imidazole-5-carbonitrile Chemical compound NC=1N(C(NC=1C#N)=O)CC1=CC=C(C=C1)Cl SAZGJPXEDWRWQT-UHFFFAOYSA-N 0.000 description 7
• FACAHUFBMGKRCZ-UHFFFAOYSA-N 6-chloro-4-N-[(2-methylpyrimidin-5-yl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC=1C=NC(=NC=1)C)N FACAHUFBMGKRCZ-UHFFFAOYSA-N 0.000 description 7
• VHLMRZXQXOAKFV-UHFFFAOYSA-N 6-chloro-9-[(2-methylpyridin-4-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=NC=C1)C)=O VHLMRZXQXOAKFV-UHFFFAOYSA-N 0.000 description 7
• CMYNXPLOCPEGOY-UHFFFAOYSA-N 9-benzyl-6-chloro-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)Cl)SCCC CMYNXPLOCPEGOY-UHFFFAOYSA-N 0.000 description 7
• XMZDKNOVRKWWBN-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]-2-methylpentanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CCC)C)=O)SCCC XMZDKNOVRKWWBN-UHFFFAOYSA-N 0.000 description 7
• 102000002689 Toll-like receptor Human genes 0.000 description 7
• 108020000411 Toll-like receptor Proteins 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
• 238000011534 incubation Methods 0.000 description 7
• 238000001990 intravenous administration Methods 0.000 description 7
• 230000002503 metabolic effect Effects 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 230000000638 stimulation Effects 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 6
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• DNCQUWBSWUTJPX-UHFFFAOYSA-N 4-N-benzyl-6-chloro-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound C(C1=CC=CC=C1)NC1=NC(=NC(=C1N)Cl)SCCC DNCQUWBSWUTJPX-UHFFFAOYSA-N 0.000 description 6
• LBJHPOUSJLRRIE-UHFFFAOYSA-N 4-[(6-amino-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzonitrile Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C#N)C=C1)=O LBJHPOUSJLRRIE-UHFFFAOYSA-N 0.000 description 6
• PIUCBAFXLHFCIE-UHFFFAOYSA-N 4-[(6-amino-8-oxo-2-propylsulfinyl-7H-purin-9-yl)methyl]benzamide Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C(=O)N)C=C1)=O PIUCBAFXLHFCIE-UHFFFAOYSA-N 0.000 description 6
• CBMWXHQXHJQKDE-UHFFFAOYSA-N 4-[(6-amino-8-oxo-2-propylsulfinyl-7H-purin-9-yl)methyl]benzonitrile Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C#N)C=C1)=O CBMWXHQXHJQKDE-UHFFFAOYSA-N 0.000 description 6
• LALNEYRQNPHKNY-UHFFFAOYSA-N 4-[(6-chloro-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzonitrile Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C#N)C=C1)=O LALNEYRQNPHKNY-UHFFFAOYSA-N 0.000 description 6
• ZMXIMWNANZYPQP-UHFFFAOYSA-N 4-[[6-[(4-methoxyphenyl)methylamino]-8-oxo-2-propylsulfanyl-7H-purin-9-yl]methyl]benzonitrile Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C#N)C=C1)=O ZMXIMWNANZYPQP-UHFFFAOYSA-N 0.000 description 6
• NMXGUZXVUKGKIR-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-2-methylsulfanyl-9-(pyridin-4-ylmethyl)-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SC)CC1=CC=NC=C1)=O NMXGUZXVUKGKIR-UHFFFAOYSA-N 0.000 description 6
• OSGAFGPHWBCQFX-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-9-[[4-(trifluoromethyl)phenyl]methyl]-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)C(F)(F)F)=O OSGAFGPHWBCQFX-UHFFFAOYSA-N 0.000 description 6
• WRRFKRBECKNCGX-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-9-(2-methylpropyl)-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C(C)C)N1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC WRRFKRBECKNCGX-UHFFFAOYSA-N 0.000 description 6
• OSYCZRISWVFFMJ-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-9-[(2-methylpyridin-4-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=NC=C1)C)=O OSYCZRISWVFFMJ-UHFFFAOYSA-N 0.000 description 6
• XVEYGRNBLXCEPN-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-9-[(2-methylpyrimidin-5-yl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC=1C=NC(=NC=1)C)=O XVEYGRNBLXCEPN-UHFFFAOYSA-N 0.000 description 6
• LPOIXDRFQWIDSA-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-9-[(6-methylpyridin-3-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=CC=1)C)=O LPOIXDRFQWIDSA-UHFFFAOYSA-N 0.000 description 6
• GHUKPLITXIFSRK-UHFFFAOYSA-N 6-amino-2-ethylsulfanyl-9-[(4-fluorophenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCC)CC1=CC=C(C=C1)F)=O GHUKPLITXIFSRK-UHFFFAOYSA-N 0.000 description 6
• LHRSFBRLPAJSMK-UHFFFAOYSA-N 6-amino-2-ethylsulfanyl-9-[(4-methylphenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCC)CC1=CC=C(C=C1)C)=O LHRSFBRLPAJSMK-UHFFFAOYSA-N 0.000 description 6
• KAPQRBANZCFAFB-UHFFFAOYSA-N 6-amino-2-ethylsulfinyl-9-[(4-fluorophenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC)CC1=CC=C(C=C1)F)=O KAPQRBANZCFAFB-UHFFFAOYSA-N 0.000 description 6
• IXERKOMQMNLWAX-UHFFFAOYSA-N 6-amino-2-ethylsulfinyl-9-[(4-methylphenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC)CC1=CC=C(C=C1)C)=O IXERKOMQMNLWAX-UHFFFAOYSA-N 0.000 description 6
• CTOBGOYAJNXTEK-UHFFFAOYSA-N 6-amino-2-methylsulfanyl-9-(pyridin-4-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SC)CC1=CC=NC=C1)=O CTOBGOYAJNXTEK-UHFFFAOYSA-N 0.000 description 6
• COTFBCNBTRCHOI-UHFFFAOYSA-N 6-amino-9-(2-methylpropyl)-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC(C)C)=O COTFBCNBTRCHOI-UHFFFAOYSA-N 0.000 description 6
• REAXDVUVMGLJJT-UHFFFAOYSA-N 6-amino-9-[(2,4-difluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=C(C=C(C=C1)F)F)=O REAXDVUVMGLJJT-UHFFFAOYSA-N 0.000 description 6
• CMOPSXCJQWZWNI-UHFFFAOYSA-N 6-amino-9-[(3,4-dichlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)Cl)Cl)=O CMOPSXCJQWZWNI-UHFFFAOYSA-N 0.000 description 6
• AWMRXUUYVORZPB-UHFFFAOYSA-N 6-amino-9-[(3,4-difluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)F)F)=O AWMRXUUYVORZPB-UHFFFAOYSA-N 0.000 description 6
• JAOGLXMHMAGPSB-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-ethylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC)CC1=CC=C(C=C1)Cl)=O JAOGLXMHMAGPSB-UHFFFAOYSA-N 0.000 description 6
• NBHMULUYJAUPGF-UHFFFAOYSA-N 6-amino-9-[(4-fluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)F)=O NBHMULUYJAUPGF-UHFFFAOYSA-N 0.000 description 6
• FXQAYXPLOMMSDA-UHFFFAOYSA-N 6-amino-9-[(4-fluorophenyl)methyl]-2-sulfanylidene-1,7-dihydropurin-8-one Chemical compound OC1=NC=2C(N)=NC(S)=NC=2N1CC1=CC=C(F)C=C1 FXQAYXPLOMMSDA-UHFFFAOYSA-N 0.000 description 6
• WFPGKBGNSQAKOR-UHFFFAOYSA-N 6-amino-9-[(4-methylphenyl)methyl]-2-sulfanylidene-1,7-dihydropurin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S)CC1=CC=C(C=C1)C)=O WFPGKBGNSQAKOR-UHFFFAOYSA-N 0.000 description 6
• CDHYXPUAMUVANH-UHFFFAOYSA-N 6-amino-9-[(4-methylsulfonylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)S(=O)(=O)C)=O CDHYXPUAMUVANH-UHFFFAOYSA-N 0.000 description 6
• IUTPEKYCPYPRHG-UHFFFAOYSA-N 6-amino-9-[2-(4-chlorophenyl)ethyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CCC1=CC=C(C=C1)Cl)=O IUTPEKYCPYPRHG-UHFFFAOYSA-N 0.000 description 6
• MCBGAVARLDFVPY-UHFFFAOYSA-N 6-amino-9-benzyl-2-propylsulfanyl-7h-purin-8-one Chemical compound C12=NC(SCCC)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 MCBGAVARLDFVPY-UHFFFAOYSA-N 0.000 description 6
• KRZHDKNRAJEVTE-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-4-N-(pyridin-2-ylmethyl)pyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SC)NCC1=NC=CC=C1)N KRZHDKNRAJEVTE-UHFFFAOYSA-N 0.000 description 6
• QXUVSSHJGKGJNJ-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-4-N-(pyridin-3-ylmethyl)pyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SC)NCC=1C=NC=CC=1)N QXUVSSHJGKGJNJ-UHFFFAOYSA-N 0.000 description 6
• WNRUNFGVYGGGEW-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-4-N-(pyridin-4-ylmethyl)pyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SC)NCC1=CC=NC=C1)N WNRUNFGVYGGGEW-UHFFFAOYSA-N 0.000 description 6
• LJGIPYPDOABDLJ-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-9-(pyridin-3-ylmethyl)-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SC)CC=1C=NC=CC=1)=O LJGIPYPDOABDLJ-UHFFFAOYSA-N 0.000 description 6
• WRAPBXXZFBVXPB-UHFFFAOYSA-N 6-chloro-2-propylsulfanyl-9-(pyrimidin-5-ylmethyl)-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC=NC=1)=O WRAPBXXZFBVXPB-UHFFFAOYSA-N 0.000 description 6
• PGAZPPBBUCHVLC-UHFFFAOYSA-N 6-chloro-4-N-[(4-chlorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)Cl)N PGAZPPBBUCHVLC-UHFFFAOYSA-N 0.000 description 6
• AOKMWWYZIJZZPG-UHFFFAOYSA-N 6-chloro-4-N-[(4-methylsulfonylphenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)S(=O)(=O)C)N AOKMWWYZIJZZPG-UHFFFAOYSA-N 0.000 description 6
• VVUGFKRMHUVWKW-UHFFFAOYSA-N 6-chloro-9-(2-methylpropyl)-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC(C)C)=O VVUGFKRMHUVWKW-UHFFFAOYSA-N 0.000 description 6
• VMRLPDGYMSGDAJ-UHFFFAOYSA-N 6-chloro-9-[(2,4-difluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=C(C=C(C=C1)F)F)=O VMRLPDGYMSGDAJ-UHFFFAOYSA-N 0.000 description 6
• ADSPKPCBBNTTHA-UHFFFAOYSA-N 6-chloro-9-[(2-methylpyrimidin-5-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=NC=1)C)=O ADSPKPCBBNTTHA-UHFFFAOYSA-N 0.000 description 6
• BCVOPHQQQAQPJC-UHFFFAOYSA-N 6-chloro-9-[(3,4-difluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)F)F)=O BCVOPHQQQAQPJC-UHFFFAOYSA-N 0.000 description 6
• BCCIMILKWSTHDD-UHFFFAOYSA-N 6-chloro-9-[(3-chloro-4-methylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)C)Cl)=O BCCIMILKWSTHDD-UHFFFAOYSA-N 0.000 description 6
• JDOBRVSTRUYTDL-UHFFFAOYSA-N 6-chloro-9-[(4-chloro-3-methylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)Cl)C)=O JDOBRVSTRUYTDL-UHFFFAOYSA-N 0.000 description 6
• CXIZBZRUTNLIFN-UHFFFAOYSA-N 6-chloro-9-[(4-methylsulfonylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)S(=O)(=O)C)=O CXIZBZRUTNLIFN-UHFFFAOYSA-N 0.000 description 6
• HUEILCRXENNYJE-UHFFFAOYSA-N 6-chloro-N-[(2,4-difluorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=C(C=C(C=C1)F)F)[N+](=O)[O-] HUEILCRXENNYJE-UHFFFAOYSA-N 0.000 description 6
• XYUIZXKZMNNNJW-UHFFFAOYSA-N 9-[(2,4-difluorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound FC1=C(C=CC(=C1)F)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC XYUIZXKZMNNNJW-UHFFFAOYSA-N 0.000 description 6
• LTHOHQUDPIEOKR-UHFFFAOYSA-N 9-[(3,4-dichlorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC=1C=C(C=CC=1Cl)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC LTHOHQUDPIEOKR-UHFFFAOYSA-N 0.000 description 6
• SAZWRDWEJQCTOS-UHFFFAOYSA-N 9-[(4-chloro-3-fluorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C(C=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC)F SAZWRDWEJQCTOS-UHFFFAOYSA-N 0.000 description 6
• MGHINPRYGWYVFO-UHFFFAOYSA-N 9-[(4-chlorophenyl)methyl]-6-(ethylamino)-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC)SCCC MGHINPRYGWYVFO-UHFFFAOYSA-N 0.000 description 6
• GCKJISLYRYLNAR-UHFFFAOYSA-N 9-benzyl-6-(cyclopropylamino)-2-propylsulfinyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC1CC1)S(=O)CCC GCKJISLYRYLNAR-UHFFFAOYSA-N 0.000 description 6
• ATJCVTPFAIOTFI-UHFFFAOYSA-N 9-benzyl-6-(ethylamino)-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NCC)SCCC ATJCVTPFAIOTFI-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• YWVAUZDITDUOIK-UHFFFAOYSA-N N-(9-benzyl-8-oxo-2-propylsulfinyl-7H-purin-6-yl)-2-propylpentanamide Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(C(CCC)CCC)=O)S(=O)CCC YWVAUZDITDUOIK-UHFFFAOYSA-N 0.000 description 6
• GXBDXJALKOQXRE-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]-2,2-dimethylpropanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(C)(C)C)=O)S(=O)CCC GXBDXJALKOQXRE-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 102100033110 Toll-like receptor 8 Human genes 0.000 description 6
• 230000001684 chronic effect Effects 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 108020004999 messenger RNA Proteins 0.000 description 6
• LBVOQOIJQBTHOE-UHFFFAOYSA-N methyl 4-[(6-amino-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzoate Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C(=O)OC)C=C1)=O LBVOQOIJQBTHOE-UHFFFAOYSA-N 0.000 description 6
• UIBNRGRUBIMSKX-UHFFFAOYSA-N methyl 4-[(6-chloro-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzoate Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C(=O)OC)C=C1)=O UIBNRGRUBIMSKX-UHFFFAOYSA-N 0.000 description 6
• WMLAZUKQQASVQF-UHFFFAOYSA-N methyl 4-[[(6-chloro-5-methyl-2-propylsulfanylpyrimidin-4-yl)amino]methyl]benzoate Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C(=O)OC)C=C1)C WMLAZUKQQASVQF-UHFFFAOYSA-N 0.000 description 6
• KTFYBDJCUFOZHM-UHFFFAOYSA-N methyl 4-[[6-[(4-methoxyphenyl)methylamino]-8-oxo-2-propylsulfanyl-7H-purin-9-yl]methyl]benzoate Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C(=O)OC)C=C1)=O KTFYBDJCUFOZHM-UHFFFAOYSA-N 0.000 description 6
• PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 description 6
• 239000007800 oxidant agent Substances 0.000 description 6
• DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 239000002953 phosphate buffered saline Substances 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• 229950003036 vesatolimod Drugs 0.000 description 6
• OYRGKUTZSTXSQS-UHFFFAOYSA-N (2-methylpyrimidin-5-yl)methanamine Chemical compound CC1=NC=C(CN)C=N1 OYRGKUTZSTXSQS-UHFFFAOYSA-N 0.000 description 5
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 5
• DDEDQHVHVPJFAC-UHFFFAOYSA-N 4,6-dichloro-5-nitro-2-propylsulfanylpyrimidine Chemical compound CCCSC1=NC(Cl)=C([N+]([O-])=O)C(Cl)=N1 DDEDQHVHVPJFAC-UHFFFAOYSA-N 0.000 description 5
• BJFRWQNIMZVQCT-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-9-(pyrimidin-5-ylmethyl)-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC=NC=1)=O BJFRWQNIMZVQCT-UHFFFAOYSA-N 0.000 description 5
• FBFBHKHVBSHQDY-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)Cl)=O FBFBHKHVBSHQDY-UHFFFAOYSA-N 0.000 description 5
• XNENYEMLFACNFU-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-sulfanylidene-1,7-dihydropurin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S)CC1=CC=C(C=C1)Cl)=O XNENYEMLFACNFU-UHFFFAOYSA-N 0.000 description 5
• ZTYJONMNFGRHOV-UHFFFAOYSA-N 6-amino-9-[(4-methylsulfonylphenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C=C1)S(=O)(=O)C)=O ZTYJONMNFGRHOV-UHFFFAOYSA-N 0.000 description 5
• LANQXZNXIDTWRX-UHFFFAOYSA-N 6-amino-9-benzyl-2-(butylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCCC)CC1=CC=CC=C1)=O LANQXZNXIDTWRX-UHFFFAOYSA-N 0.000 description 5
• ZCPVHVBGHGLDMY-UHFFFAOYSA-N 6-chloro-4-N-[(2-methylpyridin-4-yl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=NC=C1)C)N ZCPVHVBGHGLDMY-UHFFFAOYSA-N 0.000 description 5
• POOOKUXMUVRWEZ-UHFFFAOYSA-N 6-chloro-4-N-[(4-chloro-3-methylphenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)Cl)C)N POOOKUXMUVRWEZ-UHFFFAOYSA-N 0.000 description 5
• ZDZWHRKMDNGFPZ-UHFFFAOYSA-N 6-chloro-N-[(3,4-difluorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)F)F)[N+](=O)[O-] ZDZWHRKMDNGFPZ-UHFFFAOYSA-N 0.000 description 5
• 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 5
• AZUYFCZSTRNRJG-UHFFFAOYSA-N 9-[(4-chloro-3-methylphenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C(C=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC)C AZUYFCZSTRNRJG-UHFFFAOYSA-N 0.000 description 5
• OWUFMTCUOJNOCA-UHFFFAOYSA-N 9-benzyl-6-(propylamino)-2-propylsulfinyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NCCC)S(=O)CCC OWUFMTCUOJNOCA-UHFFFAOYSA-N 0.000 description 5
• 108091006146 Channels Proteins 0.000 description 5
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 5
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 5
• 241000711549 Hepacivirus C Species 0.000 description 5
• 108010050904 Interferons Proteins 0.000 description 5
• 102000014150 Interferons Human genes 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• SMJYMSAPPGLBAR-UHFFFAOYSA-N chloromethyl acetate Chemical compound CC(=O)OCCl SMJYMSAPPGLBAR-UHFFFAOYSA-N 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 229940079322 interferon Drugs 0.000 description 5
• 230000004060 metabolic process Effects 0.000 description 5
• 239000002207 metabolite Substances 0.000 description 5
• IRHUOBBBQIWSET-UHFFFAOYSA-N methyl 4-[(6-amino-8-oxo-2-propylsulfinyl-7H-purin-9-yl)methyl]benzoate Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C(=O)OC)C=C1)=O IRHUOBBBQIWSET-UHFFFAOYSA-N 0.000 description 5
• OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 5
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 5
• KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 4
• DPRJPRMZJGWLHY-HNGSOEQISA-N (e,3r,5s)-7-[5-(4-fluorophenyl)-3-propan-2-yl-1-pyrazin-2-ylpyrazol-4-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)/C=C/C=1C(C(C)C)=NN(C=2N=CC=NC=2)C=1C1=CC=C(F)C=C1 DPRJPRMZJGWLHY-HNGSOEQISA-N 0.000 description 4
• SBWJLHPCEHEABR-UHFFFAOYSA-N 2-methylpyridine-4-carbonitrile Chemical compound CC1=CC(C#N)=CC=N1 SBWJLHPCEHEABR-UHFFFAOYSA-N 0.000 description 4
• CCVSDUKQNMVXAV-UHFFFAOYSA-N 6-(ethylamino)-9-[(6-methylpyridin-3-yl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound C(C)NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC(=CC=1)C)=O CCVSDUKQNMVXAV-UHFFFAOYSA-N 0.000 description 4
• DKVUFKHNPXDUEA-UHFFFAOYSA-N 6-amino-2-methylsulfinyl-9-(pyridin-2-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C)CC1=NC=CC=C1)=O DKVUFKHNPXDUEA-UHFFFAOYSA-N 0.000 description 4
• HMWSWNCISULJJJ-UHFFFAOYSA-N 6-amino-9-[(3-chloro-4-methylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)C)Cl)=O HMWSWNCISULJJJ-UHFFFAOYSA-N 0.000 description 4
• AEVQYQZGVSLRES-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-methylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SC)CC1=CC=C(C=C1)Cl)=O AEVQYQZGVSLRES-UHFFFAOYSA-N 0.000 description 4
• KIHSDTHJQITPOC-UHFFFAOYSA-N 6-amino-9-[(4-methoxyphenyl)methyl]-2-sulfanylidene-1,7-dihydropurin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S)CC1=CC=C(C=C1)OC)=O KIHSDTHJQITPOC-UHFFFAOYSA-N 0.000 description 4
• QMUUHLBGKXHOMV-UHFFFAOYSA-N 6-amino-9-[(6-chloropyridin-3-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=CC=1)Cl)=O QMUUHLBGKXHOMV-UHFFFAOYSA-N 0.000 description 4
• VGSBMDOWAWHTIU-UHFFFAOYSA-N 6-amino-9-benzyl-2-ethylsulfanyl-7h-purin-8-one Chemical compound C12=NC(SCC)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 VGSBMDOWAWHTIU-UHFFFAOYSA-N 0.000 description 4
• CQVGRZRTSHHQAQ-UHFFFAOYSA-N 6-chloro-N-[(4-fluorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)F)[N+](=O)[O-] CQVGRZRTSHHQAQ-UHFFFAOYSA-N 0.000 description 4
• HGNGKXBOLIGONP-UHFFFAOYSA-N 9-benzyl-6-(propylamino)-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NCCC)SCCC HGNGKXBOLIGONP-UHFFFAOYSA-N 0.000 description 4
• QUMCIHKVKQYNPA-RUZDIDTESA-N C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC Chemical compound C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC QUMCIHKVKQYNPA-RUZDIDTESA-N 0.000 description 4
• 108090000695 Cytokines Proteins 0.000 description 4
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
• 208000005176 Hepatitis C Diseases 0.000 description 4
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 229940124614 TLR 8 agonist Drugs 0.000 description 4
• 230000000840 anti-viral effect Effects 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 239000004202 carbamide Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 208000010710 hepatitis C virus infection Diseases 0.000 description 4
• 230000002779 inactivation Effects 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 210000004185 liver Anatomy 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
• LVDLXEFCWOMUGO-UHFFFAOYSA-N n,6-dimethylpyridin-3-amine Chemical compound CNC1=CC=C(C)N=C1 LVDLXEFCWOMUGO-UHFFFAOYSA-N 0.000 description 4
• QVIOSGUKMDGWNN-UHFFFAOYSA-N n-hydroxy-n-isopropyloxamic acid Chemical compound CC(C)N(O)C(=O)C(O)=O QVIOSGUKMDGWNN-UHFFFAOYSA-N 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
• FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 3
• LAJAFFLJAJMYLK-CVOKMOJFSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[[(7s)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5h-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N1([C@H]2CCC3=CC=C(C(=C3CC2)OC)NC=2N=C(C(=CN=2)Cl)N[C@H]2[C@H]([C@@]3([H])C[C@@]2(C=C3)[H])C(N)=O)CCOCC1 LAJAFFLJAJMYLK-CVOKMOJFSA-N 0.000 description 3
• HOBMGFDJYBEWLS-UHFFFAOYSA-N (2-methylpyrimidin-5-yl)methanol Chemical compound CC1=NC=C(CO)C=N1 HOBMGFDJYBEWLS-UHFFFAOYSA-N 0.000 description 3
• SLTBMTIRYMGWLX-XMMPIXPASA-N (2r)-2-[(4-chloroanilino)carbamoylamino]-3-(1h-indol-3-yl)-n-(2-phenylethyl)propanamide Chemical compound C1=CC(Cl)=CC=C1NNC(=O)N[C@@H](C(=O)NCCC=1C=CC=CC=1)CC1=CNC2=CC=CC=C12 SLTBMTIRYMGWLX-XMMPIXPASA-N 0.000 description 3
• ZXGVFUKWWWNTTQ-VSGBNLITSA-N (3r,5r)-7-[4-[[3-(2-amino-2-oxoethyl)phenyl]sulfamoyl]-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)CCN1C(C(C)C)=C(S(=O)(=O)NC=2C=C(CC(N)=O)C=CC=2)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 ZXGVFUKWWWNTTQ-VSGBNLITSA-N 0.000 description 3
• FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 3
• JHLIGYPHPBLDDL-UHFFFAOYSA-N (5-pyridin-3-ylthiophen-2-yl)methanamine Chemical compound S1C(CN)=CC=C1C1=CC=CN=C1 JHLIGYPHPBLDDL-UHFFFAOYSA-N 0.000 description 3
• RXNPEQZHMGFNAY-GEALJGNFSA-N (5R)-4-[(1S,6R)-5-[(2S)-2-(4-chlorophenyl)-3-(propan-2-ylamino)propanoyl]-2,5-diazabicyclo[4.1.0]heptan-2-yl]-5-methyl-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one Chemical compound C[C@@H]1CC(=O)NC2=C1C(=NC=N2)N3CCN([C@H]4[C@@H]3C4)C(=O)[C@H](CNC(C)C)C5=CC=C(C=C5)Cl RXNPEQZHMGFNAY-GEALJGNFSA-N 0.000 description 3
• IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 3
• VICOOSNNZUPVHM-IGPZRPDBSA-M (e,3r,5s)-7-[2-(4-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl]-3,5-dihydroxyhept-6-enoate Chemical compound C=1C=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=CC=1C(CC)(CC)C1=CC=CC=C1 VICOOSNNZUPVHM-IGPZRPDBSA-M 0.000 description 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
• MXPCZHSTOIKVST-UHFFFAOYSA-N 1-[3-amino-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(2-hydroxyethoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=CC(N)=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OCCO)=C1 MXPCZHSTOIKVST-UHFFFAOYSA-N 0.000 description 3
• OXTVBHDILDPYAS-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OCCCO)=C1 OXTVBHDILDPYAS-UHFFFAOYSA-N 0.000 description 3
• YRTFLDFDKPFNCJ-UHFFFAOYSA-N 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-2-oxo-4-[3-(3-pyrrolidin-1-ylpropoxy)phenyl]-1,8-naphthyridin-3-yl]urea;dihydrochloride Chemical compound Cl.Cl.CC(C)C=1C=C(N)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C(C=1)=CC=CC=1OCCCN1CCCC1 YRTFLDFDKPFNCJ-UHFFFAOYSA-N 0.000 description 3
• ZFNNBIMQDHBELV-UHFFFAOYSA-N 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(3-cyclohexylpropoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;dihydrochloride Chemical compound Cl.Cl.CC(C)C=1C=C(N)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C(C=1)=CC=CC=1OCCCC1CCCCC1 ZFNNBIMQDHBELV-UHFFFAOYSA-N 0.000 description 3
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 3
• CGKKDGMMKSOGLM-UHFFFAOYSA-N 1-chloroethyl acetate Chemical compound CC(Cl)OC(C)=O CGKKDGMMKSOGLM-UHFFFAOYSA-N 0.000 description 3
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• YKYWUHHZZRBGMG-JWTNVVGKSA-N 1-methyl-2-[[(1r,5s)-6-[[5-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-3-azabicyclo[3.1.0]hexan-3-yl]methyl]benzimidazole Chemical compound C1([C@@H]2CN(C[C@@H]21)CC=1N(C2=CC=CC=C2N=1)C)COCC1=CC=C(C(F)(F)F)C=N1 YKYWUHHZZRBGMG-JWTNVVGKSA-N 0.000 description 3
• FJMQJSUOOGOWBD-UHFFFAOYSA-N 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-5,6-dihydropyrazolo[3,4-f][1,4]oxazepin-8-one Chemical compound O=C1N(CC(F)(F)C)CCOC=2C1=NN(C=1C(=CC=CC=1)Cl)C=2C1=CC=C(Cl)C=C1 FJMQJSUOOGOWBD-UHFFFAOYSA-N 0.000 description 3
• XZORQADPEUSNQJ-UHFFFAOYSA-N 2-(3-piperidin-4-yloxy-1-benzothiophen-2-yl)-5-[(1,3,5-trimethylpyrazol-4-yl)methyl]-1,3,4-oxadiazole Chemical compound CC1=NN(C)C(C)=C1CC1=NN=C(C2=C(C3=CC=CC=C3S2)OC2CCNCC2)O1 XZORQADPEUSNQJ-UHFFFAOYSA-N 0.000 description 3
• CJLZUKCACMUYFP-GOSISDBHSA-N 2-[(5R)-4-[2-[3-(3-methylbutanoyloxy)phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid Chemical compound CC(C)CC(=O)OC1=CC=CC(CC(=O)N2[C@@H](C3=CC=C(N=C3NCC2)C(F)(F)F)CC(O)=O)=C1 CJLZUKCACMUYFP-GOSISDBHSA-N 0.000 description 3
• PFOQIHIIOLBCEQ-UHFFFAOYSA-N 2-[4-[2-(2,6-dimethoxyphenyl)-7-methyl-3h-benzimidazol-5-yl]piperidin-1-yl]-n-methylethanamine Chemical compound C1CN(CCNC)CCC1C1=CC(C)=C(NC(=N2)C=3C(=CC=CC=3OC)OC)C2=C1 PFOQIHIIOLBCEQ-UHFFFAOYSA-N 0.000 description 3
• AXHVEQQLKVIZLO-UHFFFAOYSA-N 2-[4-[2-[5-(2,2-dimethylbutyl)-1h-imidazol-2-yl]ethyl]phenyl]benzoic acid Chemical compound CCC(C)(C)CC1=CNC(CCC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=N1 AXHVEQQLKVIZLO-UHFFFAOYSA-N 0.000 description 3
• BCSHRERPHLTPEE-NRFANRHFSA-N 2-[[5-chloro-2-[[(6s)-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methoxy-6,7,8,9-tetrahydro-5h-benzo[7]annulen-2-yl]amino]pyrimidin-4-yl]amino]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NC1=NC(NC=2C(=C3CCC[C@@H](CC3=CC=2)N2CCN(CCO)CC2)OC)=NC=C1Cl BCSHRERPHLTPEE-NRFANRHFSA-N 0.000 description 3
• MEUWQVWJLLBVQI-UHFFFAOYSA-N 2-aminopropanedinitrile;4-methylbenzenesulfonic acid Chemical compound N#CC([NH3+])C#N.CC1=CC=C(S([O-])(=O)=O)C=C1 MEUWQVWJLLBVQI-UHFFFAOYSA-N 0.000 description 3
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 3
• NCYCWNILADFMPI-UHFFFAOYSA-N 2-methylpentanoyl 2-methylpentanoate Chemical compound CCCC(C)C(=O)OC(=O)C(C)CCC NCYCWNILADFMPI-UHFFFAOYSA-N 0.000 description 3
• IJBONYUNKRDIFC-UHFFFAOYSA-N 2-methylpyrimidine-5-carbaldehyde Chemical compound CC1=NC=C(C=O)C=N1 IJBONYUNKRDIFC-UHFFFAOYSA-N 0.000 description 3
• HBVIITUOCCASKD-UHFFFAOYSA-N 3-[[(6-chloro-5-nitro-2-propylsulfanylpyrimidin-4-yl)amino]methyl]benzonitrile Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC=1C=C(C#N)C=CC=1)[N+](=O)[O-] HBVIITUOCCASKD-UHFFFAOYSA-N 0.000 description 3
• VIDVDRAYLLBTEI-UHFFFAOYSA-N 3-[[6-[(4-methoxyphenyl)methylamino]-8-oxo-2-propylsulfanyl-7H-purin-9-yl]methyl]benzonitrile Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=C(C#N)C=CC=1)=O VIDVDRAYLLBTEI-UHFFFAOYSA-N 0.000 description 3
• GHAWBARMICSLQS-UHFFFAOYSA-N 4,6-dichloro-2-methylsulfanyl-5-nitropyrimidine Chemical compound CSC1=NC(Cl)=C([N+]([O-])=O)C(Cl)=N1 GHAWBARMICSLQS-UHFFFAOYSA-N 0.000 description 3
• LBJANQPGPWNJTJ-UHFFFAOYSA-N 4-[(6-amino-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzamide Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C(=O)N)C=C1)=O LBJANQPGPWNJTJ-UHFFFAOYSA-N 0.000 description 3
• TXEBWPPWSVMYOA-UHFFFAOYSA-N 4-[3-[(1-amino-2-chloroethyl)amino]propyl]-1-[[3-(2-chlorophenyl)phenyl]methyl]-5-hydroxyimidazolidin-2-one Chemical compound NC(CCl)NCCCC1NC(=O)N(Cc2cccc(c2)-c2ccccc2Cl)C1O TXEBWPPWSVMYOA-UHFFFAOYSA-N 0.000 description 3
• NGASIZRYYFJUCS-UHFFFAOYSA-N 4-[[(5-amino-6-chloro-2-propylsulfanylpyrimidin-4-yl)amino]methyl]benzonitrile Chemical compound NC=1C(=NC(=NC=1Cl)SCCC)NCC1=CC=C(C#N)C=C1 NGASIZRYYFJUCS-UHFFFAOYSA-N 0.000 description 3
• WCDJOBJYEDOSQS-UHFFFAOYSA-N 4-[[(6-chloro-5-nitro-2-propylsulfanylpyrimidin-4-yl)amino]methyl]benzonitrile Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C#N)C=C1)[N+](=O)[O-] WCDJOBJYEDOSQS-UHFFFAOYSA-N 0.000 description 3
• MFLMXRSHJVIMRF-DHIUTWEWSA-L 4-[[[5-[(3r,5r)-6-carboxylato-3,5-dihydroxyhexyl]-1-ethyl-4-(4-fluorophenyl)-3-methylpyrrole-2-carbonyl]amino]methyl]benzoate Chemical compound CCN1C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=2C=CC(F)=CC=2)C(C)=C1C(=O)NCC1=CC=C(C([O-])=O)C=C1 MFLMXRSHJVIMRF-DHIUTWEWSA-L 0.000 description 3
• KQXAFVQKMMSRFL-UHFFFAOYSA-N 4-amino-3-[(4-fluorophenyl)methyl]-2-oxo-1h-imidazole-5-carbonitrile Chemical compound NC1=C(C#N)N=C(O)N1CC1=CC=C(F)C=C1 KQXAFVQKMMSRFL-UHFFFAOYSA-N 0.000 description 3
• WBQWVGJKURKLHU-UHFFFAOYSA-N 4-amino-3-[(4-methoxyphenyl)methyl]-2-oxo-1h-imidazole-5-carbonitrile Chemical compound C1=CC(OC)=CC=C1CN1C(=O)NC(C#N)=C1N WBQWVGJKURKLHU-UHFFFAOYSA-N 0.000 description 3
• VFRQJCXMZAJFNM-UHFFFAOYSA-N 4-amino-3-[(4-methylphenyl)methyl]-2-oxo-1h-imidazole-5-carbonitrile Chemical compound C1=CC(C)=CC=C1CN1C(=O)NC(C#N)=C1N VFRQJCXMZAJFNM-UHFFFAOYSA-N 0.000 description 3
• VTFFVSSBNRTWCJ-UHFFFAOYSA-N 4-amino-3-[(6-chloropyridin-3-yl)methyl]-2-oxo-1H-imidazole-5-carbonitrile Chemical compound NC=1N(C(NC=1C#N)=O)CC=1C=NC(=CC=1)Cl VTFFVSSBNRTWCJ-UHFFFAOYSA-N 0.000 description 3
• JJNLGGQLCGZEIB-UHFFFAOYSA-N 4-amino-3-benzyl-2-oxo-1h-imidazole-5-carbonitrile Chemical compound NC1=C(C#N)N=C(O)N1CC1=CC=CC=C1 JJNLGGQLCGZEIB-UHFFFAOYSA-N 0.000 description 3
• DLJHMBHVBDEAOX-UHFFFAOYSA-N 4-chloro-n,3-dimethylaniline Chemical compound CNC1=CC=C(Cl)C(C)=C1 DLJHMBHVBDEAOX-UHFFFAOYSA-N 0.000 description 3
• MVXAKOGJWVQPKC-UHFFFAOYSA-N 5-(3-ethynyl-5-fluorophenyl)-2-pyridin-2-yl-4,6,7,8-tetrahydro-[1,3]oxazolo[4,5-c]azepine Chemical compound FC1=CC(C#C)=CC(N2CC=3N=C(OC=3CCC2)C=2N=CC=CC=2)=C1 MVXAKOGJWVQPKC-UHFFFAOYSA-N 0.000 description 3
• OXVHQOPLGOPEQO-UHFFFAOYSA-N 5-(azidomethyl)-2-methylpyrimidine Chemical compound CC1=NC=C(CN=[N+]=[N-])C=N1 OXVHQOPLGOPEQO-UHFFFAOYSA-N 0.000 description 3
• OQCBZUQZGVEIGQ-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-2-methylsulfanyl-9-(pyridin-2-ylmethyl)-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SC)CC1=NC=CC=C1)=O OQCBZUQZGVEIGQ-UHFFFAOYSA-N 0.000 description 3
• VDOPMXYXDRHECX-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-2-methylsulfanyl-9-(pyridin-3-ylmethyl)-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SC)CC=1C=NC=CC=1)=O VDOPMXYXDRHECX-UHFFFAOYSA-N 0.000 description 3
• XKRVQTQQYGDWKO-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-9-[(4-methylsulfonylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)S(=O)(=O)C)=O XKRVQTQQYGDWKO-UHFFFAOYSA-N 0.000 description 3
• XDBHURGONHZNJF-UHFFFAOYSA-N 6-[2-(3,4-diethoxyphenyl)-1,3-thiazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=C(OCC)C(OCC)=CC=C1C1=NC(C=2N=C(C=CC=2)C(O)=O)=CS1 XDBHURGONHZNJF-UHFFFAOYSA-N 0.000 description 3
• KSYPYLZXEACSIR-UHFFFAOYSA-N 6-amino-2-(propylsulfonimidoyl)-9-(pyrimidin-5-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC=1C=NC=NC=1)=O KSYPYLZXEACSIR-UHFFFAOYSA-N 0.000 description 3
• ZUOHLJLBZUSZLB-UHFFFAOYSA-N 6-amino-2-(propylsulfonimidoyl)-9-[[4-(pyrrolidine-1-carbonyl)phenyl]methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=C(C=C1)C(=O)N1CCCC1)=O ZUOHLJLBZUSZLB-UHFFFAOYSA-N 0.000 description 3
• YMHLABHVGRFDEB-UHFFFAOYSA-N 6-amino-2-methylsulfanyl-9-(pyridin-2-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SC)CC1=NC=CC=C1)=O YMHLABHVGRFDEB-UHFFFAOYSA-N 0.000 description 3
• OWHOVQKHZCNMAL-UHFFFAOYSA-N 6-amino-2-methylsulfanyl-9-(pyridin-3-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SC)CC=1C=NC=CC=1)=O OWHOVQKHZCNMAL-UHFFFAOYSA-N 0.000 description 3
• GJZIAFLOUZRSMO-UHFFFAOYSA-N 6-amino-2-methylsulfinyl-9-(pyridin-3-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C)CC=1C=NC=CC=1)=O GJZIAFLOUZRSMO-UHFFFAOYSA-N 0.000 description 3
• XQIXBJPSZOOHPE-UHFFFAOYSA-N 6-amino-2-methylsulfinyl-9-(pyridin-4-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C)CC1=CC=NC=C1)=O XQIXBJPSZOOHPE-UHFFFAOYSA-N 0.000 description 3
• QJWPPRMYXGFYES-UHFFFAOYSA-N 6-amino-2-propylsulfanyl-9-(pyridin-2-ylmethyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=NC=CC=C1)=O QJWPPRMYXGFYES-UHFFFAOYSA-N 0.000 description 3
• FWOGSCODNNTDOW-UHFFFAOYSA-N 6-amino-2-propylsulfanyl-9-[[4-(trifluoromethyl)phenyl]methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)C(F)(F)F)=O FWOGSCODNNTDOW-UHFFFAOYSA-N 0.000 description 3
• GNNWYIXQIMYPDF-UHFFFAOYSA-N 6-amino-2-propylsulfinyl-9-[[4-(trifluoromethyl)phenyl]methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C=C1)C(F)(F)F)=O GNNWYIXQIMYPDF-UHFFFAOYSA-N 0.000 description 3
• XZRDJQIOVPPCBM-UHFFFAOYSA-N 6-amino-9-(2-methylpropyl)-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC(C)C)=O XZRDJQIOVPPCBM-UHFFFAOYSA-N 0.000 description 3
• GHNZGJFSLUTYGY-UHFFFAOYSA-N 6-amino-9-[(2-methylpyridin-4-yl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC(=NC=C1)C)=O GHNZGJFSLUTYGY-UHFFFAOYSA-N 0.000 description 3
• AKYNQXFQVZXKTE-UHFFFAOYSA-N 6-amino-9-[(2-methylpyridin-4-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=NC=C1)C)=O AKYNQXFQVZXKTE-UHFFFAOYSA-N 0.000 description 3
• HJWKAYBROIQCQP-UHFFFAOYSA-N 6-amino-9-[(2-methylpyridin-4-yl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC(=NC=C1)C)=O HJWKAYBROIQCQP-UHFFFAOYSA-N 0.000 description 3
• NXUYFJDQVXISPX-UHFFFAOYSA-N 6-amino-9-[(3-chlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=CC=C1)Cl)=O NXUYFJDQVXISPX-UHFFFAOYSA-N 0.000 description 3
• RIACPLVJPWLPJW-UHFFFAOYSA-N 6-amino-9-[(3-chlorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC(=CC=C1)Cl)=O RIACPLVJPWLPJW-UHFFFAOYSA-N 0.000 description 3
• YEOAWWOBFYFPBW-UHFFFAOYSA-N 6-amino-9-[(4-bromophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)Br)=O YEOAWWOBFYFPBW-UHFFFAOYSA-N 0.000 description 3
• SKXREALOLSMPMS-UHFFFAOYSA-N 6-amino-9-[(4-bromophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C=C1)Br)=O SKXREALOLSMPMS-UHFFFAOYSA-N 0.000 description 3
• PAAMUPBWXLCXNH-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-ethylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCC)CC1=CC=C(C=C1)Cl)=O PAAMUPBWXLCXNH-UHFFFAOYSA-N 0.000 description 3
• YBRNOHZENVVILZ-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-methylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C)CC1=CC=C(C=C1)Cl)=O YBRNOHZENVVILZ-UHFFFAOYSA-N 0.000 description 3
• MRXWPJFERAESDD-UHFFFAOYSA-N 6-amino-9-[(4-chlorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C=C1)Cl)=O MRXWPJFERAESDD-UHFFFAOYSA-N 0.000 description 3
• CIJFULQSEGMRNI-UHFFFAOYSA-N 6-amino-9-[(4-fluorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C=C1)F)=O CIJFULQSEGMRNI-UHFFFAOYSA-N 0.000 description 3
• FLASPAQGZOEWHF-UHFFFAOYSA-N 6-amino-9-[(4-methoxyphenyl)methyl]-2-methylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SC)CC1=CC=C(C=C1)OC)=O FLASPAQGZOEWHF-UHFFFAOYSA-N 0.000 description 3
• TWIUELNOSZKELU-UHFFFAOYSA-N 6-amino-9-[(6-chloropyridin-3-yl)methyl]-2-sulfanylidene-1,7-dihydropurin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S)CC=1C=NC(=CC=1)Cl)=O TWIUELNOSZKELU-UHFFFAOYSA-N 0.000 description 3
• XTYSOULVGVCCTL-UHFFFAOYSA-N 6-amino-9-[(6-methylpyridin-3-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=CC=1)C)=O XTYSOULVGVCCTL-UHFFFAOYSA-N 0.000 description 3
• KOWJQKOPIUCLLW-UHFFFAOYSA-N 6-amino-9-[(6-methylpyridin-3-yl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC=1C=NC(=CC=1)C)=O KOWJQKOPIUCLLW-UHFFFAOYSA-N 0.000 description 3
• RKOAQZHSBQHMDM-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2-methoxyethylsulfinyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCOC)CC1=CC=CC=C1)=O RKOAQZHSBQHMDM-UHFFFAOYSA-N 0.000 description 3
• FGGHMITXKSUZKF-UHFFFAOYSA-N 6-amino-9-benzyl-2-(cyclohexylmethylsulfanyl)-7h-purin-8-one Chemical compound N=1C=2N(CC=3C=CC=CC=3)C(O)=NC=2C(N)=NC=1SCC1CCCCC1 FGGHMITXKSUZKF-UHFFFAOYSA-N 0.000 description 3
• DFPKSCBPNVPRIY-UHFFFAOYSA-N 6-amino-9-benzyl-2-(cyclohexylmethylsulfinyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC1CCCCC1)CC1=CC=CC=C1)=O DFPKSCBPNVPRIY-UHFFFAOYSA-N 0.000 description 3
• RUCNHSPYGHWHHI-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-5-nitro-N-(pyridin-2-ylmethyl)pyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SC)NCC1=NC=CC=C1)[N+](=O)[O-] RUCNHSPYGHWHHI-UHFFFAOYSA-N 0.000 description 3
• UJASXHABCYKAAY-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-5-nitro-N-(pyridin-3-ylmethyl)pyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SC)NCC=1C=NC=CC=1)[N+](=O)[O-] UJASXHABCYKAAY-UHFFFAOYSA-N 0.000 description 3
• ZUWKQLJELLHMNF-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-5-nitro-N-(pyridin-4-ylmethyl)pyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SC)NCC1=CC=NC=C1)[N+](=O)[O-] ZUWKQLJELLHMNF-UHFFFAOYSA-N 0.000 description 3
• AYHFCRLYOXQOIM-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-9-(pyridin-2-ylmethyl)-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SC)CC1=NC=CC=C1)=O AYHFCRLYOXQOIM-UHFFFAOYSA-N 0.000 description 3
• YPWGGFUUDUCVMW-UHFFFAOYSA-N 6-chloro-2-methylsulfanyl-9-(pyridin-4-ylmethyl)-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SC)CC1=CC=NC=C1)=O YPWGGFUUDUCVMW-UHFFFAOYSA-N 0.000 description 3
• NMFIDGJEOBNXRX-UHFFFAOYSA-N 6-chloro-2-propylsulfanyl-4-N-(pyrimidin-5-ylmethyl)pyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC=1C=NC=NC=1)N NMFIDGJEOBNXRX-UHFFFAOYSA-N 0.000 description 3
• WLQUEKUHGFEFBK-UHFFFAOYSA-N 6-chloro-2-propylsulfanyl-9-[[4-(trifluoromethyl)phenyl]methyl]-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)C(F)(F)F)=O WLQUEKUHGFEFBK-UHFFFAOYSA-N 0.000 description 3
• XEAFUKUFFYDCJW-UHFFFAOYSA-N 6-chloro-4-N-(2-methylpropyl)-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC(C)C)N XEAFUKUFFYDCJW-UHFFFAOYSA-N 0.000 description 3
• SGBUPHFNZJHTSW-UHFFFAOYSA-N 6-chloro-4-N-[(3-chloro-4-methylphenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)C)Cl)N SGBUPHFNZJHTSW-UHFFFAOYSA-N 0.000 description 3
• QKYJEBSTOJMWSP-UHFFFAOYSA-N 6-chloro-5-nitro-2-propylsulfanyl-N-(pyrimidin-5-ylmethyl)pyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC=1C=NC=NC=1)[N+](=O)[O-] QKYJEBSTOJMWSP-UHFFFAOYSA-N 0.000 description 3
• ICHLHUJTUCTZOV-UHFFFAOYSA-N 6-chloro-9-[(3,4-dichlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)Cl)Cl)=O ICHLHUJTUCTZOV-UHFFFAOYSA-N 0.000 description 3
• FELAQEZHOPNTLG-UHFFFAOYSA-N 6-chloro-9-[(3-chlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=CC=C1)Cl)=O FELAQEZHOPNTLG-UHFFFAOYSA-N 0.000 description 3
• RSSUZYSUKRLKJD-UHFFFAOYSA-N 6-chloro-9-[(4-chloro-3-fluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)Cl)F)=O RSSUZYSUKRLKJD-UHFFFAOYSA-N 0.000 description 3
• AFWDOXBIZKOMKO-UHFFFAOYSA-N 6-chloro-9-[(4-fluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)F)=O AFWDOXBIZKOMKO-UHFFFAOYSA-N 0.000 description 3
• ORDPCCHDEXLZTD-UHFFFAOYSA-N 6-chloro-N-(2-methylpropyl)-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC(C)C)[N+](=O)[O-] ORDPCCHDEXLZTD-UHFFFAOYSA-N 0.000 description 3
• BNOSSHBESCFNTN-UHFFFAOYSA-N 6-chloro-N-[(2-methylpyridin-4-yl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=NC=C1)C)[N+](=O)[O-] BNOSSHBESCFNTN-UHFFFAOYSA-N 0.000 description 3
• MUYFKRZEPDBDKF-UHFFFAOYSA-N 6-chloro-N-[(3-chlorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=CC=C1)Cl)[N+](=O)[O-] MUYFKRZEPDBDKF-UHFFFAOYSA-N 0.000 description 3
• BFUSDYFIXSTGJB-UHFFFAOYSA-N 6-chloro-N-[(4-chloro-3-fluorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)Cl)F)[N+](=O)[O-] BFUSDYFIXSTGJB-UHFFFAOYSA-N 0.000 description 3
• VVSKHEUAQMVQFU-UHFFFAOYSA-N 6-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)Cl)[N+](=O)[O-] VVSKHEUAQMVQFU-UHFFFAOYSA-N 0.000 description 3
• KUISQZDVMKSVNP-UHFFFAOYSA-N 6-chloro-N-[(4-methylsulfonylphenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)S(=O)(=O)C)[N+](=O)[O-] KUISQZDVMKSVNP-UHFFFAOYSA-N 0.000 description 3
• HHHPGQBUWHNQDE-UHFFFAOYSA-N 6-chloro-N-[(6-methylpyridin-3-yl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC=1C=NC(=CC=1)C)[N+](=O)[O-] HHHPGQBUWHNQDE-UHFFFAOYSA-N 0.000 description 3
• PBLOYQAQGYUPCM-UHFFFAOYSA-N 6-methylpyridine-3-carbonitrile Chemical compound CC1=CC=C(C#N)C=N1 PBLOYQAQGYUPCM-UHFFFAOYSA-N 0.000 description 3
• XTJZKALDRPVFSN-HNNXBMFYSA-N 8-n-[(2s)-3,3-dimethylbutan-2-yl]-2-n-[2-methoxy-4-(1-methylpyrazol-4-yl)phenyl]pyrido[3,4-d]pyrimidine-2,8-diamine Chemical compound C=1C=C(NC=2N=C3C(N[C@@H](C)C(C)(C)C)=NC=CC3=CN=2)C(OC)=CC=1C=1C=NN(C)C=1 XTJZKALDRPVFSN-HNNXBMFYSA-N 0.000 description 3
• MCMSJVMUSBZUCN-UHFFFAOYSA-N 9,10-dimethoxy-3-methyl-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(N2C)=O)C1=CC2=NC1=C(C)C=C(C)C=C1C MCMSJVMUSBZUCN-UHFFFAOYSA-N 0.000 description 3
• KSNWHZKBCNEOCV-UHFFFAOYSA-N 9-[(3,4-difluorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound FC=1C=C(C=CC=1F)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC KSNWHZKBCNEOCV-UHFFFAOYSA-N 0.000 description 3
• YMCQCKIZSFHFFM-UHFFFAOYSA-N 9-[(3-chlorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC=1C=C(C=CC=1)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC YMCQCKIZSFHFFM-UHFFFAOYSA-N 0.000 description 3
• LASYSHUXPGRDMN-UHFFFAOYSA-N 9-[(4-bromophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound BrC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC LASYSHUXPGRDMN-UHFFFAOYSA-N 0.000 description 3
• JUQMATGKETVMOU-UHFFFAOYSA-N 9-[(4-bromophenyl)methyl]-6-chloro-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)Br)=O JUQMATGKETVMOU-UHFFFAOYSA-N 0.000 description 3
• NVMDIWOICAPQTA-UHFFFAOYSA-N 9-[(4-chlorophenyl)methyl]-6-(ethylamino)-2-propylsulfinyl-7H-purin-8-one Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC)S(=O)CCC NVMDIWOICAPQTA-UHFFFAOYSA-N 0.000 description 3
• WOUHLAXHUODHMZ-UHFFFAOYSA-N 9-[(4-fluorophenyl)methyl]-6-[(4-methoxyphenyl)methylamino]-2-propylsulfanyl-7H-purin-8-one Chemical compound FC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NCC1=CC=C(C=C1)OC)SCCC WOUHLAXHUODHMZ-UHFFFAOYSA-N 0.000 description 3
• IFWBZWHYVNRMMC-UHFFFAOYSA-N 9-benzyl-6-(cyclopropylamino)-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC1CC1)SCCC IFWBZWHYVNRMMC-UHFFFAOYSA-N 0.000 description 3
• TWWIKYSVNRCTOK-UHFFFAOYSA-N 9-benzyl-6-(ethylamino)-2-propylsulfinyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NCC)S(=O)CCC TWWIKYSVNRCTOK-UHFFFAOYSA-N 0.000 description 3
• BEACBILQFFTGQE-UHFFFAOYSA-N 9-benzyl-6-(propan-2-ylamino)-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(C)C)SCCC BEACBILQFFTGQE-UHFFFAOYSA-N 0.000 description 3
• IRMPAYQHUIXYHY-UHFFFAOYSA-N 9-benzyl-6-(propan-2-ylamino)-2-propylsulfinyl-7H-purin-8-one Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(C)C)S(=O)CCC IRMPAYQHUIXYHY-UHFFFAOYSA-N 0.000 description 3
• VWVKUNOPTJGDOB-BDHVOXNPSA-N Anhydrous tofogliflozin Chemical compound C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 VWVKUNOPTJGDOB-BDHVOXNPSA-N 0.000 description 3
• JAOGFYSXDYNYSX-UHFFFAOYSA-N CC(C)(C(N=CC(Cl)=C1)=C1C(C=CC(Cl)=C1)=C1N1C(C=C2)=CC=C2N(C2)CC2(CNC(CC2)CCC2C(O)=O)F)C1=O Chemical compound CC(C)(C(N=CC(Cl)=C1)=C1C(C=CC(Cl)=C1)=C1N1C(C=C2)=CC=C2N(C2)CC2(CNC(CC2)CCC2C(O)=O)F)C1=O JAOGFYSXDYNYSX-UHFFFAOYSA-N 0.000 description 3
• WUZBOJXXYMKMMF-UHFFFAOYSA-N COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F Chemical compound COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F WUZBOJXXYMKMMF-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 229940126657 Compound 17 Drugs 0.000 description 3
• 102000004127 Cytokines Human genes 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 101000652482 Homo sapiens TBC1 domain family member 8 Proteins 0.000 description 3
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
• OTRGZTCSPCNJCQ-UHFFFAOYSA-N N-(9-benzyl-8-oxo-2-propylsulfanyl-7H-purin-6-yl)-2-propylpentanamide Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(C(CCC)CCC)=O)SCCC OTRGZTCSPCNJCQ-UHFFFAOYSA-N 0.000 description 3
• WXCATEWRWJKDJL-UHFFFAOYSA-N N-(9-benzyl-8-oxo-2-propylsulfanyl-7H-purin-6-yl)pentanamide Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(CCCC)=O)SCCC WXCATEWRWJKDJL-UHFFFAOYSA-N 0.000 description 3
• XJEVQCHAETXVIB-UHFFFAOYSA-N N-(9-benzyl-8-oxo-2-propylsulfinyl-7H-purin-6-yl)pentanamide Chemical compound C(C1=CC=CC=C1)N1C2=NC(=NC(=C2NC1=O)NC(CCCC)=O)S(=O)CCC XJEVQCHAETXVIB-UHFFFAOYSA-N 0.000 description 3
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
• OHVIRCSJFFPEGC-XMMPIXPASA-N N-[3-[[4-[[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]phenyl]methoxy]phenyl]benzamide Chemical compound OC[C@H]1CCCN1Cc1ccc(COc2cccc(NC(=O)c3ccccc3)c2)cc1 OHVIRCSJFFPEGC-XMMPIXPASA-N 0.000 description 3
• YCLSUCMIRCSBJJ-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]-2,2-dimethylpropanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(C)(C)C)=O)SCCC YCLSUCMIRCSBJJ-UHFFFAOYSA-N 0.000 description 3
• IWRSPXMJFKGXRG-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]-2-ethylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CC)CC)=O)SCCC IWRSPXMJFKGXRG-UHFFFAOYSA-N 0.000 description 3
• WSLPWOKZOATGMZ-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]acetamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C)=O)SCCC WSLPWOKZOATGMZ-UHFFFAOYSA-N 0.000 description 3
• PWULVKSLTGNTHD-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]-2-ethylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CC)CC)=O)S(=O)CCC PWULVKSLTGNTHD-UHFFFAOYSA-N 0.000 description 3
• YDZYETTUFASZKH-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]-2-methylpentanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CCC)C)=O)S(=O)CCC YDZYETTUFASZKH-UHFFFAOYSA-N 0.000 description 3
• CLNXVCDSACPEIT-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]acetamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C)=O)S(=O)CCC CLNXVCDSACPEIT-UHFFFAOYSA-N 0.000 description 3
• ZVDOSPMSDOICBO-UHFFFAOYSA-N N-benzyl-6-chloro-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound C(C1=CC=CC=C1)NC1=NC(=NC(=C1[N+](=O)[O-])Cl)SCCC ZVDOSPMSDOICBO-UHFFFAOYSA-N 0.000 description 3
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 3
• KISZAGQTIXIVAR-UHFFFAOYSA-N OC(=O)c1ccc2c(CCCC(c3ccc(Cl)cc3Cl)=C2c2ccc(OC3CCN(CCCF)C3)cc2)c1 Chemical compound OC(=O)c1ccc2c(CCCC(c3ccc(Cl)cc3Cl)=C2c2ccc(OC3CCN(CCCF)C3)cc2)c1 KISZAGQTIXIVAR-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• 102100030302 TBC1 domain family member 8 Human genes 0.000 description 3
• KZVWEOXAPZXAFB-BQFCYCMXSA-N Temocaprilat Chemical compound C([C@H](N[C@H]1CS[C@@H](CN(C1=O)CC(=O)O)C=1SC=CC=1)C(O)=O)CC1=CC=CC=C1 KZVWEOXAPZXAFB-BQFCYCMXSA-N 0.000 description 3
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 150000001263 acyl chlorides Chemical class 0.000 description 3
• SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
• AJRQIXBBIDPNGK-BVSLBCMMSA-N benzyl n-[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(=O)OCC1=CC=CC=C1 AJRQIXBBIDPNGK-BVSLBCMMSA-N 0.000 description 3
• OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 3
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229940127206 compound 14d Drugs 0.000 description 3
• 229940126209 compound 43b Drugs 0.000 description 3
• 229940126211 compound 54c Drugs 0.000 description 3
• 229940125873 compound 60b Drugs 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 230000001086 cytosolic effect Effects 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 230000008406 drug-drug interaction Effects 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• KUCDOJMOTMEEOF-UHFFFAOYSA-N gtpl6345 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(SC=2C3=C4NCCOC4=CN=2)=C3N=C1 KUCDOJMOTMEEOF-UHFFFAOYSA-N 0.000 description 3
• FODONWGPMXPGNC-UHFFFAOYSA-N gtpl6346 Chemical compound C1=CC(Cl)=CC=C1N1C(=O)C(SC=2C3=C4NCCOC4=CN=2)=C3N=C1 FODONWGPMXPGNC-UHFFFAOYSA-N 0.000 description 3
• 210000003494 hepatocyte Anatomy 0.000 description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 239000000411 inducer Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 3
• GYDHDHHCACIZIC-UHFFFAOYSA-N methyl 4-[[(6-chloro-5-nitro-2-propylsulfanylpyrimidin-4-yl)amino]methyl]benzoate Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C(=O)OC)C=C1)[N+](=O)[O-] GYDHDHHCACIZIC-UHFFFAOYSA-N 0.000 description 3
• 230000007886 mutagenicity Effects 0.000 description 3
• 231100000299 mutagenicity Toxicity 0.000 description 3
• HCUFKIUYBRJORR-UHFFFAOYSA-N n,2-dimethylpyridin-4-amine Chemical compound CNC1=CC=NC(C)=C1 HCUFKIUYBRJORR-UHFFFAOYSA-N 0.000 description 3
• NFPUARSXIMWASK-GOEBONIOSA-N n-[(5r,7s)-2-(3-chlorophenyl)-1-oxa-3-azaspiro[4.5]dec-2-en-7-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCC[C@@]11OC(C=2C=C(Cl)C=CC=2)=NC1 NFPUARSXIMWASK-GOEBONIOSA-N 0.000 description 3
• PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 3
• MUJNAWXXOJRNGK-UHFFFAOYSA-N n-[3-(6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)propyl]cyclohexanamine Chemical compound C1=2CCCCC=2C2=CC(C)=CC=C2N1CCCNC1CCCCC1 MUJNAWXXOJRNGK-UHFFFAOYSA-N 0.000 description 3
• CJPMSUUANYLPET-UHFFFAOYSA-N n-[3-[[5-cyclopropyl-2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCNC(C(=CN=1)C2CC2)=NC=1NC(C=C1)=CC=C1N1CCOCC1 CJPMSUUANYLPET-UHFFFAOYSA-N 0.000 description 3
• MUWDEQLPHWVPPA-GOTSBHOMSA-N n-[6-oxo-6-[(3s,4s)-3-[(4-phenoxyphenyl)sulfonylamino]-4-sulfanylpyrrolidin-1-yl]hexyl]acetamide Chemical compound C1N(C(=O)CCCCCNC(=O)C)C[C@H](S)[C@H]1NS(=O)(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 MUWDEQLPHWVPPA-GOTSBHOMSA-N 0.000 description 3
• LVBWRNKEBGYENR-UHFFFAOYSA-N n-cyclopropyl-4-[8-(oxan-4-ylmethylamino)-6-[(1,1,1-trifluoro-2-methylpropan-2-yl)amino]imidazo[1,2-b]pyridazin-3-yl]benzamide Chemical compound C12=NC=C(C=3C=CC(=CC=3)C(=O)NC3CC3)N2N=C(NC(C)(C)C(F)(F)F)C=C1NCC1CCOCC1 LVBWRNKEBGYENR-UHFFFAOYSA-N 0.000 description 3
• ASOADIZOVZTJSR-UHFFFAOYSA-N opicapone Chemical compound CC1=C(Cl)C(C)=[N+]([O-])C(Cl)=C1C1=NOC(C=2C=C(C(O)=C(O)C=2)[N+]([O-])=O)=N1 ASOADIZOVZTJSR-UHFFFAOYSA-N 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 239000013641 positive control Substances 0.000 description 3
• 238000011533 pre-incubation Methods 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• YKEGUYTXACKXKS-IRXDYDNUSA-N tert-butyl (1s,5s)-3-[5-methyl-6-(2-methylpyridin-3-yl)oxypyrimidin-4-yl]oxy-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=NC=CC=C1OC1=NC=NC(OC2C[C@@H]3CC[C@H](N3C(=O)OC(C)(C)C)C2)=C1C YKEGUYTXACKXKS-IRXDYDNUSA-N 0.000 description 3
• FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• ASQOQJYHIYYTEJ-GBESFXJTSA-N (1r,7s,9as)-7-decyl-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizin-1-ol Chemical compound O[C@@H]1CCCN2C[C@@H](CCCCCCCCCC)CC[C@H]21 ASQOQJYHIYYTEJ-GBESFXJTSA-N 0.000 description 2
• KSOVGRCOLZZTPF-QMKUDKLTSA-N (1s,2s,3r,4r)-3-[[5-fluoro-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N([C@H]1[C@H]([C@@]2([H])C[C@@]1(C=C2)[H])C(N)=O)C(C(=CN=1)F)=NC=1NC(C=C1C)=CC=C1N1CCN(C)CC1 KSOVGRCOLZZTPF-QMKUDKLTSA-N 0.000 description 2
• SYSGWPLRRPINQC-UHFFFAOYSA-N (2-methylpyridin-4-yl)methanamine Chemical compound CC1=CC(CN)=CC=N1 SYSGWPLRRPINQC-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
• LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 2
• VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 2
• BSGIKRCNMBTGEB-UHFFFAOYSA-N (5-bromo-1-methylpyrrolo[2,3-c]pyridin-2-yl)-[6-[(dimethylamino)methyl]-4-methyl-3,4-dihydro-1h-isoquinolin-2-yl]methanone Chemical compound BrC1=NC=C2N(C)C(C(=O)N3CC(C4=CC(CN(C)C)=CC=C4C3)C)=CC2=C1 BSGIKRCNMBTGEB-UHFFFAOYSA-N 0.000 description 2
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
• OVBFMEVBMNZIBR-UHFFFAOYSA-N 2-methylvaleric acid Chemical compound CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 description 2
• ODZCKFNCAFHXRG-UHFFFAOYSA-N 3-[(6-amino-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzonitrile Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=C(C#N)C=CC=1)=O ODZCKFNCAFHXRG-UHFFFAOYSA-N 0.000 description 2
• UGLXOFQQLROLFX-UHFFFAOYSA-N 3-[(6-amino-8-oxo-2-propylsulfinyl-7H-purin-9-yl)methyl]benzonitrile Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC=1C=C(C#N)C=CC=1)=O UGLXOFQQLROLFX-UHFFFAOYSA-N 0.000 description 2
• UTOQNBVFPWFMNZ-UHFFFAOYSA-N 3-[(6-chloro-2-methylsulfanyl-8-oxo-7H-purin-9-yl)methyl]benzonitrile Chemical compound ClC1=C2NC(N(C2=NC(=N1)SC)CC=1C=C(C#N)C=CC=1)=O UTOQNBVFPWFMNZ-UHFFFAOYSA-N 0.000 description 2
• HCLQARMRCPEALF-DNQXCXABSA-N 3-[[(2r)-2-[(1r)-2-[[1-(1-benzothiophen-2-yl)-2-methylpropan-2-yl]amino]-1-hydroxyethyl]pyrrolidin-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1[C@H](O)CNC(C)(CC=2SC3=CC=CC=C3C=2)C)CCN1CC1=CC=CC(C#N)=C1 HCLQARMRCPEALF-DNQXCXABSA-N 0.000 description 2
• XYLHEQDKJGBQSZ-UHFFFAOYSA-N 3-[[(5-amino-6-chloro-2-propylsulfanylpyrimidin-4-yl)amino]methyl]benzonitrile Chemical compound NC=1C(=NC(=NC=1Cl)SCCC)NCC=1C=C(C#N)C=CC=1 XYLHEQDKJGBQSZ-UHFFFAOYSA-N 0.000 description 2
• NVVPMZUGELHVMH-UHFFFAOYSA-N 3-ethyl-4-[4-[4-(1-methylpyrazol-4-yl)imidazol-1-yl]-3-propan-2-ylpyrazolo[3,4-b]pyridin-1-yl]benzamide Chemical compound CCC1=CC(C(N)=O)=CC=C1N1C2=NC=CC(N3C=C(N=C3)C3=CN(C)N=C3)=C2C(C(C)C)=N1 NVVPMZUGELHVMH-UHFFFAOYSA-N 0.000 description 2
• JLOFVZKCYFDECG-UHFFFAOYSA-N 4-N-[(4-bromophenyl)methyl]-6-chloro-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)Br)N JLOFVZKCYFDECG-UHFFFAOYSA-N 0.000 description 2
• NHWTUJPCXDRQNF-UHFFFAOYSA-N 4-chloro-3-methylbenzamide Chemical compound CC1=CC(C(N)=O)=CC=C1Cl NHWTUJPCXDRQNF-UHFFFAOYSA-N 0.000 description 2
• MMZMROHDQCJAJT-UHFFFAOYSA-N 4-chloro-4-oxobutanoic acid Chemical compound OC(=O)CCC(Cl)=O MMZMROHDQCJAJT-UHFFFAOYSA-N 0.000 description 2
• VLWRKVBQUANIGI-UHFFFAOYSA-N 4-fluoro-n-methylaniline Chemical compound CNC1=CC=C(F)C=C1 VLWRKVBQUANIGI-UHFFFAOYSA-N 0.000 description 2
• ZDHQVQVNOIWLNX-UHFFFAOYSA-N 5-(7-chloro-10h-benzo[1,2]cyclohepta[2,4-c][1,3]thiazol-10-yl)-1-methyl-4-sulfanylidenepyrimidin-2-one Chemical compound S=C1NC(=O)N(C)C=C1C1C2=CC=C(Cl)C=C2C=CC2=C1N=CS2 ZDHQVQVNOIWLNX-UHFFFAOYSA-N 0.000 description 2
• SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 2
• JHJXDGMATBLARH-UHFFFAOYSA-N 6-(ethylamino)-9-[(6-methylpyridin-3-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound C(C)NC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=CC=1)C)=O JHJXDGMATBLARH-UHFFFAOYSA-N 0.000 description 2
• AOIPJFRADPKAFS-UHFFFAOYSA-N 6-(ethylamino)-9-[(6-methylpyridin-3-yl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound C(C)NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC=1C=NC(=CC=1)C)=O AOIPJFRADPKAFS-UHFFFAOYSA-N 0.000 description 2
• UIBHXZITWIPTPT-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-2-propylsulfinyl-9-(pyrimidin-5-ylmethyl)-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC=1C=NC=NC=1)=O UIBHXZITWIPTPT-UHFFFAOYSA-N 0.000 description 2
• DBMPIOFKGCJGNJ-UHFFFAOYSA-N 6-amino-2-(3-chloropropylsulfanyl)-9-[(4-methoxyphenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCCCl)CC1=CC=C(C=C1)OC)=O DBMPIOFKGCJGNJ-UHFFFAOYSA-N 0.000 description 2
• JYEGCOQQEWQOMI-UHFFFAOYSA-N 6-amino-9-[(2,4-difluorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=C(C=C(C=C1)F)F)=O JYEGCOQQEWQOMI-UHFFFAOYSA-N 0.000 description 2
• HJPNICYHBIWMIN-UHFFFAOYSA-N 6-amino-9-[(3-chloro-4-methylphenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC(=C(C=C1)C)Cl)=O HJPNICYHBIWMIN-UHFFFAOYSA-N 0.000 description 2
• SITQWHVVXNSHSG-UHFFFAOYSA-N 6-amino-9-[(4-chloro-3-fluorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)Cl)F)=O SITQWHVVXNSHSG-UHFFFAOYSA-N 0.000 description 2
• LCZPJVDNHFISPW-UHFFFAOYSA-N 6-amino-9-[(4-chloro-3-methylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC(=C(C=C1)Cl)C)=O LCZPJVDNHFISPW-UHFFFAOYSA-N 0.000 description 2
• ICPOUPIDKAVXEK-UHFFFAOYSA-N 6-amino-9-[(4-chloro-3-methylphenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC(=C(C=C1)Cl)C)=O ICPOUPIDKAVXEK-UHFFFAOYSA-N 0.000 description 2
• QRYTZSJRGCPRGO-UHFFFAOYSA-N 6-amino-9-[(4-methoxyphenyl)methyl]-2-methylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C)CC1=CC=C(C=C1)OC)=O QRYTZSJRGCPRGO-UHFFFAOYSA-N 0.000 description 2
• FATSPKACVVCXGN-UHFFFAOYSA-N 6-amino-9-[(4-methylphenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=C(C=C1)C)=O FATSPKACVVCXGN-UHFFFAOYSA-N 0.000 description 2
• RGODUQNFWRVDPN-UHFFFAOYSA-N 6-amino-9-[(6-chloropyridin-3-yl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC=1C=NC(=CC=1)Cl)=O RGODUQNFWRVDPN-UHFFFAOYSA-N 0.000 description 2
• BMIUMQBNFDNIMK-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2-methoxyethylsulfanyl)-7h-purin-8-one Chemical compound C12=NC(SCCOC)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 BMIUMQBNFDNIMK-UHFFFAOYSA-N 0.000 description 2
• ITQQLOHSLWRIEY-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2-methoxypropylsulfinyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC(C)OC)CC1=CC=CC=C1)=O ITQQLOHSLWRIEY-UHFFFAOYSA-N 0.000 description 2
• QJEZJZYVQKNOII-UHFFFAOYSA-N 6-amino-9-benzyl-2-butan-2-ylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C(C)CC)CC1=CC=CC=C1)=O QJEZJZYVQKNOII-UHFFFAOYSA-N 0.000 description 2
• UYYSNQIRKWLHAD-UHFFFAOYSA-N 6-amino-9-benzyl-2-butylsulfanyl-7h-purin-8-one Chemical compound C12=NC(SCCCC)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 UYYSNQIRKWLHAD-UHFFFAOYSA-N 0.000 description 2
• RYANVUBTQQMWTQ-UHFFFAOYSA-N 6-amino-9-benzyl-2-butylsulfinyl-7h-purin-8-one Chemical compound C12=NC([S+]([O-])CCCC)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 RYANVUBTQQMWTQ-UHFFFAOYSA-N 0.000 description 2
• PYDXLEOHCQSCCE-UHFFFAOYSA-N 6-amino-9-benzyl-2-ethylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC)CC1=CC=CC=C1)=O PYDXLEOHCQSCCE-UHFFFAOYSA-N 0.000 description 2
• RVOTWKKVMSPCLK-UHFFFAOYSA-N 6-amino-9-benzyl-2-propan-2-ylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)C(C)C)CC1=CC=CC=C1)=O RVOTWKKVMSPCLK-UHFFFAOYSA-N 0.000 description 2
• AYNPKJQFAPISAZ-UHFFFAOYSA-N 6-chloro-2-propylsulfanyl-4-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)C(F)(F)F)N AYNPKJQFAPISAZ-UHFFFAOYSA-N 0.000 description 2
• JGJZMBYOSLNMPD-UHFFFAOYSA-N 6-chloro-4-N-[(2,4-difluorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=C(C=C(C=C1)F)F)N JGJZMBYOSLNMPD-UHFFFAOYSA-N 0.000 description 2
• LSGHMFVUOHSPAY-UHFFFAOYSA-N 6-chloro-4-N-[(3,4-difluorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)F)F)N LSGHMFVUOHSPAY-UHFFFAOYSA-N 0.000 description 2
• CIONPFPQYXHPEX-UHFFFAOYSA-N 6-chloro-4-N-[(3-chlorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=CC=C1)Cl)N CIONPFPQYXHPEX-UHFFFAOYSA-N 0.000 description 2
• QZDNOLMTPVUQHZ-UHFFFAOYSA-N 6-chloro-4-N-[(4-fluorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)F)N QZDNOLMTPVUQHZ-UHFFFAOYSA-N 0.000 description 2
• LXXRXUXKBMMOND-UHFFFAOYSA-N 6-chloro-5-nitro-2-propylsulfanyl-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)C(F)(F)F)[N+](=O)[O-] LXXRXUXKBMMOND-UHFFFAOYSA-N 0.000 description 2
• JMVGWDKXXPHGBQ-UHFFFAOYSA-N 6-chloro-9-[(4-chlorophenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)Cl)=O JMVGWDKXXPHGBQ-UHFFFAOYSA-N 0.000 description 2
• FXCLRQAKICJUSM-UHFFFAOYSA-N 6-chloro-N-[(2-methylpyrimidin-5-yl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC=1C=NC(=NC=1)C)[N+](=O)[O-] FXCLRQAKICJUSM-UHFFFAOYSA-N 0.000 description 2
• FDLQLLZNIHGIRR-UHFFFAOYSA-N 6-chloro-N-[(3,4-dichlorophenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)Cl)Cl)[N+](=O)[O-] FDLQLLZNIHGIRR-UHFFFAOYSA-N 0.000 description 2
• DPQXAZCRPOKENP-UHFFFAOYSA-N 6-chloro-N-[(3-chloro-4-methylphenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)C)Cl)[N+](=O)[O-] DPQXAZCRPOKENP-UHFFFAOYSA-N 0.000 description 2
• WOQFKWOLHQNZSN-UHFFFAOYSA-N 6-chloro-N-[(4-chloro-3-methylphenyl)methyl]-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)Cl)C)[N+](=O)[O-] WOQFKWOLHQNZSN-UHFFFAOYSA-N 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 2
• 206010048610 Cardiotoxicity Diseases 0.000 description 2
• 208000000419 Chronic Hepatitis B Diseases 0.000 description 2
• 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 2
• 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 101100501444 Escherichia phage P1 17 gene Proteins 0.000 description 2
• 101710142246 External core antigen Proteins 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
• 229930182566 Gentamicin Natural products 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• 108010024636 Glutathione Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 102100026720 Interferon beta Human genes 0.000 description 2
• 108090000467 Interferon-beta Proteins 0.000 description 2
• 108010063738 Interleukins Proteins 0.000 description 2
• 102000015696 Interleukins Human genes 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 2
• TWTXTWSFXYSAGO-UHFFFAOYSA-N N-[(4-bromophenyl)methyl]-6-chloro-5-nitro-2-propylsulfanylpyrimidin-4-amine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)Br)[N+](=O)[O-] TWTXTWSFXYSAGO-UHFFFAOYSA-N 0.000 description 2
• USMWWQSLSNFTDU-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]-2-methylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CC)C)=O)SCCC USMWWQSLSNFTDU-UHFFFAOYSA-N 0.000 description 2
• RPDIXUIUXREWAI-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]-2-methylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CC)C)=O)S(=O)CCC RPDIXUIUXREWAI-UHFFFAOYSA-N 0.000 description 2
• 229930182555 Penicillin Natural products 0.000 description 2
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 208000018452 Torsade de pointes Diseases 0.000 description 2
• 208000002363 Torsades de Pointes Diseases 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 230000009287 biochemical signal transduction Effects 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 231100000259 cardiotoxicity Toxicity 0.000 description 2
• JQXXHWHPUNPDRT-YOPQJBRCSA-N chembl1332716 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CCN(C)CC1 JQXXHWHPUNPDRT-YOPQJBRCSA-N 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000012228 culture supernatant Substances 0.000 description 2
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 238000009509 drug development Methods 0.000 description 2
• 238000000132 electrospray ionisation Methods 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 229960002518 gentamicin Drugs 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 229960002885 histidine Drugs 0.000 description 2
• 102000045715 human TLR7 Human genes 0.000 description 2
• 102000045720 human TLR8 Human genes 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 2
• 239000012535 impurity Substances 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 230000015788 innate immune response Effects 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
• 239000004310 lactic acid Substances 0.000 description 2
• 235000014655 lactic acid Nutrition 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 229910001629 magnesium chloride Inorganic materials 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 239000001630 malic acid Substances 0.000 description 2
• 235000011090 malic acid Nutrition 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 230000003228 microsomal effect Effects 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 229960000381 omeprazole Drugs 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 244000052769 pathogen Species 0.000 description 2
• 229940049954 penicillin Drugs 0.000 description 2
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
• 229960002695 phenobarbital Drugs 0.000 description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 230000000704 physical effect Effects 0.000 description 2
• 210000002381 plasma Anatomy 0.000 description 2
• 239000011148 porous material Substances 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000008057 potassium phosphate buffer Substances 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 230000009257 reactivity Effects 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000008929 regeneration Effects 0.000 description 2
• 238000011069 regeneration method Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 229960001225 rifampicin Drugs 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 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 2
• JYRWUSXRTGACLY-UHFFFAOYSA-N tert-butyl 4-[[3-(4-methylsulfonylphenyl)-[1,2]oxazolo[4,5-d]pyrimidin-7-yl]oxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=NC=NC2=C1ON=C2C1=CC=C(S(C)(=O)=O)C=C1 JYRWUSXRTGACLY-UHFFFAOYSA-N 0.000 description 2
• 125000001302 tertiary amino group Chemical group 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-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
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• DAAXYQZSKBPJOX-FQEVSTJZSA-N (2S)-2-amino-3-[4-[5-[3-(4-hydroxyphenyl)-4-methoxyphenyl]-1,2,4-oxadiazol-3-yl]phenyl]propanoic acid Chemical compound COC1=C(C=C(C=C1)C2=NC(=NO2)C3=CC=C(C=C3)C[C@@H](C(=O)O)N)C4=CC=C(C=C4)O DAAXYQZSKBPJOX-FQEVSTJZSA-N 0.000 description 1
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
• AEVBPXDFDKBGLT-YOUFYPILSA-N (2s,3s,4r,5r)-n-[2-[4-(diethoxyphosphorylmethyl)anilino]-2-oxoethyl]-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C1=CC(CP(=O)(OCC)OCC)=CC=C1NC(=O)CNC(=O)[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 AEVBPXDFDKBGLT-YOUFYPILSA-N 0.000 description 1
• TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 1
• IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• XPARFBOWIYMLMY-UHFFFAOYSA-N (6-chloropyridin-3-yl)methanamine Chemical compound NCC1=CC=C(Cl)N=C1 XPARFBOWIYMLMY-UHFFFAOYSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 1
• DJMOXMNDXFFONV-UHFFFAOYSA-N 1,3-dimethyl-7-[2-(n-methylanilino)ethyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCN(C)C1=CC=CC=C1 DJMOXMNDXFFONV-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• CEVMYGZHEJSOHZ-UHFFFAOYSA-N 1-bromo-3-methoxypropane Chemical compound COCCCBr CEVMYGZHEJSOHZ-UHFFFAOYSA-N 0.000 description 1
• VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 1
• PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
• RPGDVPAENGWKAO-UHFFFAOYSA-N 2,4-difluoro-n-methylaniline Chemical compound CNC1=CC=C(F)C=C1F RPGDVPAENGWKAO-UHFFFAOYSA-N 0.000 description 1
• FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
• WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• QRXBTPFMCTXCRD-UHFFFAOYSA-N 2-chloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC=N1 QRXBTPFMCTXCRD-UHFFFAOYSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• YCURDTPXHPXCKH-UHFFFAOYSA-N 2-ethylbutanoyl 2-ethylbutanoate Chemical compound CCC(CC)C(=O)OC(=O)C(CC)CC YCURDTPXHPXCKH-UHFFFAOYSA-N 0.000 description 1
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• WRTPVONNQPWNRH-UHFFFAOYSA-N 2-methylbutanoyl 2-methylbutanoate Chemical compound CCC(C)C(=O)OC(=O)C(C)CC WRTPVONNQPWNRH-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• SULGSLUIIZBEEN-UHFFFAOYSA-N 3,4-difluoro-n-methylaniline Chemical compound CNC1=CC=C(F)C(F)=C1 SULGSLUIIZBEEN-UHFFFAOYSA-N 0.000 description 1
• VGOALPIDEXVYQI-UHFFFAOYSA-N 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-n-[3-imidazol-1-yl-5-(trifluoromethyl)phenyl]-4-methylbenzamide Chemical compound C1=C(C#CC=2N3N=CC=CC3=NC=2)C(C)=CC=C1C(=O)NC(C=C(C=1)C(F)(F)F)=CC=1N1C=CN=C1 VGOALPIDEXVYQI-UHFFFAOYSA-N 0.000 description 1
• XFKPORAVEUOIRF-UHFFFAOYSA-N 3-(aminomethyl)benzonitrile Chemical compound NCC1=CC=CC(C#N)=C1 XFKPORAVEUOIRF-UHFFFAOYSA-N 0.000 description 1
• WSFZCPSHUKUTFD-UHFFFAOYSA-N 3-[(6-chloro-8-oxo-2-propylsulfanyl-7H-purin-9-yl)methyl]benzonitrile Chemical compound ClC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=C(C#N)C=CC=1)=O WSFZCPSHUKUTFD-UHFFFAOYSA-N 0.000 description 1
• HNFMVVHMKGFCMB-UHFFFAOYSA-N 3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Chemical compound NC1=NC=CC=C1C1=NC2=CC=C(C=3C=CC=CC=3)N=C2N1C1=CC=C(C2(N)CCC2)C=C1 HNFMVVHMKGFCMB-UHFFFAOYSA-N 0.000 description 1
• UNSHMXUHOHBLIQ-UHFFFAOYSA-N 3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione Chemical compound ClC1=C(C=C(C2=CC=CC=C12)N1C(NC(=CC1=O)C(F)(F)F)=O)OC1=C(C=CC=C1)C UNSHMXUHOHBLIQ-UHFFFAOYSA-N 0.000 description 1
• IWPOXJOSPLPXLN-UHFFFAOYSA-N 3-[[(5-amino-6-chloro-2-methylsulfanylpyrimidin-4-yl)amino]methyl]benzonitrile Chemical compound NC=1C(=NC(=NC=1Cl)SC)NCC=1C=C(C#N)C=CC=1 IWPOXJOSPLPXLN-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• UFBWOBPUOXILAT-UHFFFAOYSA-N 3-chloro-4-methylbenzamide Chemical compound CC1=CC=C(C(N)=O)C=C1Cl UFBWOBPUOXILAT-UHFFFAOYSA-N 0.000 description 1
• JDGUVFZDTYKQJS-UHFFFAOYSA-N 3-chloro-n,4-dimethylaniline Chemical compound CNC1=CC=C(C)C(Cl)=C1 JDGUVFZDTYKQJS-UHFFFAOYSA-N 0.000 description 1
• WFGYSQDPURFIFL-UHFFFAOYSA-N 3-chloro-n-methylaniline Chemical compound CNC1=CC=CC(Cl)=C1 WFGYSQDPURFIFL-UHFFFAOYSA-N 0.000 description 1
• LFIWXXXFJFOECP-UHFFFAOYSA-N 4-(aminomethyl)benzonitrile Chemical compound NCC1=CC=C(C#N)C=C1 LFIWXXXFJFOECP-UHFFFAOYSA-N 0.000 description 1
• WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 1
• AYVPVDWQZAAZCM-UHFFFAOYSA-N 4-bromo-n-methylaniline Chemical compound CNC1=CC=C(Br)C=C1 AYVPVDWQZAAZCM-UHFFFAOYSA-N 0.000 description 1
• MRUKIIWRMSYKML-UHFFFAOYSA-N 4-chloro-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1Cl MRUKIIWRMSYKML-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• TZKBVRDEOITLRB-UHFFFAOYSA-N 4-methyl-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1h-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2C=C3C=NNC3=NC=2)=C1 TZKBVRDEOITLRB-UHFFFAOYSA-N 0.000 description 1
• QBXKHAIAWWJEDP-UHFFFAOYSA-N 6-[(4-methoxyphenyl)methylamino]-9-[(2-methylpyrimidin-5-yl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound COC1=CC=C(C=C1)CNC1=C2NC(N(C2=NC(=N1)SCCC)CC=1C=NC(=NC=1)C)=O QBXKHAIAWWJEDP-UHFFFAOYSA-N 0.000 description 1
• WZLWMPJFCVDACR-UHFFFAOYSA-N 6-amino-2-(3-chloropropylsulfinyl)-9-[(4-methoxyphenyl)methyl]-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCCCl)CC1=CC=C(C=C1)OC)=O WZLWMPJFCVDACR-UHFFFAOYSA-N 0.000 description 1
• AABAIKFHSWQIFO-UHFFFAOYSA-N 6-amino-9-(3,4-dichlorophenyl)-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)C1=CC(=C(C=C1)Cl)Cl)=O AABAIKFHSWQIFO-UHFFFAOYSA-N 0.000 description 1
• OYDTTXSWKNTOFY-UHFFFAOYSA-N 6-amino-9-[(2,4-difluorophenyl)methyl]-2-(propylsulfonimidoyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=C(C=C(C=C1)F)F)=O OYDTTXSWKNTOFY-UHFFFAOYSA-N 0.000 description 1
• WBFUQOPVMJQIAL-UHFFFAOYSA-N 6-amino-9-[(3,4-dichlorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC(=C(C=C1)Cl)Cl)=O WBFUQOPVMJQIAL-UHFFFAOYSA-N 0.000 description 1
• OEMOAEPBLIYKJT-UHFFFAOYSA-N 6-amino-9-[(3,4-difluorophenyl)methyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC(=C(C=C1)F)F)=O OEMOAEPBLIYKJT-UHFFFAOYSA-N 0.000 description 1
• PPVXJMYJMODOPW-UHFFFAOYSA-N 6-amino-9-[(4-methylphenyl)methyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CC1=CC=C(C=C1)C)=O PPVXJMYJMODOPW-UHFFFAOYSA-N 0.000 description 1
• OKXDMOOKPVCQGS-UHFFFAOYSA-N 6-amino-9-[2-(4-methylphenyl)ethyl]-2-propylsulfanyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCC)CCC1=CC=C(C=C1)C)=O OKXDMOOKPVCQGS-UHFFFAOYSA-N 0.000 description 1
• HCUAMAOLLLTPQG-UHFFFAOYSA-N 6-amino-9-[2-(4-methylphenyl)ethyl]-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CCC1=CC=C(C=C1)C)=O HCUAMAOLLLTPQG-UHFFFAOYSA-N 0.000 description 1
• VFZUVWZQMMOSCU-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2,2,2-trifluoroethylsulfanyl)-7h-purin-8-one Chemical compound OC1=NC=2C(N)=NC(SCC(F)(F)F)=NC=2N1CC1=CC=CC=C1 VFZUVWZQMMOSCU-UHFFFAOYSA-N 0.000 description 1
• FDLPDJHVEKXWLI-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2,2,2-trifluoroethylsulfinyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CC(F)(F)F)CC1=CC=CC=C1)=O FDLPDJHVEKXWLI-UHFFFAOYSA-N 0.000 description 1
• ILDXPPZRFKYDCQ-UHFFFAOYSA-N 6-amino-9-benzyl-2-(2-methoxypropylsulfanyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCC(C)OC)CC1=CC=CC=C1)=O ILDXPPZRFKYDCQ-UHFFFAOYSA-N 0.000 description 1
• BYCVOHQIYWOEQU-UHFFFAOYSA-N 6-amino-9-benzyl-2-(3-methoxypropylsulfanyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)SCCCOC)CC1=CC=CC=C1)=O BYCVOHQIYWOEQU-UHFFFAOYSA-N 0.000 description 1
• XDLSAEMIECHJEI-UHFFFAOYSA-N 6-amino-9-benzyl-2-(3-methoxypropylsulfinyl)-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCCOC)CC1=CC=CC=C1)=O XDLSAEMIECHJEI-UHFFFAOYSA-N 0.000 description 1
• AXDQSGFYWDRPFK-UHFFFAOYSA-N 6-amino-9-benzyl-2-methylsulfonyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)(=O)C)CC1=CC=CC=C1)=O AXDQSGFYWDRPFK-UHFFFAOYSA-N 0.000 description 1
• XJZJHVOQISEZRS-UHFFFAOYSA-N 6-amino-9-benzyl-2-propan-2-ylsulfanyl-7h-purin-8-one Chemical compound C12=NC(SC(C)C)=NC(N)=C2N=C(O)N1CC1=CC=CC=C1 XJZJHVOQISEZRS-UHFFFAOYSA-N 0.000 description 1
• XMBWXMCTNHNBEU-UHFFFAOYSA-N 6-amino-9-benzyl-2-propylsulfinyl-7H-purin-8-one Chemical compound NC1=C2NC(N(C2=NC(=N1)S(=O)CCC)CC1=CC=CC=C1)=O XMBWXMCTNHNBEU-UHFFFAOYSA-N 0.000 description 1
• JVUUXKKIOZXODB-UHFFFAOYSA-N 6-amino-9-benzyl-7-sulfanyl-2-(2,2,2-trifluoroethyl)purin-8-one Chemical compound NC1=C2N(C(N(C2=NC(=N1)CC(F)(F)F)CC1=CC=CC=C1)=O)S JVUUXKKIOZXODB-UHFFFAOYSA-N 0.000 description 1
• TUVQTRGKVDPLDU-UHFFFAOYSA-N 6-chloro-4-N-[(3,4-dichlorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)Cl)Cl)N TUVQTRGKVDPLDU-UHFFFAOYSA-N 0.000 description 1
• RBZBVXCLOKTTQT-UHFFFAOYSA-N 6-chloro-4-N-[(4-chloro-3-fluorophenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC(=C(C=C1)Cl)F)N RBZBVXCLOKTTQT-UHFFFAOYSA-N 0.000 description 1
• MIOZVXHNRGUNCK-UHFFFAOYSA-N 6-chloro-4-N-[(4-methylphenyl)methyl]-2-propylsulfanylpyrimidine-4,5-diamine Chemical compound ClC1=C(C(=NC(=N1)SCCC)NCC1=CC=C(C=C1)C)N MIOZVXHNRGUNCK-UHFFFAOYSA-N 0.000 description 1
• RZOKQIPOABEQAM-UHFFFAOYSA-N 6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=N1 RZOKQIPOABEQAM-UHFFFAOYSA-N 0.000 description 1
• MDHIDSVJFILSJC-UHFFFAOYSA-N 7-methyl-2-propylsulfinyl-9H-purin-8-one Chemical compound CN1C(NC2=NC(=NC=C12)S(=O)CCC)=O MDHIDSVJFILSJC-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• LPWKFUVWWQYLOD-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-methylphenyl)pyrido[2,3]thieno[2,4-d]pyrimidin-4-one Chemical compound C1=2C(N(C)C)=CN=CC=2SC(C2=O)=C1N=CN2C1=CC=C(C)C=C1 LPWKFUVWWQYLOD-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 238000010953 Ames test Methods 0.000 description 1
• 231100000039 Ames test Toxicity 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 208000006154 Chronic hepatitis C Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 102000012422 Collagen Type I Human genes 0.000 description 1
• 108010022452 Collagen Type I Proteins 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 229940127007 Compound 39 Drugs 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• 102000008144 Cytochrome P-450 CYP1A2 Human genes 0.000 description 1
• 108010074922 Cytochrome P-450 CYP1A2 Proteins 0.000 description 1
• 208000005038 Cytochrome P-450 CYP1A2 Inducers Diseases 0.000 description 1
• 102000009666 Cytochrome P-450 CYP2B6 Human genes 0.000 description 1
• 108010020070 Cytochrome P-450 CYP2B6 Proteins 0.000 description 1
• 208000004836 Cytochrome P-450 CYP2B6 Inducers Diseases 0.000 description 1
• 208000000130 Cytochrome P-450 CYP3A Inducers Diseases 0.000 description 1
• NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• ODBLHEXUDAPZAU-ZAFYKAAXSA-N D-threo-isocitric acid Chemical compound OC(=O)[C@H](O)[C@@H](C(O)=O)CC(O)=O ODBLHEXUDAPZAU-ZAFYKAAXSA-N 0.000 description 1
• 230000009946 DNA mutation Effects 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 206010019851 Hepatotoxicity Diseases 0.000 description 1
• 101000855342 Homo sapiens Cytochrome P450 1A2 Proteins 0.000 description 1
• 101000957383 Homo sapiens Cytochrome P450 2B6 Proteins 0.000 description 1
• 101000745711 Homo sapiens Cytochrome P450 3A4 Proteins 0.000 description 1
• 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
• 101001057508 Homo sapiens Ubiquitin-like protein ISG15 Proteins 0.000 description 1
• 241000701806 Human papillomavirus Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• 102000012011 Isocitrate Dehydrogenase Human genes 0.000 description 1
• 108010075869 Isocitrate Dehydrogenase Proteins 0.000 description 1
• ODBLHEXUDAPZAU-FONMRSAGSA-N Isocitric acid Natural products OC(=O)[C@@H](O)[C@H](C(O)=O)CC(O)=O ODBLHEXUDAPZAU-FONMRSAGSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 229910010082 LiAlH Inorganic materials 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 description 1
• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
• 101000574441 Mus musculus Alkaline phosphatase, germ cell type Proteins 0.000 description 1
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
• STBYSMGZDRLNMG-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-(propylsulfonimidoyl)-7H-purin-6-yl]-2-methylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(C(CC)C)=O)S(=O)(=N)CCC STBYSMGZDRLNMG-UHFFFAOYSA-N 0.000 description 1
• USPSZVPVMZWLLM-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfanyl-7H-purin-6-yl]-3-methylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(CC(C)C)=O)SCCC USPSZVPVMZWLLM-UHFFFAOYSA-N 0.000 description 1
• IOHGLVGCGLPUQS-UHFFFAOYSA-N N-[9-[(4-chlorophenyl)methyl]-8-oxo-2-propylsulfinyl-7H-purin-6-yl]-3-methylbutanamide Chemical compound ClC1=CC=C(C=C1)CN1C2=NC(=NC(=C2NC1=O)NC(CC(C)C)=O)S(=O)CCC IOHGLVGCGLPUQS-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• ZNSPHKJFQDEABI-NZQKXSOJSA-N Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 Chemical compound Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 ZNSPHKJFQDEABI-NZQKXSOJSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 239000006057 Non-nutritive feed additive Substances 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 102000004257 Potassium Channel Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 239000012162 RNA isolation reagent Substances 0.000 description 1
• 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229940124615 TLR 7 agonist Drugs 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
• 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 1
• 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
• 108020004566 Transfer RNA Proteins 0.000 description 1
• 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
• 102100027266 Ubiquitin-like protein ISG15 Human genes 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• NPUXORBZRBIOMQ-RUZDIDTESA-N [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]-2-pyrrolidinyl]methanol Chemical compound C=1C(OCC=2C=CC(CN3[C@H](CCC3)CO)=CC=2)=CC(C)=CC=1CS(=O)(=O)C1=CC=CC=C1 NPUXORBZRBIOMQ-RUZDIDTESA-N 0.000 description 1
• HOOMGTNENMZAFP-NYNCVSEMSA-N [(2r,3r,5s)-2-(5-amino-2-oxo-[1,3]thiazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1C[C@@H](CO)O[C@H]1N1C(=O)SC2=CN=C(N)N=C21 HOOMGTNENMZAFP-NYNCVSEMSA-N 0.000 description 1
• MATCCHJZJHJDTA-UHFFFAOYSA-N [3-(dimethylamino)-2-(dimethylazaniumylidenemethyl)prop-2-enylidene]-dimethylazanium Chemical compound CN(C)C=C(C=[N+](C)C)C=[N+](C)C MATCCHJZJHJDTA-UHFFFAOYSA-N 0.000 description 1
• JORKMXMMDKLULK-UHFFFAOYSA-N [6-amino-9-benzyl-2-(propylsulfonimidoyl)purin-8-yl] N-ethyl-N-methylcarbamate Chemical compound NC1=C2N=C(N(C2=NC(=N1)S(=O)(=N)CCC)CC1=CC=CC=C1)OC(N(C)CC)=O JORKMXMMDKLULK-UHFFFAOYSA-N 0.000 description 1
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
• BAWFJGJZGIEFAR-DQQFMEOOSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)O[P@@](O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-DQQFMEOOSA-N 0.000 description 1
• YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
• 239000008351 acetate buffer Substances 0.000 description 1
• 235000011054 acetic acid Nutrition 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 108091005764 adaptor proteins Proteins 0.000 description 1
• 102000035181 adaptor proteins Human genes 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000001270 agonistic effect Effects 0.000 description 1
• 229940060265 aldara Drugs 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 239000012491 analyte Substances 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 229960004977 anhydrous lactose Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 230000008238 biochemical pathway Effects 0.000 description 1
• 230000036782 biological activation Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000013060 biological fluid Substances 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical compound OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 1
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
• UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000008366 buffered solution Substances 0.000 description 1
• 239000004067 bulking agent Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 238000011088 calibration curve Methods 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000006037 cell lysis Effects 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 208000016350 chronic hepatitis B virus infection Diseases 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125876 compound 15a Drugs 0.000 description 1
• 229940126212 compound 17a Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125877 compound 31 Drugs 0.000 description 1
• 229940127573 compound 38 Drugs 0.000 description 1
• 229940125900 compound 59 Drugs 0.000 description 1
• 238000011970 concomitant therapy Methods 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 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 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
• 229960001259 diclofenac Drugs 0.000 description 1
• PQZTVWVYCLIIJY-UHFFFAOYSA-N diethyl(propyl)amine Chemical compound CCCN(CC)CC PQZTVWVYCLIIJY-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 230000007831 electrophysiology Effects 0.000 description 1
• 238000002001 electrophysiology Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000001163 endosome Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• IXZFDJXHLQQSGQ-UHFFFAOYSA-N ethyl 4-chloro-4-oxobutanoate Chemical compound CCOC(=O)CCC(Cl)=O IXZFDJXHLQQSGQ-UHFFFAOYSA-N 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 244000144993 groups of animals Species 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 231100000304 hepatotoxicity Toxicity 0.000 description 1
• 230000007686 hepatotoxicity Effects 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 102000057459 human CYP1A2 Human genes 0.000 description 1
• 102000047894 human CYP2B6 Human genes 0.000 description 1
• 102000044284 human CYP3A4 Human genes 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 238000010191 image analysis Methods 0.000 description 1
• 229960002751 imiquimod Drugs 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 238000005040 ion trap Methods 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 210000004731 jugular vein Anatomy 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 238000012006 liquid chromatography with tandem mass spectrometry Methods 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
• 208000021039 metastatic melanoma Diseases 0.000 description 1
• AQBJGAUQEJFPKZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CN)C=C1 AQBJGAUQEJFPKZ-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
• SKEAGJWUKCNICJ-LSDHHAIUSA-N n-[(4-fluoro-3-methoxyphenyl)methyl]-6-[2-[[(2s,5r)-5-(hydroxymethyl)-1,4-dioxan-2-yl]methyl]tetrazol-5-yl]-2-methylpyrimidine-4-carboxamide Chemical compound C1=C(F)C(OC)=CC(CNC(=O)C=2N=C(C)N=C(C=2)C2=NN(C[C@@H]3OC[C@@H](CO)OC3)N=N2)=C1 SKEAGJWUKCNICJ-LSDHHAIUSA-N 0.000 description 1
• HFMDLUQUEXNBOP-UHFFFAOYSA-N n-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18-tris(2-aminoethyl)-15-benzyl-3-(1-hydroxyethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl] Chemical compound OS(O)(=O)=O.N1C(=O)C(CCN)NC(=O)C(NC(=O)C(CCN)NC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)CCCCC(C)CC)CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C1CC1=CC=CC=C1 HFMDLUQUEXNBOP-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• UTUYWZJPVLDHJJ-UHFFFAOYSA-N n-methyl-4-(trifluoromethyl)aniline Chemical compound CNC1=CC=C(C(F)(F)F)C=C1 UTUYWZJPVLDHJJ-UHFFFAOYSA-N 0.000 description 1
• RQEYQVCVGXCQQN-UHFFFAOYSA-N n-methyl-4-methylsulfonylaniline Chemical compound CNC1=CC=C(S(C)(=O)=O)C=C1 RQEYQVCVGXCQQN-UHFFFAOYSA-N 0.000 description 1
• VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 1
• 229960001800 nefazodone Drugs 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 239000003002 pH adjusting agent Substances 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000008055 phosphate buffer solution Substances 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 108020001213 potassium channel Proteins 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 229910001414 potassium ion Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 1
• 238000010839 reverse transcription Methods 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000004062 sedimentation Methods 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 231100000161 signs of toxicity Toxicity 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 206010040882 skin lesion Diseases 0.000 description 1
• 231100000444 skin lesion Toxicity 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000012064 sodium phosphate buffer Substances 0.000 description 1
• 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000004544 sputter deposition Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 229940014800 succinic anhydride Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000001839 systemic circulation Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 238000004885 tandem mass spectrometry Methods 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• ODBLHEXUDAPZAU-UHFFFAOYSA-N threo-D-isocitric acid Natural products OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 239000008181 tonicity modifier Substances 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
• 229960001641 troglitazone Drugs 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 229940005605 valeric acid Drugs 0.000 description 1
• JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1