UA120450C2 - Сполуки і похідні сульфонімідоїлпуринону для лікування і профілактики вірусної інфекції - Google Patents

Info

Publication number

UA120450C2

UA120450C2 UAA201712023A UAA201712023A UA120450C2 UA 120450 C2 UA120450 C2 UA 120450C2 UA A201712023 A UAA201712023 A UA A201712023A UA A201712023 A UAA201712023 A UA A201712023A UA 120450 C2 UA120450 C2 UA 120450C2

Authority

UA

Ukraine

Prior art keywords

purin

methyl

amino

compound

alkyl

Prior art date

2015-05-08

Links

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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 909
• 238000011282 treatment Methods 0.000 title claims description 38
• 230000002265 prevention Effects 0.000 title claims description 10
• 230000009385 viral infection Effects 0.000 title description 5
• 208000036142 Viral infection Diseases 0.000 title description 4
• 150000003839 salts Chemical class 0.000 claims abstract description 62
• 238000000034 method Methods 0.000 claims abstract description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 655
• 238000002360 preparation method Methods 0.000 claims description 295
• -1 cyano, carboxy, carbamoyl Chemical group 0.000 claims description 211
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 108
• 125000000217 alkyl group Chemical group 0.000 claims description 83
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 51
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 43
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 26
• 239000003153 chemical reaction reagent Substances 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
• 239000000556 agonist Substances 0.000 claims description 20
• 230000006698 induction Effects 0.000 claims description 20
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 239000002253 acid Substances 0.000 claims description 16
• 238000007866 imination reaction Methods 0.000 claims description 16
• 238000006243 chemical reaction Methods 0.000 claims description 14
• 125000004803 chlorobenzyl group Chemical group 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 230000003993 interaction Effects 0.000 claims description 12
• 125000006178 methyl benzyl group Chemical group 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 9
• 208000002672 hepatitis B Diseases 0.000 claims description 9
• 125000004543 purin-7-yl group Chemical group N1=CN=C2N=CN(C2=C1)* 0.000 claims description 9
• 239000005711 Benzoic acid Substances 0.000 claims description 8
• 235000010233 benzoic acid Nutrition 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
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 8
• 125000004175 fluorobenzyl group Chemical group 0.000 claims description 7
• 239000007800 oxidant agent Substances 0.000 claims description 7
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 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
• 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
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000006287 difluorobenzyl group Chemical group 0.000 claims description 5
• 229910052736 halogen Inorganic materials 0.000 claims description 5
• 150000002367 halogens Chemical class 0.000 claims description 5
• 229940126601 medicinal product Drugs 0.000 claims description 5
• IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-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 4
• 150000001263 acyl chlorides Chemical class 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000002946 cyanobenzyl group Chemical group 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
• CNMFHDIDIMZHKY-UHFFFAOYSA-N methyl 2,2-dimethylpropanoate Chemical compound COC(=O)C(C)(C)C CNMFHDIDIMZHKY-UHFFFAOYSA-N 0.000 claims description 4
• 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 3
• 239000013543 active substance Substances 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
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 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 2
• 229910052698 phosphorus Inorganic materials 0.000 claims description 2
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 2
• WPYMKLBDIGXBTP-VQEHIDDOSA-N benzoic acid Chemical compound OC(=O)C1=CC=C[13CH]=C1 WPYMKLBDIGXBTP-VQEHIDDOSA-N 0.000 claims 2
• 150000002466 imines Chemical class 0.000 claims 1
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 46
• 239000000651 prodrug Substances 0.000 abstract description 23
• 229940002612 prodrug Drugs 0.000 abstract description 23
• 239000007787 solid Substances 0.000 description 296
• 238000001819 mass spectrum Methods 0.000 description 97
• 238000005481 NMR spectroscopy Methods 0.000 description 96
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 83
• 239000000243 solution Substances 0.000 description 51
• 239000011541 reaction mixture Substances 0.000 description 42
• 239000011572 manganese Substances 0.000 description 39
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 238000012360 testing method Methods 0.000 description 36
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
• 238000010828 elution Methods 0.000 description 29
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
• 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 27
• 210000004027 cell Anatomy 0.000 description 27
• 229940125876 compound 15a Drugs 0.000 description 27
• KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 26
• 238000000926 separation method Methods 0.000 description 24
• 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 24
• 241000282414 Homo sapiens Species 0.000 description 22
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 22
• 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 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 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
• 239000012044 organic layer Substances 0.000 description 16
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 15
• 229940126543 compound 14 Drugs 0.000 description 15
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 14
• 235000019439 ethyl acetate Nutrition 0.000 description 14
• 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
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 13
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
• 230000004913 activation Effects 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
• 238000000746 purification Methods 0.000 description 12
• BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 11
• OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 11
• 229940125758 compound 15 Drugs 0.000 description 11
• 229940079593 drug Drugs 0.000 description 11
• 239000003814 drug Substances 0.000 description 11
• 229910052740 iodine Inorganic materials 0.000 description 11
• 238000002560 therapeutic procedure Methods 0.000 description 11
• PPAULTVPKLVLII-UHFFFAOYSA-N 4,5-diaminopyrimidine Chemical compound NC1=CN=CN=C1N PPAULTVPKLVLII-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
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 10
• 239000000523 sample Substances 0.000 description 10
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000002609 medium Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 8
• 108700008625 Reporter Genes Proteins 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 210000001853 liver microsome Anatomy 0.000 description 8
• 230000004060 metabolic process Effects 0.000 description 8
• 229920000137 polyphosphoric acid Polymers 0.000 description 8
• 238000002953 preparative HPLC Methods 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• 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 description 7
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 210000002381 plasma Anatomy 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
• GYIUDLLQLVWKPP-UHFFFAOYSA-N 2-propylpentanoyl 2-propylpentanoate Chemical compound CCCC(CCC)C(=O)OC(=O)C(CCC)CCC GYIUDLLQLVWKPP-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
• 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 6
• 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 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 6
• 230000001270 agonistic effect Effects 0.000 description 6
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 230000001684 chronic effect Effects 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
• 239000000411 inducer Substances 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
• DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 6
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 5
• IJBONYUNKRDIFC-UHFFFAOYSA-N 2-methylpyrimidine-5-carbaldehyde Chemical compound CC1=NC=C(C=O)C=N1 IJBONYUNKRDIFC-UHFFFAOYSA-N 0.000 description 5
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
• JHNLZOVBAQWGQU-UHFFFAOYSA-N 380814_sial Chemical compound CS(O)(=O)=O.O=P(=O)OP(=O)=O JHNLZOVBAQWGQU-UHFFFAOYSA-N 0.000 description 5
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