ZA200301641B - Peptidomimetic protease inhibitors. - Google Patents

Info

Publication number

ZA200301641B

ZA200301641B ZA200301641A ZA200301641A ZA200301641B ZA 200301641 B ZA200301641 B ZA 200301641B ZA 200301641 A ZA200301641 A ZA 200301641A ZA 200301641 A ZA200301641 A ZA 200301641A ZA 200301641 B ZA200301641 B ZA 200301641B

Authority

ZA

South Africa

Prior art keywords

compound

optionally substituted

hepatitis

group

interferon

Prior art date

2000-08-31

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000137 peptide hydrolase inhibitor Substances 0.000 title claims description 9
• 239000000816 peptidomimetic Substances 0.000 title description 13
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title description 7
• -1 cycloalkenly Chemical group 0.000 claims description 442
• 150000001875 compounds Chemical class 0.000 claims description 296
• 125000000217 alkyl group Chemical group 0.000 claims description 114
• 125000003118 aryl group Chemical group 0.000 claims description 106
• 125000001424 substituent group Chemical group 0.000 claims description 105
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 93
• 125000001072 heteroaryl group Chemical group 0.000 claims description 87
• 125000001931 aliphatic group Chemical group 0.000 claims description 82
• 125000004122 cyclic group Chemical group 0.000 claims description 81
• 102000014150 Interferons Human genes 0.000 claims description 76
• 108010050904 Interferons Proteins 0.000 claims description 76
• 238000000034 method Methods 0.000 claims description 76
• 229940079322 interferon Drugs 0.000 claims description 71
• 229910052739 hydrogen Inorganic materials 0.000 claims description 67
• 230000000694 effects Effects 0.000 claims description 63
• 239000001257 hydrogen Substances 0.000 claims description 62
• 239000002253 acid Substances 0.000 claims description 60
• 229910052757 nitrogen Inorganic materials 0.000 claims description 58
• 241000711549 Hepacivirus C Species 0.000 claims description 54
• 125000004432 carbon atom Chemical group C* 0.000 claims description 49
• 208000005176 Hepatitis C Diseases 0.000 claims description 48
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
• 241000700605 Viruses Species 0.000 claims description 44
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 41
• 239000003001 serine protease inhibitor Substances 0.000 claims description 40
• 125000003435 aroyl group Chemical group 0.000 claims description 39
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 38
• 125000002252 acyl group Chemical group 0.000 claims description 37
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 37
• 229910052799 carbon Inorganic materials 0.000 claims description 35
• 229940122055 Serine protease inhibitor Drugs 0.000 claims description 34
• 101710102218 Serine protease inhibitor Proteins 0.000 claims description 34
• 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 34
• 239000000203 mixture Substances 0.000 claims description 34
• 239000000126 substance Substances 0.000 claims description 33
• 125000006239 protecting group Chemical group 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 125000003342 alkenyl group Chemical group 0.000 claims description 25
• 150000002431 hydrogen Chemical group 0.000 claims description 25
• 125000003107 substituted aryl group Chemical group 0.000 claims description 25
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• 108010047761 Interferon-alpha Proteins 0.000 claims description 22
• 102000006992 Interferon-alpha Human genes 0.000 claims description 22
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 125000004423 acyloxy group Chemical group 0.000 claims description 21
• 125000004414 alkyl thio group Chemical group 0.000 claims description 21
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 21
• 230000008569 process Effects 0.000 claims description 21
• 125000005333 aroyloxy group Chemical group 0.000 claims description 20
• 125000004104 aryloxy group Chemical group 0.000 claims description 20
• 208000015181 infectious disease Diseases 0.000 claims description 20
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 20
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 19
• 125000003545 alkoxy group Chemical group 0.000 claims description 19
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 19
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 19
• 125000005110 aryl thio group Chemical group 0.000 claims description 19
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 19
• 229940002612 prodrug Drugs 0.000 claims description 19
• 239000000651 prodrug Substances 0.000 claims description 19
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
• UVPSSGJTBLNVRE-UHFFFAOYSA-N Moniliformin Natural products O=C1C(OC)=CC(=O)C=2C1=C1C(=O)C(OC)=CC(=O)C1=CC=2 UVPSSGJTBLNVRE-UHFFFAOYSA-N 0.000 claims description 17
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
• 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 17
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 17
• KGPQKNJSZNXOPV-UHFFFAOYSA-N moniliformin Chemical compound OC1=CC(=O)C1=O KGPQKNJSZNXOPV-UHFFFAOYSA-N 0.000 claims description 17
• 125000002950 monocyclic group Chemical group 0.000 claims description 16
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
• 229920006395 saturated elastomer Polymers 0.000 claims description 16
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
• 102100040018 Interferon alpha-2 Human genes 0.000 claims description 14
• 108010079944 Interferon-alpha2b Proteins 0.000 claims description 14
• 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 150000001408 amides Chemical group 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 125000005750 substituted cyclic group Chemical group 0.000 claims description 13
• 102000035195 Peptidases Human genes 0.000 claims description 12
• 108091005804 Peptidases Proteins 0.000 claims description 12
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 12
• 125000000304 alkynyl group Chemical group 0.000 claims description 12
• 229960000329 ribavirin Drugs 0.000 claims description 12
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 12
• 239000012453 solvate Substances 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• 230000002401 inhibitory effect Effects 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 10
• 238000011161 development Methods 0.000 claims description 10
• 238000002560 therapeutic procedure Methods 0.000 claims description 10
• 230000029812 viral genome replication Effects 0.000 claims description 10
• 102000012479 Serine Proteases Human genes 0.000 claims description 9
• 108010022999 Serine Proteases Proteins 0.000 claims description 9
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
• 239000004365 Protease Substances 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 230000001225 therapeutic effect Effects 0.000 claims description 8
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 7
• 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 7
• 108700027921 interferon tau Proteins 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 239000003112 inhibitor Substances 0.000 claims description 6
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 6
• 230000004962 physiological condition Effects 0.000 claims description 6
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
• 239000005977 Ethylene Substances 0.000 claims description 5
• 125000005647 linker group Chemical group 0.000 claims description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
• 238000006845 Michael addition reaction Methods 0.000 claims description 3
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 3
• 208000006454 hepatitis Diseases 0.000 claims description 3
• 239000003444 phase transfer catalyst Substances 0.000 claims description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
• 125000005518 carboxamido group Chemical group 0.000 claims description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 150000002430 hydrocarbons Chemical group 0.000 claims description 2
• 150000003951 lactams Chemical group 0.000 claims description 2
• 125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 23
• 150000003573 thiols Chemical class 0.000 claims 14
• 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 13
• 210000004027 cell Anatomy 0.000 claims 12
• 230000002265 prevention Effects 0.000 claims 12
• UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 claims 8
• 102000013462 Interleukin-12 Human genes 0.000 claims 8
• 108010065805 Interleukin-12 Proteins 0.000 claims 8
• 102000000588 Interleukin-2 Human genes 0.000 claims 8
• 108010002350 Interleukin-2 Proteins 0.000 claims 8
• 102000004889 Interleukin-6 Human genes 0.000 claims 8
• 108090001005 Interleukin-6 Proteins 0.000 claims 8
• 230000005867 T cell response Effects 0.000 claims 8
• 210000002443 helper t lymphocyte Anatomy 0.000 claims 8
• DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims 8
• 229960002751 imiquimod Drugs 0.000 claims 8
• 229940117681 interleukin-12 Drugs 0.000 claims 8
• 229940100601 interleukin-6 Drugs 0.000 claims 8
• 229960000888 rimantadine Drugs 0.000 claims 8
• NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 claims 8
• 229960000707 tobramycin Drugs 0.000 claims 8
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims 6
• 229960003805 amantadine Drugs 0.000 claims 6
• 208000010710 hepatitis C virus infection Diseases 0.000 claims 6
• 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 claims 5
• 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims 3
• HAEJPQIATWHALX-KQYNXXCUSA-N ITP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CNC2=O)=C2N=C1 HAEJPQIATWHALX-KQYNXXCUSA-N 0.000 claims 3
• 241000596110 Biosteres Species 0.000 claims 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 2
• FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 claims 1
• 101000912181 Arabidopsis thaliana Cysteine synthase, mitochondrial Proteins 0.000 claims 1
• 102000018361 Contactin Human genes 0.000 claims 1
• 108060003955 Contactin Proteins 0.000 claims 1
• 101000687727 Homo sapiens Transcriptional regulator PINT87aa Proteins 0.000 claims 1
• 229910003844 NSO2 Inorganic materials 0.000 claims 1
• 229910004734 Oy H Inorganic materials 0.000 claims 1
• 102100024797 Transcriptional regulator PINT87aa Human genes 0.000 claims 1
• 239000008186 active pharmaceutical agent Substances 0.000 claims 1
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims 1
• 239000013256 coordination polymer Substances 0.000 claims 1
• LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentenylidene Natural products C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 claims 1
• 150000004712 monophosphates Chemical class 0.000 claims 1
• RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 1
• 229910052698 phosphorus Inorganic materials 0.000 claims 1
• 230000000063 preceeding effect Effects 0.000 claims 1
• 239000007790 solid phase Substances 0.000 claims 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
• 238000004416 surface enhanced Raman spectroscopy Methods 0.000 claims 1
• YSHDPXQDVKNPKA-UHFFFAOYSA-N tert-butyl 2-(benzhydrylideneamino)acetate Chemical group C=1C=CC=CC=1C(=NCC(=O)OC(C)(C)C)C1=CC=CC=C1 YSHDPXQDVKNPKA-UHFFFAOYSA-N 0.000 claims 1
• 229940024606 amino acid Drugs 0.000 description 40
• 150000001413 amino acids Chemical class 0.000 description 37
• 235000001014 amino acid Nutrition 0.000 description 36
• 125000006413 ring segment Chemical group 0.000 description 21
• 125000004434 sulfur atom Chemical group 0.000 description 17
• 150000001204 N-oxides Chemical class 0.000 description 12
• 125000004429 atom Chemical group 0.000 description 12
• 238000006243 chemical reaction Methods 0.000 description 12
• 239000001301 oxygen Substances 0.000 description 12
• 238000004364 calculation method Methods 0.000 description 11
• 238000005984 hydrogenation reaction Methods 0.000 description 11
• 125000006242 amine protecting group Chemical group 0.000 description 10
• 230000000875 corresponding effect Effects 0.000 description 10
• 238000010790 dilution Methods 0.000 description 10
• 239000012895 dilution Substances 0.000 description 10
• 238000002474 experimental method Methods 0.000 description 10
• 241000534944 Thia Species 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 125000005349 heteroarylcycloalkyl group Chemical group 0.000 description 9
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 108010076039 Polyproteins Proteins 0.000 description 6
• 230000002378 acidificating effect Effects 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000003776 cleavage reaction Methods 0.000 description 6
• 238000009510 drug design Methods 0.000 description 6
• 125000003396 thiol group Chemical class [H]S* 0.000 description 6
• 241000282414 Homo sapiens Species 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 229940047124 interferons Drugs 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• 125000004043 oxo group Chemical group O=* 0.000 description 5
• 238000012545 processing Methods 0.000 description 5
• 230000007017 scission Effects 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• 102000004127 Cytokines Human genes 0.000 description 4
• 108090000695 Cytokines Proteins 0.000 description 4
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
• 239000004471 Glycine Substances 0.000 description 4
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
• 239000004472 Lysine Substances 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• 101800001838 Serine protease/helicase NS3 Proteins 0.000 description 4
• 230000000840 anti-viral effect Effects 0.000 description 4
• 125000000732 arylene group Chemical group 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 230000001747 exhibiting effect Effects 0.000 description 4
• 125000001153 fluoro group Chemical group F* 0.000 description 4
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 229960002449 glycine Drugs 0.000 description 4
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 4
• 230000002519 immonomodulatory effect Effects 0.000 description 4
• 230000003308 immunostimulating effect Effects 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 235000018977 lysine Nutrition 0.000 description 4
• 229960003646 lysine Drugs 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 230000000707 stereoselective effect Effects 0.000 description 4
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 239000004475 Arginine Substances 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 3
• 235000009697 arginine Nutrition 0.000 description 3
• 229960003121 arginine Drugs 0.000 description 3
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
• 235000003704 aspartic acid Nutrition 0.000 description 3
• 229960005261 aspartic acid Drugs 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 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 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
• 235000019833 protease Nutrition 0.000 description 3
• 235000019419 proteases Nutrition 0.000 description 3
• 235000018102 proteins Nutrition 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
• OYIFNHCXNCRBQI-UHFFFAOYSA-N 2-aminoadipic acid Chemical compound OC(=O)C(N)CCCC(O)=O OYIFNHCXNCRBQI-UHFFFAOYSA-N 0.000 description 2
• SNDPXSYFESPGGJ-UHFFFAOYSA-N 2-aminopentanoic acid Chemical compound CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
• 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• 206010019799 Hepatitis viral Diseases 0.000 description 2
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 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 2
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical compound CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 108700010756 Viral Polyproteins Proteins 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 229960003767 alanine Drugs 0.000 description 2
• 125000003302 alkenyloxy group Chemical group 0.000 description 2
• 125000003368 amide group Chemical group 0.000 description 2
• 125000000539 amino acid group Chemical group 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 235000018417 cysteine Nutrition 0.000 description 2
• 229960002433 cysteine Drugs 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 2
• 230000032050 esterification Effects 0.000 description 2
• 238000005886 esterification reaction Methods 0.000 description 2
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• 229960002989 glutamic acid Drugs 0.000 description 2
• 239000004220 glutamic acid Substances 0.000 description 2
• 231100000283 hepatitis Toxicity 0.000 description 2
• 235000014304 histidine Nutrition 0.000 description 2
• 229960002885 histidine Drugs 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 229960000310 isoleucine Drugs 0.000 description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
• 125000001786 isothiazolyl group Chemical group 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 229960004452 methionine Drugs 0.000 description 2
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 230000000269 nucleophilic effect Effects 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 230000008520 organization Effects 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 229960005190 phenylalanine Drugs 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 229960002429 proline Drugs 0.000 description 2
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 235000004400 serine Nutrition 0.000 description 2
• 229960001153 serine Drugs 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
• WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 235000008521 threonine Nutrition 0.000 description 2
• 229960002898 threonine Drugs 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
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 229960004799 tryptophan Drugs 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• 229960004295 valine Drugs 0.000 description 2
• 235000014393 valine Nutrition 0.000 description 2
• 201000001862 viral hepatitis Diseases 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
• VBXZSFNZVNDOPB-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidine Chemical compound C1CNC=NC1 VBXZSFNZVNDOPB-UHFFFAOYSA-N 0.000 description 1
• JHTPBGFVWWSHDL-UHFFFAOYSA-N 1,4-dichloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=S)=C1 JHTPBGFVWWSHDL-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 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
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
• UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
• 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
• NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical class C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 description 1
• WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical class OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
• GMKMEZVLHJARHF-UHFFFAOYSA-N 2,6-diaminopimelic acid Chemical compound OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
• BLDFSDCBQJUWFG-UHFFFAOYSA-N 2-(methylamino)-1,2-diphenylethanol Chemical compound C=1C=CC=CC=1C(NC)C(O)C1=CC=CC=C1 BLDFSDCBQJUWFG-UHFFFAOYSA-N 0.000 description 1
• JUQLUIFNNFIIKC-UHFFFAOYSA-N 2-aminopimelic acid Chemical compound OC(=O)C(N)CCCCC(O)=O JUQLUIFNNFIIKC-UHFFFAOYSA-N 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• RVHOBHMAPRVOLO-UHFFFAOYSA-N 2-ethylbutanedioic acid Chemical class CCC(C(O)=O)CC(O)=O RVHOBHMAPRVOLO-UHFFFAOYSA-N 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• 125000005979 2-naphthyloxy group Chemical group 0.000 description 1
• FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical compound C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-UHFFFAOYSA-N 0.000 description 1
• DNNVRTZJRKIUFK-UHFFFAOYSA-N 3,4-dihydroquinoline Chemical compound C1=CC=C2N=CCCC2=C1 DNNVRTZJRKIUFK-UHFFFAOYSA-N 0.000 description 1
• XABCFXXGZPWJQP-UHFFFAOYSA-N 3-aminoadipic acid Chemical compound OC(=O)CC(N)CCC(O)=O XABCFXXGZPWJQP-UHFFFAOYSA-N 0.000 description 1
• 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
• FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
• 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
• LZJGQIVWUKFTRD-UHFFFAOYSA-N 7-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC2=C1NC=C2 LZJGQIVWUKFTRD-UHFFFAOYSA-N 0.000 description 1
• 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 1
• OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 241001136792 Alle Species 0.000 description 1
• 101000825192 Arabidopsis thaliana Arginine decarboxylase 2 Proteins 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
• 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 206010010144 Completed suicide Diseases 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical group C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 229940124771 HCV-NS3 protease inhibitor Drugs 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000738322 Homo sapiens Prothymosin alpha Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• 102000003996 Interferon-beta Human genes 0.000 description 1
• 108090000467 Interferon-beta Proteins 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-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
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• OLNLSTNFRUFTLM-BYPYZUCNSA-N N-ethyl-L-asparagine Chemical compound CCN[C@H](C(O)=O)CC(N)=O OLNLSTNFRUFTLM-BYPYZUCNSA-N 0.000 description 1
• YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-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
• 229910002651 NO3 Inorganic materials 0.000 description 1
• RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 101800000515 Non-structural protein 3 Proteins 0.000 description 1
• 101710144111 Non-structural protein 3 Proteins 0.000 description 1
• 101800001020 Non-structural protein 4A Proteins 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 241000282577 Pan troglodytes Species 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• 239000002262 Schiff base Substances 0.000 description 1
• 150000004753 Schiff bases Chemical class 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 102100033632 Tropomyosin alpha-1 chain Human genes 0.000 description 1
• 241000710772 Yellow fever virus Species 0.000 description 1
• 101900322197 Yellow fever virus Serine protease NS3 Proteins 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000002339 acetoacetyl group Chemical group O=C([*])C([H])([H])C(=O)C([H])([H])[H] 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
• 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000004945 acylaminoalkyl group Chemical group 0.000 description 1
• 125000005041 acyloxyalkyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
• 125000006307 alkoxy benzyl group Chemical group 0.000 description 1
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
• 125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 125000005336 allyloxy group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• 229940124277 aminobutyric acid Drugs 0.000 description 1
• 229960002684 aminocaproic acid Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
• 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000005513 benzoazaindolyl group Chemical group 0.000 description 1
• 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 239000000920 calcium hydroxide Substances 0.000 description 1
• 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 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
• 230000001684 chronic effect Effects 0.000 description 1
• 208000020403 chronic hepatitis C virus infection Diseases 0.000 description 1
• 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 235000013477 citrulline Nutrition 0.000 description 1
• 229960002173 citrulline Drugs 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000000000 cycloalkoxy group Chemical group 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000006639 cyclohexyl carbonyl group Chemical group 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
• 125000004956 cyclohexylene group Chemical group 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 125000005070 decynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
• 125000005072 dihydrothiopyranyl group Chemical group S1C(CCC=C1)* 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 231100000676 disease causative agent Toxicity 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000000921 elemental analysis Methods 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 230000005021 gait Effects 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 235000004554 glutamine Nutrition 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229960002743 glutamine Drugs 0.000 description 1
• 108700012707 hepatitis C virus NS3 Proteins 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 239000004030 hiv protease inhibitor Substances 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
• 125000005945 imidazopyridyl group Chemical group 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 125000005835 indanylene group Chemical group 0.000 description 1
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229960001388 interferon-beta Drugs 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 150000002611 lead compounds Chemical class 0.000 description 1
• 229960003136 leucine Drugs 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide 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
• 150000002690 malonic acid derivatives Chemical class 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• HOGDNTQCSIKEEV-UHFFFAOYSA-N n'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 description 1
• 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
• 125000005487 naphthalate group Chemical group 0.000 description 1
• 125000004957 naphthylene group Chemical group 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 125000006502 nitrobenzyl group Chemical group 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
• 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 229940039748 oxalate Drugs 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
• 125000003884 phenylalkyl group Chemical group 0.000 description 1
• HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 230000003389 potentiating effect Effects 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
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000020978 protein processing Effects 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 238000009877 rendering Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 229940043230 sarcosine Drugs 0.000 description 1
• HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 239000001433 sodium tartrate Substances 0.000 description 1
• 229960002167 sodium tartrate Drugs 0.000 description 1
• 235000011004 sodium tartrates Nutrition 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 238000001179 sorption measurement Methods 0.000 description 1
• PWEBUXCTKOWPCW-UHFFFAOYSA-N squaric acid Chemical compound OC1=C(O)C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-N 0.000 description 1
• 125000005504 styryl group Chemical group 0.000 description 1
• 125000005017 substituted alkenyl group Chemical group 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000004426 substituted alkynyl group Chemical group 0.000 description 1
• 125000005717 substituted cycloalkylene group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 235000002374 tyrosine Nutrition 0.000 description 1
• 229960004441 tyrosine Drugs 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000017613 viral reproduction Effects 0.000 description 1
• 229940051021 yellow-fever virus Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
• 229940007718 zinc hydroxide Drugs 0.000 description 1
• 229910021511 zinc hydroxide Inorganic materials 0.000 description 1