EA020815B1 - Ингибиторы вируса гепатита с - Google Patents
Ингибиторы вируса гепатита с Download PDFInfo
- Publication number
- EA020815B1 EA020815B1 EA201270656A EA201270656A EA020815B1 EA 020815 B1 EA020815 B1 EA 020815B1 EA 201270656 A EA201270656 A EA 201270656A EA 201270656 A EA201270656 A EA 201270656A EA 020815 B1 EA020815 B1 EA 020815B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- sar
- mmol
- found
- nmr
- analytically calculated
- Prior art date
Links
- 241000711549 Hepacivirus C Species 0.000 title abstract description 5
- 239000003112 inhibitor Substances 0.000 title description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 212
- 229910052739 hydrogen Inorganic materials 0.000 claims description 150
- 150000003839 salts Chemical class 0.000 claims description 86
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 79
- -1 cyano, cyclopropyl halogen Chemical group 0.000 claims description 79
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- YOXHCYXIAVIFCZ-UHFFFAOYSA-N cyclopropanol Chemical compound OC1CC1 YOXHCYXIAVIFCZ-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 342
- 238000000034 method Methods 0.000 abstract description 87
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 17
- 208000015181 infectious disease Diseases 0.000 abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 675
- 238000005481 NMR spectroscopy Methods 0.000 description 310
- 239000000243 solution Substances 0.000 description 252
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 243
- 229910001868 water Inorganic materials 0.000 description 228
- 239000002904 solvent Substances 0.000 description 200
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 195
- 239000011541 reaction mixture Substances 0.000 description 151
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 141
- 239000007787 solid Substances 0.000 description 141
- 239000003921 oil Substances 0.000 description 87
- 239000012044 organic layer Substances 0.000 description 87
- 235000019198 oils Nutrition 0.000 description 86
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
- 239000010410 layer Substances 0.000 description 70
- 239000000047 product Substances 0.000 description 67
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 64
- 229910052757 nitrogen Inorganic materials 0.000 description 61
- 238000000746 purification Methods 0.000 description 59
- 239000000725 suspension Substances 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 239000000741 silica gel Substances 0.000 description 57
- 229910002027 silica gel Inorganic materials 0.000 description 57
- 125000000217 alkyl group Chemical group 0.000 description 52
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
- 239000012267 brine Substances 0.000 description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- 238000003818 flash chromatography Methods 0.000 description 42
- 238000003756 stirring Methods 0.000 description 42
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 40
- 230000014759 maintenance of location Effects 0.000 description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 37
- 230000000840 anti-viral effect Effects 0.000 description 36
- 239000012230 colorless oil Substances 0.000 description 34
- 239000006260 foam Substances 0.000 description 34
- 230000002829 reductive effect Effects 0.000 description 33
- 238000007792 addition Methods 0.000 description 32
- 125000003118 aryl group Chemical group 0.000 description 32
- 238000010828 elution Methods 0.000 description 32
- 239000000706 filtrate Substances 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 239000012043 crude product Substances 0.000 description 29
- 125000000623 heterocyclic group Chemical group 0.000 description 29
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 28
- 239000013058 crude material Substances 0.000 description 28
- 108010050904 Interferons Proteins 0.000 description 27
- 102000014150 Interferons Human genes 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 229940079322 interferon Drugs 0.000 description 27
- 239000011777 magnesium Substances 0.000 description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 26
- 238000004128 high performance liquid chromatography Methods 0.000 description 26
- 229910052740 iodine Inorganic materials 0.000 description 26
- 239000000126 substance Substances 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000002953 preparative HPLC Methods 0.000 description 24
- 238000004007 reversed phase HPLC Methods 0.000 description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 21
- 239000012071 phase Substances 0.000 description 21
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 20
- 239000002253 acid Substances 0.000 description 20
- 150000002148 esters Chemical class 0.000 description 20
- 239000008346 aqueous phase Substances 0.000 description 19
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 18
- 101100405319 Arabidopsis thaliana NSI gene Proteins 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 101150016222 SNAT1 gene Proteins 0.000 description 18
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 102100037580 Sesquipedalian-1 Human genes 0.000 description 17
- 101710169844 Sesquipedalian-1 Proteins 0.000 description 17
- 239000000843 powder Substances 0.000 description 17
- 239000005909 Kieselgur Substances 0.000 description 16
- 125000003545 alkoxy group Chemical group 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 15
- 125000003710 aryl alkyl group Chemical group 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 15
- ZWQXJUFYGXPBTB-UHFFFAOYSA-N cycloocta-1,3-diene;rhodium Chemical compound [Rh].C1CCC=CC=CC1 ZWQXJUFYGXPBTB-UHFFFAOYSA-N 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 239000005695 Ammonium acetate Substances 0.000 description 14
- 235000019257 ammonium acetate Nutrition 0.000 description 14
- 229940043376 ammonium acetate Drugs 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 14
- 125000000753 cycloalkyl group Chemical group 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 150000001408 amides Chemical class 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 13
- 238000000926 separation method Methods 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 125000004438 haloalkoxy group Chemical group 0.000 description 12
- 125000001188 haloalkyl group Chemical group 0.000 description 12
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 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 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 229960000329 ribavirin Drugs 0.000 description 11
- 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 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 229910052720 vanadium Inorganic materials 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000004296 chiral HPLC Methods 0.000 description 10
- 239000003039 volatile agent Substances 0.000 description 10
- 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 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 150000001413 amino acids Chemical group 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 9
- 239000011259 mixed solution Substances 0.000 description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 229940122055 Serine protease inhibitor Drugs 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 8
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000003001 serine protease inhibitor Substances 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 101150072179 ATP1 gene Proteins 0.000 description 7
- 101100003366 Arabidopsis thaliana ATPA gene Proteins 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
- 102100021649 Elongator complex protein 6 Human genes 0.000 description 7
- 101100065219 Homo sapiens ELP6 gene Proteins 0.000 description 7
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 101150105046 atpI gene Proteins 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 239000003937 drug carrier Substances 0.000 description 7
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 125000006626 methoxycarbonylamino group Chemical group 0.000 description 7
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 7
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 6
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 6
- 101710179624 Antiviral serine protease Proteins 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- 108010047761 Interferon-alpha Proteins 0.000 description 6
- 102000006992 Interferon-alpha Human genes 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- BRGZEQXWZWBPJH-UHFFFAOYSA-N 1,3-dichloroisoquinoline Chemical compound C1=CC=C2C(Cl)=NC(Cl)=CC2=C1 BRGZEQXWZWBPJH-UHFFFAOYSA-N 0.000 description 5
- MSQCQINLJMEVNJ-UHFFFAOYSA-N 1-chloroisoquinoline Chemical class C1=CC=C2C(Cl)=NC=CC2=C1 MSQCQINLJMEVNJ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 5
- 235000019502 Orange oil Nutrition 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000006196 drop Substances 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 5
- 229910052745 lead Inorganic materials 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000010502 orange oil Substances 0.000 description 5
- 229910052698 phosphorus Inorganic materials 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000012047 saturated solution Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000005292 vacuum distillation Methods 0.000 description 5
- RAAUBRQLKXXMQK-BYPYZUCNSA-N (2s)-2-azaniumyl-5-chloro-4-oxopentanoate Chemical compound OC(=O)[C@@H](N)CC(=O)CCl RAAUBRQLKXXMQK-BYPYZUCNSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 108060004795 Methyltransferase Proteins 0.000 description 4
- 101100084626 Mus musculus Psmb4 gene Proteins 0.000 description 4
- 229940123066 Polymerase inhibitor Drugs 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 4
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003729 cation exchange resin Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000004316 dimethyl dicarbonate Substances 0.000 description 4
- 235000010300 dimethyl dicarbonate Nutrition 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000002955 immunomodulating agent Substances 0.000 description 4
- 229940121354 immunomodulator Drugs 0.000 description 4
- 230000002584 immunomodulator Effects 0.000 description 4
- 229910052738 indium Inorganic materials 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 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 4
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 229960004295 valine Drugs 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 101100324465 Caenorhabditis elegans arr-1 gene Proteins 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 229930105110 Cyclosporin A Natural products 0.000 description 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 229960003767 alanine Drugs 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 150000002012 dioxanes Chemical class 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000008241 heterogeneous mixture Substances 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical compound COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 3
- WEDZBNHWDBCBEF-UHFFFAOYSA-N methyl 3-(trifluoromethylsulfonyloxy)pyridine-2-carboxylate Chemical compound COC(=O)C1=NC=CC=C1OS(=O)(=O)C(F)(F)F WEDZBNHWDBCBEF-UHFFFAOYSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Substances CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-N 0.000 description 2
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
- SAMNBOHOBWEEEU-UHFFFAOYSA-N 1,1,3,3-tetrabromopropan-2-one Chemical compound BrC(Br)C(=O)C(Br)Br SAMNBOHOBWEEEU-UHFFFAOYSA-N 0.000 description 2
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- FOZVXADQAHVUSV-UHFFFAOYSA-N 1-bromo-2-(2-bromoethoxy)ethane Chemical compound BrCCOCCBr FOZVXADQAHVUSV-UHFFFAOYSA-N 0.000 description 2
- PSQUIUNIVDKHJK-UHFFFAOYSA-N 1-bromoisoquinolin-3-amine Chemical compound C1=CC=C2C(Br)=NC(N)=CC2=C1 PSQUIUNIVDKHJK-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RTSLQVZQORGDQQ-UHFFFAOYSA-N 2-bromo-1-[4-[4-(2-bromoacetyl)phenyl]phenyl]ethanone Chemical compound C1=CC(C(=O)CBr)=CC=C1C1=CC=C(C(=O)CBr)C=C1 RTSLQVZQORGDQQ-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 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 2
- MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 description 2
- MZFPAWGWFDGCHP-UHFFFAOYSA-N 5-diphenylphosphanylpentyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 MZFPAWGWFDGCHP-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- 101100534162 Arabidopsis thaliana SPS3 gene Proteins 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- 102100029721 DnaJ homolog subfamily B member 1 Human genes 0.000 description 2
- 102100027094 Echinoderm microtubule-associated protein-like 1 Human genes 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101000866018 Homo sapiens DnaJ homolog subfamily B member 1 Proteins 0.000 description 2
- 101001057941 Homo sapiens Echinoderm microtubule-associated protein-like 1 Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 108010079944 Interferon-alpha2b Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 229930194542 Keto Natural products 0.000 description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910017976 MgO 4 Inorganic materials 0.000 description 2
- 101000653787 Mus musculus Protein S100-A11 Proteins 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 101100419716 Podospora anserina RPS9 gene Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010076039 Polyproteins Proteins 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- 108700022715 Viral Proteases Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 125000003302 alkenyloxy group Chemical group 0.000 description 2
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 2
- 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 208000030961 allergic reaction Diseases 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 229960003805 amantadine Drugs 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000011609 ammonium molybdate Substances 0.000 description 2
- 235000018660 ammonium molybdate Nutrition 0.000 description 2
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 2
- 229940010552 ammonium molybdate Drugs 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- UEFXBEKKUJOIHI-UHFFFAOYSA-N benzyl 2-(4-methylphenyl)sulfonyloxy-2-phenylacetate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC(C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 UEFXBEKKUJOIHI-UHFFFAOYSA-N 0.000 description 2
- MZGZFSCCDFOQOY-UHFFFAOYSA-N benzyl 2-(4-methylpiperazin-1-yl)-2-phenylacetate Chemical compound C1CN(C)CCN1C(C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 MZGZFSCCDFOQOY-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 description 2
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethyl monosulfide Natural products CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 2
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- QUGJYNGNUBHTNS-UHFFFAOYSA-N ethyl 2-(benzhydrylideneamino)acetate Chemical compound C=1C=CC=CC=1C(=NCC(=O)OCC)C1=CC=CC=C1 QUGJYNGNUBHTNS-UHFFFAOYSA-N 0.000 description 2
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000002466 imines Chemical class 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
- 229960002751 imiquimod Drugs 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 229940117681 interleukin-12 Drugs 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- UNEHOGBDOBZLOA-UHFFFAOYSA-N methyl 2-(methoxycarbonylamino)-2-(oxetan-3-yl)acetate Chemical compound COC(=O)NC(C(=O)OC)C1COC1 UNEHOGBDOBZLOA-UHFFFAOYSA-N 0.000 description 2
- GIAXMSUPTGGVFG-UHFFFAOYSA-N methyl 2-amino-5-ethyl-1,3-thiazole-4-carboxylate Chemical compound CCC=1SC(N)=NC=1C(=O)OC GIAXMSUPTGGVFG-UHFFFAOYSA-N 0.000 description 2
- INNRHBUYGJHSGL-UHFFFAOYSA-N methyl 2-chloro-5-ethyl-1,3-thiazole-4-carboxylate Chemical compound CCC=1SC(Cl)=NC=1C(=O)OC INNRHBUYGJHSGL-UHFFFAOYSA-N 0.000 description 2
- ISFTTZZKJCHKIA-UHFFFAOYSA-N methyl 3-ethenylpyridine-2-carboxylate Chemical compound COC(=O)C1=NC=CC=C1C=C ISFTTZZKJCHKIA-UHFFFAOYSA-N 0.000 description 2
- WFNCZUIGZZVNKH-UHFFFAOYSA-N methyl 3-ethylpyridine-2-carboxylate Chemical compound CCC1=CC=CN=C1C(=O)OC WFNCZUIGZZVNKH-UHFFFAOYSA-N 0.000 description 2
- UJWHTPUQSUHEGZ-UHFFFAOYSA-N methyl 5-ethyl-1,3-thiazole-4-carboxylate Chemical compound CCC=1SC=NC=1C(=O)OC UJWHTPUQSUHEGZ-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000005416 organic matter Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- URUUZIAJVSGYRC-UHFFFAOYSA-N oxan-3-one Chemical compound O=C1CCCOC1 URUUZIAJVSGYRC-UHFFFAOYSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229960000888 rimantadine Drugs 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 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
- 238000012546 transfer Methods 0.000 description 2
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 2
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- JLVPLCVIBPZJQG-UHFFFAOYSA-N (1-carboxy-1-phenylethyl)azanium;chloride Chemical compound Cl.OC(=O)C(N)(C)C1=CC=CC=C1 JLVPLCVIBPZJQG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- PASOFFRBGIVJET-YRKGHMEHSA-N (2r,3r,4r,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 PASOFFRBGIVJET-YRKGHMEHSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N (trimethylsilyl)diazomethane Substances C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NPWSCICJCAGHOX-UHFFFAOYSA-N 1,3-dichloro-5-ethoxyisoquinoline Chemical compound N1=C(Cl)C=C2C(OCC)=CC=CC2=C1Cl NPWSCICJCAGHOX-UHFFFAOYSA-N 0.000 description 1
- DHWYGSPWPQXKME-UHFFFAOYSA-N 1,3-dichloro-5-methoxyisoquinoline Chemical compound N1=C(Cl)C=C2C(OC)=CC=CC2=C1Cl DHWYGSPWPQXKME-UHFFFAOYSA-N 0.000 description 1
- SZVHDRLVQJXQBT-UHFFFAOYSA-N 1,3-dimethoxypropan-2-one Chemical compound COCC(=O)COC SZVHDRLVQJXQBT-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 1
- NRBSVPXPMBQUGX-UHFFFAOYSA-N 1,7-dichloroisoquinoline Chemical compound C1=CN=C(Cl)C2=CC(Cl)=CC=C21 NRBSVPXPMBQUGX-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- OCKPEBVTWOEXDC-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]-2,3-dihydroisoindol-2-ium-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC(C)(C)C)(C(O)=O)NCC2=C1 OCKPEBVTWOEXDC-UHFFFAOYSA-N 0.000 description 1
- LGBKSXLLSRNAAB-UHFFFAOYSA-N 1-amino-2-[(2-methylpropan-2-yl)oxycarbonyl]-2,3-dihydroindene-1-carboxylic acid Chemical compound C1=CC=C2C(C(O)=O)(N)C(C(=O)OC(C)(C)C)CC2=C1 LGBKSXLLSRNAAB-UHFFFAOYSA-N 0.000 description 1
- KKKDZZRICRFGSD-UHFFFAOYSA-N 1-benzylimidazole Chemical compound C1=CN=CN1CC1=CC=CC=C1 KKKDZZRICRFGSD-UHFFFAOYSA-N 0.000 description 1
- HETYZWATQDOPIV-UHFFFAOYSA-N 1-bromo-3-fluoroisoquinoline Chemical compound C1=CC=C2C(Br)=NC(F)=CC2=C1 HETYZWATQDOPIV-UHFFFAOYSA-N 0.000 description 1
- UTZJYSXOFHCSGZ-UHFFFAOYSA-N 1-chloro-6-methoxyisoquinoline Chemical compound ClC1=NC=CC2=CC(OC)=CC=C21 UTZJYSXOFHCSGZ-UHFFFAOYSA-N 0.000 description 1
- PEELFWZCBLBEET-UHFFFAOYSA-N 1-chloroisoquinoline-3-carbonitrile Chemical compound C1=CC=C2C(Cl)=NC(C#N)=CC2=C1 PEELFWZCBLBEET-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- HLXOVAMYQUFLPE-UHFFFAOYSA-N 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound CN1N=CC=C1B1OC(C)(C)C(C)(C)O1 HLXOVAMYQUFLPE-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- BWMNOXJVRHGUQM-UHFFFAOYSA-N 2,2-dimethyloxan-4-one Chemical compound CC1(C)CC(=O)CCO1 BWMNOXJVRHGUQM-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-M 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S([O-])(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-M 0.000 description 1
- VSYFZULSKMFUJJ-UHFFFAOYSA-N 2,6-dimethylpyran-4-one Chemical compound CC1=CC(=O)C=C(C)O1 VSYFZULSKMFUJJ-UHFFFAOYSA-N 0.000 description 1
- RPTRFSADOICSSK-UHFFFAOYSA-N 2-(2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1F RPTRFSADOICSSK-UHFFFAOYSA-N 0.000 description 1
- KGSVNOLLROCJQM-UHFFFAOYSA-N 2-(benzylamino)acetic acid Chemical compound OC(=O)CNCC1=CC=CC=C1 KGSVNOLLROCJQM-UHFFFAOYSA-N 0.000 description 1
- SHXXEAFPTYEBJH-UHFFFAOYSA-N 2-(methoxycarbonylamino)-3-(2h-triazol-4-yl)propanoic acid Chemical compound COC(=O)NC(C(O)=O)CC=1C=NNN=1 SHXXEAFPTYEBJH-UHFFFAOYSA-N 0.000 description 1
- RFYCQJHCAPCSTA-UHFFFAOYSA-N 2-[2-(chloromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1CCl RFYCQJHCAPCSTA-UHFFFAOYSA-N 0.000 description 1
- GOSVNXMOCBVLPW-UHFFFAOYSA-N 2-[2-(morpholin-4-ylmethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1CN1CCOCC1 GOSVNXMOCBVLPW-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
- BLRQXMHAGNJVHO-UHFFFAOYSA-N 2-[benzyl(methyl)azaniumyl]-3-methylbutanoate Chemical compound CC(C)C(C(O)=O)N(C)CC1=CC=CC=C1 BLRQXMHAGNJVHO-UHFFFAOYSA-N 0.000 description 1
- OZKZHAPLKMRAQT-UHFFFAOYSA-N 2-[benzyl(methyl)azaniumyl]acetate Chemical compound OC(=O)CN(C)CC1=CC=CC=C1 OZKZHAPLKMRAQT-UHFFFAOYSA-N 0.000 description 1
- UHQFXIWMAQOCAN-UHFFFAOYSA-N 2-amino-1,3-dihydroindene-2-carboxylic acid Chemical compound C1=CC=C2CC(N)(C(O)=O)CC2=C1 UHQFXIWMAQOCAN-UHFFFAOYSA-N 0.000 description 1
- IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 description 1
- UBXUDSPYIGPGGP-UHFFFAOYSA-N 2-azaniumyl-2-phenylbutanoate Chemical compound CCC(N)(C(O)=O)C1=CC=CC=C1 UBXUDSPYIGPGGP-UHFFFAOYSA-N 0.000 description 1
- WAKFRZBXTKUFIW-UHFFFAOYSA-N 2-bromo-2-phenylacetic acid Chemical compound OC(=O)C(Br)C1=CC=CC=C1 WAKFRZBXTKUFIW-UHFFFAOYSA-N 0.000 description 1
- DDRNQKVAGAWDEE-UHFFFAOYSA-N 2-chlorobutanediamide Chemical compound NC(=O)CC(Cl)C(N)=O DDRNQKVAGAWDEE-UHFFFAOYSA-N 0.000 description 1
- FOHSVPIFZASOED-UHFFFAOYSA-N 2-fluoroethyl carbonochloridate Chemical compound FCCOC(Cl)=O FOHSVPIFZASOED-UHFFFAOYSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 1
- GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- ZGIKWINFUGEQEO-UHFFFAOYSA-N 3-bromoquinoline Chemical compound C1=CC=CC2=CC(Br)=CN=C21 ZGIKWINFUGEQEO-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-UHFFFAOYSA-N 0.000 description 1
- SCRBSGZBTHKAHU-UHFFFAOYSA-N 4-bromoisoquinoline Chemical compound C1=CC=C2C(Br)=CN=CC2=C1 SCRBSGZBTHKAHU-UHFFFAOYSA-N 0.000 description 1
- CXBLQEIODBBSQD-UHFFFAOYSA-N 4-methylpiperidin-4-ol Chemical compound CC1(O)CCNCC1 CXBLQEIODBBSQD-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 1
- GYCPLYCTMDTEPU-UHFFFAOYSA-N 5-bromopyrimidine Chemical compound BrC1=CN=CN=C1 GYCPLYCTMDTEPU-UHFFFAOYSA-N 0.000 description 1
- NPMCAVBMOTZUPD-UHFFFAOYSA-N 6-bromonaphthalene-2-carboxylic acid Chemical compound C1=C(Br)C=CC2=CC(C(=O)O)=CC=C21 NPMCAVBMOTZUPD-UHFFFAOYSA-N 0.000 description 1
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 description 1
- HYQXNCDBSALQLB-UHFFFAOYSA-N 9-bromo-9-phenylfluorene Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(Br)C1=CC=CC=C1 HYQXNCDBSALQLB-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 229940096888 Beta tubulin inhibitor Drugs 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- QJCMUIYAWUEVNA-UHFFFAOYSA-N C1=CC=CCCCC1.CC Chemical compound C1=CC=CCCCC1.CC QJCMUIYAWUEVNA-UHFFFAOYSA-N 0.000 description 1
- 101150043532 CISH gene Proteins 0.000 description 1
- 101100148729 Caenorhabditis elegans sar-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229940123169 Caspase inhibitor Drugs 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 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
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 241000252233 Cyprinus carpio Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 244000309456 Decussocarpus nagi Species 0.000 description 1
- 235000008375 Decussocarpus nagi Nutrition 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-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
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- 101150040795 EIS1 gene Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-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
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
- 241000206672 Gelidium Species 0.000 description 1
- 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 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 229910003953 H3PO2 Inorganic materials 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000938676 Homo sapiens Liver carboxylesterase 1 Proteins 0.000 description 1
- 101000987488 Homo sapiens Protein pelota homolog Proteins 0.000 description 1
- 101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 1
- 101000701815 Homo sapiens Spermidine synthase Proteins 0.000 description 1
- 101000773116 Homo sapiens Thioredoxin domain-containing protein 3 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- 102000016600 Inosine-5'-monophosphate dehydrogenases Human genes 0.000 description 1
- 108050006182 Inosine-5'-monophosphate dehydrogenases Proteins 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100030817 Liver carboxylesterase 1 Human genes 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
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 241000907681 Morpho Species 0.000 description 1
- 101100166829 Mus musculus Cenpk gene Proteins 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- AKCRVYNORCOYQT-UHFFFAOYSA-N N-methylvaline Chemical compound CNC(C(C)C)C(O)=O AKCRVYNORCOYQT-UHFFFAOYSA-N 0.000 description 1
- 102000008021 Nucleoside-Triphosphatase Human genes 0.000 description 1
- 108010075285 Nucleoside-Triphosphatase Proteins 0.000 description 1
- FYCWLJLGIAUCCL-DMTCNVIQSA-N O-methyl-L-threonine Chemical compound CO[C@H](C)[C@H](N)C(O)=O FYCWLJLGIAUCCL-DMTCNVIQSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- HLCFGWHYROZGBI-JJKGCWMISA-M Potassium gluconate Chemical compound [K+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O HLCFGWHYROZGBI-JJKGCWMISA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 101710188306 Protein Y Proteins 0.000 description 1
- 102100028485 Protein pelota homolog Human genes 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 102100031163 Selenide, water dikinase 1 Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 101100494729 Syncephalastrum racemosum SPSR gene Proteins 0.000 description 1
- 102100030271 Thioredoxin domain-containing protein 3 Human genes 0.000 description 1
- 108010078233 Thymalfasin Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- TVRCRTJYMVTEFS-ICGCPXGVSA-N [(2r,3r,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)-4-methyloxolan-3-yl] (2s)-2-amino-3-methylbutanoate Chemical compound C[C@@]1(O)[C@H](OC(=O)[C@@H](N)C(C)C)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 TVRCRTJYMVTEFS-ICGCPXGVSA-N 0.000 description 1
- LRRIKHYTEBNQQI-UHFFFAOYSA-N [(9-phenylfluoren-9-yl)amino] butanoate Chemical compound C(CCC)(=O)ONC1(C2=CC=CC=C2C=2C=CC=CC12)C1=CC=CC=C1 LRRIKHYTEBNQQI-UHFFFAOYSA-N 0.000 description 1
- BYKQIRVBKICOHH-UHFFFAOYSA-N [Rh+].C1=CC=CCCCC1.C1=CC=CC=C1 Chemical compound [Rh+].C1=CC=CCCCC1.C1=CC=CC=C1 BYKQIRVBKICOHH-UHFFFAOYSA-N 0.000 description 1
- FMWCCLGTTTUVFF-UHFFFAOYSA-N [Rh+].C1=CC=CCCCC1.CC Chemical compound [Rh+].C1=CC=CCCCC1.CC FMWCCLGTTTUVFF-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 238000007630 basic procedure Methods 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- YUHGUEJGEGDDFJ-UHFFFAOYSA-N benzyl 2-(4-hydroxypiperidin-1-yl)-2-phenylacetate Chemical compound C1CC(O)CCN1C(C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 YUHGUEJGEGDDFJ-UHFFFAOYSA-N 0.000 description 1
- PZFWCINJAZLKPA-UHFFFAOYSA-N benzyl 2-(7-azabicyclo[2.2.1]heptan-7-yl)-2-phenylacetate Chemical compound C1CC2CCC1N2C(C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 PZFWCINJAZLKPA-UHFFFAOYSA-N 0.000 description 1
- ORKWOWVNPONBOR-UHFFFAOYSA-N benzyl 2-(diethylamino)-3-hydroxypropanoate Chemical compound CCN(CC)C(CO)C(=O)OCC1=CC=CC=C1 ORKWOWVNPONBOR-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 229940126212 compound 17a Drugs 0.000 description 1
- 239000004567 concrete Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000005144 cycloalkylsulfonyl 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
- WEIMJSIRDZDHAH-UHFFFAOYSA-N cyclopent-3-en-1-ol Chemical compound OC1CC=CC1 WEIMJSIRDZDHAH-UHFFFAOYSA-N 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
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 229910000117 dibromine monoxide Inorganic materials 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical class OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 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
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 208000001321 ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 1 Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- LJWKFGGDMBPPAZ-UHFFFAOYSA-N ethoxyethane;toluene Chemical compound CCOCC.CC1=CC=CC=C1 LJWKFGGDMBPPAZ-UHFFFAOYSA-N 0.000 description 1
- MGHVHQLCGVMIPR-UHFFFAOYSA-N ethyl 2-bromo-2-pyridin-4-ylacetate Chemical compound CCOC(=O)C(Br)C1=CC=NC=C1 MGHVHQLCGVMIPR-UHFFFAOYSA-N 0.000 description 1
- QVLJLWHOILVHJJ-UHFFFAOYSA-N ethyl 2-pyridin-4-ylacetate Chemical compound CCOC(=O)CC1=CC=NC=C1 QVLJLWHOILVHJJ-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N ethylene glycol dimethyl ether Natural products COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- PHTXVQQRWJXYPP-UHFFFAOYSA-N ethyltrifluoromethylaminoindane Chemical compound C1=C(C(F)(F)F)C=C2CC(NCC)CC2=C1 PHTXVQQRWJXYPP-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- OHNNZOOGWXZCPZ-UHFFFAOYSA-N exo-norbornene oxide Chemical compound C1CC2C3OC3C1C2 OHNNZOOGWXZCPZ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- ARRNBPCNZJXHRJ-UHFFFAOYSA-M hydron;tetrabutylazanium;phosphate Chemical compound OP(O)([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC ARRNBPCNZJXHRJ-UHFFFAOYSA-M 0.000 description 1
- 125000005182 hydroxyalkylcarbonyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- CZALJDQHONFVFU-UHFFFAOYSA-N isocyanatocyclopentane Chemical compound O=C=NC1CCCC1 CZALJDQHONFVFU-UHFFFAOYSA-N 0.000 description 1
- CSNXUYRHPXGSJD-UHFFFAOYSA-N isoquinolin-5-ol Chemical compound N1=CC=C2C(O)=CC=CC2=C1 CSNXUYRHPXGSJD-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- FFPWOKGITYUQON-UHFFFAOYSA-M lithium;2-(methoxycarbonylamino)-2-(oxetan-3-yl)acetate Chemical compound [Li+].COC(=O)NC(C([O-])=O)C1COC1 FFPWOKGITYUQON-UHFFFAOYSA-M 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 230000004060 metabolic process 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
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- NDTBYBDHYVFWSM-UHFFFAOYSA-N methyl 2-(oxetan-3-ylidene)-2-(phenylmethoxycarbonylamino)acetate Chemical compound C1OCC1=C(C(=O)OC)NC(=O)OCC1=CC=CC=C1 NDTBYBDHYVFWSM-UHFFFAOYSA-N 0.000 description 1
- MHKKUZDJUGIOBC-UHFFFAOYSA-N methyl 3-hydroxypyridine-2-carboxylate Chemical compound COC(=O)C1=NC=CC=C1O MHKKUZDJUGIOBC-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- CNCMVGXVKBJYNU-UHFFFAOYSA-N methyl oxane-4-carboxylate Chemical compound COC(=O)C1CCOCC1 CNCMVGXVKBJYNU-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000011294 monotherapeutic Methods 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- ICWPRFNZEBFLPT-UHFFFAOYSA-N n-(2-hydroxyphenyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NC1=CC=CC=C1O ICWPRFNZEBFLPT-UHFFFAOYSA-N 0.000 description 1
- NQBKFULMFQMZBE-UHFFFAOYSA-N n-bz-3-benzanthronylpyrazolanthron Chemical compound C12=CC=CC(C(=O)C=3C4=CC=CC=3)=C2C4=NN1C1=CC=C2C3=C1C1=CC=CC=C1C(=O)C3=CC=C2 NQBKFULMFQMZBE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 229910017051 nitrogen difluoride Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-M phenylacetate Chemical compound [O-]C(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-M 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 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
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012107 replication analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- CIFHCSWDDGYAGB-UHFFFAOYSA-N sulfuric acid;2,4,6-trinitrophenol Chemical compound OS(O)(=O)=O.OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O CIFHCSWDDGYAGB-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- OWBFRQWDQDYNNF-IBTYICNHSA-N tert-butyl (2s,3r)-2-amino-3-hydroxybutanoate;hydrochloride Chemical compound Cl.C[C@@H](O)[C@H](N)C(=O)OC(C)(C)C OWBFRQWDQDYNNF-IBTYICNHSA-N 0.000 description 1
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical group C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 1
- HQDWPVYKOJWACL-UHFFFAOYSA-N tert-butyl 2-(cyclopentylcarbamoylamino)-2-phenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)OC(C)(C)C)NC(=O)NC1CCCC1 HQDWPVYKOJWACL-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical class [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28694209P | 2009-12-16 | 2009-12-16 | |
| US12/957,512 US8377980B2 (en) | 2009-12-16 | 2010-12-01 | Hepatitis C virus inhibitors |
| PCT/US2010/060077 WO2011075439A1 (en) | 2009-12-16 | 2010-12-13 | Hepatitis c virus inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201270656A1 EA201270656A1 (ru) | 2012-11-30 |
| EA020815B1 true EA020815B1 (ru) | 2015-01-30 |
Family
ID=43479603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201270656A EA020815B1 (ru) | 2009-12-16 | 2010-12-13 | Ингибиторы вируса гепатита с |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US8377980B2 (OSRAM) |
| EP (1) | EP2513091B1 (OSRAM) |
| JP (1) | JP5785189B2 (OSRAM) |
| KR (1) | KR20120107991A (OSRAM) |
| CN (1) | CN102741242B (OSRAM) |
| AR (1) | AR079634A1 (OSRAM) |
| AU (1) | AU2010332034B2 (OSRAM) |
| BR (1) | BR112012014677A2 (OSRAM) |
| CA (1) | CA2784662A1 (OSRAM) |
| CL (1) | CL2012001637A1 (OSRAM) |
| CO (1) | CO6561788A2 (OSRAM) |
| EA (1) | EA020815B1 (OSRAM) |
| MA (1) | MA33806B1 (OSRAM) |
| MX (1) | MX2012006635A (OSRAM) |
| NZ (1) | NZ601220A (OSRAM) |
| PE (1) | PE20121479A1 (OSRAM) |
| PH (1) | PH12012500979A1 (OSRAM) |
| SG (1) | SG181700A1 (OSRAM) |
| TN (1) | TN2012000264A1 (OSRAM) |
| TW (1) | TWI487702B (OSRAM) |
| WO (1) | WO2011075439A1 (OSRAM) |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8329159B2 (en) * | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8303944B2 (en) | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| ES2567047T3 (es) | 2008-12-23 | 2016-04-19 | Abbvie Inc. | Derivados de pirimidina anti-virales |
| EP2367823A1 (en) | 2008-12-23 | 2011-09-28 | Abbott Laboratories | Anti-viral compounds |
| US8394968B2 (en) | 2009-02-17 | 2013-03-12 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN102361874A (zh) | 2009-03-23 | 2012-02-22 | 格兰马克药品股份有限公司 | 作为trpa1调节剂的呋喃并嘧啶二酮衍生物 |
| KR101387274B1 (ko) | 2009-03-27 | 2014-04-25 | 머크 샤프 앤드 돔 코포레이션 | Ｃ형 간염 바이러스 복제의 억제제 |
| US20190127365A1 (en) | 2017-11-01 | 2019-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of hepatitis c virus replication |
| US8796466B2 (en) | 2009-03-30 | 2014-08-05 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TW201038559A (en) | 2009-04-09 | 2010-11-01 | Bristol Myers Squibb Co | Hepatitis C virus inhibitors |
| US8143414B2 (en) | 2009-04-13 | 2012-03-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP5734956B2 (ja) * | 2009-04-15 | 2015-06-17 | アッヴィ・インコーポレイテッド | 抗ウィルス化合物 |
| JP2012526834A (ja) | 2009-05-12 | 2012-11-01 | シェーリング コーポレイション | ウイルス疾患治療に有用な縮合型三環式アリール化合物 |
| MX363732B (es) | 2009-05-13 | 2019-04-01 | Gilead Pharmasset Llc Star | Compuestos antivirales. |
| AU2010253790A1 (en) | 2009-05-29 | 2011-12-15 | Merck Sharp & Dohme Corp. | Antiviral compounds composed of three aligned aryl moieties to treat diseases such as Hepatitis C |
| US8138215B2 (en) | 2009-05-29 | 2012-03-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8980920B2 (en) | 2009-05-29 | 2015-03-17 | Merck Sharp & Dohme Corp. | Antiviral compounds of three linked aryl moieties to treat diseases such as hepatitis C |
| US8211928B2 (en) | 2009-05-29 | 2012-07-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| AR077060A1 (es) | 2009-06-11 | 2011-07-27 | Abbott Lab | Compuestos antivirales |
| US9394279B2 (en) | 2009-06-11 | 2016-07-19 | Abbvie Inc. | Anti-viral compounds |
| US8937150B2 (en) | 2009-06-11 | 2015-01-20 | Abbvie Inc. | Anti-viral compounds |
| US8716454B2 (en) | 2009-06-11 | 2014-05-06 | Abbvie Inc. | Solid compositions |
| JP2012533569A (ja) | 2009-07-16 | 2012-12-27 | ヴァーテックス ファーマシューティカルズ、 インコーポレイテッド | フラビウイルス感染症を治療又は予防するためのベンゾイミダゾール類似体 |
| US20110274648A1 (en) | 2009-11-11 | 2011-11-10 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110269956A1 (en) | 2009-11-11 | 2011-11-03 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110281910A1 (en) | 2009-11-12 | 2011-11-17 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20130156731A1 (en) | 2009-12-22 | 2013-06-20 | Kevin X. Chen | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseas |
| CA2784036A1 (en) * | 2009-12-24 | 2011-06-30 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8609635B2 (en) | 2010-03-09 | 2013-12-17 | Merck Sharp & Dohme Corp. | Fused tricyclic silyl compounds and methods of use thereof for the treatment of viral diseases |
| CA2794145A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| NZ605440A (en) | 2010-06-10 | 2014-05-30 | Abbvie Bahamas Ltd | Solid compositions comprising an hcv inhibitor |
| EP2616461A4 (en) * | 2010-08-26 | 2014-03-26 | Rfs Pharma Llc | POTENTIVE AND SELECTIVE INHIBITORS OF HEPATITIS C VIRUS |
| CA2812779A1 (en) | 2010-09-29 | 2012-04-19 | Merck Sharp & Dohme Corp. | Fused tetracycle derivatives and methods of use thereof for the treatment of viral diseases |
| WO2012048421A1 (en) * | 2010-10-14 | 2012-04-19 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor compounds |
| CN103189371B (zh) | 2010-11-04 | 2015-04-01 | 施万生物制药研发Ip有限责任公司 | 丙型肝炎病毒抑制剂 |
| JP5905020B2 (ja) | 2010-11-17 | 2016-04-20 | ギリアド ファーマセット エルエルシー | 抗ウイルス化合物 |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2012122716A1 (en) | 2011-03-17 | 2012-09-20 | Merck Sharp & Dohme Corp. | Tetracyclic xanthene derivatives and methods of use thereof for treatment of viral diseases |
| US9546160B2 (en) | 2011-05-12 | 2017-01-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| PH12014500386A1 (en) * | 2011-08-24 | 2019-10-07 | Glaxosmithkline Llc | Combination treatment for hepatitis c |
| WO2013030750A1 (en) | 2011-09-01 | 2013-03-07 | Lupin Limited | Antiviral compounds |
| US20150057246A1 (en) * | 2011-09-14 | 2015-02-26 | Michael P. Dwyer | Silyl-containing heterocyclic compounds and methods of use thereof for the treatment of viral diseases |
| EP2709613B2 (en) | 2011-09-16 | 2020-08-12 | Gilead Pharmasset LLC | Methods for treating hcv |
| BR112014010401A8 (pt) | 2011-11-03 | 2017-12-19 | Theravance Inc | Inibidores do vírus da hepatite c rod-like que contêm o fragmento {2-[4-(bifenil-4-il)-1h-imidazo-2-il] pirrolidina-1-carbonilmetil}amina |
| PT3431477T (pt) | 2011-11-16 | 2020-12-15 | Gilead Pharmasset Llc | Imidazolilimidazolos condensados como compostos antivirais |
| US9034832B2 (en) | 2011-12-29 | 2015-05-19 | Abbvie Inc. | Solid compositions |
| US9326973B2 (en) | 2012-01-13 | 2016-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| AU2013217224B2 (en) | 2012-02-10 | 2017-04-06 | Lupin Limited | Antiviral compounds with a dibenzooxaheterocycle moiety |
| CN104302636B (zh) | 2012-04-25 | 2017-03-29 | 施万生物制药研发Ip有限责任公司 | C型肝炎病毒抑制剂 |
| JP6069491B2 (ja) | 2012-04-25 | 2017-02-01 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | Ｃ型肝炎ウイルス阻害剤としてのピペラジン−ピペリジン化合物 |
| US20130309196A1 (en) | 2012-05-16 | 2013-11-21 | Gilead Sciences, Inc. | Antiviral compounds |
| US9079887B2 (en) * | 2012-05-16 | 2015-07-14 | Gilead Sciences, Inc. | Antiviral compounds |
| JP6196678B2 (ja) * | 2012-10-24 | 2017-09-13 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｃ型肝炎ウイルス阻害剤 |
| WO2014110687A1 (en) | 2013-01-16 | 2014-07-24 | Merck Sharp & Dohme Corp. | Thiazolyl-substitued tetracyclic compounds and methods of use thereof for treatment of viral diseases |
| PL2950786T3 (pl) | 2013-01-31 | 2020-05-18 | Gilead Pharmasset Llc | Formulacja skojarzona dwóch związków przeciwwirusowych |
| US11484534B2 (en) | 2013-03-14 | 2022-11-01 | Abbvie Inc. | Methods for treating HCV |
| US9717712B2 (en) | 2013-07-02 | 2017-08-01 | Bristol-Myers Squibb Company | Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus |
| US20150023913A1 (en) | 2013-07-02 | 2015-01-22 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20160158200A1 (en) | 2013-07-09 | 2016-06-09 | Bristol-Myers Squibb Company | Combinations of Hepatitis C Virus Inhibitors |
| WO2015009744A1 (en) | 2013-07-17 | 2015-01-22 | Bristol-Myers Squibb Company | Combinations comprising biphenyl derivatives for use in the treatment of hcv |
| PL3038601T3 (pl) | 2013-08-27 | 2020-08-24 | Gilead Pharmasset Llc | Formulacja złożona dwóch związków przeciwwirusowych |
| CN103450071A (zh) * | 2013-09-05 | 2013-12-18 | 南京工业大学 | 一种医药中间体2-氮杂双环[3.1.0]己烷-2,3-二碳酸叔丁酯的不对称合成方法 |
| US20160311806A1 (en) * | 2013-12-11 | 2016-10-27 | Bristol-Myers Squibb Company | 4,4'-biphenyldiyl-bis-(1 h-imidazolyl) derivatives as hepatitis hcv inhibitors |
| EP3089757A1 (en) | 2014-01-03 | 2016-11-09 | AbbVie Inc. | Solid antiviral dosage forms |
| CN104860931A (zh) * | 2014-02-21 | 2015-08-26 | 常州寅盛药业有限公司 | 丙肝病毒抑制剂及其制药用途 |
| AU2015247706A1 (en) * | 2014-04-15 | 2016-10-27 | Cocrystal Pharma, Inc. | Potent and selective inhibitors of hepatitis C virus |
| TWI721947B (zh) | 2014-06-11 | 2021-03-21 | 美商基利法瑪席特有限責任公司 | 抗病毒化合物的固態形式 |
| WO2016141890A1 (en) * | 2015-03-12 | 2016-09-15 | Sunshine Lake Pharma Co., Ltd. | Compounds as hepatitis c virus inhibitors and pharmaceutical uses thereof |
| WO2017023631A1 (en) | 2015-08-06 | 2017-02-09 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| CN113045480A (zh) * | 2019-12-27 | 2021-06-29 | 尚科生物医药（上海）有限公司 | 一种沙格列汀杂环中间体的差向异构体的制备方法 |
| CN112679407B (zh) * | 2021-03-17 | 2021-06-04 | 南京桦冠生物技术有限公司 | 一种手性5-取代脯氨酸类化合物的制备方法 |
| WO2022246072A1 (en) | 2021-05-21 | 2022-11-24 | Gilead Sciences, Inc. | Tetracyclic compounds for the treatment of zika virus infection |
| CN117460734A (zh) | 2021-05-21 | 2024-01-26 | 吉利德科学公司 | 作为寨卡病毒抑制剂的五环衍生物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090202478A1 (en) * | 2008-02-13 | 2009-08-13 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| WO2009102325A1 (en) * | 2008-02-13 | 2009-08-20 | Bristol-Myers Squibb Company | Imidazolyl biphenyl imidazoles as hepatitis c virus inhibitors |
| WO2010062821A1 (en) * | 2008-11-28 | 2010-06-03 | Glaxosmithkline Llc | Anti-viral compounds, compositions, and methods of use |
| WO2010111673A1 (en) * | 2009-03-27 | 2010-09-30 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic hcv inhibitors |
Family Cites Families (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10889A (en) | 1854-05-09 | Machineey pok | ||
| EP0679153A4 (en) | 1993-01-14 | 1996-05-15 | Magainin Pharma | FINALLY MODIFIED AMINO ACIDS AND PEPTIDES. |
| US5654451B1 (en) | 1993-01-14 | 2000-02-22 | Magainin Pharma | Amino acids and peptides having modified c-terminals and modified n-terminals |
| MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| AU2003249977A1 (en) | 2002-07-05 | 2004-01-23 | Axxima Pharmaceuticals Ag | Imidazole compounds for the treatment of hepatitis c virus infections |
| US20050069522A1 (en) | 2002-08-12 | 2005-03-31 | Richard Colonno | Combination pharmaceutical agents as inhibitors of HCV replication |
| US7420079B2 (en) | 2002-12-09 | 2008-09-02 | Bristol-Myers Squibb Company | Methods and compounds for producing dipeptidyl peptidase IV inhibitors and intermediates thereof |
| US7135462B2 (en) | 2003-11-20 | 2006-11-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| DE102004036971B4 (de) | 2004-07-30 | 2009-07-30 | Advanced Micro Devices, Inc., Sunnyvale | Technik zur Bewertung lokaler elektrischer Eigenschaften in Halbleiterbauelementen |
| WO2006022442A1 (ja) | 2004-08-24 | 2006-03-02 | Santen Pharmaceutical Co., Ltd. | ジヒドロオロテートデヒドロゲナーゼ阻害活性を有する新規複素環アミド誘導体 |
| JP4717457B2 (ja) | 2005-02-08 | 2011-07-06 | 株式会社島精機製作所 | 紡績糸の糸継ぎ方法および糸継ぎを含む編地 |
| WO2006093867A1 (en) | 2005-02-28 | 2006-09-08 | The Rockefeller University | Structure of the hepatitits c virus ns5a protein |
| US8143288B2 (en) | 2005-06-06 | 2012-03-27 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| ES2348332T3 (es) | 2005-09-16 | 2010-12-02 | Arrow Therapeutics Limited | Derivados de bifenilo y su uso en el tratamiento de la hepatitis c. |
| WO2007058384A1 (en) | 2005-11-17 | 2007-05-24 | Osaka University | Method of suppressing replication of hepatitis c virus, inhibitor of replication of the virus and method of screening for the same |
| US7910595B2 (en) | 2005-12-21 | 2011-03-22 | Abbott Laboratories | Anti-viral compounds |
| ES2395386T3 (es) | 2005-12-21 | 2013-02-12 | Abbott Laboratories | Compuestos antivirales |
| SG133452A1 (en) | 2005-12-30 | 2007-07-30 | Novartis Ag | Peptide deformylase inhibitors for treatment of mycobacterial and other parasitic diseases |
| BRPI0712806A2 (pt) | 2006-05-30 | 2012-10-23 | Arrow Therapeutics Ltd | uso de um composto, derivado de bifenila ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, produto, e, método para melhorar uma infecção por hepatite c em um paciente |
| US9873667B2 (en) | 2006-07-27 | 2018-01-23 | Emisphere Technologies Inc. | Arylsulfanyl compounds and compositions for delivering active agents |
| US8303944B2 (en) | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US20100158862A1 (en) | 2006-08-11 | 2010-06-24 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US7659270B2 (en) | 2006-08-11 | 2010-02-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8329159B2 (en) | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7759495B2 (en) | 2006-08-11 | 2010-07-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2097405A2 (en) | 2006-11-21 | 2009-09-09 | Smithkline Beecham Corporation | Anti-viral compounds |
| TWI399380B (zh) | 2006-12-20 | 2013-06-21 | Abbott Lab | 抗病毒化合物 |
| US8629171B2 (en) | 2007-08-08 | 2014-01-14 | Bristol-Myers Squibb Company | Crystalline form of methyl ((1S)-1-((25)-2-(5-(4'-(2-((25)-1((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate dihydrochloride salt |
| US7728027B2 (en) | 2007-08-08 | 2010-06-01 | Bristol-Myers Squibb Company | Process for synthesizing compounds useful for treating hepatitis C |
| CA2715400A1 (en) | 2008-02-12 | 2009-08-20 | Bristol-Myers Squibb Company | Heterocyclic derivatives as hepatitis c virus inhibitors |
| KR101468765B1 (ko) | 2008-02-12 | 2014-12-04 | 브리스톨-마이어스 스큅 컴퍼니 | Ｃ형 간염 바이러스 억제제 |
| US7704992B2 (en) | 2008-02-13 | 2010-04-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7906655B2 (en) | 2008-08-07 | 2011-03-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8383094B2 (en) | 2008-10-01 | 2013-02-26 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| SG171890A1 (en) | 2008-12-03 | 2011-07-28 | Presidio Pharmaceuticals Inc | Inhibitors of hcv ns5a |
| BRPI0922366B8 (pt) | 2008-12-03 | 2021-05-25 | Presidio Pharmaceuticals Inc | composto, composição farmacêutica e uso de um composto |
| ES2567047T3 (es) | 2008-12-23 | 2016-04-19 | Abbvie Inc. | Derivados de pirimidina anti-virales |
| EP2393359A4 (en) | 2009-02-09 | 2012-10-03 | Enanta Pharm Inc | COMPOUND DIBENZIMIDAZOLE DERIVATIVES |
| TWI438200B (zh) | 2009-02-17 | 2014-05-21 | 必治妥美雅史谷比公司 | Ｃ型肝炎病毒抑制劑 |
| WO2010096462A1 (en) | 2009-02-17 | 2010-08-26 | Enanta Pharmaceuticals, Inc | Linked diimidazole derivatives |
| WO2010096777A1 (en) | 2009-02-23 | 2010-08-26 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| WO2010094977A1 (en) | 2009-02-23 | 2010-08-26 | Arrow Therapeutics Limited | Novel biphenyl compounds useful for the treatment of hepatitis c |
| MX2011008982A (es) | 2009-02-27 | 2011-09-15 | Enata Pharmaceuticals Inc | Inhibidores del virus de la hepatitis c. |
| EP2410843A4 (en) | 2009-03-27 | 2012-08-08 | Presidio Pharmaceuticals Inc | FUSIONED CORE INHIBITORS OF HEPATITIS C |
| US8796466B2 (en) | 2009-03-30 | 2014-08-05 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TWI476190B (zh) | 2009-03-30 | 2015-03-11 | 必治妥美雅史谷比公司 | Ｃ型肝炎病毒抑制劑 |
| TW201038559A (en) | 2009-04-09 | 2010-11-01 | Bristol Myers Squibb Co | Hepatitis C virus inhibitors |
| US8143414B2 (en) | 2009-04-13 | 2012-03-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP5734956B2 (ja) | 2009-04-15 | 2015-06-17 | アッヴィ・インコーポレイテッド | 抗ウィルス化合物 |
| RU2528231C2 (ru) | 2009-04-24 | 2014-09-10 | Тиботек Фармасьютикалз | Диариловые эфиры |
| JP2012526834A (ja) | 2009-05-12 | 2012-11-01 | シェーリング コーポレイション | ウイルス疾患治療に有用な縮合型三環式アリール化合物 |
| MX363732B (es) | 2009-05-13 | 2019-04-01 | Gilead Pharmasset Llc Star | Compuestos antivirales. |
| US8211928B2 (en) | 2009-05-29 | 2012-07-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8138215B2 (en) | 2009-05-29 | 2012-03-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| AU2010253790A1 (en) | 2009-05-29 | 2011-12-15 | Merck Sharp & Dohme Corp. | Antiviral compounds composed of three aligned aryl moieties to treat diseases such as Hepatitis C |
| US8980920B2 (en) | 2009-05-29 | 2015-03-17 | Merck Sharp & Dohme Corp. | Antiviral compounds of three linked aryl moieties to treat diseases such as hepatitis C |
| AR077060A1 (es) | 2009-06-11 | 2011-07-27 | Abbott Lab | Compuestos antivirales |
| WO2010148006A1 (en) | 2009-06-16 | 2010-12-23 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| WO2011004276A1 (en) | 2009-07-06 | 2011-01-13 | Pfizer Limited | Hepatitis c virus inhibitors |
| JP2012533569A (ja) | 2009-07-16 | 2012-12-27 | ヴァーテックス ファーマシューティカルズ、 インコーポレイテッド | フラビウイルス感染症を治療又は予防するためのベンゾイミダゾール類似体 |
| WO2011015657A1 (en) | 2009-08-07 | 2011-02-10 | Tibotec Pharmaceuticals | Phenyl ethynyl derivatives as hepatitis c virus inhibitors |
| WO2011015658A1 (en) | 2009-08-07 | 2011-02-10 | Tibotec Pharmaceuticals | Bis-benzimidazole derivatives as hepatitis c virus inhibitors |
| EP2473503B1 (en) | 2009-09-03 | 2014-07-23 | Janssen R&D Ireland | Bis-benzimidazole derivatives |
| EP2473056A4 (en) | 2009-09-04 | 2013-02-13 | Glaxosmithkline Llc | CHEMICAL COMPOUNDS |
| EP2475256A4 (en) | 2009-09-11 | 2013-06-05 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| WO2011031934A1 (en) | 2009-09-11 | 2011-03-17 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| US8415374B2 (en) | 2009-10-12 | 2013-04-09 | Bristol-Myers Squibb Company | Combinations of hepatitis C virus inhibitors |
| WO2011050146A1 (en) | 2009-10-23 | 2011-04-28 | Glaxosmithkline Llc | Chemical compounds |
| UA108211C2 (uk) | 2009-11-04 | 2015-04-10 | Янссен Рід Айрленд | Бензімідазолімідазольні похідні |
| US20110274648A1 (en) | 2009-11-11 | 2011-11-10 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110269956A1 (en) | 2009-11-11 | 2011-11-03 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110281910A1 (en) | 2009-11-12 | 2011-11-17 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| EP2503881B1 (en) | 2009-11-25 | 2015-05-13 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds and derivatives thereof useful for the treatment of viral diseases |
| AU2010325980B2 (en) | 2009-12-04 | 2016-04-07 | National Health Research Institutes | Proline derivatives |
| WO2011081918A1 (en) | 2009-12-14 | 2011-07-07 | Enanta Pharmaceuticals, Inc | Hepatitis c virus inhibitors |
| WO2011075607A1 (en) | 2009-12-18 | 2011-06-23 | Intermune, Inc. | Novel inhibitors of hepatitis c virus replication |
| AR079528A1 (es) | 2009-12-18 | 2012-02-01 | Idenix Pharmaceuticals Inc | Inhibidores de arileno o heteroarileno 5,5-fusionado del virus de la hepatitis c |
| US20130156731A1 (en) | 2009-12-22 | 2013-06-20 | Kevin X. Chen | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseas |
| CA2784036A1 (en) | 2009-12-24 | 2011-06-30 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2011091446A1 (en) | 2010-01-22 | 2011-07-28 | Glaxosmithkline Llc | Chemical compounds |
| BR112012018529A2 (pt) | 2010-01-25 | 2016-08-09 | Enanta Pharm Inc | inibidores do vírus de hepatite c, sua composição farmacêutica e seu uso, e método para inibição da replicação de um vírus contendo rna |
| WO2011091532A1 (en) | 2010-01-28 | 2011-08-04 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor compounds |
-
2010
- 2010-12-01 US US12/957,512 patent/US8377980B2/en active Active
- 2010-12-10 TW TW099143331A patent/TWI487702B/zh not_active IP Right Cessation
- 2010-12-13 CA CA2784662A patent/CA2784662A1/en not_active Abandoned
- 2010-12-13 WO PCT/US2010/060077 patent/WO2011075439A1/en not_active Ceased
- 2010-12-13 EP EP10796540.2A patent/EP2513091B1/en not_active Not-in-force
- 2010-12-13 JP JP2012544681A patent/JP5785189B2/ja not_active Expired - Fee Related
- 2010-12-13 PH PH1/2012/500979A patent/PH12012500979A1/en unknown
- 2010-12-13 KR KR1020127018317A patent/KR20120107991A/ko not_active Withdrawn
- 2010-12-13 PE PE2012000831A patent/PE20121479A1/es not_active Application Discontinuation
- 2010-12-13 BR BR112012014677A patent/BR112012014677A2/pt not_active IP Right Cessation
- 2010-12-13 EA EA201270656A patent/EA020815B1/ru not_active IP Right Cessation
- 2010-12-13 CN CN201080062796.3A patent/CN102741242B/zh not_active Expired - Fee Related
- 2010-12-13 NZ NZ601220A patent/NZ601220A/en not_active IP Right Cessation
- 2010-12-13 MX MX2012006635A patent/MX2012006635A/es active IP Right Grant
- 2010-12-13 SG SG2012043857A patent/SG181700A1/en unknown
- 2010-12-13 AU AU2010332034A patent/AU2010332034B2/en not_active Ceased
- 2010-12-16 AR ARP100104697A patent/AR079634A1/es unknown
-
2012
- 2012-05-25 TN TNP2012000264A patent/TN2012000264A1/en unknown
- 2012-06-06 MA MA34944A patent/MA33806B1/fr unknown
- 2012-06-15 CL CL2012001637A patent/CL2012001637A1/es unknown
- 2012-07-04 CO CO12111939A patent/CO6561788A2/es not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090202478A1 (en) * | 2008-02-13 | 2009-08-13 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| WO2009102325A1 (en) * | 2008-02-13 | 2009-08-20 | Bristol-Myers Squibb Company | Imidazolyl biphenyl imidazoles as hepatitis c virus inhibitors |
| WO2010062821A1 (en) * | 2008-11-28 | 2010-06-03 | Glaxosmithkline Llc | Anti-viral compounds, compositions, and methods of use |
| WO2010111673A1 (en) * | 2009-03-27 | 2010-09-30 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic hcv inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| TN2012000264A1 (en) | 2013-12-12 |
| MA33806B1 (fr) | 2012-12-03 |
| CN102741242B (zh) | 2015-07-01 |
| NZ601220A (en) | 2014-07-25 |
| JP2013514359A (ja) | 2013-04-25 |
| EP2513091A1 (en) | 2012-10-24 |
| PH12012500979A1 (en) | 2014-09-05 |
| CL2012001637A1 (es) | 2012-10-12 |
| EA201270656A1 (ru) | 2012-11-30 |
| CN102741242A (zh) | 2012-10-17 |
| MX2012006635A (es) | 2012-06-21 |
| JP5785189B2 (ja) | 2015-09-24 |
| TW201130825A (en) | 2011-09-16 |
| AU2010332034A1 (en) | 2012-08-02 |
| AU2010332034B2 (en) | 2016-04-14 |
| TWI487702B (zh) | 2015-06-11 |
| US20110286961A1 (en) | 2011-11-24 |
| CA2784662A1 (en) | 2011-06-23 |
| EP2513091B1 (en) | 2017-04-12 |
| CO6561788A2 (es) | 2012-11-15 |
| US8377980B2 (en) | 2013-02-19 |
| PE20121479A1 (es) | 2012-11-07 |
| BR112012014677A2 (pt) | 2015-09-15 |
| KR20120107991A (ko) | 2012-10-04 |
| WO2011075439A1 (en) | 2011-06-23 |
| SG181700A1 (en) | 2012-07-30 |
| AR079634A1 (es) | 2012-02-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA020815B1 (ru) | Ингибиторы вируса гепатита с | |
| CN102143959B (zh) | 丙型肝炎病毒抑制剂 | |
| JP5558556B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| CN102378762B (zh) | 丙型肝炎病毒抑制剂 | |
| JP5611959B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| CN101998954B (zh) | 用作丙型肝炎病毒抑制剂的构象受限的联苯衍生物 | |
| CN102459250B (zh) | 丙型肝炎病毒抑制剂 | |
| JP5632910B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| CN102177141B (zh) | 作为丙型肝炎病毒抑制剂的联-1h-苯并咪唑 | |
| CN102448956B (zh) | 丙型肝炎病毒抑制剂 | |
| CN103827108B (zh) | 丙型肝炎病毒抑制剂 | |
| EA018088B1 (ru) | Имидазолилбифенильные имидазолы в качестве ингибиторов вируса гепатита с | |
| EA024171B1 (ru) | Ингибиторы вируса гепатита с | |
| CN104884455B (zh) | 丙型肝炎病毒抑制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM |
|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): RU |