TW201609752A - 抗病毒化合物之晶形 - Google Patents

Info

Publication number

TW201609752A

TW201609752A TW103144805A TW103144805A TW201609752A TW 201609752 A TW201609752 A TW 201609752A TW 103144805 A TW103144805 A TW 103144805A TW 103144805 A TW103144805 A TW 103144805A TW 201609752 A TW201609752 A TW 201609752A

Authority

TW

Taiwan

Prior art keywords

compound

diffraction pattern

crystal form

ray powder

curve

Prior art date

2013-12-23

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 815
• 230000000840 anti-viral effect Effects 0.000 title description 2
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 120
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 119
• 238000000034 method Methods 0.000 claims abstract description 97
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 206
• 238000002411 thermogravimetry Methods 0.000 claims description 206
• 239000013078 crystal Substances 0.000 claims description 194
• VNXBKJFUJUWOCW-UHFFFAOYSA-N methylcyclopropane Chemical compound CC1CC1 VNXBKJFUJUWOCW-UHFFFAOYSA-N 0.000 claims description 112
• 238000000113 differential scanning calorimetry Methods 0.000 claims description 106
• 230000005855 radiation Effects 0.000 claims description 95
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 82
• 239000000203 mixture Substances 0.000 claims description 82
• 238000001179 sorption measurement Methods 0.000 claims description 80
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 78
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 69
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 69
• 238000001757 thermogravimetry curve Methods 0.000 claims description 63
• 125000000623 heterocyclic group Chemical group 0.000 claims description 53
• 238000005481 NMR spectroscopy Methods 0.000 claims description 52
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 48
• 239000012453 solvate Substances 0.000 claims description 47
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 44
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 32
• 241000711549 Hepacivirus C Species 0.000 claims description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 19
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
• 238000010438 heat treatment Methods 0.000 claims description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 150000004683 dihydrates Chemical class 0.000 claims description 7
• 238000002076 thermal analysis method Methods 0.000 claims description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 238000004458 analytical method Methods 0.000 claims description 4
• 238000010586 diagram Methods 0.000 claims description 4
• 150000004685 tetrahydrates Chemical group 0.000 claims description 4
• 239000000126 substance Substances 0.000 claims description 2
• LQERIDTXQFOHKA-UHFFFAOYSA-N nonadecane Chemical compound CCCCCCCCCCCCCCCCCCC LQERIDTXQFOHKA-UHFFFAOYSA-N 0.000 claims 2
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims 1
• HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
• CCZHABWIXLIPJP-UHFFFAOYSA-N 3h-dioxadiazole Chemical compound N1OOC=N1 CCZHABWIXLIPJP-UHFFFAOYSA-N 0.000 claims 1
• 229940125904 compound 1 Drugs 0.000 claims 1
• 229940125797 compound 12 Drugs 0.000 claims 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 22
• 239000007787 solid Substances 0.000 abstract description 19
• 230000008569 process Effects 0.000 abstract description 4
• 238000004519 manufacturing process Methods 0.000 abstract description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 100
• 125000000217 alkyl group Chemical group 0.000 description 73
• 239000000243 solution Substances 0.000 description 73
• 125000001424 substituent group Chemical group 0.000 description 73
• 238000006243 chemical reaction Methods 0.000 description 71
• 150000001412 amines Chemical class 0.000 description 69
• 125000001072 heteroaryl group Chemical group 0.000 description 68
• 125000003118 aryl group Chemical group 0.000 description 65
• -1 indoleamine dihydrate Chemical compound 0.000 description 65
• 238000002360 preparation method Methods 0.000 description 56
• XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 45
• 239000004480 active ingredient Substances 0.000 description 44
• 125000000753 cycloalkyl group Chemical group 0.000 description 40
• 150000003839 salts Chemical class 0.000 description 36
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
• 239000002002 slurry Substances 0.000 description 32
• 125000003342 alkenyl group Chemical group 0.000 description 31
• 239000010410 layer Substances 0.000 description 31
• 125000004432 carbon atom Chemical group C* 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• 125000000304 alkynyl group Chemical group 0.000 description 28
• 230000015572 biosynthetic process Effects 0.000 description 28
• 238000003786 synthesis reaction Methods 0.000 description 27
• 125000003545 alkoxy group Chemical group 0.000 description 25
• 235000019439 ethyl acetate Nutrition 0.000 description 24
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 23
• 125000004093 cyano group Chemical class *C#N 0.000 description 23
• 229910052736 halogen Inorganic materials 0.000 description 23
• 150000002367 halogens Chemical class 0.000 description 23
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 22
• 125000002887 hydroxy group Chemical class [H]O* 0.000 description 22
• 125000003178 carboxy group Chemical class [H]OC(*)=O 0.000 description 21
• 125000004181 carboxyalkyl group Chemical class 0.000 description 21
• 239000003112 inhibitor Substances 0.000 description 21
• 239000002904 solvent Substances 0.000 description 21
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 19
• 229910052757 nitrogen Inorganic materials 0.000 description 19
• 239000012071 phase Substances 0.000 description 19
• 125000000547 substituted alkyl group Chemical group 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 18
• 238000003756 stirring Methods 0.000 description 18
• 239000001257 hydrogen Substances 0.000 description 17
• 229910052739 hydrogen Inorganic materials 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 description 16
• FYZZJDABXBPMOG-UHFFFAOYSA-N ethanol;n-methylmethanamine Chemical compound CCO.CNC FYZZJDABXBPMOG-UHFFFAOYSA-N 0.000 description 16
• 239000000725 suspension Substances 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• 239000003814 drug Substances 0.000 description 13
• 239000004475 Arginine Substances 0.000 description 12
• 108010050904 Interferons Proteins 0.000 description 12
• 102000014150 Interferons Human genes 0.000 description 12
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 12
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 12
• 229960001231 choline Drugs 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• 229960003194 meglumine Drugs 0.000 description 12
• 125000004193 piperazinyl group Chemical group 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 229910052708 sodium Inorganic materials 0.000 description 12
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
• 229940079322 interferon Drugs 0.000 description 11
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 150000003248 quinolines Chemical group 0.000 description 11
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 10
• FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 150000002148 esters Chemical class 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
• RMIAZGFKBPOZLX-NLRFIBDTSA-N 4-methylbenzenesulfonic acid methyl (2S,3S,4R)-3-ethyl-4-hydroxypyrrolidine-2-carboxylate Chemical compound Cc1ccc(cc1)S(O)(=O)=O.CC[C@@H]1[C@@H](O)CN[C@@H]1C(=O)OC RMIAZGFKBPOZLX-NLRFIBDTSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 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 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• 150000002431 hydrogen Chemical class 0.000 description 9
• 235000019198 oils Nutrition 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 239000003995 emulsifying agent Substances 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• 208000015181 infectious disease Diseases 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 125000003107 substituted aryl group Chemical group 0.000 description 8
• 229940124597 therapeutic agent Drugs 0.000 description 8
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 7
• 125000004414 alkyl thio group Chemical group 0.000 description 7
• 125000005110 aryl thio group Chemical class 0.000 description 7
• 125000004465 cycloalkenyloxy group Chemical group 0.000 description 7
• 125000005842 heteroatom Chemical group 0.000 description 7
• 239000004615 ingredient Substances 0.000 description 7
• QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 7
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
• OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical group O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 6
• BPSVWHVEZIDAHQ-UHFFFAOYSA-N 3-chloro-2-(1,1-difluorobut-3-enyl)-6-methoxyquinoxaline Chemical compound ClC=1C(=NC2=CC=C(C=C2N1)OC)C(CC=C)(F)F BPSVWHVEZIDAHQ-UHFFFAOYSA-N 0.000 description 6
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 6
• 238000013019 agitation Methods 0.000 description 6
• 125000000033 alkoxyamino group Chemical group 0.000 description 6
• 125000004466 alkoxycarbonylamino group Chemical class 0.000 description 6
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 6
• 239000003443 antiviral agent Substances 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 125000004104 aryloxy group Chemical group 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 125000000852 azido group Chemical class *N=[N+]=[N-] 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• 239000011203 carbon fibre reinforced carbon Substances 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
• 125000000000 cycloalkoxy group Chemical group 0.000 description 6
• 235000014113 dietary fatty acids Nutrition 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 239000000839 emulsion Substances 0.000 description 6
• NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical group CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 6
• 239000000194 fatty acid Substances 0.000 description 6
• 229930195729 fatty acid Natural products 0.000 description 6
• 150000004665 fatty acids Chemical class 0.000 description 6
• 235000003599 food sweetener Nutrition 0.000 description 6
• 239000003205 fragrance Substances 0.000 description 6
• 125000005553 heteroaryloxy group Chemical group 0.000 description 6
• 150000002430 hydrocarbons Chemical group 0.000 description 6
• 239000007937 lozenge Substances 0.000 description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 6
• 229910052938 sodium sulfate Inorganic materials 0.000 description 6
• 235000011152 sodium sulphate Nutrition 0.000 description 6
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 125000002813 thiocarbonyl group Chemical class *C(*)=S 0.000 description 6
• 238000011282 treatment Methods 0.000 description 6
• MAQDQJWCSSCURR-UHFFFAOYSA-N 4-[5-(cyclopropanecarbonylamino)-2-(trifluoromethoxy)phenyl]-n-[4-[(4-propylsulfonylpiperazin-1-yl)methyl]phenyl]benzamide Chemical compound C1CN(S(=O)(=O)CCC)CCN1CC(C=C1)=CC=C1NC(=O)C1=CC=C(C=2C(=CC=C(NC(=O)C3CC3)C=2)OC(F)(F)F)C=C1 MAQDQJWCSSCURR-UHFFFAOYSA-N 0.000 description 5
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical group COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 5
• 108010047761 Interferon-alpha Proteins 0.000 description 5
• 102000006992 Interferon-alpha Human genes 0.000 description 5
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 125000002947 alkylene group Chemical group 0.000 description 5
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 229940011051 isopropyl acetate Drugs 0.000 description 5
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
• 125000000468 ketone group Chemical class 0.000 description 5
• 238000011068 loading method Methods 0.000 description 5
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 5
• 239000002777 nucleoside Substances 0.000 description 5
• 239000002674 ointment Substances 0.000 description 5
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 5
• 239000003755 preservative agent Substances 0.000 description 5
• 229960000329 ribavirin Drugs 0.000 description 5
• 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 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 125000005017 substituted alkenyl group Chemical group 0.000 description 5
• 239000000375 suspending agent Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
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