CZ20023321A3 - Makrocyklická sloučenina a farmaceutický prostředek - Google Patents

Info

Publication number

CZ20023321A3

CZ20023321A3 CZ20023321A CZ20023321A CZ20023321A3 CZ 20023321 A3 CZ20023321 A3 CZ 20023321A3 CZ 20023321 A CZ20023321 A CZ 20023321A CZ 20023321 A CZ20023321 A CZ 20023321A CZ 20023321 A3 CZ20023321 A3 CZ 20023321A3

Authority

CZ

Czechia

Prior art keywords

compound

alkyl

mmol

conhch

chr

Prior art date

2000-04-05

Links

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• Global Dossier
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• 150000002678 macrocyclic compounds Chemical class 0.000 title claims abstract description 47
• 239000000825 pharmaceutical preparation Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 293
• 238000000034 method Methods 0.000 claims abstract description 57
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
• 108091005804 Peptidases Proteins 0.000 claims abstract description 22
• 239000004365 Protease Substances 0.000 claims abstract description 22
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 7
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 316
• 239000000460 chlorine Substances 0.000 claims description 93
• -1 aryiheteroaryl Chemical group 0.000 claims description 64
• 125000000217 alkyl group Chemical group 0.000 claims description 61
• 229910052739 hydrogen Inorganic materials 0.000 claims description 46
• 125000003118 aryl group Chemical group 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 24
• 150000002148 esters Chemical class 0.000 claims description 22
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 20
• 239000004480 active ingredient Substances 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 229910005965 SO 2 Inorganic materials 0.000 claims description 17
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 16
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 15
• 239000004202 carbamide Substances 0.000 claims description 13
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 9
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 150000001299 aldehydes Chemical class 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 150000001346 alkyl aryl ethers Chemical class 0.000 claims description 4
• 150000005215 alkyl ethers Chemical class 0.000 claims description 4
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 4
• 125000004414 alkyl thio group Chemical group 0.000 claims description 4
• 125000003368 amide group Chemical group 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 150000002576 ketones Chemical class 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000004437 phosphorous atom Chemical group 0.000 claims description 4
• 150000003462 sulfoxides Chemical class 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 102000006992 Interferon-alpha Human genes 0.000 claims description 3
• 108010047761 Interferon-alpha Proteins 0.000 claims description 3
• 102000014150 Interferons Human genes 0.000 claims description 3
• 108010050904 Interferons Proteins 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 3
• 125000005842 heteroatom Chemical group 0.000 claims description 3
• 125000000623 heterocyclic group Chemical group 0.000 claims description 3
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
• 229940079322 interferon Drugs 0.000 claims description 3
• 239000012453 solvate Substances 0.000 claims description 3
• RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims description 2
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 2
• 229940100389 Sulfonylurea Drugs 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• 150000003973 alkyl amines Chemical class 0.000 claims description 2
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 2
• 125000000304 alkynyl group Chemical group 0.000 claims description 2
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
• 125000001769 aryl amino group Chemical group 0.000 claims description 2
• 150000008378 aryl ethers Chemical class 0.000 claims description 2
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
• 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 2
• UZMZVDOOVXLRID-UHFFFAOYSA-N azanylidyne-(nitrosulfonylamino)methane Chemical compound [O-][N+](=O)S(=O)(=O)NC#N UZMZVDOOVXLRID-UHFFFAOYSA-N 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
• 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 2
• 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 229910052698 phosphorus Inorganic materials 0.000 claims description 2
• 229960000329 ribavirin Drugs 0.000 claims description 2
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 2
• 150000003457 sulfones Chemical class 0.000 claims description 2
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
• 239000003443 antiviral agent Substances 0.000 claims 2
• 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
• 125000001511 cyclopentyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
• 125000004076 pyridyl group Chemical class 0.000 claims 2
• 125000001544 thienyl group Chemical class 0.000 claims 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
• 150000001408 amides Chemical class 0.000 claims 1
• 150000001721 carbon Chemical group 0.000 claims 1
• 125000001559 cyclopropyl group Chemical class [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
• 150000002825 nitriles Chemical class 0.000 claims 1
• MGQNMYSRDBFUIR-UHFFFAOYSA-N nitro cyanoformate Chemical compound [O-][N+](=O)OC(=O)C#N MGQNMYSRDBFUIR-UHFFFAOYSA-N 0.000 claims 1
• 125000005936 piperidyl group Chemical class 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 237
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 230
• 239000000047 product Substances 0.000 description 196
• 239000000243 solution Substances 0.000 description 189
• 238000002360 preparation method Methods 0.000 description 164
• 239000000203 mixture Substances 0.000 description 137
• 235000019439 ethyl acetate Nutrition 0.000 description 105
• 238000000746 purification Methods 0.000 description 101
• 239000011541 reaction mixture Substances 0.000 description 100
• 238000003818 flash chromatography Methods 0.000 description 95
• 238000006243 chemical reaction Methods 0.000 description 79
• 150000001412 amines Chemical class 0.000 description 74
• 239000007787 solid Substances 0.000 description 74
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 71
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
• 239000000463 material Substances 0.000 description 59
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 48
• 239000011734 sodium Substances 0.000 description 47
• 239000012267 brine Substances 0.000 description 45
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
• 230000003647 oxidation Effects 0.000 description 44
• 238000007254 oxidation reaction Methods 0.000 description 44
• 241000711549 Hepacivirus C Species 0.000 description 43
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• 239000012044 organic layer Substances 0.000 description 40
• 239000010410 layer Substances 0.000 description 37
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 239000013058 crude material Substances 0.000 description 34
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 30
• 239000000543 intermediate Substances 0.000 description 30
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
• 239000007858 starting material Substances 0.000 description 27
• 239000000758 substrate Substances 0.000 description 27
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 26
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
• 238000004440 column chromatography Methods 0.000 description 25
• 229920006395 saturated elastomer Polymers 0.000 description 25
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 21
• 239000002253 acid Substances 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 21
• 238000004809 thin layer chromatography Methods 0.000 description 21
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• 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 20
• 101710144111 Non-structural protein 3 Proteins 0.000 description 19
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 17
• 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 16
• 235000018102 proteins Nutrition 0.000 description 16
• 108090000623 proteins and genes Proteins 0.000 description 16
• 102000004169 proteins and genes Human genes 0.000 description 16
• 238000003786 synthesis reaction Methods 0.000 description 16
• 238000003776 cleavage reaction Methods 0.000 description 15
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 15
• 230000007017 scission Effects 0.000 description 15
• 235000002639 sodium chloride Nutrition 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• 229910004298 SiO 2 Inorganic materials 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 14
• 239000012528 membrane Substances 0.000 description 14
• 235000019441 ethanol Nutrition 0.000 description 13
• 108090000765 processed proteins & peptides Proteins 0.000 description 13
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
• 239000007864 aqueous solution Substances 0.000 description 12
• 239000012043 crude product Substances 0.000 description 12
• 239000003112 inhibitor Substances 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• 235000019341 magnesium sulphate Nutrition 0.000 description 12
• FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 239000002904 solvent Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• 108010022999 Serine Proteases Proteins 0.000 description 10
• 102000012479 Serine Proteases Human genes 0.000 description 10
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
• 150000004702 methyl esters Chemical class 0.000 description 10
• IDWHSUSIOBKSKI-UHFFFAOYSA-N 2-[cyclohexyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)N(CC(O)=O)C1CCCCC1 IDWHSUSIOBKSKI-UHFFFAOYSA-N 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 229940024606 amino acid Drugs 0.000 description 9
• 235000001014 amino acid Nutrition 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• 239000003085 diluting agent Substances 0.000 description 9
• 239000007788 liquid Substances 0.000 description 9
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 9
• 239000011780 sodium chloride Substances 0.000 description 9
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 239000008187 granular material Substances 0.000 description 8
• 239000005090 green fluorescent protein Substances 0.000 description 8
• 150000002431 hydrogen Chemical class 0.000 description 8
• 102000004196 processed proteins & peptides Human genes 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• AVWQQPYHYQKEIZ-UHFFFAOYSA-K trisodium;2-dodecylbenzenesulfonate;3-dodecylbenzenesulfonate;4-dodecylbenzenesulfonate Chemical compound [Na+].[Na+].[Na+].CCCCCCCCCCCCC1=CC=C(S([O-])(=O)=O)C=C1.CCCCCCCCCCCCC1=CC=CC(S([O-])(=O)=O)=C1.CCCCCCCCCCCCC1=CC=CC=C1S([O-])(=O)=O AVWQQPYHYQKEIZ-UHFFFAOYSA-K 0.000 description 8
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 7
• 229920002472 Starch Polymers 0.000 description 7
• 150000001413 amino acids Chemical class 0.000 description 7
• 239000011230 binding agent Substances 0.000 description 7
• 125000004430 oxygen atom Chemical group O* 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 238000012545 processing Methods 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 235000019698 starch Nutrition 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 239000003039 volatile agent Substances 0.000 description 7
• 208000005176 Hepatitis C Diseases 0.000 description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 6
• 229910052786 argon Inorganic materials 0.000 description 6
• 108091005948 blue fluorescent proteins Proteins 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000007884 disintegrant Substances 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 238000005984 hydrogenation reaction Methods 0.000 description 6
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 6
• 239000013612 plasmid Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 238000001890 transfection Methods 0.000 description 6
• LRFZIPCTFBPFLX-UHFFFAOYSA-N 3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)C(C)(C)C LRFZIPCTFBPFLX-UHFFFAOYSA-N 0.000 description 5
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