EA031106B1 - Диоксолановые аналоги уридина для лечения рака - Google Patents

Info

Publication number

EA031106B1

EA031106B1 EA201790328A EA201790328A EA031106B1 EA 031106 B1 EA031106 B1 EA 031106B1 EA 201790328 A EA201790328 A EA 201790328A EA 201790328 A EA201790328 A EA 201790328A EA 031106 B1 EA031106 B1 EA 031106B1

Authority

EA

Eurasian Patent Office

Prior art keywords

mmol

alkyl

dia

mixture

compound

Prior art date

2014-08-25

Links

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• 206010028980 Neoplasm Diseases 0.000 title claims abstract description 39
• 201000011510 cancer Diseases 0.000 title claims abstract description 32
• 238000011282 treatment Methods 0.000 title claims abstract description 24
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 title 1
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 title 1
• 150000004862 dioxolanes Chemical class 0.000 title 1
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 title 1
• 229940045145 uridine Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 264
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 40
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 26
• 125000001624 naphthyl group Chemical group 0.000 claims abstract description 17
• -1 2-propylpentyl Chemical group 0.000 claims description 120
• 229910052736 halogen Inorganic materials 0.000 claims description 29
• 150000002367 halogens Chemical class 0.000 claims description 28
• 201000007270 liver cancer Diseases 0.000 claims description 23
• 208000014018 liver neoplasm Diseases 0.000 claims description 23
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 150000003839 salts Chemical class 0.000 claims description 22
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
• 150000001721 carbon Chemical group 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
• 150000008575 L-amino acids Chemical class 0.000 claims description 3
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 abstract description 12
• 229910052731 fluorine Inorganic materials 0.000 abstract description 9
• 125000004076 pyridyl group Chemical group 0.000 abstract description 7
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 128
• 239000000203 mixture Substances 0.000 description 101
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 98
• 239000000243 solution Substances 0.000 description 96
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 88
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 78
• 235000019439 ethyl acetate Nutrition 0.000 description 58
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
• 238000000034 method Methods 0.000 description 46
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• 239000011541 reaction mixture Substances 0.000 description 43
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 41
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
• 239000007787 solid Substances 0.000 description 36
• 229940002612 prodrug Drugs 0.000 description 34
• 239000000651 prodrug Substances 0.000 description 34
• 230000002829 reductive effect Effects 0.000 description 34
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
• 239000000543 intermediate Substances 0.000 description 29
• 125000000217 alkyl group Chemical group 0.000 description 27
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 26
• 210000004185 liver Anatomy 0.000 description 25
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 238000006243 chemical reaction Methods 0.000 description 24
• 125000000753 cycloalkyl group Chemical group 0.000 description 24
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 24
• 210000004027 cell Anatomy 0.000 description 23
• 239000012074 organic phase Substances 0.000 description 22
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 22
• 239000003814 drug Substances 0.000 description 21
• 239000002777 nucleoside Substances 0.000 description 21
• 239000011734 sodium Substances 0.000 description 21
• 239000002904 solvent Substances 0.000 description 21
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• 239000002808 molecular sieve Substances 0.000 description 20
• 229950010147 troxacitabine Drugs 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 19
• RXRGZNYSEHTMHC-BQBZGAKWSA-N troxacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)OC1 RXRGZNYSEHTMHC-BQBZGAKWSA-N 0.000 description 19
• 238000002360 preparation method Methods 0.000 description 18
• 239000000741 silica gel Substances 0.000 description 18
• 229910002027 silica gel Inorganic materials 0.000 description 18
• 125000003118 aryl group Chemical group 0.000 description 17
• 239000000460 chlorine Substances 0.000 description 17
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 17
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 17
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• 239000012267 brine Substances 0.000 description 15
• 229910052757 nitrogen Inorganic materials 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• 229910052760 oxygen Inorganic materials 0.000 description 14
• 239000012071 phase Substances 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• 239000013058 crude material Substances 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 238000010992 reflux Methods 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• 229910052717 sulfur Inorganic materials 0.000 description 12
• 239000001226 triphosphate Substances 0.000 description 12
• 235000011178 triphosphate Nutrition 0.000 description 12
• 238000004440 column chromatography Methods 0.000 description 11
• 239000003208 petroleum Substances 0.000 description 11
• 239000008194 pharmaceutical composition Substances 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 11
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 125000003342 alkenyl group Chemical group 0.000 description 10
• 229910052794 bromium Inorganic materials 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• 125000005842 heteroatom Chemical group 0.000 description 10
• 229910052698 phosphorus Inorganic materials 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 229940024606 amino acid Drugs 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
• 125000002950 monocyclic group Chemical group 0.000 description 9
• 150000003833 nucleoside derivatives Chemical class 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 9
• 239000012453 solvate Substances 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 8
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 8
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• 239000002246 antineoplastic agent Substances 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 8
• IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 8
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
• 239000005695 Ammonium acetate Substances 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 125000000304 alkynyl group Chemical group 0.000 description 7
• 150000001413 amino acids Chemical class 0.000 description 7
• 229940043376 ammonium acetate Drugs 0.000 description 7
• 235000019257 ammonium acetate Nutrition 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 238000005160 1H NMR spectroscopy Methods 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 229910052801 chlorine Inorganic materials 0.000 description 6
• 229940127089 cytotoxic agent Drugs 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
• 229910052740 iodine Inorganic materials 0.000 description 6
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
• 150000004712 monophosphates Chemical class 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
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• 125000004437 phosphorous atom Chemical group 0.000 description 6
• 230000026731 phosphorylation Effects 0.000 description 6
• 238000006366 phosphorylation reaction Methods 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 239000002671 adjuvant Substances 0.000 description 5
• 125000004414 alkyl thio group Chemical group 0.000 description 5
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• 230000001093 anti-cancer Effects 0.000 description 5
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• 239000012043 crude product Substances 0.000 description 5
• TXFOLHZMICYNRM-UHFFFAOYSA-N dichlorophosphoryloxybenzene Chemical compound ClP(Cl)(=O)OC1=CC=CC=C1 TXFOLHZMICYNRM-UHFFFAOYSA-N 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
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• 230000014509 gene expression Effects 0.000 description 5
• 210000003494 hepatocyte Anatomy 0.000 description 5
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• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
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• 239000007832 Na2SO4 Substances 0.000 description 4
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• 108091000080 Phosphotransferase Proteins 0.000 description 4
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• 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 125000002993 cycloalkylene group Chemical group 0.000 description 4
• 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 4
• 230000001472 cytotoxic effect Effects 0.000 description 4
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
• 150000002148 esters Chemical group 0.000 description 4
• FDLDWKIEWAWOSL-UHFFFAOYSA-N ethyl acetate;2-methylpentane Chemical compound CCCC(C)C.CCOC(C)=O FDLDWKIEWAWOSL-UHFFFAOYSA-N 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
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• 239000011777 magnesium Substances 0.000 description 4
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• 239000012044 organic layer Substances 0.000 description 4
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• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
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• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 239000012047 saturated solution Substances 0.000 description 4
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 238000004808 supercritical fluid chromatography Methods 0.000 description 4
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 4
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• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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• 206010009944 Colon cancer Diseases 0.000 description 3
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
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• 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 3
• 241000725303 Human immunodeficiency virus Species 0.000 description 3
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• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
• 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 3
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
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• 229940041181 antineoplastic drug Drugs 0.000 description 3
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