NO322930B1 - Acykliske nukleosidderivater, farmasoytisk sammensetning innbefattende samme, anvendelse av samme for fremstilling av medikament og fremgangsmate for fremstilling av samme. - Google Patents

Info

Publication number

NO322930B1

NO322930B1 NO19983216A NO983216A NO322930B1 NO 322930 B1 NO322930 B1 NO 322930B1 NO 19983216 A NO19983216 A NO 19983216A NO 983216 A NO983216 A NO 983216A NO 322930 B1 NO322930 B1 NO 322930B1

Authority

NO

Norway

Prior art keywords

butyl

guanine

valyloxy

compound

amino

Prior art date

1996-02-16

Links

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• Global Dossier
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• -1 Acyclic nucleoside derivatives Chemical class 0.000 title claims description 86
• 238000000034 method Methods 0.000 title claims description 28
• 238000002360 preparation method Methods 0.000 title claims description 26
• 239000003814 drug Substances 0.000 title claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
• 229940079593 drug Drugs 0.000 title claims description 5
• 230000008569 process Effects 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims description 124
• UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 97
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 62
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 55
• 150000003839 salts Chemical class 0.000 claims description 27
• 229920006395 saturated elastomer Polymers 0.000 claims description 21
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 13
• 239000004474 valine Substances 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 125000006239 protecting group Chemical group 0.000 claims description 12
• 229910052739 hydrogen Inorganic materials 0.000 claims description 11
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 6
• 238000011282 treatment Methods 0.000 claims description 6
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 5
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
• 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 4
• 206010038997 Retroviral infections Diseases 0.000 claims description 4
• ACBSZTQIFTYFGH-IAPPQJPRSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] octadecanoate Chemical compound N1C(N)=NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCC)C=N2 ACBSZTQIFTYFGH-IAPPQJPRSA-N 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 208000015181 infectious disease Diseases 0.000 claims description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
• 208000031886 HIV Infections Diseases 0.000 claims description 3
• 206010019973 Herpes virus infection Diseases 0.000 claims description 3
• 208000036142 Viral infection Diseases 0.000 claims description 3
• JWNMJTOKXBWOSA-IAPPQJPRSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] octadecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCCCCCCCCCC)C=N2 JWNMJTOKXBWOSA-IAPPQJPRSA-N 0.000 claims description 3
• 125000001589 carboacyl group Chemical group 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 238000011321 prophylaxis Methods 0.000 claims description 3
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000001424 substituent group Chemical group 0.000 claims description 3
• 230000009385 viral infection Effects 0.000 claims description 3
• 241000701085 Human alphaherpesvirus 3 Species 0.000 claims description 2
• 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 2
• 241000701027 Human herpesvirus 6 Species 0.000 claims description 2
• NGDOMQQXNRCULU-QUCCMNQESA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] decanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCC)C=N2 NGDOMQQXNRCULU-QUCCMNQESA-N 0.000 claims description 2
• KZDLNFQWACYUTK-RSXGOPAZSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] hexadecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCC)C=N2 KZDLNFQWACYUTK-RSXGOPAZSA-N 0.000 claims description 2
• YZMDTCUUDPCFHM-OFSOJUDTSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] octadecanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCC)C=NC2=C1 YZMDTCUUDPCFHM-OFSOJUDTSA-N 0.000 claims description 2
• SSGTYBVOJOJVNQ-ARNLJNQMSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] tetradecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCC)C=N2 SSGTYBVOJOJVNQ-ARNLJNQMSA-N 0.000 claims description 2
• JBRLSJSMIRGMHP-OCCSQVGLSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-butanoyloxybutyl] (2s)-2-amino-3-methylbutanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCC)C=N2 JBRLSJSMIRGMHP-OCCSQVGLSA-N 0.000 claims description 2
• IVSXFFJGASXYCL-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=NC=N[C]21 IVSXFFJGASXYCL-UHFFFAOYSA-N 0.000 claims 5
• ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 2
• WNFUFWFKJDGBDN-BHYZAODMSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] docosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCCCCCC)C=N2 WNFUFWFKJDGBDN-BHYZAODMSA-N 0.000 claims 1
• HBYQXLUGUCJNFT-VWNXMTODSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] tetradecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCC)C=N2 HBYQXLUGUCJNFT-VWNXMTODSA-N 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 239000008024 pharmaceutical diluent Substances 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 88
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
• 239000000047 product Substances 0.000 description 61
• 239000000203 mixture Substances 0.000 description 56
• 238000006243 chemical reaction Methods 0.000 description 55
• 239000000243 solution Substances 0.000 description 55
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
• SCBFBAWJWLXVHS-ZCFIWIBFSA-N 2-amino-9-[(2r)-4-hydroxy-2-(hydroxymethyl)butyl]-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N(C[C@H](CO)CCO)C=N2 SCBFBAWJWLXVHS-ZCFIWIBFSA-N 0.000 description 52
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 46
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• 238000005481 NMR spectroscopy Methods 0.000 description 34
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• 239000011541 reaction mixture Substances 0.000 description 30
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 28
• 229940024606 amino acid Drugs 0.000 description 28
• 150000002148 esters Chemical class 0.000 description 28
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 27
• 235000001014 amino acid Nutrition 0.000 description 26
• 239000007787 solid Substances 0.000 description 26
• 235000002639 sodium chloride Nutrition 0.000 description 24
• 235000019441 ethanol Nutrition 0.000 description 23
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 23
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• 239000000460 chlorine Substances 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• 235000019439 ethyl acetate Nutrition 0.000 description 20
• 239000000194 fatty acid Substances 0.000 description 20
• 239000012442 inert solvent Substances 0.000 description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
• 239000002253 acid Substances 0.000 description 19
• 235000014113 dietary fatty acids Nutrition 0.000 description 19
• 229930195729 fatty acid Natural products 0.000 description 19
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 18
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 18
• 230000000052 comparative effect Effects 0.000 description 17
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• WTBAHSZERDXKKZ-UHFFFAOYSA-N octadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCC(Cl)=O WTBAHSZERDXKKZ-UHFFFAOYSA-N 0.000 description 14
• 150000001413 amino acids Chemical class 0.000 description 13
• 150000004665 fatty acids Chemical class 0.000 description 13
• 238000004128 high performance liquid chromatography Methods 0.000 description 13
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 230000010933 acylation Effects 0.000 description 12
• 238000005917 acylation reaction Methods 0.000 description 12
• 239000012043 crude product Substances 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• 229960004295 valine Drugs 0.000 description 12
• OZPCMYKOSKILNC-UHFFFAOYSA-N 2-(butylamino)-3,7-dihydropurin-6-one Chemical compound N1C(NCCCC)=NC(=O)C2=C1N=CN2 OZPCMYKOSKILNC-UHFFFAOYSA-N 0.000 description 11
• 239000004367 Lipase Substances 0.000 description 11
• 102000004882 Lipase Human genes 0.000 description 11
• 108090001060 Lipase Proteins 0.000 description 11
• 241001465754 Metazoa Species 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 201000006747 infectious mononucleosis Diseases 0.000 description 11
• 229940040461 lipase Drugs 0.000 description 11
• 235000019421 lipase Nutrition 0.000 description 11
• 238000009472 formulation Methods 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 238000005886 esterification reaction Methods 0.000 description 9
• 239000002777 nucleoside Substances 0.000 description 9
• 238000010898 silica gel chromatography Methods 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
• 241000700159 Rattus Species 0.000 description 8
• 125000002015 acyclic group Chemical group 0.000 description 8
• 125000002252 acyl group Chemical group 0.000 description 8
• 238000010511 deprotection reaction Methods 0.000 description 8
• 239000012044 organic layer Substances 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 7
• 150000008064 anhydrides Chemical class 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 239000012267 brine Substances 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 230000032050 esterification Effects 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
• 229940002612 prodrug Drugs 0.000 description 7
• 239000000651 prodrug Substances 0.000 description 7
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 6
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• 229960004150 aciclovir Drugs 0.000 description 6
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 6
• 239000003443 antiviral agent Substances 0.000 description 6
• 235000019445 benzyl alcohol Nutrition 0.000 description 6
• IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 6
• 229960002963 ganciclovir Drugs 0.000 description 6
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• 238000005160 1H NMR spectroscopy Methods 0.000 description 5
• CVVBPBHBMYSGCY-UHFFFAOYSA-N 4-chloropurin-2-amine Chemical compound C1=NC(N)=NC2(Cl)N=CN=C21 CVVBPBHBMYSGCY-UHFFFAOYSA-N 0.000 description 5
• 125000001931 aliphatic group Chemical group 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 230000002255 enzymatic effect Effects 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 238000011084 recovery Methods 0.000 description 5
• 239000002002 slurry Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 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 5
• 210000002700 urine Anatomy 0.000 description 5
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 125000006241 alcohol protecting group Chemical group 0.000 description 4
• 239000003638 chemical reducing agent Substances 0.000 description 4
• 150000002009 diols Chemical class 0.000 description 4
• 238000001035 drying Methods 0.000 description 4
• 239000012065 filter cake Substances 0.000 description 4
• 229910052736 halogen Inorganic materials 0.000 description 4
• 150000002367 halogens Chemical class 0.000 description 4
• 229950003188 isovaleryl diethylamide Drugs 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 235000019198 oils Nutrition 0.000 description 4
• 239000012074 organic phase Substances 0.000 description 4
• ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 238000000825 ultraviolet detection Methods 0.000 description 4
• QJCNLJWUIOIMMF-YUMQZZPRSA-N (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-YUMQZZPRSA-N 0.000 description 3
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
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• ALQSEJWVPKZNDU-IRLDBZIGSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] dodecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCC)C=N2 ALQSEJWVPKZNDU-IRLDBZIGSA-N 0.000 description 1
• VDWPIZQLHIOAJP-DGPALRBDSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] icosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCCCC)C=N2 VDWPIZQLHIOAJP-DGPALRBDSA-N 0.000 description 1
• YAXIRSHTKRPBGT-AEFFLSMTSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] octanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCC)C=N2 YAXIRSHTKRPBGT-AEFFLSMTSA-N 0.000 description 1
• IFKFDWWRFYIIIX-QAPCUYQASA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] 5-oxohexanoate Chemical compound N1=C(N)N=C2N(C[C@H](COC(=O)CCCC(C)=O)CCOC(=O)[C@@H](N)C(C)C)C=NC2=C1 IFKFDWWRFYIIIX-QAPCUYQASA-N 0.000 description 1
• PDRZADZPCOGUDA-KNQAVFIVSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] decanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCC)C=NC2=C1 PDRZADZPCOGUDA-KNQAVFIVSA-N 0.000 description 1
• WISSYNKKXRYGCF-FJQKOURKSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] docosanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCCCCCC)C=NC2=C1 WISSYNKKXRYGCF-FJQKOURKSA-N 0.000 description 1
• LLHURTUHPWCZOS-QPPBQGQZSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] dodecanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCC)C=NC2=C1 LLHURTUHPWCZOS-QPPBQGQZSA-N 0.000 description 1
• YXKWTUYXTWERLG-QAPCUYQASA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] hexanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCC)C=NC2=C1 YXKWTUYXTWERLG-QAPCUYQASA-N 0.000 description 1
• GTTSKQBXZFMAHY-PPTMTGTBSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] icosanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCCCC)C=NC2=C1 GTTSKQBXZFMAHY-PPTMTGTBSA-N 0.000 description 1
• RMSUXPCMDFGLHO-BVAGGSTKSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] tetradecanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCC)C=NC2=C1 RMSUXPCMDFGLHO-BVAGGSTKSA-N 0.000 description 1
• XHMVDZZYKWFJOI-ZVDOUQERSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] decanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCC)C=N2 XHMVDZZYKWFJOI-ZVDOUQERSA-N 0.000 description 1
• LOGVNZUDBJLFRD-PZWMIYICSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] docos-13-enoate Chemical compound N1C(N)=NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCC=CCCCCCCCC)C=N2 LOGVNZUDBJLFRD-PZWMIYICSA-N 0.000 description 1
• KIQIVYSEHFOVGA-PZWMIYICSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] docosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCCCCCCCCCC)C=N2 KIQIVYSEHFOVGA-PZWMIYICSA-N 0.000 description 1
• KHTTZPZEZLBGPA-XJUOHMSHSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] dodecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCC)C=N2 KHTTZPZEZLBGPA-XJUOHMSHSA-N 0.000 description 1
• BIWZMVDPBSEDQS-WEWMWRJBSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] hexadec-9-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCC=CCCCCCC)C=N2 BIWZMVDPBSEDQS-WEWMWRJBSA-N 0.000 description 1
• OQPJSWNVDBDBNS-WEWMWRJBSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] hexadecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCCCC)C=N2 OQPJSWNVDBDBNS-WEWMWRJBSA-N 0.000 description 1
• HMTWUWZHRRDHRC-FLBADVGZSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] icosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCCCCCCCC)C=N2 HMTWUWZHRRDHRC-FLBADVGZSA-N 0.000 description 1
• SEBFCDQNHCRZCQ-GKRYNVPLSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] octadec-6-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCC=CCCCCCCCCCCC)C=N2 SEBFCDQNHCRZCQ-GKRYNVPLSA-N 0.000 description 1
• QKODBNVWYJKPQS-GKRYNVPLSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] octadecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCCCCCC)C=N2 QKODBNVWYJKPQS-GKRYNVPLSA-N 0.000 description 1
• GTESYUMLHKXBLD-SCTDSRPQSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] octanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCC)C=N2 GTESYUMLHKXBLD-SCTDSRPQSA-N 0.000 description 1
• VBXOPVBEUQCSRH-ARNLJNQMSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] tetradec-9-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCC=CCCCC)C=N2 VBXOPVBEUQCSRH-ARNLJNQMSA-N 0.000 description 1
• UFHMBVIDRVGQFS-UKAHRKLESA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] docos-13-enoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCC=CCCCCCCCC)C=NC2=C1 UFHMBVIDRVGQFS-UKAHRKLESA-N 0.000 description 1
• QIVCVTHSSYDFPC-HFASVGIHSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] hexadec-9-enoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCC=CCCCCCC)C=NC2=C1 QIVCVTHSSYDFPC-HFASVGIHSA-N 0.000 description 1
• TUWYLNSHWUITOC-HFASVGIHSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] hexadecanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCCCC)C=NC2=C1 TUWYLNSHWUITOC-HFASVGIHSA-N 0.000 description 1
• SDJJOBYTINBVTQ-QXIHQKPUSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] octadec-6-enoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCC=CCCCCCCCCCCC)C=NC2=C1 SDJJOBYTINBVTQ-QXIHQKPUSA-N 0.000 description 1
• NDQLUHMKGYCRSB-UEXGIBASSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] octanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCC)C=NC2=C1 NDQLUHMKGYCRSB-UEXGIBASSA-N 0.000 description 1
• MNZMFWNCFZPREH-XFAFFCHDSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] tetradec-9-enoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCC=CCCCC)C=NC2=C1 MNZMFWNCFZPREH-XFAFFCHDSA-N 0.000 description 1
• YWLREHSUTPRPEF-XFAFFCHDSA-N [(2r)-4-[(2s,3s)-2-amino-3-methylpentanoyl]oxy-2-[(2-aminopurin-9-yl)methyl]butyl] tetradecanoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCCCCCCCCCC)C=NC2=C1 YWLREHSUTPRPEF-XFAFFCHDSA-N 0.000 description 1
• QDPOLXKQBYJKJB-MVSFAKPFSA-N [(3R)-3-[(2S)-2-amino-3-methylbutanoyl]oxy-4-(2-aminopurin-9-yl)butyl] icos-11-enoate Chemical compound N1=C(N)N=C2N(C[C@@H](CCOC(=O)CCCCCCCCCC=CCCCCCCCC)OC(=O)[C@@H](N)C(C)C)C=NC2=C1 QDPOLXKQBYJKJB-MVSFAKPFSA-N 0.000 description 1
• WXSVWJZFTWRPPF-LXZKKBNFSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-(5-oxohexanoyloxy)butyl] (2s,3s)-2-amino-3-methylpentanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)CCCC(C)=O)CCOC(=O)[C@@H](N)[C@@H](C)CC)C=N2 WXSVWJZFTWRPPF-LXZKKBNFSA-N 0.000 description 1
• ZPIWQKRPFIDOCG-VEEOACQBSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-[(2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]oxybutyl] octadecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)CCOC(=O)CCCCCCCCCCCCCCCCC)C=N2 ZPIWQKRPFIDOCG-VEEOACQBSA-N 0.000 description 1
• JGLLCMBIABLAIO-GUTXKFCHSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-butanoyloxybutyl] (2s,3s)-2-amino-3-methylpentanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCC)C=N2 JGLLCMBIABLAIO-GUTXKFCHSA-N 0.000 description 1
• NXSOYJGJRXSCCG-UXLLHSPISA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-hexanoyloxybutyl] (2s,3s)-2-amino-3-methylpentanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)[C@@H](C)CC)COC(=O)CCCCC)C=N2 NXSOYJGJRXSCCG-UXLLHSPISA-N 0.000 description 1
• GWYCIDGEZCZAJL-HHHXNRCGSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-hydroxybutyl] docosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](CO)CCOC(=O)CCCCCCCCCCCCCCCCCCCCC)C=N2 GWYCIDGEZCZAJL-HHHXNRCGSA-N 0.000 description 1
• SLVSDFLCAWLJLR-QGZVFWFLSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-hydroxybutyl] dodecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](CO)CCOC(=O)CCCCCCCCCCC)C=N2 SLVSDFLCAWLJLR-QGZVFWFLSA-N 0.000 description 1
• AYGGWEOUPWYALX-OAQYLSRUSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-hydroxybutyl] hexadecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](CO)CCOC(=O)CCCCCCCCCCCCCCC)C=N2 AYGGWEOUPWYALX-OAQYLSRUSA-N 0.000 description 1
• AREWMMUMSJJLDY-RUZDIDTESA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-hydroxybutyl] icosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](CO)CCOC(=O)CCCCCCCCCCCCCCCCCCC)C=N2 AREWMMUMSJJLDY-RUZDIDTESA-N 0.000 description 1
• PZLYIEXLENMLJI-LJQANCHMSA-N [(3r)-3-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-4-hydroxybutyl] tetradecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](CO)CCOC(=O)CCCCCCCCCCCCC)C=N2 PZLYIEXLENMLJI-LJQANCHMSA-N 0.000 description 1
• ATGZURPALDBGHY-PWSUYJOCSA-N [(3r)-3-[(2-aminopurin-9-yl)methyl]-4-hydroxybutyl] (2s)-2-amino-3-methylbutanoate Chemical compound N1=C(N)N=C2N(C[C@H](CO)CCOC(=O)[C@@H](N)C(C)C)C=NC2=C1 ATGZURPALDBGHY-PWSUYJOCSA-N 0.000 description 1
• VMXFMYKLBRDSPN-RDBSUJKOSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] (2s)-2-amino-3-methylbutanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)[C@@H](N)C(C)C)C=N2 VMXFMYKLBRDSPN-RDBSUJKOSA-N 0.000 description 1
• OAVXEJYNORNJRH-ZBFHGGJFSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] 5-oxohexanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@@H](CCOC(=O)CCCC(C)=O)COC(=O)[C@@H](N)C(C)C)C=N2 OAVXEJYNORNJRH-ZBFHGGJFSA-N 0.000 description 1
• VSJRXCQAVKYKPG-QUCCMNQESA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] decanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCC)C=N2 VSJRXCQAVKYKPG-QUCCMNQESA-N 0.000 description 1
• TULSCQJTRBWUIZ-BHYZAODMSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] docos-13-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCCCCC=CCCCCCCCC)C=N2 TULSCQJTRBWUIZ-BHYZAODMSA-N 0.000 description 1
• AVYUEMLBLPJPOJ-BHYZAODMSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] docosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCCCCCCCCCCCCCC)C=N2 AVYUEMLBLPJPOJ-BHYZAODMSA-N 0.000 description 1
• QKYKEMHYEOCMTR-IRLDBZIGSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] dodecanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCCCC)C=N2 QKYKEMHYEOCMTR-IRLDBZIGSA-N 0.000 description 1
• BVYRBYCDWBDGAH-RSXGOPAZSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] hexadec-9-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCC=CCCCCCC)C=N2 BVYRBYCDWBDGAH-RSXGOPAZSA-N 0.000 description 1
• DZEWCYDEQPYCGG-ZBFHGGJFSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] hexanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCC)C=N2 DZEWCYDEQPYCGG-ZBFHGGJFSA-N 0.000 description 1
• GITVPBCOFOMHEN-DGPALRBDSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] icos-11-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCCC=CCCCCCCCC)C=N2 GITVPBCOFOMHEN-DGPALRBDSA-N 0.000 description 1
• ZJAGFRFHBPHMNI-DGPALRBDSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] icosanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCCCCCCCCCCCCCC)C=N2 ZJAGFRFHBPHMNI-DGPALRBDSA-N 0.000 description 1
• LJSPEZTWWTTXMN-IAPPQJPRSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] octadec-6-enoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCC=CCCCCCCCCCCC)C=N2 LJSPEZTWWTTXMN-IAPPQJPRSA-N 0.000 description 1
• OFRHYMLADILOLL-AEFFLSMTSA-N [(3r)-3-[[(2s)-2-amino-3-methylbutanoyl]oxymethyl]-4-(2-amino-6-oxo-3h-purin-9-yl)butyl] octanoate Chemical compound N1=C(N)NC(=O)C2=C1N(C[C@H](COC(=O)[C@@H](N)C(C)C)CCOC(=O)CCCCCCC)C=N2 OFRHYMLADILOLL-AEFFLSMTSA-N 0.000 description 1
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