NZ567952A

NZ567952A - Long acting biologically active conjugates

Long acting biologically active conjugates

Info

Publication number: NZ567952A
Authority: NZ; New Zealand
Prior art keywords: group; inhibitors; compounds; peptide; protein
Prior art date: 2003-03-24

Application number

NZ567952A

Other languages

English (en)

Inventor

Abelardo Silva

John E Erickson

Michael Eissenstat

Elena Afonina

Seigei Gulnik

Original Assignee

Sequoia Pharmaceuticals Inc

Priority date

2003-03-24

Filing date

2004-03-24

Publication date

2009-12-24

2004-03-24 Application filed by Sequoia Pharmaceuticals Inc filed Critical Sequoia Pharmaceuticals Inc

2009-12-24 Publication of NZ567952A publication Critical patent/NZ567952A/en

Links

150000001875 compounds Chemical group 0.000 claims abstract description 333
108090000623 proteins and genes Proteins 0.000 claims abstract description 116
102000004169 proteins and genes Human genes 0.000 claims abstract description 112
239000000203 mixture Substances 0.000 claims abstract description 93
230000000840 anti-viral effect Effects 0.000 claims abstract description 81
239000003814 drug Substances 0.000 claims abstract description 70
239000012503 blood component Substances 0.000 claims abstract description 47
238000002360 preparation method Methods 0.000 claims abstract description 42
102000004506 Blood Proteins Human genes 0.000 claims abstract description 29
108010017384 Blood Proteins Proteins 0.000 claims abstract description 29
239000000306 component Substances 0.000 claims abstract description 27
108060003951 Immunoglobulin Proteins 0.000 claims abstract description 13
102000018358 immunoglobulin Human genes 0.000 claims abstract description 13
102000007562 Serum Albumin Human genes 0.000 claims abstract description 10
108010071390 Serum Albumin Proteins 0.000 claims abstract description 10
-1 succinimidyl Chemical group 0.000 claims description 78
239000003112 inhibitor Substances 0.000 claims description 69
238000001727 in vivo Methods 0.000 claims description 53
125000000524 functional group Chemical group 0.000 claims description 35
239000003443 antiviral agent Substances 0.000 claims description 34
241000700605 Viruses Species 0.000 claims description 31
239000002253 acid Substances 0.000 claims description 31
230000003612 virological effect Effects 0.000 claims description 28
PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 18
230000004927 fusion Effects 0.000 claims description 17
150000008064 anhydrides Chemical class 0.000 claims description 14
150000001299 aldehydes Chemical class 0.000 claims description 11
102000004338 Transferrin Human genes 0.000 claims description 10
108090000901 Transferrin Proteins 0.000 claims description 10
229940072221 immunoglobulins Drugs 0.000 claims description 10
150000003573 thiols Chemical class 0.000 claims description 10
239000012581 transferrin Substances 0.000 claims description 10
KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical class C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 claims description 9
150000001350 alkyl halides Chemical class 0.000 claims description 9
150000001541 aziridines Chemical class 0.000 claims description 9
AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims description 9
210000003743 erythrocyte Anatomy 0.000 claims description 9
239000002777 nucleoside Substances 0.000 claims description 9
125000003729 nucleotide group Chemical group 0.000 claims description 9
239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 9
239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 9
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 8
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical class ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 claims description 8
150000001718 carbodiimides Chemical class 0.000 claims description 8
VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical class NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 claims description 8
150000002118 epoxides Chemical class 0.000 claims description 8
150000003833 nucleoside derivatives Chemical class 0.000 claims description 8
150000007659 semicarbazones Chemical class 0.000 claims description 8
RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium group Chemical group [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims description 8
GWIKYPMLNBTJHR-UHFFFAOYSA-M thiosulfonate group Chemical group S(=S)(=O)[O-] GWIKYPMLNBTJHR-UHFFFAOYSA-M 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
150000002902 organometallic compounds Chemical class 0.000 claims description 7
ZYJSTSMEUKNCEV-UHFFFAOYSA-N 3-diazo-1-diazonioprop-1-en-2-olate Chemical class [N-]=[N+]=CC(=O)C=[N+]=[N-] ZYJSTSMEUKNCEV-UHFFFAOYSA-N 0.000 claims description 6
102000014914 Carrier Proteins Human genes 0.000 claims description 6
102000008857 Ferritin Human genes 0.000 claims description 6
108050000784 Ferritin Proteins 0.000 claims description 6
238000008416 Ferritin Methods 0.000 claims description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
108091008324 binding proteins Proteins 0.000 claims description 6
VYLDEYYOISNGST-UHFFFAOYSA-N bissulfosuccinimidyl suberate Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)C(S(O)(=O)=O)CC1=O VYLDEYYOISNGST-UHFFFAOYSA-N 0.000 claims description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
ZLFRJHOBQVVTOJ-UHFFFAOYSA-N dimethyl hexanediimidate Chemical compound COC(=N)CCCCC(=N)OC ZLFRJHOBQVVTOJ-UHFFFAOYSA-N 0.000 claims description 6
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 6
229960001936 indinavir Drugs 0.000 claims description 6
CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 claims description 6
239000002773 nucleotide Substances 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 6
229940080818 propionamide Drugs 0.000 claims description 6
102000005963 steroid binding proteins Human genes 0.000 claims description 6
108020003178 steroid binding proteins Proteins 0.000 claims description 6
150000007970 thio esters Chemical class 0.000 claims description 6
GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 claims description 5
MDNSLPICAWKNAG-UHFFFAOYSA-N 2-(2,5-dioxopyrrol-1-yl)propanoic acid Chemical compound OC(=O)C(C)N1C(=O)C=CC1=O MDNSLPICAWKNAG-UHFFFAOYSA-N 0.000 claims description 5
CXGYVVWOYNOMBX-UHFFFAOYSA-N 3-benzoylpyrrolidine-2,5-dione;pyrrole-2,5-dione Chemical compound O=C1NC(=O)C=C1.C=1C=CC=CC=1C(=O)C1CC(=O)NC1=O CXGYVVWOYNOMBX-UHFFFAOYSA-N 0.000 claims description 5
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 5
229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 5
150000003926 acrylamides Chemical class 0.000 claims description 5
NXVYSVARUKNFNF-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxybutanedioate Chemical compound O=C1CCC(=O)N1OC(=O)C(O)C(O)C(=O)ON1C(=O)CCC1=O NXVYSVARUKNFNF-UHFFFAOYSA-N 0.000 claims description 5
239000012948 isocyanate Substances 0.000 claims description 5
150000002513 isocyanates Chemical class 0.000 claims description 5
150000002825 nitriles Chemical class 0.000 claims description 5
229940044551 receptor antagonist Drugs 0.000 claims description 5
239000002464 receptor antagonist Substances 0.000 claims description 5
238000013518 transcription Methods 0.000 claims description 5
230000035897 transcription Effects 0.000 claims description 5
PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 claims description 4
BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 claims description 4
XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 claims description 4
108010032976 Enfuvirtide Proteins 0.000 claims description 4
150000001252 acrylic acid derivatives Chemical class 0.000 claims description 4
WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 4
229960003804 efavirenz Drugs 0.000 claims description 4
XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 claims description 4
NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 claims description 4
238000001179 sorption measurement Methods 0.000 claims description 4
229960002317 succinimide Drugs 0.000 claims description 4
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 claims description 3
YZHIXLCGPOTQNB-UHFFFAOYSA-N 2-methyl-furan-3-carbothioic acid [4-chloro-3-(3-methyl-but-2-enyloxy)-phenyl]-amide Chemical compound C1=C(Cl)C(OCC=C(C)C)=CC(NC(=S)C2=C(OC=C2)C)=C1 YZHIXLCGPOTQNB-UHFFFAOYSA-N 0.000 claims description 3
229950010817 alvocidib Drugs 0.000 claims description 3
BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
150000007942 carboxylates Chemical class 0.000 claims description 3
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 3
AYXBAIULRDEVAS-UHFFFAOYSA-N dimethyl-[[4-[[3-(4-methylphenyl)-8,9-dihydro-7h-benzo[7]annulene-6-carbonyl]amino]phenyl]methyl]-(oxan-4-yl)azanium;iodide Chemical compound [I-].C1=CC(C)=CC=C1C1=CC=C(CCCC(=C2)C(=O)NC=3C=CC(C[N+](C)(C)C4CCOCC4)=CC=3)C2=C1 AYXBAIULRDEVAS-UHFFFAOYSA-N 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 claims description 3
229960001627 lamivudine Drugs 0.000 claims description 3
JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 3
229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 3
239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 claims description 3
230000024275 uncoating of virus Effects 0.000 claims description 3
229960002555 zidovudine Drugs 0.000 claims description 3
KYRSNWPSSXSNEP-ZRTHHSRSSA-N (4r,5s,6s,7r)-1,3-bis[(3-aminophenyl)methyl]-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one Chemical compound NC1=CC=CC(CN2C(N(CC=3C=C(N)C=CC=3)[C@H](CC=3C=CC=CC=3)[C@H](O)[C@@H](O)[C@H]2CC=2C=CC=CC=2)=O)=C1 KYRSNWPSSXSNEP-ZRTHHSRSSA-N 0.000 claims description 2
BEMROAADXJFLBI-UHFFFAOYSA-N 1-(cyclopent-3-en-1-ylmethyl)-6-(3,5-dimethylbenzoyl)-5-ethylpyrimidine-2,4-dione Chemical compound C1C=CCC1CN1C(=O)NC(=O)C(CC)=C1C(=O)C1=CC(C)=CC(C)=C1 BEMROAADXJFLBI-UHFFFAOYSA-N 0.000 claims description 2
QBRCQKYEBCOZPI-HCWSKCQFSA-N 1-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-iodyloxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@@]1(I(=O)=O)N1C(=O)NC(=O)C=C1 QBRCQKYEBCOZPI-HCWSKCQFSA-N 0.000 claims description 2
GWFOVSGRNGAGDL-FSDSQADBSA-N 2-amino-9-[(1r,2r,3s)-2,3-bis(hydroxymethyl)cyclobutyl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1C[C@H](CO)[C@H]1CO GWFOVSGRNGAGDL-FSDSQADBSA-N 0.000 claims description 2
QGJZLNKBHJESQX-UHFFFAOYSA-N 3-Epi-Betulin-Saeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(=C)C)C5C4CCC3C21C QGJZLNKBHJESQX-UHFFFAOYSA-N 0.000 claims description 2
CLOUCVRNYSHRCF-UHFFFAOYSA-N 3beta-Hydroxy-20(29)-Lupen-3,27-oic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C(O)=O)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C CLOUCVRNYSHRCF-UHFFFAOYSA-N 0.000 claims description 2
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 2
102000005234 Adenosylhomocysteinase Human genes 0.000 claims description 2
108020002202 Adenosylhomocysteinase Proteins 0.000 claims description 2
AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 claims description 2
108010019625 Atazanavir Sulfate Proteins 0.000 claims description 2
239000004156 Azodicarbonamide Substances 0.000 claims description 2
DIZWSDNSTNAYHK-XGWVBXMLSA-N Betulinic acid Natural products CC(=C)[C@@H]1C[C@H]([C@H]2CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(=O)O DIZWSDNSTNAYHK-XGWVBXMLSA-N 0.000 claims description 2
QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 claims description 2
VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 claims description 2
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
229940127399 DNA Polymerase Inhibitors Drugs 0.000 claims description 2
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229940121672 Glycosylation inhibitor Drugs 0.000 claims description 2
KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 claims description 2
230000004988 N-glycosylation Effects 0.000 claims description 2
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 claims description 2
NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims description 2
SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 claims description 2
OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 claims description 2
XLPGURCDSRIXFL-JGVFFNPUSA-N [(2s,5r)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl dihydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](COP(O)(O)=O)O1 XLPGURCDSRIXFL-JGVFFNPUSA-N 0.000 claims description 2
229960004748 abacavir Drugs 0.000 claims description 2
MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims description 2
229960004150 aciclovir Drugs 0.000 claims description 2
MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 2
229960001997 adefovir Drugs 0.000 claims description 2
229960003205 adefovir dipivoxil Drugs 0.000 claims description 2
229940064734 aminobenzoate Drugs 0.000 claims description 2
229960001830 amprenavir Drugs 0.000 claims description 2
YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 claims description 2
229960003277 atazanavir Drugs 0.000 claims description 2
AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 claims description 2
XOZUGNYVDXMRKW-AATRIKPKSA-N azodicarbonamide Chemical compound NC(=O)\N=N\C(N)=O XOZUGNYVDXMRKW-AATRIKPKSA-N 0.000 claims description 2
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