JP2008531704A - ウイルス感染症の治療のための三環式ヌクレオシド化合物 - Google Patents

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Publication number

JP2008531704A

JP2008531704A JP2007558142A JP2007558142A JP2008531704A JP 2008531704 A JP2008531704 A JP 2008531704A JP 2007558142 A JP2007558142 A JP 2007558142A JP 2007558142 A JP2007558142 A JP 2007558142A JP 2008531704 A JP2008531704 A JP 2008531704A

Authority

JP

Japan

Prior art keywords

methyl

ribofuranosyl

benzo

dihydro

group

Prior art date

2005-02-28

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

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• 208000036142 Viral infection Diseases 0.000 title claims abstract description 11
• 230000009385 viral infection Effects 0.000 title claims abstract description 11
• HOGVTUZUJGHKPL-HTVVRFAVSA-N triciribine Chemical class C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HOGVTUZUJGHKPL-HTVVRFAVSA-N 0.000 title abstract 2
• 238000000034 method Methods 0.000 claims abstract description 42
• 241000710781 Flaviviridae Species 0.000 claims abstract description 10
• 230000001404 mediated effect Effects 0.000 claims abstract description 9
• 150000001875 compounds Chemical class 0.000 claims description 313
• -1 amino, aminocarbonyl Chemical group 0.000 claims description 135
• 229910052739 hydrogen Inorganic materials 0.000 claims description 119
• 239000001257 hydrogen Substances 0.000 claims description 117
• 239000000203 mixture Substances 0.000 claims description 112
• 229910052721 tungsten Inorganic materials 0.000 claims description 74
• 241000711549 Hepacivirus C Species 0.000 claims description 61
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 57
• 125000005843 halogen group Chemical group 0.000 claims description 55
• 150000002431 hydrogen Chemical group 0.000 claims description 53
• 239000000651 prodrug Substances 0.000 claims description 48
• 229940002612 prodrug Drugs 0.000 claims description 48
• 150000003839 salts Chemical class 0.000 claims description 44
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
• 239000003814 drug Substances 0.000 claims description 31
• 125000004442 acylamino group Chemical group 0.000 claims description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
• 150000001413 amino acids Chemical class 0.000 claims description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 108010047761 Interferon-alpha Proteins 0.000 claims description 21
• 102000006992 Interferon-alpha Human genes 0.000 claims description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 150000001540 azides Chemical class 0.000 claims description 20
• 229910052799 carbon Chemical group 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 125000000033 alkoxyamino group Chemical group 0.000 claims description 17
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
• 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 16
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 16
• 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 16
• 229960000329 ribavirin Drugs 0.000 claims description 16
• 241000700605 Viruses Species 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 239000003112 inhibitor Substances 0.000 claims description 12
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 claims description 7
• 108060004795 Methyltransferase Proteins 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 239000013543 active substance Substances 0.000 claims description 6
• 229910052727 yttrium Inorganic materials 0.000 claims description 6
• BLURITVAGFDMPS-NHULRPGXSA-N (2R,3R,4R,5R)-2-(3,5,7,9,10,12-hexazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-3-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NNC=N3)=C2C3=C1 BLURITVAGFDMPS-NHULRPGXSA-N 0.000 claims description 5
• IXXVTGLQEGPRLV-KNJXUWEQSA-N (2R,3R,4R,5R)-5-(hydroxymethyl)-3-methyl-2-(3,5,7,9,10-pentazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-3-yl)oxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NNC=C3)=C2C3=C1 IXXVTGLQEGPRLV-KNJXUWEQSA-N 0.000 claims description 5
• GLOQJXCSHIAUSF-ZCLWBALQSA-N 12-amino-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaene-10-thione Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=S)C=C3N)=C2C3=C1 GLOQJXCSHIAUSF-ZCLWBALQSA-N 0.000 claims description 5
• ZKGVSTUMOHZOEQ-FRJWGUMJSA-N 12-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C1=C(C2=3)C(N)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ZKGVSTUMOHZOEQ-FRJWGUMJSA-N 0.000 claims description 5
• SFQUTMMHSCDERR-YTUKDDMISA-N 2-(2'-methyl-β-d-ribofuranosyl)-2,9-dihydro-6h-2,3,5,6,9-pentaaza-benzo[cd]azulene-7,8-dione Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C(=O)NC3=C1 SFQUTMMHSCDERR-YTUKDDMISA-N 0.000 claims description 5
• ZKJIVMQMKMMFHI-FTTKWNSESA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-11-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(F)=C3)=C2C3=C1 ZKJIVMQMKMMFHI-FTTKWNSESA-N 0.000 claims description 5
• SPHINGCEMHXYKE-VHQAPHLWSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9,10,12-hexazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-11-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NNC(=O)N3)=C2C3=C1 SPHINGCEMHXYKE-VHQAPHLWSA-N 0.000 claims description 5
• NIAJWNYWHQCZHB-YTUKDDMISA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9,12-pentazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-11-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NCC(=O)N3)=C2C3=C1 NIAJWNYWHQCZHB-YTUKDDMISA-N 0.000 claims description 5
• IQTNLLIVXRSHGW-YTUKDDMISA-N 9-amino-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6,8-pentaaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2N=C(N)C3=C1 IQTNLLIVXRSHGW-YTUKDDMISA-N 0.000 claims description 5
• JIPYIHALDIWXLT-FPOOMLEOSA-N N-[3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-12-yl]acetamide Chemical compound C1=C(C2=3)C(NC(=O)C)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O JIPYIHALDIWXLT-FPOOMLEOSA-N 0.000 claims description 5
• CKPBDTBZKMEWOU-KHTZZEJVSA-N N-[3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-12-yl]formamide Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NC=O)=C2C3=C1 CKPBDTBZKMEWOU-KHTZZEJVSA-N 0.000 claims description 5
• 108091005804 Peptidases Proteins 0.000 claims description 5
• 239000004365 Protease Substances 0.000 claims description 5
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 5
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
• RJFIQUNBXWRVTA-PMXXHBEXSA-N 12-amino-3-[(2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3N)=C2C3=C1 RJFIQUNBXWRVTA-PMXXHBEXSA-N 0.000 claims description 4
• 101710088194 Dehydrogenase Proteins 0.000 claims description 4
• 108050006182 Inosine-5'-monophosphate dehydrogenases Proteins 0.000 claims description 4
• 102000016600 Inosine-5'-monophosphate dehydrogenases Human genes 0.000 claims description 4
• 108010078233 Thymalfasin Proteins 0.000 claims description 4
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 claims description 4
• 229950006081 taribavirin Drugs 0.000 claims description 4
• NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims description 4
• 229960004231 thymalfasin Drugs 0.000 claims description 4
• GRMYVLYSBJYKBE-ZCLWBALQSA-N 12-chloro-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3Cl)=C2C3=C1 GRMYVLYSBJYKBE-ZCLWBALQSA-N 0.000 claims description 3
• OAHNQJQLXDEFCL-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-(hydroxyamino)-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NO)=C2C3=C1 OAHNQJQLXDEFCL-ZCLWBALQSA-N 0.000 claims description 3
• GVOOKYOKQRCJFT-KHTZZEJVSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-(methoxyamino)-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C1=C(C2=3)C(NOC)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O GVOOKYOKQRCJFT-KHTZZEJVSA-N 0.000 claims description 3
• IQDRYMACQDAPTL-KHTZZEJVSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-(methylamino)-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C1=C(C2=3)C(NC)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O IQDRYMACQDAPTL-KHTZZEJVSA-N 0.000 claims description 3
• WEBPMOZRCPJYAW-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3F)=C2C3=C1 WEBPMOZRCPJYAW-ZCLWBALQSA-N 0.000 claims description 3
• YDTPSIYKHMTGKX-PZTHBURQSA-N 9-amino-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(N)C3=C1 YDTPSIYKHMTGKX-PZTHBURQSA-N 0.000 claims description 3
• YCXPYXMDZXJQKB-QTDMDRALSA-N 9-carbamoyl-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(C(N)=O)C3=C1 YCXPYXMDZXJQKB-QTDMDRALSA-N 0.000 claims description 3
• JKGHPHSYUAVDSB-UIBBOPPKSA-N 9-cyano-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(C#N)C3=C1 JKGHPHSYUAVDSB-UIBBOPPKSA-N 0.000 claims description 3
• CDWPLWQNOLTUNM-PZTHBURQSA-N 9-iodo-2-(2'-methyl-β-d-ribofuranosyl)-2,6-dihydro-2,3,5,6-tetraaza-benzo[cd]azulen-7-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1N=C(C=NNC2=O)C3=C2C=C(I)C3=C1 CDWPLWQNOLTUNM-PZTHBURQSA-N 0.000 claims description 3
• GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 claims description 3
• 101800001019 Non-structural protein 4B Proteins 0.000 claims description 3
• 101800001014 Non-structural protein 5A Proteins 0.000 claims description 3
• 102400000800 Thymosin alpha-1 Human genes 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 235000013902 inosinic acid Nutrition 0.000 claims description 3
• 229910052720 vanadium Inorganic materials 0.000 claims description 3
• KYDZVISIOSNRMR-KXOWALFDSA-N 12-amino-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-11-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(F)=C3N)=C2C3=C1 KYDZVISIOSNRMR-KXOWALFDSA-N 0.000 claims description 2
• XEQDJLRBBKBFBE-ZCLWBALQSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-hydrazinyl-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NN)=C2C3=C1 XEQDJLRBBKBFBE-ZCLWBALQSA-N 0.000 claims description 2
• 102000012479 Serine Proteases Human genes 0.000 claims description 2
• 108010022999 Serine Proteases Proteins 0.000 claims description 2
• UVUFIBDXCNFICN-YTUKDDMISA-N [[(2R,3R,4R,5R)-3,4-dihydroxy-4-methyl-5-(11-oxo-3,5,7,9,12-pentazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-3-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NCC(=O)N3)=C2C3=C1 UVUFIBDXCNFICN-YTUKDDMISA-N 0.000 claims description 2
• WKKGEQIYVHERTA-ZCLWBALQSA-N [[(2R,3R,4R,5R)-3,4-dihydroxy-5-(12-iodo-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3I)=C2C3=C1 WKKGEQIYVHERTA-ZCLWBALQSA-N 0.000 claims description 2
• UGTQFAADSJDRSS-ZCLWBALQSA-N [[(2R,3R,4R,5R)-3,4-dihydroxy-5-[12-(hydroxyamino)-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl]-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NO)=C2C3=C1 UGTQFAADSJDRSS-ZCLWBALQSA-N 0.000 claims description 2
• LNEZPAJWCWZSLR-KHTZZEJVSA-N [[(2R,3R,4R,5R)-3,4-dihydroxy-5-[12-(methoxyamino)-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl]-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=C(C2=3)C(NOC)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@@]1(C)O LNEZPAJWCWZSLR-KHTZZEJVSA-N 0.000 claims description 2
• IRPWNCKXLZNAOT-FTTKWNSESA-N [[(2R,3R,4R,5R)-5-(11-fluoro-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C(F)=C3)=C2C3=C1 IRPWNCKXLZNAOT-FTTKWNSESA-N 0.000 claims description 2
• UGTXDEGAFZVXOG-FPOOMLEOSA-N [[(2R,3R,4R,5R)-5-(12-acetamido-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=C(C2=3)C(NC(=O)C)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@@]1(C)O UGTXDEGAFZVXOG-FPOOMLEOSA-N 0.000 claims description 2
• MRLRXQNXOVYHCI-ZQEXUDESSA-N [[(2R,3R,4R,5R)-5-(12-amino-10-oxo-3,5,7,9,11-pentazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)N=C3N)=C2C3=C1 MRLRXQNXOVYHCI-ZQEXUDESSA-N 0.000 claims description 2
• ZVWWKBRKHNYVPZ-ZCLWBALQSA-N [[(2R,3R,4R,5R)-5-(12-amino-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3N)=C2C3=C1 ZVWWKBRKHNYVPZ-ZCLWBALQSA-N 0.000 claims description 2
• CVWCOPFFHJDDJX-PMXXHBEXSA-N [[(2R,3R,4R,5R)-5-(12-amino-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3-hydroxy-4-methoxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound CO[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3N)=C2C3=C1 CVWCOPFFHJDDJX-PMXXHBEXSA-N 0.000 claims description 2
• JSWXEAGVIBIQKU-ZCLWBALQSA-N [[(2R,3R,4R,5R)-5-(12-chloro-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3Cl)=C2C3=C1 JSWXEAGVIBIQKU-ZCLWBALQSA-N 0.000 claims description 2
• NSZGCCIJGZZVIO-ZCLWBALQSA-N [[(2R,3R,4R,5R)-5-(12-fluoro-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3F)=C2C3=C1 NSZGCCIJGZZVIO-ZCLWBALQSA-N 0.000 claims description 2
• BICBHLMNWVBCEV-KHTZZEJVSA-N [[(2R,3R,4R,5R)-5-(12-formamido-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NC=O)=C2C3=C1 BICBHLMNWVBCEV-KHTZZEJVSA-N 0.000 claims description 2
• LCFFBOATQVXWEL-ZCLWBALQSA-N [[(2R,3R,4R,5R)-5-(12-hydrazinyl-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C[C@@]1(O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CN=C2NC(=O)C=C3NN)=C2C3=C1 LCFFBOATQVXWEL-ZCLWBALQSA-N 0.000 claims description 2
• FFCDTAKRDPJRLR-FRJWGUMJSA-N [[(2R,3S,4R,5R)-5-(12-amino-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=C(C2=3)C(N)=CC(=O)NC2=NC=NC=3N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O FFCDTAKRDPJRLR-FRJWGUMJSA-N 0.000 claims description 2
• 229910021386 carbon form Inorganic materials 0.000 claims description 2
• NSEYHMDNGSNOBQ-NZQZLILVSA-N (2R,3R,4R,5R)-2-(12-fluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-3-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NCC=C3F)=C2C3=C1 NSEYHMDNGSNOBQ-NZQZLILVSA-N 0.000 claims 2
• OESHHJVQXYGCKW-FTTKWNSESA-N 11-amino-3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(N)=C3)=C2C3=C1 OESHHJVQXYGCKW-FTTKWNSESA-N 0.000 claims 1
• CFLGNWHWVWVTMA-JEGMJTAISA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaene-11-carbonitrile Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(C#N)=C3)=C2C3=C1 CFLGNWHWVWVTMA-JEGMJTAISA-N 0.000 claims 1
• TUOWVHKWPGTSGL-ZVTMDSFCSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-10-oxo-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaene-11-carboxamide Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(C(N)=O)=C3)=C2C3=C1 TUOWVHKWPGTSGL-ZVTMDSFCSA-N 0.000 claims 1
• IWPWLRDURFXKNV-KXOWALFDSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-11,12-difluoro-3,5,7,9-tetrazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)C(F)=C3F)=C2C3=C1 IWPWLRDURFXKNV-KXOWALFDSA-N 0.000 claims 1
• RZZYLGRBIREDSW-ZQEXUDESSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-12-fluoro-3,5,7,9,11-pentazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)N=C3F)=C2C3=C1 RZZYLGRBIREDSW-ZQEXUDESSA-N 0.000 claims 1
• ODPUUCQVEIOVPK-AMJCQUEASA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9,11-pentazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8,11-pentaen-10-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)N=C3)=C2C3=C1 ODPUUCQVEIOVPK-AMJCQUEASA-N 0.000 claims 1
• XFYUUODDJHDVFN-ZQEXUDESSA-N 3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-3,5,7,9,11-pentazatricyclo[6.4.1.04,13]trideca-1,4(13),5,8-tetraene-10,12-dione Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CN=C2NC(=O)NC3=O)=C2C3=C1 XFYUUODDJHDVFN-ZQEXUDESSA-N 0.000 claims 1
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