Novel 2'-c-methyl and 4'-c-methyl nucleoside derivatives 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2007022073 A2 2007-02-22 [WO200722073]WO2007022073 A3 2007-11-15 [WO200722073] / 2007-02-222007-11-15
申请号/申请日
2006WO-US31614 / 2006-08-14
发明人
ERION MARK D;REDDY K RAJA;MACCOSS MALCOLM;OLSEN DAVID B;
申请人
MERCK SHARP & DOHME;METABASIS THERAPEUTICS;
主分类号
IPC分类号
A01N-043/00A61K-031/70
摘要
(WO200722073) Novel 2'-C-methyl nucleoside 5 '-monophosphate and 4'-C-methyl nucleoside 5'- monophosphate derivatives, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C viral infection are described.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2005US-60707767 2005-08-12 2006US-60772649 2006-02-13
主权利要求
(WO200722073) 1. A compound of Formula (IX) :  (IX) wherein: V is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl; W and W are independently selected from the group consisting of -R , optionally substituted monocyclic aryl, and optionally substituted monocyclic heteroaryl; Z is selected from the group consisting of halogen, -CN, -COR5, -CONR42, - CO2R5, -SO2R5, -SO2NR42, -OR4, -SR4, -R4, -NR42, -OCOR5, -OCO2R5, -SCOR5, - SCO2R5, -NHCOR4, -NHCO2R5, -(CH2)P-OR6, and -(CH2)P-SR6; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; or together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom; or together W and W are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms; R2is selected from the group consisting of R3and hydrogen; R3is selected from the group consisting of alkyl, aryl, heterocycloalkyl, and aralkyl; R4is selected from the group consisting of R3and hydrogen; Rsis selected from the group consisting of alkyl. aryl, heterocycloalkyl, and aralkyl; R6is selected from the group consisting of hydrogen, and lower acyl; R12is selected from the group consisting of hydrogen, and lower acyl; and p is an integer 2 or 3; or a pharmaceutically acceptable salt thereof. 2. A compound of Formula (X):  (X) wherein: V is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl; W and W are independently selected from the group consisting of -H, methyl, and V, or W and W are each methyl, with the proviso that when W is V, then W is H; Z is selected from the group consisting of -H, -OMe, -OEt, phenyl, C1-C3alkyl, -NR42, -SR4, -(CH2)p-OR6, -(CH2)p-SR6and -OCOR5; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; or together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom; or together W and W are connected via an additional 2-5 atoms to form a cyclic group; R4is C1-C4alkyl; R5is selected from the group consisting OfC1-C4alkyl, monocyclic aryl, and monocyclic aralkyl; R is C1-C4acyl; and R and R are independently selected from the group consisting of hydrogen, C1- C22 acyl, C1-C22alkoxycarbonyl, optionally substituted arylcarbonyl, optionally substituted aryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroaryloxycarbonyl, and a naturally-occurring L-amino acid connected via its carbonyl group to form an ester; or together R at the 3 '-carbon and R form a cyclic carbonate; or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1 , wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122, -CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122, -CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; and R3is C1-C6alkyl. 4. The compound of claim 3 wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, - CF3, -COCH3, -OMe, -NMe2, -OEt, -CCtø-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, Ci-C3alkyl, -CF3, - COCH3, -OMe, -NMe2, -OEt, -CCtø-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 4 atoms to form a 6-menibered ring that is fused to a phenyl or substituted phenyl at the beta and gamma position to the O attached to the phosphorus. 5. The compound of claim 4 wherein V is selected from the group consisting of phenyl; substituted phenyl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; pyridyl; substituted pyridyl with 1 substituent independently selected from the group consisting of -Cl, -Br3-F3C1-C3alkyl, and -CF3; furanyl; substituted furanyl with 1 substituent independently selected from the group consisting of -Cl3-Br, -F, C1-C3alkyl, and -CF3; thienyl; and substituted thienyl with 1 substituent independently selected from the group consisting of -Cl3-Br3-F, C1-C3alkyl, and -CF3. 6. The compound of claim 5 wherein V is selected from the group consisting of phenyl, 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3-bromo-4-fluorophenyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. 7. The compound of claim 6 wherein V is selected from the group consisting of 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3-pyridyl, and 4-pyridyl. 8. The compound of claim 1 wherein Z is selected from the group consisting of -H, -OMe, -OEt, phenyl, C1-C3alkyl, -NR42, -SR4, -(CH2)P-OR6, -(CH2)P-SR6and - OCOR5; R4is C1-C4alkyl; R5is selected from the group consisting Of C1-C4alkyl, monocyclic aryl, and monocyclic aralkyl; and R6is C1-C4acyl. 9. The compound of claim 8 wherein Z is selected from the group consisting of -H, -OMe, -OEt3and phenyl. 10. The compound of claim 1 wherein: W and W are independently selected from the group consisting of -H, C1-C6alkyl, and phenyl; or together W and W are connected via an additional 2-5 atoms to form a cyclic group. 11. The compound of claim 1 wherein W and W are independently selected from the group consisting of -H, methyl, and V, or W and W are each methyl, with the proviso that when W is V, then W is H. 12. The compound of claim 1 wherein: V is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl; W and W are independently selected from the group consisting of -H, methyl, and V, or W and W are each methyl, with the proviso that when W is V, then W is H; Z is selected from the group consisting of -H, -OMe, -OEt, phenyl, C1-C3alkyl, -NR42, -SR4, -(CH2)p-OR6, -(CH2)p-SR6and -OCOR5; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; or together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom; or together W and W are connected via an additional 2-5 atoms to form a cyclic group; and R4is C1-C4alkyl; R5is selected from the group consisting Of C1-C4alkyl, monocyclic aryl, and monocyclic aralkyl; and R6is C1-C4acyl. 13. The compound of claim 12 wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122>-CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122>-CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; and R3is C1-C6alkyl. 14. The compound of claim 13 wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of Cl, -Br, -F, C1-C3alkyl, -CF3, -COCH3, -OMe, -NMe2, -OEt, -CCV-butyl, -CQ2NH2, -SMe, -SO2Me, -SO2NH2and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of Cl, -Br, -F, C1-C3alkyl, - CF3, -COCH3, -OMe, -NMe2, -OEt, -C02t-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1- 2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S; and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 4 atoms to form a 6-membered ring that is fused to a phenyl or substituted phenyl at the beta and gamma position to the O attached to the phosphorus. 15. The compound of claim 14 wherein V is selected from the group consisting of phenyl; substituted phenyl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; pyridyl; substituted pyridyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; furanyl; substituted furanyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; thienyl; and substituted thienyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3. 16. The compound of claim 1 wherein: V is selected from the group consisting of phenyl, 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 3-bromo-4-fluorophenyl, 2- pyridyl, 3 -pyridyl, and 4-pyridyl; and Z is selected from the group consisting of -H, OMe, OEt, and phenyl; and W and W are independently selected from the group consisting of -H and phenyl, or W and W are each methyl. 17. The compound of claim 1 wherein Z, W, and W are each -H. 18. The compound of claim 1 wherein V and W are the same and each is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl. 19. The compound of claim 1 wherein V is selected from the group consisting of 3-chlorophenyl, 3,5-difluorophenyl, and 4-pyridyl; and Z, W, and W are each -H. 20. The compound of claim 19 wherein said compound is:  21. The compound of claim 19 wherein said compound is :  22. The compound of claim 1 wherein said compound is a compound of Formula (XI): wherein: V and the 5'oxymethylene group of the ribose sugar moiety are cis to one another. 23. The compound of claim 2 wherein said compound is a compound of Formula (XII): wherein: V and the 5'oxymethylene group of the ribose sugar moiety are cis to one another. 24. The compound of claim 23 wherein V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, -CF3, -COCH3, -OMe, -NMe2, -OEt, -CO2t-butyl, - CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, -CF3, -COCH3, -OMe, -NMe2, -OEt, -C02t-butyl, - CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN. 25. The compound of claim 24 wherein V is selected from the group consisting of phenyl, 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3-bromo-4-fluorophenyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. 26. The compound of claim 25 wherein said compound has R-stereochemistry at the V-attached carbon and has S-stereochemistry at the phosphorus center. 27. The compound of claim 25 wherein said compound has S-stereochemistry at the V-attached carbon and has R -stereochemistry at the phosphorus center. 28. The compound of claim 23 wherein V is selected from the group consisting of 3-chlorophenyl, 3,5-difluorophenyl, and 4-pyridyl; and together R7at the 3 '-carbon and R8form a cyclic carbonate. 29. The compound of claim 28 wherein said compound is:  30. The compound of claim 28 wherein said compound is:  31. The compound of claim 23 wherein V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, -CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122 ,- CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of halogen, C1-C6alkyl, -CF3, -OR3, -OR12, -COR3, CO2R3, -NR32, -NR122,- CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; and R3is C1-C6alkyl. 32. The compound of claim 31 wherein V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, -CF3, -COCH3, -OMe, -NMe2, -OEt, -CO2/-butyl, - CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, -CF3, -COCH3, -OMe, -NMe2, -OEt, -C02f-butyl, - CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 4 atoms to form a 6-membered ring that is fused to a phenyl or substituted phenyl at the beta and gamma position to the O attached to the phosphorus. 33. The compound of claim 32 wherein V is selected from the group consisting of phenyl; substituted phenyl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; pyridyl; substituted pyridyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; furanyl; substituted furanyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; thienyl; and substituted thienyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3. 34. The compound of claim 33 wherein V is selected from the group consisting of phenyl, 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3-bromo-4-fluorophenyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. 35. The compound of claim 34 wherein V is selected from the group consisting of 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3-pyridyl, and 4-pyridyl. 36. The compound of claim 23 wherein said compound has i?-stereochemistry at the V-attached carbon and has S-stereochemistry at the phosphorus center. 37. The compound of claim 23 wherein said compound has S-stereochemistry at the V-attached carbon and has i?-stereochemistry at the phosphorus center. 38. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 39. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 2 and a pharmaceutically acceptable carrier. 40. A method of inhibiting viral replication in a human patient comprising administering to said human patient a therapeutically effective amount of a compound of claim 1. 41. A method of inhibiting viral replication in a human patient comprising administering to said human patient a therapeutically effective amount of a compound of claim 2. 42. The method of claim 40 wherein said viral replication is RNA-dependent RNA viral replication. 43. The method of claim 40 wherein said viral replication is HCV replication. 44. A method of treating a viral infection in a human patient comprising administering to said human patient a therapeutically effective amount of a compound of claim 1. 45. A method of treating a viral infection in a human patient comprising administering to said human patient a therapeutically effective amount of a compound of claim 2. 46. The method of claim 44 wherein said viral infection is RNA-dependent RNA viral infection. 47. The method of claim 44 wherein said viral infection is HCV infection. 48. The method of claim 47 wherein said compound of Formula I is used in combination with a therapeutically effective amount of a second agent active against HCV. 49. The method of claim 48 wherein said second agent active against HCV is ribavirin; levovirin; viramidine; thymosin alpha- 1; interferon-β; an inhibitor of NS3 serine protease; an inhibitor of inosine monophosphate dehydrogenase; interferon-α or pegylated interferon-α, alone or in combination with ribavirin or levovirin. 50. The method of claim 49 wherein said second agent active against HCV is interferon-α or pegylated interferon-α, alone or in combination with ribavirin or levovirin. 51. A compound of Formula (XIII) :  (XIII) wherein: V is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl; W and W are independently selected from the group consisting of -R2, optionally substituted monocyclic aryl, and optionally substituted monocyclic heteroaryl; Z is selected from the group consisting of halogen, -CN, -COR5, -CONR42, - CO2R5, -SO2R5, -SO2NR42, -OR4, -SR4, -R4, -NR42, -OCOR5, -OCO2R5, -SCOR5, - SCO2R5, -NHCOR4, -NHCO2R5, -(CH2)P-OR6, and -(CH2)P-SR6; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; or together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom; or together W and W are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms; R is selected from the group consisting of R and hydrogen; R3is selected from the group consisting of alkyl, aryl, heterocycloalkyl, and aralkyl; R is selected from the group consisting of R3and hydrogen; R5is selected from the group consisting of alkyl, aryl, heterocycloalkyl, and aralkyl; R6is selected from the group consisting of hydrogen, and lower acyl; R12is selected from the group consisting of hydrogen, and lower acyl; and p is an integer 2 or 3; or a pharmaceutically acceptable salt thereof. 52. A compound of Formula (XIV):  (XIV) wherein: V is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl; W and W are independently selected from the group consisting of — H, methyl, and V, or W and W are each methyl, with the proviso that when W is V3then W is H; Z is selected from the group consisting of -H, -OMe, -OEt, phenyl, C1-C3alkyl, -NR42, -SR4, -(CH2)p-OR6, -(CH2)P-SR6and -OCOR5; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; or together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom; or together W and W are connected via an additional 2-5 atoms to form a cyclic group; R4is C1-C4alkyl; R5is selected from the group consisting Of C1-C4alkyl, monocyclic aryl, and monocyclic aralkyl; R6is C1-C4acyl; and R and R are independently selected from the group consisting of hydrogen, C1- C22acyl, C1-C22alkoxycarbonyl, optionally substituted arylcarbonyl, optionally substituted aryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroaryloxycarbonyl, and a naturally-occurring L-amino acid connected via its carbonyl group to form an ester; or together R7at the 3 '-oxygen and R8at the 2'-oxygen form a cyclic carbonate; or a pharmaceutically acceptable salt thereof. 53. The compound of claim 51 , wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122, -CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122, -CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; and R3is C1-C6alkyl. 54. The compound of claim 53 wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, - CF3, -COCH3, -OMe, -NMe2, -OEt, -C02t-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, -CF3, - COCH3, -OMe, -NMe2, -OEt, -COrf-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 4 atoms to form a 6-membered ring that is fused to a phenyl or substituted phenyl at the beta and gamma position to the O attached to the phosphorus. 55. The compound of claim 54 wherein V is selected from the group consisting of phenyl; substituted phenyl with 1-2 substituents independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; pyridyl; substituted pyridyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; furanyl; substituted furanyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3; thienyl; and substituted thienyl with 1 substituent independently selected from the group consisting of -Cl, -Br, -F, C1-C3alkyl, and -CF3. 56. The compound of claim 55 wherein V is selected from the group consisting of phenyl, 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3-bromo-4-fluorophenyl, 2-pyridyl, 3 -pyridyl, and 4-pyridyl. 57. The compound of claim 56 wherein V is selected from the group consisting of 3-chlorophenyl, 3-bromophenyl, 2-bromophenyl, 3,5-dichlorophenyl, 3,5- difluorophenyl, 3 -pyridyl, and 4-pyridyl. 58. The compound of claim 51 wherein Z is selected from the group consisting of -H, -OMe, -OEt, phenyl, C1-C3alkyl, -NR42, -SR4, -(CH2)p-OR6, -(CH2)P-SR6and - OCOR5; R4is C1-C4alkyl; R5is selected from the group consisting of C1-C4alkyl, monocyclic aryl, and monocyclic aralkyl; and R6is C1-C4acyl. 59. The compound of claim 58 wherein Z is selected from the group consisting of -H, -OMe, -OEt, and phenyl. 60. The compound of claim 51 wherein: W and W are independently selected from the group consisting of -H, C1-C6alkyl, and phenyl; or together W and W are connected via an additional 2-5 atoms to form a cyclic group. 61. The compound of claim 51 wherein W and W are independently selected from the group consisting of -H, methyl, and V, or W and W are each methyl, with the proviso that when W is V, then W is H. 62. The compound of claim 51 wherein: V is selected from the group consisting of optionally substituted monocyclic aryl and optionally substituted monocyclic heteroaryl; W and W are independently selected from the group consisting of -H, methyl, and V, or W and W are each methyl, with the proviso that when W is V, then W is H; Z is selected from the group consisting of -H, -OMe, -OEt, phenyl, C1-C3alkyl, -NR42, -SR4, -(CH2)p-OR6, -(CH2)p-SR6and -OCOR5; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; or together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom; or together W and W are connected via an additional 2-5 atoms to form a cyclic group; and R4is C1-C4alkyl; R5is selected from the group consisting Of C1-C4alkyl, monocyclic aryl, and monocyclic aralkyl; and R6is C1-C4acyl. 63. The compound of claim 62 wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122)-CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of halogen, C1-C6alkyl, - CF3, -OR3, -OR12, -COR3, -CO2R3, -NR32, -NR122)-CO2NR22, -SR3, -SO2R3, -SO2NR22and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S, and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; and R3is C1-C6alkyl. 64. The compound of claim 63 wherein: V is selected from the group consisting of phenyl, substituted phenyl with 1-3 substituents independently selected from the group consisting of Cl, -Br, -F, C1-C3alkyl, -CF3, -COCH3, -OMe, -NMe2, -OEt, -C02t-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, monocyclic heteroaryl, and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of Cl, -Br, -F, Cj-C3alkyl, - CF3, -COCH3, -OMe, -NMe2, -OEt, -CCtø-butyl, -CO2NH2, -SMe, -SO2Me, -SO2NH2and -CN, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1- 2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that a) when there are two heteroatoms and one is O, then the other can not be O or S; and b) when there are two heteroatoms and one is S, then the other can not be O or S; or together V and Z are connected via an additional 4 atoms to form a 6-membered ring that is fused to a phenyl or substituted phenyl at the beta and gamma position to the O attached to the phosphorus. 65. The compound of claim 64 wherein V is selected from the group consisting of phenyl; substituted phenyl with 1-2 substituents independently selected from the group consisting of -Cl, -Br5-F5C1-C3alkyl, and -CF3; pyridyl; substituted pyridyl with 1 substituent independently selected from the group consisting of -Cl5-Br, -F, C1-C3alkyl, and -CF3; furanyl; substituted furanyl with 1 substituent independently selected from the group consisting of -Cl5-Br5(...)
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