Phosphonomethoxy carbocyclic nucleosides and nucleotides
First Claim
1. A compound of the Formula I or Formula II ##STR82## wherein R1 and R2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino alkylamino and dialkylamino;
- R3 and R4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; and
B is a heterocyclic group selected from the group consisting of pyrimidine, purine, triazine, deazapurine, and triazole, attached through a ring nitrogen atom thereof optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, mercapto, amino, hydrazino, fluoro, chloro, bromo, iodo, C1 to C3 alkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C1-C3 alkoxy, and C1-C3 alkylthio;
and the pharmaceutically acceptable acid addition, metal, and amine salts thereof.
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Accused Products
Abstract
A compound of the Formula I or Formula II ##STR1## wherein R1 and R2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino, alkylamino and dialkylamino;
R3 and R4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; and
B is a heterocyclic group selected from the group consisting of pyrimidine, purine, triazine, deazapurine, and triazole, attached through a ring nitrogen atom thereof optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, mercapto, amino, hydrazino, fluoro, chloro, bromo, iodo, C1 to C3 alkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C1-C3 alkoxy, and C1-C3 alkylthio;
and the pharmaceutically acceptable acid addition, metal, and amine salts thereof.
The compositions of the invention are useful for, among other things, antiviral agents.
66 Citations
14 Claims
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1. A compound of the Formula I or Formula II ##STR82## wherein R1 and R2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino alkylamino and dialkylamino;
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R3 and R4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; and B is a heterocyclic group selected from the group consisting of pyrimidine, purine, triazine, deazapurine, and triazole, attached through a ring nitrogen atom thereof optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, mercapto, amino, hydrazino, fluoro, chloro, bromo, iodo, C1 to C3 alkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C1-C3 alkoxy, and C1-C3 alkylthio; and the pharmaceutically acceptable acid addition, metal, and amine salts thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A compound of the formula:
- ##STR83## wherein G is guanine attached through a ring nitrogen atom thereof.
- View Dependent Claims (11)
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12. A compound selected from the group consisting of:
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1- (1β
,4β
)-4-(dihydroxyphosphonyl)methoxycyclopent-2-en-1-yl!thymine,1- (1β
,4β
)-4-(dihydroxyphosphonyl)methoxycyclopent-2-en-1-yl!cytosine,9- (1β
,4β
)-4-(diethoxyphosphonyl)methoxycyclopent-2-en-1-yl!adenine,9- (1β
,4β
)-4-(ethoxyhydroxyphosphonyl)methoxycyclopent-2-en-1-yl!adenine,9- (1β
,4β
)-4-(dihydroxyphosphonyl)methoxycyclopent-2-en-1-yl!adenine,9- (1β
, 4!3β
)- 4!3-(diethoxyphosphonyl)methoxycyclopentan-1-yl!adenine, and9- (1β
, 4!3β
)- 4!3-(dihydroxyphosphonyl)methoxycyclopentan-1-yl!adenine.
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13. A compound selected from the group consisting of:
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(±
)-1-(4-β
-diethylphosphonylmethoxycyclopent-2-ene-1-β
-yl)-N.sup.3 -(2-(trimethylsilyl)-ethoxymethyl)thymine,(±
)-1-(4-β
-phosphonylmethoxycyclopent-2-ene-1-β
-yl)-N3 -(2-(trimethylsilyl)ethoxymethyl)thymine,(±
)-1-(4-β
-phosphonylmethoxycyclopent-2-ene-1-β
-yl)thymine,(±
)-1-(4-β
-phosphonylmethoxycyclopent-2-ene-1-β
-yl)-N3 -(hydroxymethyl)thymine,(±
)-1-(4-β
-diethyiphosphonylmethoxycyclopent-2-ene-1-β
-yl)-N.sup.4 -(dimethylaminomethylidene)cytosine,(±
)-1-(4-β
-phosphonylmethoxycyclopent-2-ene-1-β
-yl)cytosine,(±
)-9-(4-β
-diethylphosphonylmethoxycyclopent-2-ene-1-β
-yl)adenine,(±
)-9-(4-diethylphosphonylmethoxycyclopent-2-ene-1-β
-yl)adenine,(±
)-9-(4-β
-monoethylphosphonylmethoxycyclopent-2-ene-1-β
-yl)adenine,(±
)-9-(4-β
-phosphonylmethoxycyclopent-2-ene-1-β
-yl)adenine,(±
)-9-( 4!3-β
-diethylphosphonylmethoxycyclopentan-1-β
-yl)adenine,(±
)-9-( 4!3-β
-phosphonylmethoxycyclopentan-1-β
-yl)adenine,(±
)-N2 -monomethoxytrityl-6-O-benzyl-9-(4-β
-diethylphosphonylmethoxycyclopent-2-ene-1 -β
-yl)guanine,(±
)-9-(4-β
-diethylphosphonylmethoxycyclopent-2-ene-1-β
-yl)guanine, and(±
)-9-(4-β
-dihydroxyphosphonylmethoxycyclopent-2-ene-1-β
-yl)guanine.
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14. A compound of the Formula I or Formula II ##STR84## wherein R1 and R2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino, alkylamino and dialkylamino;
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R3 and R4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; B is selected from the group consisting of ##STR85## Pg1 is an amino protecting group;
Pg2 is a hydroxy protecting group; and
with the proviso that said Pg1 and Pg2 groups are capable of protecting amino and hydroxy groups, respectively, from reaction with tetrakis(triphenylphosphine)palladium (0) in DMF/THF.
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Specification
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- Resources
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Current AssigneeInstitute Of Organic Chemistry And Biochemistry Of The Ascr, V.V.I., REGA Stichting VZW
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Original AssigneeInstitute Of Organic Chemistry And Biochemistry Of The Ascr, V.V.I., REGA Stichting VZW
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InventorsMansuri, Muzammil M., Ferrara, Louis M., Bronson, Joanne J., Martin, John C., Hudyma, Thomas W.
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Primary Examiner(s)Berch, Mark L.
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Application NumberUS08/357,561Time in Patent Office1,229 DaysField of Search544/243, 544/244, 544/195, 546/23, 548/112US Class Current544/243CPC Class CodesC07F 9/6512 having the nitrogen atoms i...
