Abstract: The invention provides for novel 2-Deoxyadenosine compounds, which can treat HIV infection at low cytotoxicity values. Substitution at the 4?-position provided compounds which demonstrated low cytotoxicity values in an ATP-based cytotoxicity assay.

Abstract: Zebularine has hypomethylating activity, and can be used to inhibit, reverse, and/or reduce DNA methylation in vivo and in vitro. Methods are provided for treating methylation-linked conditions through the application of 2-pyrimidinone derivatives, such as Zebularine. Compositions, including pharmaceutical compositions, comprising such derivatives are also provided. Also provided are kits for use in inhibiting DNA methylation, which kits include an amount of a 2-pyrimidinone derivative.

Abstract: The invention provides for novel 2-Deoxyadenosine compounds, which can treat HIV infection at low cytotoxicity values. Substitution at the 4?-position provided compounds which demonstrated low cytotoxicity values in an ATP-based cytotoxicity assay.

Abstract: The present invention provides novel nucleoside and nucleotide derivatives that are useful agonist or antagonists of P1 and P2 receptors. For example, the present invention provides a compound of formula A-M, wherein A is modified adenine or uracil and M is a constrained cycloalkyl group. The adenine or uracil is bonded to the constrained cycloalkyl group. The compounds of the present invention are useful in the treatment or prevention of various diseases including airway diseases (through A2B, A3, P2Y2 receptors), cancer (through A3, P2 receptors), cardiac arrhythmias (through A1 receptors), cardiac ischemia (through A1, A3 receptors), epilepsy (through A1, P2X receptors), and Huntington's Disease (through A2A receptors).

Abstract: A method for the prevention or treatment of poxvirus infection by administering an effective amount of an antiviral agent comprising cyclopropanated carbocyclic 2?-deoxynucleoside to an individual in need thereof is provided.

Abstract: The present invention provides novel nucleoside and nucleotide derivatives that are useful agonists or antagonists of P1 or P2 receptors. For example, the present invention provides a compound of formula A-M, wherein A is modified adenine or uracil and M is a constrained cycloalkyl group. The adenine or uracil is bonded to the constrained cycloakyl group. The compounds of the present invention are useful in the treatment or prevention of various diseases including airway diseases (through A2B, A3, P2Y2 receptors), cancer (through A3, P2 receptors), cardiac arrhythmias (through A1 receptors), cardiac ischemia (through A1, A3 receptors), epilepsy (through A1, P2X receptors), and Huntington's Disease (through A2A receptors).

Abstract: The embodiments described herein concern 5-substituted pyrimidine derivatives of conformationally locked nucleoside analogues and to the use of these derivatives as anti-viral and anti-cancer agents. The compounds are of the formula: wherein B is uracil-1-yl or cytosin-1-yl having a 5-substituent selected from halogen, alkyl, alkenyl, and alkynyl, with the proviso that where B is uracil-1-yl, the 5-substituent is not methyl. The compounds are useful in the treatment of Herpes simplex virus (HSV).

Abstract: The present invention provides novel nucleoside and nucleotide derivatives that are useful agonists or antagonists of P1 or P2 receptors. For example, the present invention provides a compound of formula A-M, wherein A is modified adenine or uracil and M is a constrained cycloalkyl group. The adenine or uracil is bonded to the constrained cycloakyl group. The compounds of the present invention are useful in the treatment or prevention of various diseases including airway diseases (through A2B, A3, P2Y2 receptors), cancer (through A3, P2 receptors), cardiac arrhythmias (through A1 receptors), cardiac ischemia (through A1, A3 receptors), epilepsy (through A1, P2X receptors), and Huntington's Disease (through A2A receptors).

Abstract: Conformationally constrained diacylglycerol analogues, pharmaceutical compositions comprising such analogues, and methods of using such analogues as agonists and antagonists of protein kinase C.

Abstract: Conformationally locked 4',6'-cyclopropane-fused carboxylic nucleoside analogues. The compounds are prepared by condensing a cyclopropane-fused carbocyclic allylic alcohol with substituted purine or pyrimidine bases. The condensation products are then modified to produce the adenosine, guanosine, cytidine, thymidine, and uracil nucleoside analogues. The compounds are therapeutically useful as antimetabolites, or in the preparation of anti-metabolic agents.

Abstract: A method for treatment of herpes virus infection by administering an effective virus-inhibiting amount of a cyclopropanated carbocyclic 2'-deoxynucleoside to an individual in need thereof. The nucleoside analogs are effective against herpes simplex virus types 1 and 2; Epstein-Barr Virus and human cytomegalovirus.

Abstract: A method of preparing a 2'-fluoro compound of the formula ##STR1## where B is selected from the group consisting of purines and pyrimidines, both of which may be substituted, comprises reacting a compound of the formula II(a) or II(b) ##STR2## where R and R' are as defined in the specification with an acid halide under conditions effective to obtain a halide of the formula ##STR3## where X is a halogen. A silane of the formula B-Si (R").sub.3 where R" is as defined in the specification, is added to this product (III) under conditions effective to obtain a compound of the formula (IV) ##STR4## The compound of formula (IV) is reacted with a reagent selected from the group consisting of ammonia, BCl.sub.3 and ((C.sub.1 -C.sub.10)alkyl).sub.4 NF, under conditions effective to obtain the compound of formula (I). The compounds of formula (I) resulting from these methods exhibit anti-HIV activities and are useful for therapy against the HIV virus.

Abstract: Conformationally locked 4',6'-cyclopropane-fused carbocyclic nucleoside analogues. The compounds are prepared by condensing a cyclopropane-fused carbocyclic allylic alcohol with substituted purine or pyrimidine bases. The condensation products are then modified to produce the adenosine, guanosine, cytidine, thymidine and uracil nucleoside analogues. The compounds are therapeutically useful as antimetabolites, or in the preparation of anti-metabolic agents.

Abstract: Methods of treating a human infected with human immunodeficiency virus (HIV), such as a human with AIDS, with the purina nucleotides 2',3'-dideoxy-2'-beta-fluoroadenosine (FddA) and 2',3'-dideoxy-2'-beta-fluoroinosine (FddI) are disclosed. These nucleotides are stable in an acid environment and thus can be used for oral administration. Methods of inhibiting human immunodeficiency virus replication in a human T cell using these purina nucleotides are also disclosed.

Abstract: The present invention provides a novel synthetic route to a key precursor, i.e., an (S,S)-.alpha.-fluoro-2,2-dimethyl-1,3-dioxolane-4-propanoic acid ester useful in the preparation of FddA and FddC. The instant diastereoselective process utilizes a novel intermediate which contains a chiral auxiliary. The chiral auxiliary can be any chiral auxiliary moiety such as for example an auxiliary containing a substituted oxazolidinone group. The intermediate containing the chiral auxiliary is fluorinated utilizing a fluorination method applied for the first time in the synthesis of fluorinated sugars to give a fluorinated intermediate which after removal of the chiral group provides the desired key intermediate. In summary, in the instant process, a fluorine is introduced diastereoselectively into an intermediate via the reaction of a chiral enolate with an electrophilic fluorinating agent and the intermediate which is fluorinated is derived from mannitol.

Abstract: Purine nucleosides active against human immunodeficiency virus which are substituted at the 2'-position by a strong electronegative group such as fluorine are stable in an acid environment and thus can be used for oral administration.

Abstract: The present invention relates, in general, to prodrugs. In particular, the present invention relates to lipophilic, aminohydrolase-activated, anti-viral nucleoside prodrug compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds.

Abstract: A compound has the formula ##STR1## wherein R is selected from the group consisting of (C.sub.7 -C.sub.20)aroyl, (C.sub.6 -C.sub.20)aryl, aralkyl and alkylaryl, and (C.sub.1 -C.sub.10)alkyl-di(C.sub.6 -C.sub.20)aryl Si, R' is selected from the group consisting of (C.sub.1 -C.sub.10)alkyl, (C.sub.7 -C.sub.20)aroyl and (C.sub.2 -C.sub.12)acyl, all of which may be further substituted with O, S, N or alkyl, and R'" is selected from the group consisting of halogen, (C.sub.1 -C.sub.10)alkoxy, (C.sub.1 -C.sub.10)acyloxy, O-methane-sulfonyl and O-p-toluenesulfonyl. A composition of matter comprises 0.001 to 99.999 wt % of the above compound.

Abstract: 5,6-dihydro-5-azacytidine phosphoramidite is useful in the synthesis of oligonucleotides and DNA containing dihydro-5-aza- and 5-azacytosine bases. The modified oligonucleotides which contain 5-azacytosine residues at specific sites can be used to determine the mechanism of selective gene activation and the relationship existing between the presence of the triazine base and inhibition of DNA methylation.

Abstract: Cyclopentenyl pyrimidine compounds have potent anti-viral, anti-tumor and differentiating activity. Of these compounds, cyclopentenyl cytosine has proved to be particularly effective in a variety of tumors, as well as having good antiviral activity and potent differentiating properties.