Abstract: Conformationally restricted 2′, 4′-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2′ and C4′ of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.

Abstract: Methods for selectively protecting the exocyclic amino function of a purine nucleoside are provided using activating agents to effect acylation at the exocyclic amino site. Methods are also provided for recycling polymer bound coupling supports from the reaction mixtures produced upon N-acylation.

Abstract: Compounds of the formula wherein X is NR4R5, Y is selected from C1-C6 alkyl; alkoxyalkyl, C2-C6 alkenyl; C2-C6 alkynyl, alkoxy, aryl, or heteroaryl, or NR4R5, and R3 is selected from optionally substituted aryl or heteroaryl, optionally substituted, are neuropeptide antagonists and are effective in treating feeding disorders, cardiovascular diseases and other physiological disorders related to an excess of neuropeptide Y.

Abstract: The present invention relates to novel compounds, compositions and methods for inhibiting the growth, elaboration and/or replication of HIV in human patients and to the prevention and treatment of human acquired immunodeficiency syndrome (AIDS) and other diseases caused by retroviral infection. More particularly, in preferred aspects, the present invention provides a method for the use of novel prodrug forms of 9-(2,3-Dideoxy-&bgr;-D-glycero-pent-2-enofuranosyl)guanine (d4G) for the prevention and treatment of both wild type and drug-resistant Human Immunodeficiency Virus (HIV), the causative pathogen of AIDS.

Abstract: The present invention also provides a general method to whereby mono-, bi-, or tricyclic heterocycles may be modified to obtain potent antagonists at the NPY1 receptor. The present invention provides novel, potent, non-peptidic antagonists of NPY receptors, particularly, the NPY1 receptors, designed from a selection of mono-, bi-, or tri-cyclic heterocyclic cores. This invention relates to novel compounds, compositions, and methods for the treatment of physiological disorders associated with an excess of neuropeptide Y. The novel compounds encompassed by the present invention are those of the formula I-XV.

Abstract: Disclosed are compounds of the formula (I): 1

Abstract: The present invention relates to substituted xanthines of general formula 1

Abstract: Compounds which are active against viruses have the following Formulas: 1

Abstract: Peptide nucleic acids conjugated to lipophilic groups and incorporated into liposomes exhibit enhanced cellular uptake and distribution. Cellular uptake and distribution of peptide nucleic acids also increases with the introduction of an amino acid side chain into the backbone of peptide nucleic acids. Methods of modulating cellular uptake and methods for treating animals are provided. The peptide nucleic acids of the invention comprise naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone.

Abstract: Methods and novel intermediates for the preparation of and the treatment with acyclic nucleoside derivatives of the formula: 1

Abstract: Therapeutic oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. Replacement of phosphorodiester inter-sugar linkages found in wild type oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: This invention relates to novel crystalline H polymorphic forms, Form I, II and IV of Cipamfylline, methods of preparation, and use thereof in the treatment of PDE4 and TNF mediated diseases. Cipamfylline is 1,3-di-cyclopropylmethyl-8-amino xanthine, and represented by formula (I).

Abstract: A xanthine phosphodiesterase V inhibitor having the formula (I), with the variables defined herein, which is especially useful for treating male (erectile) and female sexual dysfunction and other physiological disorders: 1

Abstract: Disclosed are compositions inducing cleavage of an RNA substrate, as well as their use for inducing cleavage of RNA substrates in vitro and in vivo. The compositions contain part of an active center, with the other part of the active center provided by the RNA substrate. The subunits of the active center region of the compositions are nucleotides and/or nucleotide analogues. The disclosed compositions also have flanking regions contributing to the formation of a specific hybridization with an RNA substrate. Preferred compositions form, in combination with an RNA substrate, a structure resembling a hammerhead structure. The active center of the disclosed compositions is characterized by the presence of I15.1 which allows cleavage of RNA substrates having C16.1.

Abstract: The invention provides a processes for the preparation of a compound of Formula I, or a salt thereof wherein PG is a urethane- or trityl-type protective group; X is NH, O, or S; Y is CH2, O, or NH; and B′ is a base customary in nucleotide chemistry. The processes include reacting a compound of Formula (II) with a compound of Formula (III) a compound of Formula (V) B′—CH2—CO—R2  (V), a monohaloacetic acid derivative in a suitable solvent with an auxiliary base, or a compound of Formula (VII) B′—CH2—CO—R3  (VII), and converting the resulting compounds to that of Formula I.

Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone. Some PNAs of the invention also contain C1-C8 alkylamine side chains.

Abstract: The invention provides methods for solution-phase synthesis of nucleotide-based compounds and new libraries of such compounds. Compounds of the invention are useful for a variety of therapeutic applications, including treatment of viral or bacterial infections and associated diseases and disorders.

Abstract: Ionophores having the capacity spontaneously assemble in solution and composed of hydrogen bonded monomers of 5′-(t-butyl-dimethylsilyl)-2′,3′-O-isopropylidene-isoguanosine, 5′-(t-butyl-dimethylsilyl)-2′,3′-O-isopropylidene-thio-isoguanosine or 2′,3′-Di-O-acetyl-5′-(t-butyl-dimethylsilyl)-isoguanosine are used to remove 137-cesium ions (137Cs+) from nuclear waste.

Abstract: The invention relates to prodrugs of N-substituted derivatives of 6-aminouracils, 6-aminoisocytosines, guanines, and 2-aminoadenines. The N-linked substituents include an ester group that is cleaved upon administration into a subject to yield a substituent having a terminal hydroxyl group. Pharmaceutical compositions including these compounds, and methods for treating Gram-positive bacterial infections using these compounds, are also disclosed.

Abstract: The invention provides a compound of formula I 1

Abstract: Method for the sterospecific preparation of 2′ or 3′ deoxy and 2′, 3′-dideoxy-&bgr;-L-pentofuranonucleoside compounds. 2′ or 3′ deoxy and 2′, 3′-dideoxy-&bgr;-L-pentofuranonucleoside compounds are also described. Finally, the invention concerns the use of these compounds, and particularly 2′, 3′ dideoxy-&bgr;-L-fluorocytidine, as drugs, and especially as anti-viral agents.

Abstract: Disclosed are compounds having formula (II): wherein: Q3, Q6a, Q6b and Q8 are independently a bond, C1-8 alkylene, C2-8 alkenylene and C2-8 alkynylene, and R3, R6a, R6b and R8 are independently hydrogen, aryl or heteroraryl, optionally substituted by halogen, hydroxy, alkoxy, nitro, cyano and carboxy, provided that: Q3R3 is not hydrogen or methyl. The compounds are effective PDE IV inhibitors and possess improved PDE IV inhibition and improved selectivity with regard to PDE III inhibition.

Abstract: A cyclopentenecarboxamide derivative represented by the formula (I): 1

Abstract: The invention provides a method of rearranging a compound of formula (I), wherein R and R′ are selected independently from hydrogen and C1-12alkyl; and R1 and R2 are selected independently from hydrogen, hydroxy, halo, C1-12alkyl- or aryl carbonate, amino, mono- or di-C1-12alkylamino, C1-12alkyl or arylamido, C1-12alkyl- or arylcarbonyl, C1-12alkyl- or arylcarboxy, C1-12alkyl- or arylcarbamoyl, C1-12alkyl, C2-12alkenyl, C2-12alkynyl, aryl, heteroaryl, C1-12alkoxy, aryloxy, azido, C1-12alkyl- or arylthio, C1-12alkyl- or arylsulfonyl, C1-12alkyl- or arylsilyl, C1-12alkyl- or arylphosphoryl, and phosphato; to form a compound of formula (II), wherein R, R′, R1 and R2 are as defined for formula (I); said method comprising treating the compound of formula (I) with a palladium (0) catalyst and a (diphenylphosphino)nC1-6 alkane, wherein n is an integer of 1-6. The invention also provides methods of R making penciclovir and famciclovir using this rearrangement reaction.

Abstract: The present invention relates to prodrugs of a class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of prodrugs of HIV aspartyl protease inhibitors characterized by favorable aqueous solubility, high oral bioavailability and facile in vivo generation of the active ingredient. This invention also relates to pharmaceutical compositions comprising these prodrugs. The prodrugs and pharmaceutical compositions of this invention are particularly well suited for decreasing the pill burden and increasing patient compliance. This invention also relates to methods of treating mammals with these prodrugs and pharmaceutical compositions.

Abstract: Benzimidazole derivatives of Formula I or a pharmaceutically acceptable salt thereof are MCP-1 antagonists and are thus useful in the treatment of inflammation, atherosclerosis, restenosis, and immune disorders such as arthritis and transplant rejection 1

Abstract: The invention relates to antimicrobial compounds which interact with zinc in a zinc finger of a bacterial DNA polymerase, methods of screening for such compounds, and methods of using such compounds to inhibit polymerase activity or bacterial growth.

Abstract: Disclosed are compounds of the formula: wherein R3, R6a, R6b and R8 are substituted as disclosed herein. The compounds are effective in effecting PDE IV inhibition in patients in need thereof.

Abstract: Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein: W is oxygen or sulfur; X is (un)substituted lower alkyl; or X is (un)substituted aryl or heteroaryl; Y is hydrogen or lower alkyl; Z is lower alkenyl, lower alkynyl, or (un)substituted lower alkyl; T is (un)substituted aryl or heteroaryl. The compounds are highly selective agonists, antagonists, or inverse agonists for GABAa brain receptors, or prodrugs of agonists, antagonists, or inverse agonists for GABAa brain receptors. Thus these compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, Down's Syndrome, overdose with benzodiazepine drugs, and for the enhancement of memory.

Abstract: 1

Abstract: The present invention relates to methods and compositions for preparing biologically important nucleoside analogues containing 1,3-dioxolane sugar rings. In particular, this invention relates to the stereoselective synthesis of the beta (cis) isomer by glycosylating the base with an intermediate of formula (II) below a temperature of about −10° C.

Abstract: The present invention provides a process for the synthesis of penciclovir and famciclovir by 9-substituting 2-amino-6-chloropurine (ACP) with an appropriate side chain precursor, followed by conversion of the 6-chloro moiety to a hydroxy moiety (i.e. to form a guanine) or hydrogen (to form a 2-aminopurine), respectively.

Abstract: 2-Aryl-8-oxodihydropurine derivative of the following formula (I): wherein W is H, lower alkyl, halogen, lower alkoxy, amino, mono- or di-lower alkylamino, or substituted or unsubstituted phenyl; X is H, lower alkyl, cycloalkyl-lower alkyl, substituted or unsubstituted phenyl-lower alkyl, lower alkenyl, carbamoyl, di-lower alkylcarbamoyl, or a group of the formula (Q): —CH(R3)CON(R1)(R2); Y is H, lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, substituted or unsubstituted phenyl-lower alkyl, or a group of the formula (Q): —CH(R3)CON(R1)(R2); A is substituted or unsubstituted phenyl, or substituted or unsubstituted heteroaryl; provided that when one of X and Y of the above formula (I) is the group of the formula (Q), then the other is the same groups for X or Y as described above except for the group of the formula (Q), or a pharmaceutically acceptable acid addition salt thereof.

Abstract: The current invention is down to (+) an (−) enantiomers, as well as racemic mixtures of nucleoside analogs, wherein the carbohydrate portion of the analog is a dioxolane moiety and the nucleobase moiety is N6-carbocyclic-alkylamino-substituted-2-amino-purine moiety attached via its N9 position to the dioxolane moiety. The compounds are useful for treating viral infections such as HBV and HIV infections, alone or in combination with other therapeutic agents.

Abstract: A 2,6,9-trisubstituted purine composition that is useful for inhibiting cell proliferative disorders and as an antifungal agent.

Abstract: Compounds which are active against viruses have the following Formulas: wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

Abstract: The present invention provides AGT inactivating compounds such as substituted O6-benzylguanines of the formula 1

Abstract: The present invention is directed to a process for preparing a cyclopropane ring-cleaved purine derivative represented by the following formula: comprising hydrogenating a purine derivative having a cyclopropane ring represented by the following formula:

Abstract: wherein Z1 is hydrogen or an amino-protecting group selected from the group consisting of acyl of the formula R—C(O)—, wherein R is alkyl of 1-6 carbon atoms; trityl, optionally substituted with methoxy; and N-(9-fluorenylmethoxycarbonyl); Y1 is halo, aralkyloxy or acyloxy, wherein acyl is as defined above; and Y2 is aralkyloxy. These intermediates are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl) methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract: Disclosed herein are methods directed generally to the control of neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as neurotrophic factors through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, and cellular disorders.

Abstract: Disclosed are novel bicyclic tris(anhydride)s useful as intermediates in the synthesis of biolologically active compounds, and the compounds which may be synthesized from such intermediates.

Abstract: A compound of the formula: wherein R2 is O or S; R3, R6a and R8 are the same or different and each represent a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, alkoxy, HC═NOH, HC═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4); heterocyclyl; heterocyclylalkyl (C1-C4); and heteroaryl; R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring op

Abstract: Hypoxanthine compounds of the structure: are disclosed where R3 and R8 are as described herein. The compounds are useful as intermediates to compounds providing PDE IV inhibition activity.

Abstract: The present invention provides condensed purine derivatives or pharmacologically acceptable salts thereof exhibiting adenosine A3 acceptor antagonising activity, and having an antiasthmatic action, a bronchodilator action, an antiantiitching action, etc., and represented by the following formula (I): (wherein R1 represents substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group; R2 represents hydrogen, lower alkyl, alicyclic alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group; R3 represents hydrogen, lower alkyl, or substituted or unsubstituted aralkyl; X1 and X2 are the same or different and each represents hydrogen, lower alkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted aryl; and n represents an integer of 0 to 3).

Abstract: Method of treating a tumour or other cell proliferation disorder which comprises administering an effective amount of a purine compound which inhibits cyclic dependent kinase activity. Novel purine compounds and pharmaceutical compositions are also disclosed.

Abstract: Novel 9-substituted hypoxanthine derivatives with unexpected physiological effects are disclosed. These compounds are of formula (I) where n is an integer from 1 to 6, R1 is selected from the group consisting of H, COOH, and COOW1, where W1 is selected from the group consisting of lower alkyl, amino, and lower alkylamino, and R2 is selected from the group consisting of H and OH. Among these compounds are N-(2-(5-hydroxyindol-3-yl)ethyl-3-6-oxyhydropurin-9-yl)propanamide, N-2-(indol-3-yl)ethyl)-3-(6-oxyhydropurin-9-yl)propanamide and N-(1-carboxyl)-(2-(5-hydroxyindol-3-yl)ethyl-3-(6-oxyhydropurin-9-yl)propanamide. These compounds have a number of utilities, including inhibition of the activity of monoamine oxidases, treating obesity, lowering serum cholesterol, and increasing the level of HDL cholesterol. Also disclosed are pharmaceutical compositions and methods of use of the derivatives to treat a number of disorders or conditions.

Abstract: The present invention is directed to 9-substituted guanine derivatives in which the guanine moiety is linked to another moiety with physiological or pharmacological activity through a carboxamide linkage. The number of carbon atoms between the guanine moiety and the carboxamide linking group is typically from 1 to 6. In some cases, the chemical moieties can have carbon chains of different lengths within the moiety linked to guanine through the carboxamide linker. A large number of different chemical moieties can be linked to the guanine moiety. The invention also includes pharmaceutical compositions including the 9-substituted guanine derivatives and methods of use of the 9-substituted guanine derivatives.

Abstract: The present invention describes novel isoxazolo[1,5-a]pyrimidines of formula: wherein R is an aromatic or heteroaromatic ring, or pharmaceutically acceptable salt form thereof, which are useful as CRF antagonists.

Abstract: The present invention relates to the discovery that certain &bgr;-L-dioxolane nucleoside analogs which contain a uracil base, and preferably, a 5-halosubstituted uracil base, exhibit unexpectedly high activity against Epstein-Barr virus (EBV), Varciella-Zoster virus (VZV) and Herpes Virus 8 (HV-8). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus (viral growth) in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds are useful for treating EBV, VZV and HV-8 infections in humans.

Abstract: A method is disclosed for the preparation of novel PNA synthons compatible with DNA synthetic reagents and instrumentation. Accordingly, the PNA synthons of this invention are particularly suitable for the preparation of PNA-DNA chimeras, among other oligomers. The PNA synthons are designed to have a protecting group strategy which is orthogonal and allows removal of the protecting groups under mild conditions. Generally, an acid labile protected backbone is coupled to a nucleobase side chain moiety to form the PNA synthon. A novel method for synthesizing the acid labile protected backbone also is described. In addition, novel compositions of matter are disclosed.