Abstract: This invention provides a method of treating a subject afflicted with sickle cell disease which comprises administering to the subject an amount of an antiviral agent effective to inhibit sickling of a cell in the subject, so as to thereby treat the subject afflicted with sickle cell disease. This invention also provides a method of inhibiting polymerization of hemoglobin which comprises contacting the hemoglobin with an amount of an antiviral agent effective to inhibit polymerization of the hemoglobin, so as to thereby inhibit polymerization of the hemoglobin. This invention further provides a method of inhibiting sickling of a cell which comprises contacting the cell with an amount of an antiviral agent effective to inhibit polymerization of hemoglobin in the cell, so as to thereby inhibit sickling of the cell.

Abstract: Disclosed are novel A2B adenosine receptor antagonists of Formula I: A compound of the formula: wherein: R1 is optionally substituted alkyl or a group —Y—Z, in which Y is a covalent bond or optionally substituted alkylene, and Z is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkenyl or optionally substituted alkynyl, with the proviso that when Y is a covalent bond Z cannot be alkenyl or alkynyl; and X is oxygen, sulfur, or NH—, or a pharmaceutically acceptable salt, ester, or prodrug thereof. The compounds are particularly useful for treating asthma and diabetic retinopathy.

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

Abstract: An ophthalmic aqueous suspension preparation to serve as a cure for corneal herpes infection contains 9-[(2-hydroxyethoxy)methyl]guanine as an active ingredient and exhibits an improved stability. Specifically, the ophthalmic aqueous suspension preparation contains 0.2 to 5% by weight of 9-[(2-hydroxyethoxy)methyl]guanine or a pharmaceutically acceptable salt thereof, 0.05 to 1% by weight of a partially saponified product of polyvinyl acetate, and 0.01 to 1% by weight of a nonionic surfactant and has a pH of 6 to 8. Preferably, the fine crystals have a short axis of 50 &mgr;m or less and a long axis of 70 &mgr;m or less in length and have a ratio of the long axis to the short axis of 10:1 or less.

Abstract: The present invention relates to compounds of formula (I), in which B, D, E, G, X, Y, Z, R1, R2 and s have the meanings indicated in the claims, their physiologically tolerable salts and their prodrugs. The compounds of formula (I) are valuable pharmacologically active compounds. They are vitronectin receptor antagonist and inhibitors of cell adhesion and are suitable for the therapy and prophylaxis of illnesses which are based on the interaction between vitronectin receptors and their ligands in cell-cell or cell-matrix interaction processes or which can be prevented, alleviated or cured by influencing such interactions. For example, they can be applied for inhibiting bone resorption by osteoclasts and thus for treating and preventing osteoporosis, or for inhibiting undesired angiogenesis or prolifertion of cells of the vascular smooth musculature.

Abstract: The L-monovaline ester derived from 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Abstract: The present invention discloses a method for treating HIV that includes administering &mgr;-D-D4FC or its pharmaceutically acceptable salt or prodrug to a human in need of therapy in combination or alternation with a drug that induces a mutation in HIV-1 at a location other than the 70(K to N), 90 or the 172 codons of the reverse transcriptase region. Also disclosed is a method for using &bgr;-D-D4FC as “salvage therapy” to patients which exhibit drug resistance to other anti-HIV agents. &bgr;-D-D4FC can be used generally as salvage therapy for any patient which exhibits resistance to a drug that induces a mutation at other than the 70(K to N), 90 or the 172 codons.

Abstract: The present invention relates to novel types of peptide nucleic acids (PNAS) with improved properties. In particular, it relates to positively charged PNA units having an ethylene linker between the backbone and the nucleobase, to oligonucleotide analogs comprising these units, to oligomers comprising these units, and to the use of positively charged PNAs as novel delivery agents with therapeutic and diagnostic applications including for antisense therapy.

Abstract: Pentoxifylline, pioglitazone and metformin have been found to inhibit the nonenzymatic glycation of proteins which often results in formation of advanced glycation endproducts and crosslinks. The nonenzymatic glycation and crosslinking of proteins is a part of the aging process with the glycation endproducts and crosslinking of long-lived proteins increasing with age. This process is increased at elevated concentrations of reducing sugars in the blood and in the intracellular environment such as occurs with diabetes. The structural and functional integrity of the affected molecules become perturbed by these modifications and can result in severe consequences. The compounds of the present invention can be used to inhibit this process of nonenzymatic glycation and therefore to inhibit some of the ill effects caused by diabetes or by aging.

Abstract: The present invention relates to a method for treating a tumor in a tissue of a human or non-human animal, the tumor having an elevated level of glutathione relative to the tissue, the method comprising the steps of administering to the animal a prodrug comprising a thiopurine having a sulfur heteroatom conjugated to an alpha-, beta-unsaturated carbonyl moiety, in combination with a pharmaceutically acceptable carrier, the moiety comprising a double bond having an alpha end and a beta end, the beta end being accessible to glutathione in an addition-elimination reaction, the prodrug lacking an ionizable carboxylic acid group; and observing a reduction in growth of the tumor.

Abstract: The present invention relates to pathways for the synthesis and recycling of methylthioribose (MTR), applications in the fight against plant and vertebrate pathogens (including parasites and their vectors), application for the production of fine chemicals, and in fermentation industry. The present invention also relates to the identification of new drug targets in previously unknown metabolic pathways in living organisms, in particular in bacteria, yeasts, mold, parasites and plants.

Abstract: This invention relates to purine compounds of formula (I): 1

Abstract: The present invention provides compositions of liposomes that contain a biologically active compound and methods of manufacture thereof. Invention methods offer the ability to manufacture liposome compositions containing NSAIDs and other biologically active compounds, and the ability to attain very high encapsulation efficiencies in uniform, stable liposomes. Compositions of liposomes containing anti-viral agents and anti-fungal agents are also provided. Invention liposome compositions are useful for the treatment of a variety of conditions, including, for example, pain and inflammation, bacterial infections and viral infections.

Abstract: The present invention relates to a method for releasing an active substance from a composition. The active substance is either substantially water-insoluble and/or immobilised on or in nanosized particles. A diffusion gradient is established between the inside and the outside of the composition, which allows the transport of a nanosuspension of the active substance through the pores of the membrane.

Abstract: The invention provides combination therapies for treating papilloma virus.

Abstract: Various substituted nitrogen heterocyclic derivatives and their pharmaceutically acceptable salt derivatives are provided for use as medicaments, and particularly, as antimitotic, anti-viral, anti-cancer, anti-degenerative, immunosuppressive, and anti-microbial drugs or, vaccines. These heterocyclic derivatives can be used as an active agent in a pharmaceutical, as well as a diagnostic utility. To this end, several families of heterocyclic derivatives are provided including pyrrolopyrimidines, pyrazolopyrimidines, purines, and imidazopyridines. In particular, certain tri-substituted and tetra-substituted purines and pyrazolopyrimidines and their deaza analogues are provided for inhibiting cyclin-dependent kinase (“cdk”) proteins, viruses, and immunostimulation.

Abstract: The present invention provides novel cationic amphiphiles capable of facilitating transport of biologically active molecules into cells wherein the said amphiphiles contain cyclic head group having polar functional groups and pharmaceutical composition useful for delivering biologically active therapeutic molecules into body cells.

Abstract: The present invention relates to novel telomerase inhibitors possessing antitumor activity and to a process for preparing the same. Furthermore, these compounds enhance the efficacy of other chemotherapeutic agents, in the treatment of cancer.

Abstract: Medicines for treatment or prevention of dementia comprising 2-aryl-8-oxodihydropurine derivatives of the formula (I): 1

Abstract: The present invention relates to a novel class of sulfonamides of formula I which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity. The sulfonamides of formula I have the structure: wherein A, B, D, D′, E, G and R7 are as defined above.

Abstract: The present invention is directed to a method for treating hepatitis B virus infection in humans comprising administering a synergistically effective amount of agents having known anti-hepatitis B virus activity in combination or alternation. Specifically, the invention is directed to a method for treating hepatitis B virus infection comprising administering FTC in combination or alternation with penciclovir, famciclovir or Bis-POM-PMEA. Additionally, the invention is directed to a method for treating hepatitis B virus infection comprising administering L-FMAU in combination or alternation with DAPD, penciclovir or Bis-POM-PMEA. The invention is further directed to a method for treating hepatitis B virus infection comprising administering DAPD in combination or alternation with Bis-POM-PMEA.

Abstract: Disclosed are novel A2A adenosine receptor antagonists, useful for treating various disease states, for example cardiovascular disorders, including tissue damage due to ischemia, CNS diseases, including Parkinson's disease, depression, and the like.

Abstract: Compositions are provided, which comprise at least one nucleoside analogue inhibitor, pharmaceutically acceptable salts, solvates, or prodrugs thereof and fusaric acid, derivatives, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprising the above compositions are also provided that optionally further include another therapeutically effective compound, such as a carrier. Systemic and topical preparations comprising the above compositions are also provided as well as methods of treating viral diseases by the administration of the above antiviral agents to a patient.

Abstract: The invention involves administration of an imidazoquinoline agent in combination with another therapeutic agent. The combination of drugs may be administered in synergistic amounts or in various dosages or at various time schedules. The invention also relates to kits and compositions concerning the combination of drugs. The combinations can be used to enhance ADCC, stimulate immune responses and/or patient and treat certain disorders.

Abstract: This invention relates to formulations for the prevention of infection and/or abnormal conditions of mucosae and/or skin caused by any pathogen and/or any disease, and more particularly for the prevention of sexually transmitted infections specially HIV and HSV. This invention also relates to formulations for the treatment of infection and/or abnormal conditions of skin and/or mucosac and more particularly for the treatment of herpetic lesions. The formulations could be used as a prophylactic agent to prevent accidental infection of health care workers. The formulations could be used for the healing and/or treatment of bum wounds and prevention of further infection. This invention also relates to the development of a unique vaginal/ano-rectal applicator for the uniform delivery of any topical formulations to treat and/or prevent any infection and/or abnormal conditions of mucosa cavity caused by any pathogen and/or disease.

Abstract: A pharmaceutical formulation is provided for treating erectile dysfunction in a mammalian male individual. The pharmaceutical formulation includes a phosphodiesterase inhibitor or a pharmaceutically acceptable salt, ester, amide or derivative thereof, that is administered transmucosally within the context of an effective dosing regimen. Preferred modes of administration include transbuccal, sublingual and transrectal routes. A kit for the administration of the pharmaceutical formulation is also provided.

Abstract: This invention relates to novel compositions, methods of use, regimens and kits for treating local fungal and bacterial infections that are susceptible to treatment administered either locally or topically and systemically. The methods of this invention relate to ways in which to relieve symptoms of such infections in an unexpectedly shorter timespan than with conventional treatment with greater predictability than those methods currently known.

Abstract: Provided are novel polymorphs and pseudopolymorphs of valacyclovir hydrochloride and pharmaceutical compositions containing these. Also provided are methods for making the novel polymorphs and pseudopolymorphs, which include valacyclovir hydrochloride monohydrate and valacyclovir hydrochloride dihydrate.

Abstract: The present invention relates generally to the use of compositions comprising IL-18, also known as interferon-&ggr;-inducing factor (IGIF), and IL-18 in combination with other agents, for the prevention and/or treatment of viral diseases caused by HIV, HSV, HPV, HAV, HBV, and HCV.

Abstract: A pharmaceutical formulation for valaciclovir comprising carrier beads coated with one or more layers of pharmaceutically acceptable substances, wherein, at least one layer comprises valaciclovir, or a pharmaceutically acceptable derivative thereof, as the active ingredient. There is also provided a process for the preparation of such a formulation.

Abstract: The invention relates to the identification of cdk inhibitors as inhibitors of pathogen gene expression, replication and reactivation. The invention also relates to the identification of a combination therapy to inhibit pathogen replication in which a drug that inhibits pathogen replication by targeting a specific pathogen-encoded protein is administered in combination with a drug that inhibits pathogen replication by targeting host-encoded cdk proteins.

Abstract: Methods are provided for treating or preventing infections by obligate intracellular prokaryotes, including mycoplasma, rickettsia and chlamydia, and DNA viruses, including herpes viruses, papillomaviruses, adenoviruses and hepatitis B virus. The methods involve the administration of 3:1 complexes of 3-hydroxy-4-pyrones with gallium, e.g., gallium maltolate. Therapies incorporating gallium maltolate in combination with agents used against obligate intracellular prokaryote and DNA virus pathogens are also provided, as are multi-combination therapies designed to treat co-infection by an obligate intracellular prokaryote or DNA virus in an immunocompromised individual. These multi-combination therapies rely on the ability of gallium maltolate to complement antiviral medication regimes against both HIV and other pathogens such as herpesvirus infections, including Kaposi sarcoma, CMV retinitis and blindness, and lymphomas, in patients immunocompromised by HIV infection.

Abstract: The invention provides methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

Abstract: A3 agonists having Formula I are described herein as well as methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists.

Abstract: Provided is, among other things, a method of treating in an animal infection or neoplasm of cerebrospinal tissue characterized by a risk of death, the method comprising: (a) injecting a physiologically acceptable fluid for cerebrospinal perfusion into a first catheter into the cerebrospinal pathway, which fluid for cerebrospinal perfusion has an therapeutically effective amount an agent, the agent selected for effectiveness against the infection as identified or diagnosed; (b) withdrawing fluid at a second catheter into the cerebrospinal pathway to create a flow and flow pathway between the first and second catheters; and (c) maintaining the flow for a period of time adapted to perfuse at least 1 CSF volume.

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

Abstract: A method of preparing a human recipient for a graft from a human which includes: administering donor peripheral blood progenitor cells to the recipient, and providing a minimally ablative.

Abstract: The invention features a method of treating rheumatoid arthritis in a mammal comprising administering an agent that inhibits prostaglandin EP4 receptor (EP4) activity. Also featured is a method of identifying agents that selectively inhibit EP4 activity in vivo.

Abstract: The present invention relates to promoters, enhancers and other regulatory elements that direct expression within tumor and tissue cells with calcification potential. In particular, it relates to compositions comprising nucleotide sequences from the 5′ regulatory region, and transcriptionally active fragments thereof, that control expression of a bone sialoprotein (“BSP”). Specifically provided are expression vectors, host cells and transgenic animals wherein a BSP regulatory region is capable of controlling expression of a heterologous coding sequence, over-expressing an endogenous BSP coding sequence or an inhibitor of a pathological process or knocking out expression of a specific gene believed to be important for a calcification-related disease in tumor and tissue cells with calcification potential.