Abstract: An antisense oligomer capable of inhibiting production of interleukin-15 (IL-15) by hybridizing to the mRNA of IL-15. Also disclosed is a pharmaceutical composition for treating diseases associated with the production of IL-15 comprising said antisense oligomer and a pharmaceutically acceptable carrier.

Abstract: The invention relates to compositions comprising oligomers antisense to bacterial 16S or 23S rRNA and capable of selectively modulating the biological activity thereof, and methods for their use. More particularly, the invention relates to antisense oligomers directed to 16S or 23S rRNA found in one or more particular bacteria, or generally conserved among bacteria in general, and to pharmaceutical compositions and methods of treatment comprising the same.

Abstract: This invention relates to compounds of the general formula: 1

Abstract: This invention relates to bicyclic heterocycles that inhibit cyclin-dependent kinase or tyrosine kinase enzymes, or both, and as such are useful to treat cell proliferative disorders such as angiogenesis, atherosclerosis, restenosis, and cancer as well as immunological disorders such as asthma, rheumatoid arthritis, autoimmune diabetes, and graft rejection associated with transplant surgery in mammals.

Abstract: The present invention relates to a composition for and a method of treating hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, hepatitis D virus (HDV) infection or a proliferative disorder in a patient using an effective amount of a compound selected from the group consisting of formulas [I]- [IV] below and mixtures of two or more thereof: 1

Abstract: This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Y12 receptor antagonist compound, wherein said amount is effective to bind the P2Y12 receptors on platelets and inhibit ADP-induced platelet aggregation. The P2Y12 receptor antagonist compounds useful for this invention include mononucleoside polyphosphates and dinucleoside polyphosphates of general Formula I, or salts thereof. The present invention also provides novel compositions comprising mononucleoside polyphosphates and dinucleoside polyphosphates according to Formula Ia and Ib.

Abstract: The invention provides crystalline forms of adefovir dipivoxil and methods to prepare the crystals. The compositions and methods of the present invention have desirable properties for large scale synthesis of crystalline adefovir dipivoxil or for its formulation into therapeutic dosages. Invention compositions include an anhydrous crystal form of adefovir dipivoxil.

Abstract: Tricyclic triazolobenzazepine derivatives in the form or a prodrug are provided. The compounds according to the present invention are those represented by formula (I) and pharmacologically acceptable salts and solvates thereof. The compounds are useful as antiallergic agents and exhibit excellent bioavailability.

Abstract: The present invention provides a method of treating amyotrophic lateral sclerosis and other neurologic diseases by administering a compound of the formula where R is selected from the group consisting of (C6H4)CO2H, (C6H4)CO2CH3, (C6H4)(3,5-OH)2, (C6H4)CH2OH, (C6H4)OCH3, (C6H4)PO3H, (C6H4)SO3H, (C6H4)(3-NO2-4-OH), (C6H4)NO2, (C6H4)OPO3H, (C6H4)OSO3H, (C6H4)CH2CO2H, (C6H4)NH2, and (C6H4)CONH2. Also provided is a method for preserving donor organs using a solution comprising the instant compounds.

Abstract: Methods, formulations and kits are described for resuscitating a patient suffering from cardiac arrest, for enhancing the efficacy of cardiopulmonary resuscitation, for treating post-resuscitation hypotension, and for reducing the incidence of ventricular arrhythmias and myocardial dysfunction in a patient following cardiopulmonary resuscitation. Prior methods and agents often cause inotropic or chronotropic effects, which can lead to undesirable post-resuscitation myocardial dysfunction. The invention comprises administering a therapeutically effective amount of an &agr;2-receptor agonist that does not cross the blood-brain barrier, such as &agr;-methylnorepinephrine, to enhance cardiopulmonary resuscitation.

Abstract: This invention relates to novel fused heterocycles which are useful as antagonists of the &agr;v&bgr;3 and related integrin receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

Abstract: Compounds that are agonists of P2 purinoceptors, such as 5-adenylylimidodiphosphate, are used to treat conditions such as pain, hormonal imbalance, high blood pressure, thermoregulation, respiration, learning, patter recognition and memory.

Abstract: Photochemical tissue bonding methods include the application of a photosensitizer to a tissue, e.g., cornea, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for wound repair, or other tissue repair.

Abstract: The present invention concerns antiviral compounds, their methods of preparation and their compositions, and use in the treatment of viral infections. More particularly, the invention provides imidazopyridine and imidazopyrimidine derivatives (Formula I) for the treatment of respiratory syncytial virus infection.

Abstract: The present invention provides for pyridoxine phosphonate analogues such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)alkylphosphonates, and (2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)azaalkylphosphonates) and to pyridoxine malonate analogues, such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridylmethyl)malonates), pharmaceutical compositions, and methods for treatment of cardiovascular and related diseases, and diabetes mellitus and related diseases.

Abstract: The present invention relates to methods for stimulating bone formation in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype agonist.

Abstract: The invention relates to pharmaceutical compositions for topical administration comprising a topically acceptable antiviral substance and an antiinflammatory glucocorticoid in a pharmaceutically acceptable carrier. The pharmaceutical composition can be used in the prophylactic and curative treatment of herpesvirus infections in mammals including man. The invention also relates to the use of a combination of a topically acceptable antiviral substance and an antiinflammatory glucocorticoid for the manufacture of a medicament for said prophylactic and curative treatment.

Abstract: A method of treating a cerebrovascular disease, particularly stroke, is described. A method of treating a cerebrovascular disease includes administering pyridoxal-5′-phosphate, pyridoxal, pyridoxine, pyridoxamine, 3-acylated analogues of pyridoxal, 3-acylated analogues of pyridoxal-4,5-aminal, pyridoxine phosphonate analogues, or pharmaceutical compositions thereof.

Abstract: The invention relates to polymeric conjugates of 20-O-[glycyl-aminoacyl-glycyl]-camptothecins and a process for producing the same.

Abstract: In accordance with the present invention there is provided a nucleoside analogue of formula (I) or (Ia) which is useful as an antiviral agent.

Abstract: A composition for preventing and treating milk fever in freshening cows, and a method of administering the composition. The basic composition is a mixture of water, calcium chloride, propylene glycol, B vitamins and minerals. The calcium content is lower than conventional calcium treatments used for this purpose. The propylene glycol gives the cow an energy boost and sweetens the taste so the cow does not object to it as it does to conventional gels and liquids. The B vitamins stimulate the cow's appetite. The minerals replace minerals lost in the milk and also help the cow absorb calcium. The composition of the present invention is in a liquid form and is preferably administered using a 200-300 cc drench gun. The end of the dispensing tube of the drench gun is placed between the teeth and cheek of the cow near the receptors that stimulate the esophageal groove reflex.

Abstract: It consists of using a precursor compound of cyclic AMP, or an inhibitor compound of the enzymes of the Phosphodiesterases family, or a stimulating compound of the enzymes of the Adenyl-Cyclase family, or an agonist compound of the &bgr;-adrenergic receptors to which arachidonic acid or a prostaglandin is added. The composition object of the invention can be presented mixed with mineral fertilizers (such as amonic nitrate, monopotassium phosphate, etc.), with phytoregulators (such as cytoquinines, auxines, giberelines, polyamines, n-ethanolamines, sugars . . . ) or with any type of phytosanitary product (such as fungicides, herbicides etc.). The composition object of the invention can be formulated with tensoactive agents (such as Tween 80), moistening agents etc. The composition object of the invention can be applied to any species of plant and at any point in its life cycle.

Abstract: The invention relates to the method of use of compounds with B3-agonist activity for inhibiting uterine contractions, preventing or slowing down premature labor, or for the treatment and/or prophylaxis of dysmenorrhea.

Abstract: Chemical compounds comprising nucleoside phosphoramides, their preparation and their therapeutic use in treating viral infections, particularly HIV and HBV are disclosed. The compounds contain a substituted adenine analogue moiety comprising 2-amino-6-(cyclopropylamino)-9H-purin-9-yl. The compounds show both anti-viral activity and acid stability. Salts and esters of the phosphoramidates are included. A representative compound is (1S, 4R), -4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol1 O-[phenyl-(methoxy-L-alaninyl)]-phosphate.

Abstract: This invention relates to compounds, pharmaceutical compositions, and methods of using the disclosed compounds for inhibiting PARP.

Abstract: Novel purine compounds of the following structure and their use as fructose-1,6-bisphosphatase inhibitors is described.

Abstract: Antiviral compounds have the formula wherein m is zero, 1, 2 or 3; n is from 1 to 8, preferably 1, 2 or 3; most preferably 1 or 2; R is independently selected from the group consisting of  provided that all R may not be R1 is independently selected from the group consisting of hydroxyl and hydrogen; R2 is independently selected from the group consisting of oxygen and sulfur; or water soluble salts thereof.

Abstract: Substituted triols are prepared by reducing appropriately substituted carboxylic esters. The substituted triols can be used as active substances in medicaments.

Abstract: Disclosed are novel prodrugs represented by the following structural formula: 1

Abstract: A compound represented by the formula: wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; R2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

Abstract: Disclosed are novel prodrugs represented by the following structural formula; Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Abstract: A phosphonate nucleotide compound represented by formula (I): (wherein R1 is a C1-C6 alkyl group or the like, R2 is a hydrogen atom, a C1-C4 alkyl group substituted by one or more halogen atoms or the like, R3 is a hydrogen atom, a C1-C4 alkyl group substituted by one or more halogen atoms or the like, R4 is a hydrogen atom, a C1-C4 alkyl group substituted by one or more halogen atoms and X is a carbon atom or a nitrogen atom), a salt thereof, a hydrate thereof or a solvate thereof, as well as a medicament containing the same. It is useful as an antiviral agent for human immunodeficiency virus, herpes simplex virus, hepatitis B virus or the like and as an antitumor agent.

Abstract: Quinoxalinedione derivatives of formula (I) ##STR1## are described, and their use in pharmaceutical agents.

Abstract: A compound of formula I: ##STR1## or a pharmaceutically acceptable salt, hydrate, ester, solvate, prodrug, metabolite, stereoisomer, or mixtures thereof, wherein:Y represents the atoms necessary to form a fused 5- to 6-membered, aromatic or non-aromatic, heterocyclic ring containing at least one nitrogen heteroatom in a 1,3-relationship with the nitrogen atom depicted in formula I, wherein Y may be unsubstituted or substituted with at least one alkyl, alkenyl, cycloalkyl, cycloalkenyl, aralkyl, aryl, double bonded oxygen, or --COOR.sup.5 group, or a moiety selected from the group consisting of: ##STR2## wherein R.sup.5 and R.sup.7 are independently hydrogen or alkyl, alkenyl, cycloalkyl, cycloalkenyl, aralkyl, or aryl.

Abstract: This invention is directed to transition-state analog compounds and to the use of said compounds as inhibitors of nucleoside hydrolase and transferase enzyme activity of parasites. This invention is further directed to the use of said compounds to treat infections and diseases caused by certain bacterial and plant toxins.

Abstract: The present invention relates to 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives having antiviral activity, represented by formula [I]: ##STR1## wherein B represents a base selected from the group consisting of purine, azapurine and deazapurine, which may be substituted with halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, alkylamino, hydroxyl, hydroxyamino, aminoxy, alkoxy, mercapto, alkylmercapto, aryl, aryloxy or cyano; and R represents a hydrogen atom or a phosphoric acid residue, and to a process for the production and use thereof.

Abstract: The present invention relates to water soluble, camptothecin derivatives of formula (I). ##STR1## wherein A represents a moiety of the formula (IIA), (IIB) or (IIC): ##STR2## X is selected from the group consisting of alkyl, aryl, (CH.sub.2).sub.m OR.sup.1, (CH.sub.2).sub.m SR.sup.1 and (CH.sub.2).sub.m NR.sup.1 R.sup.2 wherein m is an integer of 0 to 6, and R.sup.1 and R.sup.2 are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.

Abstract: A 1,2,3,4-tetrahydroquinoxalinedione derivative represented by the following formula (I) or salt thereof, an NMDA-glycine receptor and/or AMPA receptor antagonist or kainic acid neurotoxicity inhibitor containing the derivative or salt. In addition, a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier: ##STR1## wherein the substituents are as described in the specification.

Abstract: The present invention is directed to new phospholipid derivatives of acyclovir and ganciclovir that link a lipid moiety, which represents a substituted C3 backbone, to acyclovir or ganciclovir via phosphate or thiophosphate. The compounds are particularly suitable for the therapy of viral infections.

Abstract: A compound represented by the formula: ##STR1## wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R.sup.1 represents an optionally substituted hydrocarbon group; R.sup.2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

Abstract: Neuroprotective agents have forumula I ##STR1## wherein a is a ring of 6 to 8 members; n and n' are 1 or 2,R.sub.2 is hydrogen or oxygen of carbonyl,R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 independently include hydrogen, alkyl, aralkyl, and carboxyalkyl.

Abstract: Methods for treatment of conditions of abnormally increased intraocular pressure, particularly those caused by glaucoma, by administration of phosphonylmethoxyalkyl nucleoside analogs are provided. Compositions formulated and packaged for intraocular administration for use in the methods are also provided. Administration of the compound may be by intravitreal injection, aqueous humor injection, injection into the external layers of the eye, such as subconjunctival injection or subtenon injection, or may be, when penetrating derivatives are used, by topical application to the eye. The degree of reduction in pressure is dosage-dependent, and significant reduction in pressure is obtained. A single injection can produce prolonged, and perhaps permanent, lowering of the intraocular pressure.

Abstract: Resolved enantiomers of the formula ##STR1## wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.

Abstract: The use of a compound of formula (A): ##STR1## or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing in the manufacture of a medicament for use in the treatment (including prophylaxis) of HHV-7 infection.

Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure -OC(R.sup.2).sub.2 OC(O) X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, axido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.

Abstract: Phosphonate-nucleotide ester compounds of the formula (I) have excellent antiviral activity and antineoplastic activity. Further, they can be orally administered. ##STR1## wherein ring A represents ##STR2## wherein R.sup.1 and R.sup.2 independently represent hydrogen, halogen, hydroxyl, mercapto, C.sub.6 -C.sub.10 arylthio or amino; R.sup.3 represents C.sub.1 -C.sub.4 alkyl or ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; R.sup.4 represents ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; X, Y and Z independently represent methyne or nitrogen atom; or a pharmaceutically acceptable salt thereof.

Abstract: Imidazopyridine derivatives ad pharmacologically acceptable salts having antagonistic properties towards angiotensin II can be used for the treatment of hypertension, aldosteronism and cardiac insufficiency.

Abstract: The invention provides a synthetic bone precursor material comprising amorphous calcium phosphate and a constituent that inhibits the crystallisation of calcium hydroxyapatite to amorphous calcium phosphate. The synthetic bone precursor may comprise a material of formula CaxMgyPO4 wherein Mg acts as an inhibitor for crystallisation. Other crystallisation inhibitors such as pyrophosphate may be present. The inhibitor is capable of dissolving in physiological saline. Loss of inhibitor from the precursor allows crystallisation of hydroxyapatite. The invention relates to use of a synthetic bone precursor to form bone in vivo, by a transformation of the amorphous precursor material to crystalline hydroxyapatite bone material by the leaching action on inhibitory ions body fluids. it is envisaged that the material will be useful in facilitating bone repair, inducing bone formation or assisting in the attachment of prostheses.

Abstract: Oligonucleotide surrogates comprising a plurality of cyclobutyl moieties covalently joined by linking moieties are prepared and used as antisense diagnostics, therapeutics and research reagents. Methods of synthesis and use of both the oligonucleotide surrogates and intermediates thereof are disclosed.

Abstract: The present invention relates to [1,2,4]triazolo[4,3-a]quinoxalinone compounds of the formula ##STR1## wherein R.sup.1 is POX'X" or alkyl substituted with COX' or POX'X", and X' and X" independently are hydroxy or alkoxy, and R.sup.7 is trifluoromethyl, and R.sup.6, R.sup.8 and R.sup.9 independently are piperidino, piperazinyl, morpholino, or thiomorpholino, which rings are optionally substituted with one or more of phenyl or C.sub.1-6 -alkyl and phenyl optionally being substituted with C.sub.1-6 -alkoxy; and pharmaceutically acceptable salts thereof. The compounds of the present invention are useful in the treatment of indications caused by hyperactivity of the excitatory neurotransmitters.