Abstract: The present invention relates to PMEA lipid conjugates and to methods of using the conjugates to treat diseases caused by viruses such as herpes, cytomegalovirus, varicella, paramyxovirus, polyoma virus, and human papillomavirus. Methods for making the PMEA lipid conjugates are also provided.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the enzyme Thimet oligopeptidase, or TOP. Also disclosed are methods of designing prodrugs by utilizing TOP-cleavable sequences within the conjugate and methods of treating patients with prodrugs of the invention.

Abstract: The present invention provides methods of identifying agents that reduce a level of active APOBEC3C in a cell. The present invention provides agents that reduce a level of active APOBEC3C in a cell; and compositions comprising the agents. The present invention further provides methods of reducing the mutation rate of a lentivirus in a cell; and methods of reducing the emergence of drug-resistant strains of lentivirus. The present invention further provides methods for treating lentivirus infections.

Abstract: In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: The invention encompasses methods of increasing platelet levels in a patient having or at risk for immune thrombocytopenia comprising co-administering a Syk kinase inhibitor and a thrombopoietin receptor agonist, and methods of treating thrombocytopenia comprising co-administering a Syk kinase inhibitor and a thrombopoietin receptor agonist to a patient in need thereof, as well as pharmaceutical compositions for use in these methods.

Abstract: The present invention provides compounds which inhibit poly(ADP-ribose) polymerase (“PARP”), compositions containing these compounds and methods for using these PARP inhibitors to treat, prevent and/or ameliorate the effects of the conditions described herein.

Abstract: The invention encompasses a series of bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

Abstract: This invention is directed to selective antagonists of A2A and/or A2B adenosine receptors having the general formula (I); to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.

Abstract: A method for reducing psychological opioid dependence includes selecting a patient addicted to an opioid and administering to the patient an opioid agonist-antagonist for at least 14 days, thereby reducing craving for the opioid in the patient. An opioid agonist-antagonist is administered in a patient needing an average adherence to a treatment protocol of at least 95 percent. A non-injectable formulation containing an agonist-antagonist also is disclosed.

Abstract: The invention encompasses a series of bicyclic heterocyclic compounds of Formula I which are inhibitors of HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

Abstract: The present disclosure provides methods for the inhibiting proliferation of tumor cells, and methods for treating solid tumor cancers in a subject by administration of 2,4-pyrimidinediamine compounds.

Abstract: The present invention relates to therapeutic combinations of [2-(6-amino-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropoxycarbonyloxymethyl ester (tenofovir disoproxil fumarate, Viread®) and (2R,5S, cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one (emtricitabine, Emtriva™, (?)-cis FTC) and their physiologically functional derivatives. The combinations may be useful in the treatment of HIV infections, including infections with HIV mutants bearing resistance to nucleoside and/or non-nucleoside inhibitors. The present invention is also concerned with pharmaceutical compositions and formulations of said combinations of tenofovir disoproxil fumarate and emtricitabine, and their physiologically functional derivatives, as well as therapeutic methods of use of those compositions and formulations.

Abstract: Tricyclic compounds according to the structure below, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed. A1 and A2 are moieties forming a five, six, or seven membered ring. L is a bond or a linker connecting a ring atom of Ar to N. X is O, S, or substituted nitrogen. Ar is aryl or heteroaryl, Q is N, +NR, or CR4. The aryl carbons may be independently substituted with substituents other than hydrogen. The compounds may include prodrug moieties covalently attached at any site.

Abstract: Methods for treating increased intraocular pressure by administering agents that interfere with activities of integrin-linked kinase. By interfering with the ability of integrin-linked kinase to couple integrin signaling to the actin cytoskeleton, aqueous humor outflow facility through the trabecular meshwork is increased and intraocular pressure is decreased.

Abstract: The present invention makes available, inter alia, methods and reagents for modulating smoothened-dependent pathway activation. In certain embodiments, the subject methods can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function mutations.

Abstract: The present disclosure provides methods for the treatment of cell proliferative disorders by administration of a RET kinase inhibitor. Cell proliferative disorders treatable by the methods include, thyroid tumors.

Abstract: Nucleotide-competing reverse transcriptase inhibitors (NcRTI) bind to the active site of HIV reverse transcriptase (RT) in competition with the next incoming nucleotide. To further investigate the impact of RT inhibitor resistance mutations on the activity of NcRTIs, the susceptibility of >6000 recent clinical isolates for a prototype compound, NcRTI-1, was determined. Over 80% of the profiled clinical isolates remained susceptible for NcRTI-1 (FC<4). No cross-resistance was observed between NcRTI-1 and currently used RT inhibitors, apart from limited cross-resistance with 3TC/FTC. Analysis of the genotype of >1700 of these viruses showed that the combination of active site mutations M184V+Y115F correlated most with resistance to NcRTI-1 (FC=75). Analysis also indicated that the K65R mutation is associated with hypersusceptibility to NcRTI-1 and that it reverses the reduced susceptibility caused by M184V. These findings were confirmed in SDM strains.

Abstract: A compound which comprises a backbone having a plurality of chiral carbon atoms, the backbone bearing a plurality of ligands each being individually bound to a chiral carbon atom of the plurality of chiral carbon atoms, the ligands including one or more pair(s) of adjacent ligands each containing a moiety selected from the group consisting of a naturally occurring nucleobase and a nucleobase binding group, wherein moieties of the one or more pair(s) are directly linked to one another via a linker chain; building blocks for synthesizing the compound; and uses of the compound, particularly in antisense therapy.

Abstract: In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: The present application describes deuterium-enriched tenofovir, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: A pharmaceutical formulation for the treatment of HIV is provided. The formulation is a combination of a nucleoside reverse transcriptase inhibitor and a nucleotide reverse transcriptase inhibitor in which the combination has an increased stability over prior art combination therapies. The invention also provides a pharmaceutical product containing the formulation.

Abstract: Prodrugs of parent drugs and methods of making and using the same are described. The prodrugs comprise an amine-containing parent drug moiety and a prodrug moiety, such as methoxyphosphonic acid or ethoxyphosphonic acid. The prodrugs may be employed in therapy for the treatment of various indications, such as pain, and in methods of decreasing the abuse potential of abuse-prone drugs and/or delaying the onset of parent drug activity and/or prolonging parent drug activity as compared to administration of a parent drug.

Abstract: In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: The present invention is to provide a composition for preventing plant diseases which comprises at least Component I and Component II, is capable of obtaining a synergic effect that cannot be expected with each single component, is capable of markedly increasing a control effect in a much smaller amount of chemicals against various plant pathogens, and causes no phytotoxicity suffering. A composition for preventing plant diseases comprises Components I and II as active ingredients. The Component I is (RS)—N—[2-(1,3-dimethylbutyl)thiophen-3-yl]-1-methyl-3-tri fluoromethyl-1H-pyrazole-4-carboxamide.

Abstract: Provided herein is a method of protecting a neuron from dysfunction induced by an HIV neurotoxin, comprising contacting the cell with a therapeutically effective dose of a dopamine D1 receptor agonist. Also provided is a method of treating or preventing HIV-1 associated dementia (HAD) in a subject in need of such treatment or prevention, comprising administering to the subject a therapeutically effective dose of a dopamine D1 receptor agonist and estrogenic compound.

Abstract: The present invention is directed to a compound of formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof, and methods for treating inflammatory and serine protease mediated disorders.

Abstract: This invention provides methods, novel formulations and kits to reduce the toxicity of anticancer drugs. Disclosed are therapeutics and treatment methods employing anticancer drags that exhibit a known toxicity, including, for example, adriamycin, campthothecin, and the like, chemically linked to a phosphonoformic acid partial ester resulting in a novel formulation that significantly decreases drug-related toxicity, enhances synergy with other chemotherapeutic drugs and provides increased efficacy against drug-resistant cancers.

Abstract: The invention is directed to TRPM8 antagonists of Formula (I). More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating TRPM8-mediated disorders. Pharmaceutical and veterinary compositions and methods of treating pain and various other disease states or conditions using compounds of the invention are also described.

Abstract: An object of the present invention is to provide an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastric diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc. This problem can be solved with a pyrrolopyrimidine or pyrrolopyridine derivative substituted with a cyclic amino group represented by formula [I] below which has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

Abstract: The present invention relates to phosphonated fluoroquinolones, antibacterial analogs thereof, and methods of using such compounds. These compounds are useful as antibiotics for prevention and/or the treatment of bone and joint infections, especially for the prevention and/or treatment of osteomyelitis.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Abstract: The invention relates to a combination comprising a quinoline compound or its sail, according to general formula (I) and at least one HIV infection therapeutic agent selected from the group consisting of entry inhibitors, reverse-transcriptase inhibitors, strand-transfer inhibitors, protease inhibitors, and maturation inhibitors. Said combination has therapeutic synergy in the treatment of an HIV infection compared with the quinoline compound, or HIV infection therapeutic agent alone.

Abstract: N-substituted 5-hydroxypyrimidin-6-one-4-carboxamides of formula: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R1, R2, R3 and R4 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

Abstract: The present invention relates to compounds that inhibit phosphatases, compositions thereof, and methods of using those compounds and compositions for treating diseases.

Abstract: The invention relates to compounds of the formula 1 or a pharmaceutically acceptable salt, prodrug or hydrates thereof, wherein X, L, R1, R2, R3 and R4 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula 1.

Abstract: Novel deazapurines are disclosed which are useful for the treatment of adenosine receptor stimulated diseases.

Abstract: This invention generally relates to pyrazolo pyrimidine derivatives useful as inhibitors of short chain dehydrogenase/reductase (SDR) family of NAD(P)(H) dependent oxido-reductases. The invention further relates to pharmaceutical compositions and methods of preventing or treating disease with 1H-Pyrrolo[2.3-d]pyrimidine derivatives. More specifically, the invention relates to a 1H-Pyrrolo[2.

Abstract: The present invention features compounds that are HIV integrase inhibitors and may be useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

Abstract: A novel method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided.

Abstract: Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of cytopathic diseases. Cytopathic diseases may be caused by a variety means such as viral infections like HIV and AIDS, or the development of neoplasms in a mammalian subject. The methods and compositions of the invention are effective for inhibiting de novo HIV infections upregulating viral expression from latent provirus, inhibiting HIV-induced cytopathic effects, down regulating the HIV receptor, increasing Th1 cytokine expression, decreasing Th2 cytokine expression, increasing ERK phosphorylation, inducing apoptosis in malignant cells, inducing remission, maintaining remission, as chemotherapeutic agents, as well as for decreasing symptoms of cytopathic diseases and opportunistic infections that may accompany such diseases.

Abstract: The present intention features compounds that are HIV integrase inhibitors and may be useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

Abstract: The invention encompasses a series of pyrimidinone compounds which inhibit HIV integrase and thereby prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses intermediates useful for making the pyrimidone compounds. Additionally, pharmaceutical compositions and methods for treating those infected with HIV are encompassed.

Abstract: This invention relates to the fields of organic chemistry, pharmaceutical chemistry, biochemistry, molecular biology and medicine. In particular it relates to compounds that activate RNaseL, and to the use of the compounds for treating and/or ameliorating a disease or a condition, such as a viral infection.

Abstract: A new crystal form of adefovir dipivoxil {9-[2-[bis(pivaloyloxy)-methoxy]-phosphinyl]-methoxyl]-ethyl]-adenime} and its composition is disclosed, as is a method to prepare the crystal comprising placing adefovir dipivoxil in a round bottom flask, adding organic solvent and dissolivng adefovir dipivoxil ultrasonically to form and adefovir dipivoxil solution, and spray drying the adefovir dipivoxil solution.

Abstract: The present invention concerns combinations of a pyrimidine containing NNRTI with nucleoside reverse transcriptase inhibitors and/or nucleotide reverse transcriptase inhibitors useful for the treatment of HIV infected patients or for the prevention of HIV transmission or infection.

Abstract: The present invention features compounds that are HIV integrase inhibitors and may be useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

Abstract: [Object] Is to provide a novel compound having an anti-viral activity, particularly a HIV integrase inhibitory activity, and an agent, particularly an anti-HIV agent. [Solving means] A compound represented by the formula: (wherein Z1 is NR4 (R4 is hydrogen, optionally substituted lower alkyl etc.), O or CH2; Z2 is optionally substituted lower alkylene or optionally substituted lower alkenylene, each may be intervened by a heteroatom group selected from group consisting O, S, SO, SO2, NR5 (R5 is selected independently from the same substituent group of R4)—N? and ?N—; R1 is hydrogen or lower alkyl; X is a single bond, a heteroatom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene each may be intervened by the heteroatom group; R2 is optionally substituted aryl; R3 is hydrogen, halogen, hydroxy, optionally substituted alkyl group etc.

Abstract: A novel method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided.

Abstract: Compounds represented by the formula: A is (CH2)nR2, —CH?CH2, CH2—CH?CH2, O(CH2)nR2, CH(OH)CH3, CH(OH)CH2OH, CH2—CH(OH)CH3, CH2CH(OH)CH2OH, or CH(OH)CH(OH)CH3, R,R1 individually is H, NH2OH, Cl, Br, I, aryl, substituted aryl, heterocycle, NR3R4, OR3 or SR3, R2 is H, OH, F, N3, NH2, CO2H, SH, alkyl, substituted alkyl, S-alkyl, O-acyl, CONH2, or CONH-alkyl, n is 1-3, y is O, S or NH, W is O or S, Z, Z? individually is OR3, OR4, O(CH2)m—O—(CH2)xCH3, NH—CH(alkyl)CO2R3, alkyl, substituted alkyl, OCH2CH2S—C(O)CH3, OCH2CH2S—C(O)CH(CH3)2, OCH2CH2S—C(O)C(CH3)3, OCH2CH2—SC(O)aryl, OCH2CH2—S—S—OCH2CH2OH, OCH2OC(O)C(CH3)3, OCH2—O—C(O)OCH(CH3)2, or OCH2—O—C(O)CH(CH3)2 R3, R4 individually is H, alkyl, substituted alkyl, aryl, or substituted aryl; Both R3 and R4 can form a monocyclic ring of 4-7 atoms with N or optionally a further heteroatom in the ring; m is 1-3, x is 0-19; and pharmaceutically acceptable salts thereof and prodrugs thereof are provided.

Abstract: The present invention relates to compounds according to the general formula wherein the dotted lines denote a single bond which is optionally present, with 2 dotted lines denoting a double bond; wherein, in case no double bond is present and a free valence exists, this valence is occupied by H; and wherein the symbols have the meanings defined in the text, or a pharmaceutically acceptable salt thereof, and which lend themselves for the manufacture of drugs useful in the inhibtion of DNA methylation, the inhibition of DNA methyltransferases, and may therefore be useful for the manufacture of pharmaceuticals for the treatment of developmental disorders such as Prader-Willi-Syndrome, Angelman-Syndrome (Happy Puppet Syndrome), Beckwith-Wiedemann-Syndrome, and proliferative diseases, such as coronary restenosis and neoplastic diseases, particularly colon carcinoma, familiary adenomatous polyposis carcinoma and hereditary non-polyposis colorectal cancer, prostate carcinoma, melanoma, non-Hodgkin lymphoma, acu