Ethynyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides compounds of Formula (I): (Chemical formula should be inserted here as it appears on abstract in paper form) (I) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and pro-drugs of said compounds, wherein each of R, R 1 , X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 18 , R 19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.

USE OF 4'-THIO-2'-DEOXYNUCLEOSIDES AS ANTI ORTHOPOXVIRUS AGENTS

Compound represented by the formulae: 2. The method of wherein the orthopoxvirus comprises variola virus.4. The method of wherein said patient is suffering from smallpox claim 3 , cowpox claim 3 , monkeypox or camelpox.5. The method of wherein said wherein said patient is suffering from smallpox.6. The method of wherein said patient is suffering from monkeypox.7. The method of wherein said wherein said patient is suffering from cowpox.8. The method of wherein said wherein said patient is suffering from camelpox.9. The method of which further comprises administering a therapeutic agent in addition to said at least one compound.10. The method of which further comprises administering a therapeutic agent in addition to said at least one compound.13. The method of wherein said wherein said patient is suffering from smallpox. This invention was supported by Grant AI057175 from National institute of health and the US Government has certain rights in the invention.The present disclosure relates to certain pyrimidine nucleosides that are useful as inhibitors of orthopoxviruses including but not limited to smallpox. The present disclosure relates to methods of using the compounds for treating patients suffering, from diseases caused by orthopoxvirus infections.Orthopoxviruses include variola, cowpox, monkeypox and camelpox. Within the orthopoxvirus family variola virus, the causative agent of smallpox, is very transmissible by the air from person to person. All over the world a major population is highly susceptible to this virus. Smallpox has high morbidity and about 30% mortality. Since this disease has not been in occurrence for at least two decades, the diagnosis would be very difficult especially in a major outbreak. Currently, there is a vaccine which can be effective in the first few days of outbreak, but there is no approved drug to treat smallpox. In a post 911 world, we are living in a dangerous phase of terrorism. In a scenario of a possible bioterrorist attack ...

ANTI-VIRAL TREATMENT AND ASSAY TO SCREENFOR ANTI-VIRAL AGENT

The present disclosure relates to novel compounds of formulas (1) through (19) and to a method for treating humans infected with a virus including various respiratory viruses such as members of the Paramyxoviridae family (respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), measles virus, and mumps virus) with a compound of formulas (1) through (19). The present disclosure also relates to a cytopathic effect (CPE)-based assay that will assess virus-induced CPE for screening of compounds for treating viral diseases or inhibiting a virus. 2. The method of wherein the virus is a respiratory virus.3. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 1 , human metapneumovirus claim 1 , human parainfluenza virus claim 1 , measles virus claim 1 , and mumps virus.4. The method of wherein the virus is respiratory syncytial virus.6. The method of wherein the virus is a respiratory virus.7. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 5 , human metapneumovirus claim 5 , human parainfluenza virus claim 5 , measles virus claim 5 , and mumps virus.8. The method of wherein the virus is respiratory syncytial virus.9. A method for screening for compounds for use as an anti-viral agent against a virus which comprises obtaining frozen cells infected with said virus claim 5 , thawing said infected cells and mixing said infected cells with uninfected cells of the same type as the infected cells claim 5 , contacting the mixture of said infected cells and uninfected cells with a compound to be screened and determining the viability of said cells.10. The method of wherein the virus is a respiratory virus.11. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 9 , human metapneumovirus claim 9 , human parainfluenza virus claim 9 , measles virus claim 9 , and mumps virus. ...

Compounds and Methods for Altering Lifespan of Eukaryotic Organisms

Provided are compounds which generally have a triketone structure. Examples of the compounds include derivatives of 1,3-cyclohexanedione, such as: 1,3-cyclohexanedione, 2-propanoyl-5-cyclohexyl-; 1,3-cyclohexanedione, 2-propanoyl-5-[4-fluorophenyl]-; 1,3-cyclohexanedione, 2-acetyl-5-[thien-2-yl]-; 1,3-cyclohexanedione, 2-acetyl-5-butyl-; and 1,3-cyclohexanedione, 2-propanoyl-5-[bicyclo[2.2.1]hept-2-en-5-yl]-. The compounds can be used to alter the lifespan of eukaryotic organisms and treat inflammation. 11.) The compound of claim 1 , wherein the compound is selected from the following: 1 claim 1 ,3-cyclohexanedione claim 1 , 2-acetyl-5-[4-(N claim 1 ,N-dimethylamino)phenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-cyclopentanecarbonyl-5-[4-methylphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-cyclopentanecarbonyl-5-[4-(1-methylethyl)phenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-cyclopentanecarbonyl-5-[4-chlorophenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-cyclopentanecarbonyl-5-[fur-2-yl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-isobutyryl-5-[fur-2-yl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-benzoyl-5-[2-chloro-6-fluorophenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-propanoyl-5-[4-methoxyphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-acetyl-5-[3 claim 1 ,4-dimethoxyphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-benzoyl-5-[3 claim 1 ,4-dimethoxyphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-acetyl-5-[naphth-2-yl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-benzoyl-5-[2 claim 1 ,4-dichlorophenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-propanoyl-5-[2 claim 1 ,4 claim 1 ,5-trimethoxyphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-benzoyl-5-[4-fluorophenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-benzoyl-5-[4-methoxyphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-benzoyl-5-[fur-2-yl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2-cyclopropanecarbonyl-5-[4-methoxyphenyl]-; 1 claim 1 ,3-cyclohexanedione claim 1 , 2- ...

TRIAZOLOPYRIDAZINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF

The present invention provides novel LRRK2 kinase inhibitors and methods of treating disease states using these inhibitors.

TREATMENT OF NEURODEGENERATIVE DISEASES, CAUSATION OF MEMORY ENHANCEMENT, AND ASSAY FOR SCREENING COMPOUNDS FOR SUCH

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, and Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning. 1. (canceled)3. The method of claim 2 , wherein in formula (2) Y is S.4. The method of claim 2 , wherein in formula (2) Ris H.5. The method of claim 2 , wherein in formula (2) Ris H.6. The method of claim 2 , wherein in formula (2) Ris selected from the group consisting of H claim 2 , substituted or unsubstituted alkyl claim 2 , and substituted or unsubstituted aryl claim 2 , or R claim 2 , Rcombine with the N atom to which both groups are covalently linked as to form the morpholin-1-yl group.8. The method of claim 2 , wherein in formula (12) at least one occurrence of Ris selected from the group consisting of H claim 2 , halogen and alkoxy claim 2 , or two adjacent Rgroups on the phenyl ring combine as to form the —CHOCH— group.9. The method of claim 2 , wherein Ris H.10. The method of claim 2 , wherein Ris substituted or unsubstituted aryl.11. The method of claim 2 , wherein the carbon labeled as β is not further substituted with a methyl group.12. The method of claim 2 , wherein the carbon labeled as β is further substituted with a methyl group.14. The method of claim 2 , wherein the neurodegenerative disease is at least one selected from the group consisting of Alzheimer's Disease claim 2 , Parkinson's Disease claim 2 , amyotrophic lateral sclerosis claim 2 , spinal muscular atrophy claim 2 , brain traumatic injury and associated neurodegeneration claim 2 , vascular dementia claim 2 , Huntington's ...

Treatment of neurodegenerative diseases, causation of memory enhancement, and assay for screening compounds for such

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning.

SMALL MOLECULES THAT ENHANCE THE ACTIVITY OF OLIGONUCLEOTIDES

Methods of administering an oligonucleotide of interest into a cell in vitro or in vivo are described. In the methods, a small organic compound active agent is concurrently administered to the cell in an amount effective to increase the delivery of the oligonucleotide into the cell, and/or increase the activity of said oligonucleotide in the cell. Compositions useful for carrying out the method are also described. 2. The method of claim 1 , wherein said cell is a mammalian cell.3. The method of claim 1 , wherein said method is carried out in vitro or in vivo.4. The method of claim 1 , wherein said method is carried out by administering said oligonucleotide to a subject in need thereof claim 1 , and concurrently administering said active agent to said subject.5. The method of claim 1 , wherein said active agent is administered after said oligonucleotide.6. The method of claim 1 , wherein said oligonucleotide is single stranded.7. The method of claim 1 , wherein said oligonucleotide is from 2 claim 1 , 4 claim 1 , 6 or 8 to 100 or 200 nucleotides in length.8. The method of claim 1 , wherein said oligonucleotide is negatively charged.9. The method of claim 1 , wherein said oligonucleotide is an antisense oligonucleotide.10. The method of claim 1 , wherein said oligonucleotide is a splice switching oligonucleotide.12. (canceled)13. (canceled)15. The composition of claim 14 , wherein said oligonucleotide is single stranded.16. The composition of claim 14 , wherein said oligonucleotide is from 2 claim 14 , 4 claim 14 , 6 or 8 to 100 or 200 nucleotides in length.17. The composition of claim 14 , wherein said oligonucleotide is negatively charged.18. The composition of claim 14 , wherein said oligonucleotide is an antisense oligonucleotide.19. The composition of claim 14 , wherein said oligonucleotide is a splice switching oligonucleotide. This application claims the benefit of U.S. provisional patent application Ser. No. 62/019,549, filed Jul. 1, 2014, the disclosure of ...

TREATMENT OF NEURODEGENERATIVE DISEASES, CAUSATION OF MEMORY ENHANCEMENT, AND ASSAY FOR SCREENING COMPOUNDS FOR SUCH

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning. 1. (canceled)3. The method of claim 1 , wherein in formula (2) Y is S.4. The method of claim 1 , wherein in formula (2) Ris H.5. The method of claim 1 , wherein in formula (2) Ris H.6. The method of claim 1 , wherein in formula (2) Ris selected from the group consisting of H claim 1 , substituted or unsubstituted alkyl claim 1 , and substituted or unsubstituted aryl claim 1 , or R claim 1 , Rcombine with the N atom to which both groups are covalently linked as to form the morpholin-1-yl group.8. The method of claim 1 , wherein in formula (12) at least one occurrence of Ris selected from the group consisting of H claim 1 , halogen and alkoxy claim 1 , or two adjacent Rgroups on the phenyl ring combine as to form the —CHOCH— group.9. The method of claim 1 , wherein in formula (12) Ris H.10. The method of claim 1 , wherein in formula (12) Ris substituted or unsubstituted aryl.11. The method of claim 1 , wherein in formula (12) the carbon labeled as β is not further substituted with a methyl group.12. The method of claim 1 , wherein in formula (12) the carbon labeled as β is further substituted with a methyl group.14. The method of claim 1 , wherein the compound is administered to the patient as part of a pharmaceutical composition further comprising at least one pharmaceutically acceptable excipient.15. The method of claim 1 , wherein the compound is administered to the patient by at least one route selected ...

Benzo Annulenes as Antiviral Agents

The present disclosure is concerned with benzo annulene compounds that are capable of inhibiting a viral infection and methods of treating viral infections such as, for example, chikungunya, Venezuelan equine encephalitis, dengue, influenza, and zika, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

TREATMENT OF NEURODEGENERATIVE DISEASES, CAUSATION OF MEMORY ENHANCEMENT, AND ASSAY FOR SCREENING COMPOUNDS FOR SUCH

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning.

Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages

The present invention provides for the preparation and use of ribo- and deoxyribo-nucleosides and polynucleotide analogs. The polynucleotide analogs are made of polynucleosides which contain sulfonate and sulfonamide linkages.

Triazolopyridazine compounds, use as inhibitors of the kinase lrrk2, and methods for preparation thereof

Substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and pro-drugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.

Use of '-thio-2'-deoxynucleosides as anri orthopoxvirus agents

Compound represented by the formulae: wherein each R individually is H or aliphatic acyl or aromatic acyl group; X is selected from the group consisting of hydrogen, fiuoro, chloro, bromo, iodo, alkoxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, monoalkylamino, dialkylamino, cyano, aryl and nitro; pharmaceutically acceptable salts thereof, prodrugs thereof and mixtures thereof are used as inhibitors of orthopoxviruses and for treating patients suffering from an orthopoxvirus infection such as, but not limited to, smallpox, cowpox, monkeypox and camelpox.

Activating c1- secretion

Compounds represented by formula (I), wherein A is a 5 or 6-membered unsaturated heterocyclic ring containing at least one N atom; B is (a), NO2, N(R2)2, X2 is O, NH, NR, CH2, CHR or CR2, each R individually is alkyl, cycloalkyl, aryl, alkaryl and aralkyl, each R2 individually is H, alkyl, cycloalkyl, aryl, alkaryl, and aralkyl; Y is a halogen; alkythio group or nitrogenous moiety, are useful for activating Cl- secretion, and can be used for treating cystic fibrosis.

Treatment of neurodegenerative diseases, causation of memory enhancement, and assay for screening compounds for such

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, and Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning.

Use of 4'-thio-2'-deoxynucleosides as anti orthopoxvirus agents

Azo-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides compounds of Formula (I): (Chemical formula should be inserted here as it appears on abstract in paper form) (I) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19, and n is selected independently and as defmed herein. Compositions comprising such compounds are also pro-vided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing dieases or disorders such as viral infections and virus-related disorders.

Azo-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

Ethynyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides com-pounds of Formula (I): (Chemical formula should be in-serted here as it appears on abstract in paper form) (I) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and pro-drugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compo-sitions comprising such compounds are also provided. The compounds of the invention are effective as in-hibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing dieas-es or disorders such as viral infections and virus-related disorders.

Anti-viral treatment and assay to screen for anti-viral agent

The present disclosure relates to novel compounds of formulas (1) thorugh (19) and to a method for treating humans infected with a virus including various respiratory viruses such as members of the Paramyxoviridae family (respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), measles virus, and mumps virus) with a compound of formulas (1) through (19). The present disclosure also relates to a cytopathic effect (CPE)-based assay that will assess virus-induced CPE for screening of compounds for treating viral diseases or inhibiting a virus.

Ethenyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

Gene delivery compounds

Compounds having the structure (I) wherein R1, R2 and R3 are each independently a CO-12 substituent selected from the group consisting of: hydrogen, a heteroatom, alkyl, alkenyl, alkynyl, heteroatom substituted alkyl, heteroatom substituted alkenyl, heteroatom substituted alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl; where the heteroatom is selected from the group consisting of: N, O and S; and where (A) is a single or double bond between N and R3. Further the CO-12 substituent is linear, branched or cyclic and optionally includes a pendant moiety selected from the group consisting of: carbonyl, hydroxyl, carboxyl, amine, thiol, thioester, thioether, phosphate, alkoxy, aryl, arylalkyl, sulfonamide and alkyl halide. Further, compounds (6883, 6898, 6975, 7036, 7064 and 8496) are provided. A process is provided for activating gene transfer in a subject by administering a pharmaceutically effective amount of a gene transfer activating compound to a subject and delivering pharmaceutically effective amount of a vector containing a nucleic so that the nucleic acid is transcribed in a target cell of the subject. A process for activating gene transfer to a cell is provided. A kit for activating gene transfer is provided.

Gene delivery compounds

Compounds having the structure (I) wherein R1, R2 and R3 are each independently a CO-12 substituent selected from the group consisting of: hydrogen, a heteroatom, alkyl, alkenyl, alkynyl, heteroatom substituted alkyl, heteroatom substituted alkenyl, heteroatom substituted alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl; where the heteroatom is selected from the group consisting of: N, O and S; and where (A) is a single or double bond between N and R3. Further the CO-12 substituent is linear, branched or cyclic and optionally includes a pendant moiety selected from the group consisting of: carbonyl, hydroxyl, carboxyl, amine, thiol, thioester, thioether, phosphate, alkoxy, aryl, arylalkyl, sulfonamide and alkyl halide. Further, compounds (6883, 6898, 6975, 7036, 7064 and 8496) are provided. A process is provided for activating gene transfer in a subject by administering a pharmaceutically effective amount of a gene transfer activating compound to a subject and delivering pharmaceutically effective amount of a vector containing a nucleic so that the nucleic acid is transcribed in a target cell of the subject. A process for activating gene transfer to a cell is provided. A kit for activating gene transfer is provided.

Ethenyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides compounds of Formula (A): (Chemical formula should be inserted here as it appears on abstract in paper form) (A) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R 1 , X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 18 , R 19 , R 22 , R 23 , and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.

Ethenyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides compounds of Formula (A): (Chemical formula should be inserted here as it appears on abstract in paper form) (A) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R 1 , X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 18 , R 19 , R 22 , R 23 , and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing dieases or disorders such as viral infections and virus-related disorders.

Ethenyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

Compuestos antivirales, tratamiento y dosis.

Son apropiados los compuestos que se proporcionan aquí para inhibir un virus en un paciente y para tratar a un paciente que sufre de una infección viral, por ejemplo el virus de la influenza. También se proporciona un método para someter compuestos a una evaluación para determinar su uso en el tratamiento y prevención de infecciones virales. La prueba evalúa compuestos para determinar su actividad en contra de un virus de influenza a través de medir el efecto citopatogénico (ECP) del compuesto de células infectadas con influenza usando el porcentaje de viabilidad celular como punto final.

Ethynyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

Ethynyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

Treatment of neurodegenerative diseases, causation of memory enhancement, and assay for screening compounds for such

The invention provides methods of enhancing memory and/or learning and prevent neurodegeneration, comprising administering therapeutically effective amounts of certain heterocyclic and aromatic compounds to a patient in need thereof. In one aspect, the invention provides methods of treating patients suffering from a neurodegenerative disease, such as but not limited to, Alzheimer's, Parkinsons's, Lou Gehrig's (ALS) disease, and/or memory or learning impairment. The invention further provides neuronal human cell-based assays that assess NF-kB gene upregulation using a luciferase reporter, wherein the assays identify compounds that are useful in enhancing memory or learning.

Substituted pyridine and pyrimidine derivatives and their use in treating viral infections

The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein each of R, R 1 , X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 18 , R 19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.