Abstract: This invention relates to a stable pharmaceutical composition of freeze-dried tetrodotoxin powder which contains trace amount of tetrodotoxin, substances which can stabilizes tetrodotoxin, including disaccharide(s) or polyglucose(s) or analogues thereof and solvent(s), and solvents which can help tetrodotoxin dissolve.

Abstract: The present invention concerns the compounds of formula wherein a1-a2=a3-a4 represents a divalent radical selected from N—CH?CH—CH, N—CH?N—CH or CH—CH?N—CH; Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-6 alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O— or —NR11—; X2 represents —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen; R4 represents hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or substituted C1-4alkyloxy; R11 represents hydrogen; R12 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R13 represents morpholinyl-C1-4alkyl; Het2 represents morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.

Abstract: Screening methods for identifying compounds and compounds and pharmaceutical compositions for treating and preventing cancer are disclosed. The compounds affect signal transduction downstream of the MET receptor.

Abstract: There is provided a method for treating pulmonary hypertension in a subject, comprising: administering to the subject in need thereof a daily dose of ambrisentan from 1 mg to about 15 mg, wherein the method is carried out without drug labeling instruction to monitor liver aminotransferase levels during ambrisentan treatment.

Abstract: This disclosure is directed to pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Abstract: The invention relates to compositions and methods for inhibiting RNA binding proteins (e.g., MEX-3, MEX-5 and POS-1), as well as methods for treating and preventing disorders associated with parasitic infections and inflammatory disorders.

Abstract: This document relates to compounds as well as methods and materials involved in modulating neurotransmitter reuptake. For example, compounds, methods for synthesizing compounds, and methods for inhibiting neurotransmitter reuptake are provided.

Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

Abstract: The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides compounds as therapeutic agents against bacterial infections.

Abstract: Provided herein are compositions and methods for targeted ablation of mutational escape in the face of cancer therapeutic agents. Compositions comprising the yeast-based vehicles are used in combination with other cancer therapeutic agents.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are antagonists of the adrenergic receptor ?2A. The compounds may also bind to and are an antagonist of the adrenergic receptor ?2B; or the compounds are not antagonists of the adrenergic receptor ?2B and the compounds are administered in conjunction with a second agent that reduces, or is expected to reduce, blood pressure in an individual. The compounds may find use in therapy, e.g., to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. Use of the compounds to treat type 2 diabetes is particularly described.

Abstract: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Y represents —C3-9alkyl-, —C1-5alkyl-NR6—C1-5alkyl- or —C1-5alkyl-NR7—CO—C1-5alkyl-; X1 represents —O —; X2 represents NR5—C1-2alkyl-; R1 represents hydrogen, halo or Het3-O—; R2 represents hydrogen; R3 represents hydroxy, C1-4alkyloxy- or C1-4alkyloxy substituted with one or two substituents each independently selected from Het4, hydroxy, C1-4alkyloxy-, C1-4alkyloxy-C1-4alkyloxy and NR9R10; R5 represents hydrogen or C1-4alkyl; R6 represents hydrogen or C1-4alkyl; R7 represents hydrogen; R9 and R10 each independently represent hydrogen; C1-4alkyl-S(?O)2—C1-4alkyl-C(?O)—; C1-4alkyl or C1-4alkyl substituted with hydroxy; Het3 represents pyridinyl optionally substituted with C1-4alkyl; Het4 represents morpholinyl, piperidinyl or piperazinyl wherein said Het4 is optionally substituted with hydroxy-C1-4alkyl or C1-4alkyl-S(?O)2—C1-4a

Abstract: The invention relates to 1,2,4 oxadiazole compounds and analogs thereof, represented by formula (II), and compositions and methods of use thereof.

Abstract: The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

Abstract: Provided herein are salt forms of macrocyclic protein kinase inhibitors, pharmaceutical compositions containing the same, methods of making and using these compounds and compositions to treat proliferative disease mediated by kinase activity.

Abstract: Cells expressingHsp27 exhibit reduced levels of p27kip1. Accordingly, a method for treatment of cancer using hsp27 inhibition that includes a preliminary test to ascertain the status of the p27kip1 in the target cells. In this test, a sample of cancerous tissue from the patient from the patient (including a human patient) and evaluated to determine an expression of level of functional p27kip1. In the case where the expression level of p27kip1 is below a threshold level, a therapeutic composition comprising as an active agent a composition effective to inhibit the expression or activity of hsp27 in administered to the patient.

Abstract: The present invention discloses methods of use of facially amphiphilic polymers and oligomers, including pharmaceutical uses of the polymers and oligomers as antimicrobial agents and antidotes for hemorrhagic complications associated with heparin therapy. The present invention also discloses novel facially amphiphilic polymers and oligomers and their compositions, including pharmaceutical compositions. The present invention further discloses the design and synthesis of facially amphiphilic polymers and oligomers.

Abstract: The present invention provides compositions comprising sucralose and 4-amino-5,6-dimethylthieno[2,3-d]pyrimidine-2(1H)-one or salts, solvates, and/or esters thereof and methods of making the compositions by spray drying. The present invention also provides ingestible compositions comprising compositions of the present invention and methods of making such foods. The present invention also includes a process of preparing 2-amino-thiophene derivatives, which are key intermediates for preparing 4-amino-5,6-dimethylthieno[2,3-d]pyrimidine-2(1H)-one.

Abstract: The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: This disclosure concerns antimicrobial compositions and methods for immunoenhancement, for example methods of increasing production of a type I interferon (IFN) in response to pathogen infection, by administration of a TAM receptor inhibitor. In certain embodiments, the disclosure concerns methods of using a TAM receptor inhibitor to treat a viral or bacterial infection in a subject.

Abstract: Optionally substituted 4,5,7,8-tetrahydro-(optionally 4-oxo, 4-thioxo or 4-imino)-(1H or 2H)-imidazo[1,2-a]pyrazolo[4,3-e]pyrimidine or 4,5,7,8,9-pentahydro-(optionally 4-oxo, 4-thioxo or 4-imino)-(1H or 2H)-pyrimido[1,2-a]pyrazolo[4,3-e]pyrimidine compounds, processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

Abstract: The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are antagonists of the adrenergic receptor ?2A. The compounds may also bind to and are an antagonist of the adrenergic receptor ?2B; or the compounds are not antagonists of the adrenergic receptor ?2B and the compounds are administered in conjunction with a second agent that reduces, or is expected to reduce, blood pressure in an individual. The compounds may find use in therapy, e.g., to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. Use of the compounds to treat type 2 diabetes is particularly described.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are adrenergic receptor ?2B antagonists. The compounds may also bind to and antagonize adrenergic receptor ?1B. The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption. The compounds may also be used to treat diseases or conditions that are, or are expected to be, responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular and renal disorders is particularly described.

Abstract: The present invention relates to compounds of Formula (Ia) or (Ib), the N-oxide forms, pharmaceutically acceptable addition salts, quaternary amines, stereoisomers, tautomers, racemics, metabolites, prodrugs, hydrates, or solvates thereof, wherein Y1, m, n, R1; X1; X2; R2; X3; X4; R3; and R4 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are kinase inhibitors useful for the treatment of disease states mediated by kinase, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula Ia or Ib, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: The present invention discloses a gamboge acid cyclization analogs, their preparation methods and applications by semi-synthesis with the following structural formula I-III: Where ring A, ring B or/and ring C is 4-10 membered saturated or/and unsaturated aliphatic ring aliphatic heterocycle or aryl heterocycle. R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 or/and R12 is, independently at each occurrence, optionally substituted substituent of glycosyl, multi-hydroxyl, amino acid, acyloxy, phosphoric acid oxy, sulfonyloxy, alkoxy, aryloxy, heterocyclic oxy, thiol, aliphatic or cyclic group containing oxygen, sulfur, nitrogen or phosphorus, one of the substituents or combinations thereof. The present invention has antitumor activity management, antiviral, antibacterial and antifungal activity management, as anti-tumor, anti-viral, immune, antibacterial and antifungal agents, with other known anti-tumor, anti-viral, immune, together with the application of antibacterial and antifungal.

Abstract: The invention provides novel 7,8-dihydro-imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4-one compounds and 7,8,9-trihydro-[1H or 2H]-pyrimido[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one compounds, substituted at the 1 or 2 position with C2-9 alkyl, C3-9 cycloalkyl, heteroarylalkyl, or substituted arylalkyl, in free, salt or prodrug form, processes for their production, their use as pharmaceuticals, particularly as PDE1 inhibitors, and pharmaceutical compositions comprising them.

Abstract: The present invention relates to a therapeutic or prophylactic method for treating Parkinson's disease by administering an effective amount of a compound having a phosphodiesterase 10 inhibitory activity; and also relates to a pharmaceutical composition for treatment or prophylaxis of Parkinson's disease comprising as an active ingredient a compound having a phosphodiesterase 10 inhibitory activity. Moreover, the present invention relates to a method for enhancing dopamine signal in the brain, which comprises administering an effective amount of a compound having a phosphodiesterase 10 inhibitory activity; and also relates to pharmaceutical composition for enhancing dopamine signal in brain comprising as an active ingredient a compound having a phosphodiesterase 10 inhibitory activity.

Abstract: The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to certain indolin-2-ones and aza-indolin-2-ones which possess anti-tumor activity and are accordingly useful in methods of treatment of the human or animal body, in particular such compounds are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: The teachings provided herein generally relate to compositions comprising a rutaecarpine derivative that activates CYP1A2 through enzyme induction. The uses for such a derivative, in some embodiments can include improving sleep, as well as treating insomnia. Other uses for the derivatives are provided herein.

Abstract: The teachings provided herein generally relate to compositions comprising rutaecarpine derivatives that activates CYP1A2 through enzyme induction. The uses for such a derivative can include removing caffeine from a subject, improving sleep, treating insomnia, treating caffeine toxicity, treating caffeine addiction and withdrawal symptoms, and the like. Caffeine is just one example of a substrate that can be removed using the derivatives taught herein, and other examples, including theophylline, are provided herein.

Abstract: The teachings provided herein generally relate to compositions comprising a rutaecarpine derivative that activates CYP1A2 through enzyme induction. The compound can be used for treating caffeine toxicity, in some embodiments. Caffeine is just one example of a substrate that can be removed using the derivatives taught herein, and other examples, including theophylline, are provided herein.

Abstract: The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are polo-like kinase (PLKs) inhibitors useful for the treatment of disease states mediated by PLK, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: The present invention relates generally to methods, devices and compositions for treating mental, neurological, and cognitive diseases related to deficiencies in the biosynthesis and/or metabolism of neurotransmitters.

Abstract: The present invention provides compounds of Formula (I-IV): compositions containing the same, and methods of use thereof such as for the treatment of cancer.

Abstract: Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

Abstract: This invention relates to a stable pharmaceutical composition of freeze-dried tetrodotoxin powder which contains trace amount of tetrodotoxin, substances which can stabilizes tetrodotoxin, including disaccharide(s) or polyglucose(s) or analogues thereof and solvent(s), and solvents which can help tetrodotoxin dissolve.

Abstract: The invention is to provide a novel anticancer agent or sensitizer for cancer chemotherapy or radiotherapy. A compound of a general formula (I): wherein A means an aryl group or a heteroaryl group, or a group of a formula (a): R1 means a —(C?O)aOb(C1-C6)alkyl group, a —(C?O)aOb(C2-C6)alkenyl group, a —(C?O)aOb(C3-C6)cycloalkyl group, an aryl group or a heteroaryl group; R2 and R3 each mean a hydrogen atom, a halogen atom, a hydroxyl group, a carboxyl group, a —(C?O)aOb(C1-C6)alkyl group or a group of —(C?O)aN(R1e)R2e; R4 means a hydrogen atom or a (C1-C6)alkyl group, and the like have an excellent Wee1-kinase-inhibitory effect, and are therefore useful in the field of medicine, especially in the field of various cancer treatments.

Abstract: The invention relates to novel pyrimido-benzimidazole derivatives. Said products exhibit a good affinity for certain melanocortin receptor sub-types, in particular MC4 receptors. Said products represent a particular interest for treating pathological disorders and diseases associated with one or several melanocortin receptors. Pharmaceutical compositions containing said products and the use thereof for a drug preparation are also disclosed.

Abstract: Method for treating Alzheimer's disease, Parkinson's disease, Huntington's chorea or Pick's disease by administering to a patient a compound of formula (I) wherein R1 represents hydrogen; R2 represents hydrogen, a C1-C6 alkyl group or C3-C6 cycloalkyl group; A represents nitrogen; D represents a methylene group, a methyl methylene group, a halogen atom substituted methylene group or a halogen substituted methyl methylene group; E represents CH2, CHR3 wherein R3 represents a C1-C6 alkyl group, CH or a carbon atom substituted by a C1-C6 alkyl group; Arom represents aryl, aryl having from 1 to 3 identical or different substituent groups selected from halogen, C1-C6 alkyl, and C1-C6 alkyloxy, heteroaryl or heteroaryl having from 1 to 3 substituent groups, selected from halogen, C1-C6 alkyl and C1-C6 alkyloxy. The part represented by is a single bond or double bond.

Abstract: The present application describes substituted pyrimidine compounds of formula (I) wherein X, A1, R1, R2, R3, R4, R5, R6, R7, R8, R9, p, q, r, v, and w are defined in the specification, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions and disorders using such compounds and compositions.

Abstract: 1- or 2-substituted (6aR,9aS)-3-(phenylamino)-5-6a,7,8,9,9a-hexahydro-5-methyl-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(1H or, 2H)-one compounds of Formula (I), processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

Abstract: The invention provides novel 7,8-dihydro-imidazo[1,2-?]pyrazolo[4,3-e]pyrimidin-4-one compounds and 7,8,9-trihydro-[1H or 2/f]-pyrimido[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one compounds, substituted at the 1 or 2 position with C2-g allcyl, C3-9 cycloalkyl, heteroarylalkyl, or substituted arylalkyl, in free, salt or prodrug form, processes for their production, their use as pharmaceuticals, particularly as PDE1 inhibitors, and pharmaceutical compositions comprising them.

Abstract: 1- or 2-substituted (6aR,9aS)-3-(phenylamino)-5-6a,7,8,9,9a-hexahydro-5-methyl-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(1H or, 2H)-one compounds of Formula (I), processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

Abstract: The present invention is directed to compounds of Formulae (I), (II), (III), (IV), (V), (VI), (VII), and (VIII), pharmaceutical compositions thereof and methods of use thereof in the treatment of conditions associated with a dysfunction in proteostasis.

Abstract: The invention relates to the use of a compound of the formula (I), or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in modulating an immune or inflammatory response: wherein: Z=O or S; n=1-3; R3=—CO2R8, —C(O)SR8, —C(O)NHR8, —C(S)OR8, —C(S)SR8, —C(S)NHR8, —C(NH)SR8 or —C(NH)NHR8, wherein R8 is —H or alkyl; R4=—H, —CH2R5 or —CH2CH2R5, wherein R5 independently has one of the meanings of R3; B=—NR2—, —CH2NR2—, —CH2CH2NR2—, —CH2CHR7— or —CH2O—, wherein R2 is H or a C1-3 alkyl, alkenyl or alkynyl group, and R7 is H or a C1-3 alkyl or alkoxy group; A=wherein R1=—NH2 or —OH, C and D are each, independently, a 5- or 6-membered, substituted or unsubstituted, aromatic or non-aromatic ring which may also contain one or more heteroatoms, and C is connected to group B in any available position.

Abstract: The present invention relates to the use of carbodine and 5-F carbodine and analogs thereof for use in the treatment or prophylaxis of influenza, in particular the H5N1 strain of Avian Influenza A virus or “bird flu” strain of influenza as well as the treatment or prophylaxis of Venezuela equine encephalitis virus or VEE.

Abstract: Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, cycloalkenyl, or heteroaryl; X is alkylene or —C(O)CH2—; Y is —N(R2)CH2CH2N(R)3)—, —OCH2CH2N(R2)—, —O—, —S—, —CH2S—, —(CH2)2—NH—, or optionally substituted ?m and n are 2-3, and Q is nitrogen or optionally substituted carbon; and Z is optionally substituted phenyl, phenylalkyl or heteroaryl, diphenylmethyl, R6—C(O)—, R6—SO2—, R6—OC(O)—, R7—N(R8)—C(O)—, R7—N(R8)—C(S)—, ?phenyl-CH(OH)—, or phenyl-C(?NOR2)—; or when Q is CH, phenylamino or pyridylamino; or Z and Y together are substituted piperidinyl or substituted phenyl; and R2, R3, R6, R7, and R8 are as defined in the specification are disclosed, their use in the treatment of Parkinson's disease, alone or in combination with other agents for treating Parkinson's disease, and pharmaceutical compositions comprising them; also disclosed are a processes for preparing intermediates useful for preparing comp