Abstract: A process of obtaining a purified geometric isomer of an unsaturated macrocyclic compound is disclosed herein. The process is effected by contacting an ion exchange medium comprising silver ions with a mixture comprising at least one geometric isomer of the unsaturated macrocyclic compound, to thereby obtain at least one fraction comprising the purified geometric isomer of the macrocyclic compound. A system configured for performing the process is also disclosed.

Abstract: The present invention provides macrocycles of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

Abstract: Novel heterocyclic fused systems are disclosed herein which possess numerous biological activities, including but not limited to antibacterial activity, and usefulness to the treatment of many disease states, such as pathogenic infections. In particular, new imidazoles are disclosed along with related processes of preparation and methods of use as antibacterial agents. The disclosed compounds were found to be active against several Gram-positive bacteria, including Enterococcus faecalis and Bacillus subtilis, and were also found to be active against several species of multi-drug resistant Staphylococcus, such as S. aureus, S. saprophyticus, S. haemolyticus, and S. epidermidis.

Abstract: According to the present teachings, systems, compositions, kits and methods for protein melt analysis are provided that utilizing a dye that is a dipyrrometheneboron difluoride compound. In some embodiments, a method comprises preparing a sample by mixing at least one protein with a dye, and applying a controlled heating, while recording the fluorescence emission of the sample.

Abstract: Macrocycle containing carbamate compounds that inhibit HIV proteolytic enzymes and processes for preparing them are described. Compositions and methods for treating a patient infected with HIV are described.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The present invention is directed to hemi phorboxazole A: and its stereoisomers, as well as derivatives of hemi phorboxazole A of formula I: wherein ring A is aryl or a 5- or 6-membered heteroaryl optionally substituted with one or more of halogen, —OH, or —C1-6alkyl; and R is —CN, a 5- or 6-membered heteroaryl, or halogen; and the pharmaceutically acceptable salt forms thereof, in addition to methods of using these compounds.

Abstract: Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and 3?-position, their bioconjugates and their uses are described. 1,3?-crosslinked carbocyanines are superior to those of conjugates of spectrally similar 1,1?-crosslinked or non-crosslinked dyes. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: Cell permeable metal ion indicator compounds and methods of their use and synthesis are described. The compound comprises a metal chelating moiety (Mc), a reporter molecule and two or more lipophilic groups (GL) covalently bonded through a linker to the reporter molecule, wherein the lipophilic groups, when present in a live cell, are cleaved resulting in two or more negatively charged groups.

Abstract: Small-molecule scaffolds based on 1,2-diphenylacetylene that accurately replicate the spatial and angular projections of several side chains on both faces of an ?-helix, specifically the i and i+7 side chains on one face, and the i and i+2 side chains on the other. The amphipathic ?-helix mimetic can be used to disrupt disease-promoting protein-protein interactions that are mediated by ?-helices.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B—Z—W??(I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

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 ?2B. 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: 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 relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Abstract: Diazonamide analogs having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders, and related pharmaceutical compositions are provided.

Abstract: The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

Abstract: The present invention is directed to novel 2,3-dihydro-1H-isoindol-1-imine derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the thrombin PAR-1 receptor antagonists.

Abstract: Disclosed are rifamycin derivatives having antibacterial activities, wherein the compounds have the following general formula: wherein: R is hydrogen or acetyl; R1 and R2 are independently selected from the group consisting of hydrogen, (C1-4) alkyl, benzyloxy, mono- and di-(C1-3) alkylamino-(C1-4)alkyl, (C1-3)alkoxy, (C1-4) alkyl, hydroxy-methyl, hydroxy-(C2-4)-alkyl, and nitro or R1 and R2 taken together with two consecutive carbon atoms of the pyridine nucleus form a benzene ring optionally substituted by one or two methyl or ethyl groups and R3 is hydroxyalkyl (C1-4). In addition, processes to obtain these compounds are described.

Abstract: The present invention provides bicyclic azaheterocyclobenzylamines of Formula I: wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

Abstract: The invention relates to compounds of formula (?) as further defined herein and to the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to the uses thereof. The compounds and salts of the present invention inhibit anaplastic lymphoma kinase (ALK) and/or EML4-ALK and are useful for treating or ameliorating abnormal cell proliferative disorders, such as cancer.

Abstract: This disclosure is directed to fused tetracyclic 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: This disclosure is directed to fused tetracyclic pyrido[4,3-b]indoles and pyrido[3,4-b]indoles. 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 provides modulators for the orphan nuclear receptor ROR? and methods for treating ROR? mediated diseases by administrating these novel ROR? modulators to a human or a mammal in need thereof. Specifically, the present invention provides compounds of Formula (1) and the enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: Cell permeable metal ion indicator compounds and methods of their use and synthesis are described. The compound comprises a metal chelating moiety (Mc), a reporter molecule and two or more lipophilic groups (GL) covalently bonded through a linker to the reporter molecule, wherein the lipophilic groups, when present in a live cell, are cleaved resulting in two or more negatively charged groups.

Abstract: Diazonamide analogs having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders, and related pharmaceutical compositions are provided.

Abstract: Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and 3?-position, their bioconjugates and their uses are described. 1,3?-crosslinked carbocyanines are superior to those of conjugates of spectrally similar 1,1?-crosslinked or non-crosslinked dyes. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: The invention pertains to compound of Formula (I) wherein X, Y, Z, R1, R2, R3, R4, A and A? are as described hereinabove. Formula (I) and (II) compounds can be used in pharmaceutical compositions, useful for the treatment of diseases.

Abstract: The present invention relates to a serotonin 5-HT2C receptor activator containing a compound represented by the formula wherein ring A is a 5- or 6-membered aromatic heterocycle optionally having substituent(s), and ring B is a 7- to 9-membered ring optionally having substituent(s) other than an oxo group wherein the combination of m and n (m,n) is (1,2), (2,1), (2,2), (3,1), (3,2) or (4,1), or a salt thereof or a prodrug thereof, and a fused heterocyclic compound having a serotonin 5-HT2C receptor activating action and the like.

Abstract: Macrocycle containing carbamate compounds that inhibit HIV proteolytic enzymes and processes for preparing them are described. Compositions and methods for treating a patient infected with HIV are described.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The invention provides novel Thuggacin-Type macrolide compounds which form rearrangement products forming a lacton bond to different carbon atoms. The novel compounds can be produced by fermentation of Sorangium cellulosum and Chondromyces crocatus and can be isolated by adsorption and chromoatograhic processing steps. The compounds are found to have antibiotic activity. The invention also relates to Thuggacin A, Thuggacin B, Thuggacin C, 13-Methyl-Thuggacin A, Thuggacin CMC-A, Thuggacin CMC-B and Thuggacin CMC-C AS Antimycobacterial Agents.

Abstract: Tricyclic compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: wherein bond a, ring A, R1, R2 and R3 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset 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.

Abstract: The invention describes crown ether chelators, including crown ethers having the formula:

Abstract: The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G-protein coupled receptor (GPCR) such as GPR119 in a patient.

Abstract: The present invention relates to a process for preparing compositions of high concentrations of omega-3 fatty acids from krill. Furthermore, the invention relates to a composition comprising high concentrations of omega-3 fatty acids, and a lipid fraction from krill comprising high amounts of the fatty acids with chain length C14 and C 16.

Abstract: Provided herein include compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects in vivo and in vitro by a novel drugs mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation initiation. As with pateamine A, as described herein, suitable analogs cause cell cycle arrest or induce apoptosis in transformed cells. However, toxicity of such compounds to slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation initiation factors and are useful as anticancer and antiproliferative agents in subjects in need thereof.

Abstract: A compound represented by the following general formula (I): [wherein R1 and R2 independently represent hydrogen atom, or a group represented by the following formula (A): (wherein X1 and X2 represent hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom), provided that R1 and R2 do not simultaneously represent hydrogen atom; R3 and R6 represent an alkyl group; R4 and R7 represent hydrogen atom, an alkyl group, carboxy group, an alkoxycarbonyl group, or sulfo group; and R5 and R8 represents an alkyl group, an aryl group, an alkoxycarbonyl group, a vinyl group, a thienyl group, or a pyrrolyl group], or a salt thereof, which is usable for efficient screening for a chemical substance having applicability as a catalyst of the reaction of Michael addition.

Abstract: The invention is concerned with novel heterobicyclic derivatives of formula (I) wherein R1, R2, R3, R4, R5, R6, V, W, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.

Abstract: The present invention relates to tetracyclic indole compounds of formula (I): wherein R1, R2, A, Ar, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

Abstract: Ecteinascidin compounds with a quinone ring for ring E are active as anti-cancer agents. Related processes and compounds are provided.

Abstract: Ecteinascidin compounds with a quinone ring for ring E are active as anti-cancer agents. Related processes and compounds are provided.

Abstract: Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R1, R2, R3, R4 and R5 are each independently selected from the group consisting of H, OH, OR?, SH, SR?, SOR?, SO2R?, C(?O)R?, C(?O)OR?, NO2, NH2, NHR?, N(R?)2, NHC(O)R?, CN, halogen, ?O, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR?, CN, (?O), or H; wherein each of the R? groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, ?O, C(?O)H, C(?O)CH3, CO2H, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3, or 4, and their use as antitumoral agent.

Abstract: Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

Abstract: The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.

Abstract: The present invention relates to compounds of the formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1–R7 are as defined herein, methods for the preparation of the derivatives and intermediates thereof.