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• 7797-83-3 2H-benzo[d]1,3-dioxolane-4-carbaldehyde 
• 917-54-4 methyllithium 
• 75-16-1 methylmagnesium bromide 
• 450-95-3 2-fluoroacetophenone 
• 6698-13-1 4-bromo-benzo[1,3]dioxole 
• 75-07-0 acetaldehyde 

Relevant academic research and scientific papers

Structure-activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles

Replacing the naphthalene C-unit of the anti-tuberculosis drug bedaquiline with a range of bicyclic heterocycles of widely differing lipophilicity gave analogs with a 4.5-fold range in clogP values. The biological results for these compounds indicate on average a lower clogP limit of about 5.0 in this series for retention of potent inhibitory activity (MIC90s) against M.tb in culture. Some of the compounds also showed a significant reduction in inhibition of hERG channel potassium current compared with bedaquiline, but there was no common structural feature that distinguished these.

Development of new highly potent imidazo[1,2-b[pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1

Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were then identified, which were able to block TgCDPK1 enzymatic activity at low nanomolar concentrations, with a good selectivity profile against a panel of mammalian kinases. The potential of these inhibitors was confirmed in vitro on T. gondii growth, with EC50 values of 100 nM and 70 nM, respectively. These best candidates also displayed low toxicity to mammalian cells and were selected for further in vivo investigations on murine model of acute toxoplasmosis.

Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4)

The tyrosine kinase EphB4 is an attractive target for drug design because of its recognized role in cancer-related angiogenesis. Recently, a series of commercially available xanthine derivatives were identified as micromolar inhibitors of EphB4 by high-throughput fragment-based docking into the ATP-binding site of the kinase domain. Here, we have exploited the binding mode obtained by automatic docking for the optimization of these EphB4 inhibitors by chemical synthesis. Addition of only two heavy atoms, methyl and hydroxyl groups, to compound 4 has yielded the single-digit nanomolar inhibitor 66, with a remarkable improvement of the ligand efficiency from 0.26 to 0.37 kcal/(mol per non-hydrogen atom). Compound 66 shows very high affinity for a few other tyrosine kinases with threonine as gatekeeper residue (Abl, Lck, and Src). On the other hand, it is selective against kinases with a larger gatekeeper. A 45 ns molecular dynamics (MD) simulation of the complex of EphB4 and compound 66 provides further validation of the binding mode obtained by fragment-based docking. 2009 American Chemical Society.

BENZOFURAN AND BENZOTHIOPHENE DERIVATIVES USEFUL IN THE TREATMENT OF CANCERS OF THE CENTRAL NERVOUS SYSTEM

The present invention relates to benzofuran and benzothiophene derivatives and compositions containing such compounds for the production of medicaments for the treatment of cancers of the central nervous system as monotherapy or combination with other agents.

BENZOFURAN DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS

The invention relates to novel heterocycles of formula (I), processes for their preparation and their use for preparing medicaments for the treatment or prophylaxis of disorders, especially of hyperproliferative disorders.

1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO

Compounds of Formula (IA), IB), IC), and (ID) wherein R1, R2, R3, R4, R5, and R6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

1-PROPANOL AND 1-PROPYLAMINE DERIVATIVES AND THEIR USE AS GLUCOCORTICOID LIGANDS

Compounds of Formula (I) wherein R1, R2 R3, R4, R5, R6, and X are as defiend herein for Formula (IA) and Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocoricoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

PYRIDINE ANCHORS FOR HMG-COA REDUCTASE INHIBITORS

Compounds which are useful as inhibitors of cholesterol biosynthesis and thus as hypocholesterolemic agents are provided which have a quinoline or a pyridine anchor attached by means of a linker to a binding domain sidechain, which compounds inhibit the e