- DIACYLGLYCEROL KINASE MODULATING COMPOUNDS
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The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.
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Paragraph 1833
(2021/07/02)
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- Investigation of the molecular characteristics of bisindole inhibitors as HIV-1 glycoprotein-41 fusion inhibitors
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In previous work, we described 6-6‘-bisindole compounds targeting a hydrophobic pocket on the N-heptad repeat region of viral glycoprotein-41 as effective inhibitors of HIV-1 fusion. Two promising compounds with sub-micromolar IC50's contained a benzoic acid group and a benzoic acid ester attached at the two indole nitrogens. Here we have conducted a thorough structure-activity relationship (SAR) study evaluating the contribution of each of the ring systems and various substituents to compound potency. Hydrophobicity, polarity and charge were varied to produce 35 new compounds that were evaluated in binding, cell-cell fusion and viral infectivity assays. We found that (a) activity based solely on increasing hydrophobic content plateaued at ~ 200 nM; (b) the bisindole scaffold surpassed other heterocyclic ring systems in efficacy; (c) a polar interaction possibly involving Gln575 in the pocket could supplant less specific hydrophobic interactions; and (d) the benzoic acid ester moiety did not appear to form specific contacts with the pocket. The importance of this hydrophobic group to compound potency suggests a mechanism whereby it might interact with a tertiary component during fusion, such as membrane. A promising small molecule 10b with sub-μM activity was discovered with molecular weight 500 da and reduced logP compared to earlier compounds. The work provides insight into requirements for small molecule inhibition of HIV-1 fusion.
- Zhou, Guangyan,Chu, Shidong,Nemati, Ariana,Huang, Chunsheng,Snyder, Beth A.,Ptak, Roger G.,Gochin, Miriam
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p. 533 - 542
(2018/11/06)
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- MYST FAMILY HISTONE ACETYLTRANSFERASE INHIBITORS
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The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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- A 2,6-bis(phenylamino)pyridinato titanium catalyst for the highly regioselective hydroaminoalkylation of styrenes and 1,3-butadienes
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The C-C bond forming catalytic hydroaminoalkylation of terminal alkenes, 1,3-dienes, or styrenes allows a direct and highly atom efficient (100 %) synthesis of amines which can result in the formation of two regioisomers, the linear and the branched product. We present a new titanium catalyst with 2,6-bis(phenylamino)pyridinato ligands for intermolecular hydroaminoalkylation reactions of styrenes and 1-phenyl-1,3-butadienes that delivers the corresponding linear hydroaminoalkylation products with excellent regioselectivities. Linear progress: A new Ti complex with 2,6-bis(phenylamino) pyridinato ligands catalyzes highly regioselective hydroaminoalkylation reactions of styrenes. The process that directly gives access to the corresponding linear hydroaminoalkylation products offers a new and flexible synthetic approach towards pharmaceutically important 3-arylpropylamines. It is also possible to convert (E)-1-phenyl-1,3-butadienes into the corresponding linear products.
- Doerfler, Jaika,Preuss, Till,Schischko, Alexandra,Schmidtmann, Marc,Doye, Sven
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p. 7918 - 7922
(2014/08/05)
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- NOVEL BIAROMATIC COMPOUNDS WHICH ACTIVATE PPARγ-TYPE RECEPTORS, THEIR PROCESS OF PREPARATION AND THEIR USE IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
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The invention relates to novel biaromatic compounds which correspond to the following general formula (I) and to their method of preparation and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, in particular in
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- NOVEL BIAROMATIC COMPOUNDS WHICH ACTIVATE PPARγ TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
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The invention relates to novel biaromatic compounds which correspond to the general formula (I), and also to a process for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and also in the field of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism), or alternatively in cosmetic compositions.
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- Sulfonamide inhibitors of aspartyl protease
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The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical
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