Adam M. Levinson

CCDC 2408183: Experimental Crystal Structure Determination

Thomas J. Beauchamp, Kevin P. Cole, Howard B. Broughton, David A. Coates et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Discovery of 2H-Pyrrolo[3,4- c ]pyridin-3-one Derivatives as Type-III c-MET Inhibitors Enabled by Free-Energy Perturbation Calculations

Éric Therrien, Shulu Feng, Katherine Amberg-Johnson, Nadim Shaikh et autres

The clinical emergence of diverse c-MET mutations with resistance to approved inhibitors has created an urgent demand for next-generation inhibitors with efficacy against c-MET-resistant mutations while maintaining c-MET wild-type (WT) potency, selectivity over other kinases, and brain penetration. Here, we report a …

us (code pays fourni par la source)

Structure-Based Discovery of Imidazo[4,5- c ]pyridine SARM1 Modulators Showing Paradoxical Activation

Steven K. Albanese, Brittany E. Hopkins, Andrea Olland, Alexis Fairman et autres

.

us, de (code pays fourni par la source)

Abstract 4376: Preclinical characterization of SGR-4174, a potent and selective SOS1 inhibitor for the treatment of pan KRAS mutant cancers in combination with KRAS pathway inhibitors

Hui Wang, Felicia Gray, Christian Atsriku, Adam M. Levinson et autres

Abstract KRAS is the most frequently mutated oncogene in many tumor types including pancreatic (90%), colorectal (50%) and lung cancers (30%). KRAS mutation typically impairs the conversion of active GTP-bound KRAS to the inactive GDP-bound form, resulting in constitutively active KRAS. SOS1 …

us (code pays fourni par la source)

Preclinical Toxicology Supply for a Complex API Enabled by Asymmetric Catalysis and Rapid Chemical Development: IL-17A Inhibitor LY3509754

Thomas J. Beauchamp, Kevin P. Cole, Howard B. Broughton, David A. Coates et autres

The chemical development and production of sufficient amounts of IL-17A inhibitor LY3509754 to enable preclinical toxicology studies is described. LY3509754 is a complex small molecule that features three stereocenters, which comprised much of the synthetic challenge. Stereoselective hydrogenation and biocatalysis enabled access …

us, es (code pays fourni par la source)

Exploiting Solvent Exposed Salt-Bridge Interactions for the Discovery of Potent Inhibitors of SOS1 Using Free-Energy Perturbation Simulations

Abba E. Leffler, Evelyne M. Houang, Felicia Gray, Andrew T. Placzek et autres

Small molecules that bind the Son of Sevenless 1 protein (SOS1), thereby preventing activation of RAS, have been widely pursued as a means for cell proliferation inhibition and antitumor activity. Guided by free-energy perturbation (FEP+) simulations, we discovered that two acidic residues …

us (code pays fourni par la source)

Total Chemical Synthesis and Folding of All- l and All- d Variants of Oncogenic KRas(G12V)

Adam M. Levinson, John H. McGee, Andrew G. Roberts, Gardner S. Creech et autres

The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately …

us (code pays fourni par la source)

ChemInform Abstract: Studies in Selective 6‐Membered Bromoether Formation via Bromonium and Thiiranium‐Induced Cyclizations.

Adam M. Levinson, Phillip J. Milner, Scott A. Snyder

Abstract Several methods for the synthesis of brominated 2,2,6,6‐tertasubstituted tetrahydropyrans are explored.

us (code pays fourni par la source)

ChemInform Abstract: Total Synthesis of Aspeverin via an Iodine(III)‐Mediated Oxidative Cyclization.

Adam M. Levinson

Abstract The first total synthesis of the prenylated indole alkaloid aspeverin (I) is described.

us (code pays fourni par la source)

Studies in selective 6-membered bromoether formation via bromonium and thiiranium-induced cyclizations

Adam M. Levinson, Phillip J. Milner, Scott A. Snyder

us (code pays fourni par la source)

CCDC 1049383: Experimental Crystal Structure Determination

Adam M. Levinson

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Total Synthesis of Aspeverin via an Iodine(III)-Mediated Oxidative Cyclization

Adam M. Levinson

The first total synthesis of aspeverin, a prenylated indole alkaloid isolated from Aspergillus versicolor in 2013, is described. Key steps utilized to assemble the core structure of the target include a highly diastereoselective Diels-Alder reaction, a Curtius rearrangement, and a unique strategy …

us (code pays fourni par la source)