A5058888373- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Crystallography and molecular interactions
- Synthesis and Catalytic Reactions
- Synthetic Organic Chemistry Methods
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Histone Deacetylase Inhibitors Research
- interferon and immune responses
- Biosimilars and Bioanalytical Methods
- Immune Cell Function and Interaction
- Fluorine in Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Protein Degradation and Inhibitors
- Cholinesterase and Neurodegenerative Diseases
- Malaria Research and Control
- Multiple Myeloma Research and Treatments
- Computational Drug Discovery Methods
- Asymmetric Hydrogenation and Catalysis
- DNA and Nucleic Acid Chemistry
- Inflammatory Bowel Disease
- Receptor Mechanisms and Signaling
- Phosphodiesterase function and regulation
- Radical Photochemical Reactions
South College
2024
AbbVie (United States)
2022
Topivert (United Kingdom)
2018
Infinity Pharmaceuticals (United States)
2016
Broad Institute
2010-2014
Harvard University
2010
Massachusetts General Hospital
2010
An aldol-based build/couple/pair (B/C/P) strategy was applied to generate a collection of stereochemically and skeletally diverse small molecules. In the build phase, series asymmetric syn- anti-aldol reactions were performed produce four stereoisomers Boc-protected γ-amino acid. addition, both O-PMB-protected alaninol generated provide chiral amine coupling partner. couple step, eight stereoisomeric amides synthesized by acid building blocks. The subsequently reduced corresponding secondary...
Optimization of isoquinolinone PI3K inhibitors led to the discovery a potent inhibitor PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties robust inhibition mediated neutrophil migration in vivo is currently Phase 1 clinical evaluation subjects advanced solid tumors.
The synthesis and diversification of a densely functionalized azetidine ring system to gain access wide variety fused, bridged, spirocyclic systems is described. in vitro physicochemical pharmacokinetic properties representative library members are measured order evaluate the use these scaffolds for generation lead-like molecules be used targeting central nervous system. solid-phase 1976-membered azetidines also
Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent derived from the synthetic pathway. Structure-activity relationships focused on both appendage skeletal features yielded nanomolar inhibitor P. falciparum asexual blood-stage growth with improved solubility microsomal stability reduced hERG binding. The build/couple/pair (B/C/P) strategy, used preparation...
Human genetic evidence shows that PDE3B is associated with metabolic and dyslipidemia phenotypes. A number of PDE3 family selective inhibitors have been approved by the FDA for various indications; however, given undesirable proarrhythmic effects in heart, selectivity inhibition over closely related members (such as PDE3A; 48% identity) a critical consideration development therapeutics. Selectivity PDE3A may be achieved variety ways, including properties intrinsic to compound or...
Interleukin-1 receptor-associated kinase 3 (IRAK3) is a pseudokinase mediator in the human inflammatory pathway, and ablation of its function associated with enhanced antitumor immunity. Traditionally, pseudokinases have eluded "druggability" not been considered tractable targets pharmaceutical industry. Herein we disclose CRISPR/Cas9-mediated knockout IRAK3 monocyte-derived dendritic cells that results an increase IL-12 production upon lipopolysaccharide (LPS) stimulation. Furthermore,...
The discussion herein describes a metallaphotoredox reaction that allows for efficient exploration of benzyl structure–activity relationships in medicinal chemistry. use HTE (high-throughput experimentation) and ChemBeads rapid optimization. formation di(hetero)arylmethanes via cross-electrophile coupling between aryl bromides provides access to diverse chemical space. breadth the substrate scope will be discussed, along with utilization batch photochemistry preparation this...
TOP1288 is a topically acting, narrow spectrum kinase inhibitor that selectively targets key kinases (p38apha, Src family kinases, and Syk) involved in inflammatory signalling cells of the innate adaptive immune systems. has minimal systemic absorption, free from or local toxicities potential to provide safe efficacious, chronic dosing treatment for bowel disease (IBD) as demonstrated by prior study with rectal formulation.1,2 Combining an innovative trial design bespoke assays target...