A5014720085- Catalytic Cross-Coupling Reactions
- Protein Kinase Regulation and GTPase Signaling
- Synthesis of Tetrazole Derivatives
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- Synthesis and biological activity
- Monoclonal and Polyclonal Antibodies Research
- Catalytic C–H Functionalization Methods
- Synthetic Organic Chemistry Methods
- Radical Photochemical Reactions
- Neuroscience and Neuropharmacology Research
- Click Chemistry and Applications
- Sphingolipid Metabolism and Signaling
- Cancer Mechanisms and Therapy
- Catalytic Alkyne Reactions
- Endoplasmic Reticulum Stress and Disease
- Chemical Synthesis and Analysis
- Synthesis and pharmacology of benzodiazepine derivatives
- Sirtuins and Resveratrol in Medicine
- Multiple Myeloma Research and Treatments
- Innovative Microfluidic and Catalytic Techniques Innovation
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- Genetic Neurodegenerative Diseases
AbbVie (United States)
2015-2022
The University of Texas at El Paso
2007
Despite recent advances in the field of C(sp2)-C(sp3) cross-couplings and accompanying increase publications, it can be hard to determine which method is appropriate for a given reaction when using highly functionalized intermediates prevalent medicinal chemistry. Thus study was done comparing ability seven methods directly install diverse set alkyl groups on "drug-like" aryl structures via parallel library synthesis. Each showed substrates that excelled at coupling compared with other...
Parallel library synthesis is an important tool for drug discovery because it enables the of closely related analogues in parallel via robust and general synthetic transformations. In this perspective, we analyzed methodologies used >5000 libraries representing 15 prevalent The data set contains complex substrates diverse arrays building blocks over last 14 years at AbbVie. that have demonstrated robustness generality with proven success are described along their substrate scopes. evolution...
The synthesis of a triethoxysilyl functionalised<italic>Pd-PEPPSI</italic>–<italic>IPr</italic>complex prepared<italic>via</italic>azide–alkyne cycloaddition is described.
High-throughput experimentation (HTE) methods are central to modern medicinal chemistry. While many HTE approaches C-N and Csp
Using a convergent synthetic route to enable multiple points of diversity, series glucocorticoid receptor modulators (GRM) were profiled for potency, selectivity, and drug-like properties in vitro. Despite covering large range profiling the nonconjugated small molecule was suboptimal they conjugated mouse antitumor necrosis factor (TNF) antibody using MP-Ala-Ala linker. Screening resulting drug conjugates (ADCs) provided better assessment efficacy physical properties, reinforcing need...
S1P5 is one of 5 receptors for sphingosine-1-phosphate and highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in vitro models (J. Neuroinflamm. 2012, 9, 133). Little more known about effects modulation due to absence tool molecules with suitable selectivity drug-like properties. We recently reported that molecule A-971432 (Harris, 2010) (29 this paper) efficacious reversing lipid accumulation age-related cognitive decline rats (Van der...
A HTS campaign identified compound 1, an excellent hit-like molecule to initiate medicinal chemistry efforts optimize a dual ROCK1 and ROCK2 inhibitor. Substitution (2-Cl, 2-NH2, 2-F, 3-F) of the pyridine hinge binding motif or replacement with pyrimidine afforded compounds clean CYP inhibition profile. Cocrystal structures early lead were obtained in PKA, ROCK1, ROCK2. This provided critical structural information for drive design. The data indicated preferred configuration at central...
We describe the design, synthesis, and structure-activity relationships (SARs) of a series 2-aminobenzothiazole inhibitors Rho kinases (ROCKs) 1 2, which were optimized to low nanomolar potencies by use protein kinase A (PKA) as structure surrogate guide compound design. subset these molecules also showed robust activity in cell-based myosin phosphatase assay mechanical hyperalgesia vivo pain model.