A5066673243- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Heat shock proteins research
- X-ray Diffraction in Crystallography
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Crystallization and Solubility Studies
- Chronic Lymphocytic Leukemia Research
- Pharmaceutical Economics and Policy
- Ubiquitin and proteasome pathways
- Toxin Mechanisms and Immunotoxins
- Molecular Junctions and Nanostructures
- Synthetic Organic Chemistry Methods
- Biosimilars and Bioanalytical Methods
- Marine Sponges and Natural Products
- Immune Response and Inflammation
- Organoboron and organosilicon chemistry
- Semiconductor materials and devices
- Veterinary medicine and infectious diseases
- Multiple Myeloma Research and Treatments
- Receptor Mechanisms and Signaling
- Semiconductor materials and interfaces
- Synthesis and Catalytic Reactions
Bristol-Myers Squibb (United States)
2021-2025
Bristol-Myers Squibb (Germany)
2023-2024
Nurix (United States)
2019
Pfizer (United States)
2011-2018
Pearl River Community College
2007-2009
Princeton University
2005-2006
University of California, San Diego
1998-2005
Challenges in the selective manipulation of functional groups (chemoselectivity) organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites reactivity (protecting groups). Although electrochemistry offers precise redox control achieve unique chemoselectivity, this approach often becomes challenging presence multiple redox-active functionalities. Historically, electrosynthesis...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDiprotected Triflylguanidines: A New Class of Guanidinylation ReagentsKonrad Feichtinger, Christoph Zapf, Heather L. Sings, and Murray GoodmanView Author Information Department Chemistry Biochemistry, University California, San Diego, La Jolla, California 92093-0343 Cite this: J. Org. Chem. 1998, 63, 12, 3804–3805Publication Date (Web):May 27, 1998Publication History Received9 March 1998Published online27 May inissue 1 June...
Through fragment-based drug design focused on engaging the active site of IRAK4 and leveraging three-dimensional topology in a ligand-efficient manner, micromolar hit identified from screen Pfizer fragment library was optimized to afford inhibitors with nanomolar potency cellular assays. The medicinal chemistry effort featured judicious placement lipophilicity, informed by co-crystal structures optimization ADME properties deliver clinical candidate PF-06650833 (compound 40). This compound...
An efficient and highly diastereoselective intramolecular Diels–Alder reaction is the basis of a concise asymmetric synthesis potent antibacterial natural product abyssomicin C (see formula). The complexity target structure was reduced to three fragments required two carbonyl addition reactions achieve key bond formations. In their pioneering report on diene synthesis, or reaction, Otto Diels Kurt Alder recognized profound impact that this pericyclic would have in syntheses "complex...
We wish to report a strategy that targets interleukin-2inducible T cell kinase (Itk) with covalent inhibitors. Thus far, inhibition of Itk has not been disclosed in the literature. Structure-based drug design was utilized achieve low nanomolar potency series even at high ATP concentrations. Kinetic measurements confirmed an irreversible binding mode off-rate half-lives exceeding 24 h and moderate on-rates. The analogues are highly potent cellular IP1 assay as well human whole-blood (hWB)...
Efficiency metrics are useful in medicinal chemistry to track small molecule progress lead optimization (LO). Molecular glue degraders molecules that mediate targeted protein degradation by chemically inducing proximity between an E3 ligase and a target. The potency depth of important factors identifying molecular drug candidates. We developed efficiency based on both objectives. applied these retrospectively clinical degrader series, resulting the identification Golcadomide (CC-99282). This...
The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist anticipated to reduce production IL-17, key proinflammatory cytokine. Through high-throughput screening approach, we identified molecule displaying binding affinity RORC2, inhibition IL-17 in Th17 cells, and selectivity against related RORA RORB isoforms. Lead optimization improve potency metabolic...
Potent covalent inhibitors of Bruton's tyrosine kinase (BTK) based on an aminopyrazole carboxamide scaffold have been identified. Compared to acrylamide-based reactive groups leading irreversible protein adducts, cyanamide-based reversible-covalent provided the highest combined BTK potency and EGFR selectivity. The cyanamide mechanism with was confirmed through enzyme kinetic, NMR, MS, X-ray crystallographic studies. lead demonstrated excellent kinome selectivity rat pharmacokinetic properties.
Herein we report the discovery of an azabicyclo[2.1.1]hexane piperazinium methanesulfonate salt from unexpected rearrangement reaction in preparation ligand-directed degraders (LDDs). This bench-stable compound was found to be a versatile electrophile ring-opening with various types nucleophiles. Its utility as medicinal chemistry building block is further demonstrated synthesis LDD targeting degradation androgen receptor.
Eine effiziente und hoch diastereoselektive intramolekulare Diels-Alder-Reaktion bildet die Grundlage einer knappen asymmetrischen Synthese des wirksamen antibakteriellen Naturstoffs Abyssomicin C (siehe Formel). Die komplexe Zielstruktur wurde auf drei Fragmente zurückgeführt, durch zwei Carbonyladditionen miteinander verknüpft wurden. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z502119_s.pdf or from author. Please...
[formula: see text] We report the syntheses of peptidomimetic opioids containing core structure N-alkyl-2-alkyl-2,3-dihydro-4-pyridone. By employing imines bound on a solid support and Danishefsky diene, this [4 + 2] cyclocondensation reaction facilitates synthesis novel complex heterocycles. The central is carried out under mild conditions employs readily available building blocks. In study we demonstrate suitability N-alkyl-2-alkyl-2,3-dihydro-4-pyridones as scaffold for peptidomimetics...
We report the development of a solid support-linked guanidinylating reagent. This reagent consists urethane-protected triflyl guanidine attached to resin via carbamate linker. It allows for rapid synthesis guanidines from variety amines. provides access N-alkyl/aryl- or N,N-dialkylguanidines under mild conditions. Cleavage with 50% TFA produces target molecules in high yields and purity. The ability guanidinylate secondary amines is significant feature this
Efficiency metrics are a simple and effective medicinal chemistry tool to track small molecule progress toward preferred profile in lead optimization. Targeted protein degradation can be mediated by molecules that act as molecular glue between an E3 ligase target. Molecular compounds characterized the potency depth of their dose response measurement, representing additional complexity identifying drug candidates. We developed efficiency based on both degradation. They serve basic scoring...
Efficiency metrics are a simple and effective medicinal chemistry tool to track small molecule progress toward preferred profile in lead optimization. Targeted protein degradation can be mediated by molecules that act as molecular glue between an E3 ligase target. Molecular compounds characterized the potency depth of their dose response measurement, representing additional complexity identifying drug candidates. We developed efficiency based on both degradation. They serve basic scoring...
We have synthesized novel heterocyclic compounds from resin-bound guanidines. For this purpose, an amine immobilized on a solid support was acylated with protected amino acids. Following the deprotection, liberated amines were guanidinylated utilizing new member of family diurethane-protected triflyl guanidine reagents, N,N'-bis(allyloxycarbonyl)-N' '-triflylguanidine. The deprotected guanidines subsequently regioselectively cyclized β-keto esters yielding containing structures in high purities.
Challenges in the selective manipulation of functional groups (chemoselectivity) organic synthesis have historically been overcome using either reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites reactivity (protecting groups). Although electrochemistry offers precise redox control achieve unique chemoselectivity, this approach often becomes challenging presence multiple redox-active functionalities. Historically, electrosynthesis has...