A5027117128- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Semiconductor materials and devices
- Plasma Diagnostics and Applications
- Chemical Synthesis and Analysis
- CCD and CMOS Imaging Sensors
- Spectroscopy and Laser Applications
- Thin-Film Transistor Technologies
- Laser Design and Applications
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Analytical Chemistry and Sensors
- Gas Sensing Nanomaterials and Sensors
- Computational Drug Discovery Methods
- Multiple Myeloma Research and Treatments
- Asymmetric Synthesis and Catalysis
- Metal and Thin Film Mechanics
- Quinazolinone synthesis and applications
- Vitamin K Research Studies
- Laser-induced spectroscopy and plasma
- Synthesis and biological activity
- Infrared Target Detection Methodologies
- Synthetic Organic Chemistry Methods
- Ubiquitin and proteasome pathways
- Advancements in Semiconductor Devices and Circuit Design
Gujarat Cancer & Research Institute
2024
GlaxoSmithKline (United Kingdom)
2011-2023
North Hertfordshire College
2015-2021
University of Iowa
2010
Toshiba (United States)
2006
Sarnoff Cardiovascular Research Foundation
1997
Princeton University
1994-1997
University of Hertfordshire
1995
Stevens Institute of Technology
1994
Dyson (United Kingdom)
1993
We describe the incorporation of a bicyclo[1.1.1]pentane moiety within two known LpPLA2 inhibitors to act as bioisosteric phenyl replacements. An efficient synthesis target compounds was enabled with dichlorocarbene insertion into bicyclo[1.1.0]butane system being key transformation. Potency, physicochemical, and X-ray crystallographic data were obtained compare their counterparts, which showed isostere well tolerated positively impacted on physicochemical profile.
The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption BET-KAc binding has emerged as an attractive therapeutic strategy with a number small molecule inhibitors now under investigation clinic. However, until utility these...
Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules required to demonstrate a ligand can have disease-modifying effect. Currently, as tools reported for only fraction proteome, platforms discovery essential leverage insights from analyses. Fragment screening offers an efficient approach explore chemical space. Presented here is fragment-screening platform, termed PhABits (PhotoAffinity Bits), which...
An efficient and high-yielding synthesis of 4-guanidino Neu5Ac2en, the potent anti-influenza A B compound, is described. The route exploits a stereospecific introduction key nitrogen functionality at C-4 via an oxazoline intermediate. Three different methods for final-step conversion 4-amino into derivatives are To explore structure–activity relationship in this region molecule, series substituted guanidino were synthesized their activity
Machine learning approaches promise to accelerate and improve success rates in medicinal chemistry programs by more effectively leveraging available data guide a molecular design. A key step of an automated computational design algorithm is molecule generation, where the machine required high-quality, drug-like molecules within appropriate chemical space. Many algorithms have been proposed for generation; however, challenge how assess validity resulting molecules. Here, we report three...
Macrophages are important drivers of pathogenesis and progression to AIDS in HIV infection. The virus the later phases infection is often predominantly macrophage-tropic this tropism contributes a chronic inflammatory immune activation state that observed patients. Pattern recognition receptors innate system key molecules recognise mount responses macrophages. response against HIV-1 potent elicits caspase-1-dependent pro-inflammatory cytokine production IL-1β IL-18. Although, NLRP3 has been...
p38α MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFα and IL-1β at translational transcriptional level. In this paper, we describe how have optimized series novel p38α/β inhibitors using crystal structures our bound to p38α, classical medicinal chemistry, modeling virtual libraries derive molecule suitable progression into clinical development.
The bromodomain and extra terminal (BET) family of bromodomain-containing proteins are important epigenetic regulators that elicit their effect through binding histone tail
Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple hits were observed different regions the active site, including some that bound a pocket created by movement protein side chain (approximately 13 Å from catalytic residue Ser273). Using structure guided design, we optimized this generate low nanomolar chemotype, which...
The bromodomain and extra terminal (BET) family of proteins are an integral part human epigenome regulation, the dysregulation which is implicated in multiple oncology inflammatory diseases. Disrupting BET acetyl-lysine (KAc) histone protein-protein interaction with small-molecule KAc mimetics has proven to be a disease-relevant mechanism action, molecules currently undergoing clinical trials. This work describes efficiency analysis published GSK pan-BET inhibitors, drove strategic choice...
The peracid oxidation of hydrocarbons in chlorinated solvents is a low yielding and poorly selective process. Through combination DFT calculations, spectroscopic studies, kinetic measurement it shown that the origin this electronic nature can be influenced through addition hydrogen bond donors (HBD) acceptors (HBA). Performing reaction cycloalkane with mCPBA fluorinated alcohol solvent such as nonafluoro-tert-butanol (NFTB) or hexafluoroisopropanol (HFIP), which act strong HBD poor HBA,...
Functionalized bicyclic amino-azaheterocycles are rapidly accessed in a one-pot cross-coupling/reduction sequence enabled by the use of COware. Incompatible reagents physically separated single reaction vessel to effect two chemoselective transformations—Suzuki–Miyaura cross-coupling and heteroarene reduction. The developed method allows access novel heterocyclic templates, including semisaturated Hedgehog dual PI3K/mTOR inhibitors, which show enhanced physicochemical properties compared...
Lp-PLA2 has been explored as a target for number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery new fragment derived chemotype that interacts with active site Lp-PLA2. The starting hit was discovered through an X-ray screen showed no activity in bioassay (IC50 > 1 mM). optimized using variety structure-based drug design techniques, virtual screening, merging, improvement shape complementarity. A novel series inhibitors...
The bi-material concept for room-temperature infrared imaging has the potential of reaching an NE(Delta) T approaching theoretical limit because its high responsivity and low noise. approach, which is 100% compatible with silicon IC foundry processing, utilizes a novel combination surface micromachining conventional integrated circuits to produce bimaterial thermally sensitive element that controls position capacitive plate coupled input noise MOS amplifier. This approach can achieve...
Abstract The direct microwave‐mediated condensation between 3‐oxetanone and primary amides thioamides has delivered moderate to good yields of (hydroxymethyl)oxazoles (hydroxymethyl)thiazoles. reactions use a sustainable solvent only require short reaction times. These are highly competitive methods for the construction two classes valuable heteroarenes, which bear useful locus further elaboration. Electronic structure calculations have shown that order events involves chalcogen atom attack...
Impedance monitoring of a rf glow discharge is successfully used to determine the end point reactive ion etching. The feasibility using this technique demonstrated on diode, triode, and magnetic multipole enhanced triode reactors applied etching polycrystalline silicon SiO2 Si Si3N4 in an SF6 plasma, stripping photoresist Al O2 plasma. determined by changes induced dc bias, voltage, current, or phase relationship between them either powered electrodes (in cases configurations). This method...
Design, fabrication, operation and performance are described for a 360/spl times/360 element very high frame rate (VHFR) image sensor that can capture images at of up to 10/sup 6/ frames/s. This VHFR imager has 50/spl times/50 /spl mu/m macropixels, each consisting high-speed zero-lag photodetector with 13.5% fill factor 30 stages serial-parallel type buried-channel CCD registers storage readout the last frames acquired. Readout this is similar transfer four quadrants. Each quadrant contains...
We present a one-step Ugi reaction protocol for the expedient synthesis of photoaffinity probes live-cell MS-based proteomics. The couples an amine affinity function with commonly used photoreactive groups, and variety handle functionalities. Using this technology, series pan-BET (BET: bromodomain extra-terminal domain) selective were obtained by parallel synthesis. Studies on effects group, linker length irradiation wavelength photocrosslinking efficiency provide valuable insights into...
A sustainable flow process has been established for the application of Gröebke–Blackburn–Bienaymé reaction access to high-value fused heteroaromatics.
By applying both low-frequency wavelength modulation and high-frequency phase to a laser diode, we develop sensitive, high-bandwidth chemical diagnostic tool that is applicable variety of gas-phase processing environments. Specific species are identified monitored through their infrared absorption spectra, the methods allow for sensitive detection free window other reflection-driven interference fringes. Absorbance limits 5.3 × 10−8 1.9 10−7 obtained an AlGaAs diode lead-salt laser,...