A5102951501- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Asymmetric Synthesis and Catalysis
- Synthesis of Organic Compounds
- Neuroscience and Neuropharmacology Research
- Marine Sponges and Natural Products
- Synthetic Organic Chemistry Methods
- Ion Channels and Receptors
- Stress Responses and Cortisol
- Oxidative Organic Chemistry Reactions
- Bioactive Compounds and Antitumor Agents
- Synthesis and Biological Activity
- Computational Drug Discovery Methods
- Cyclopropane Reaction Mechanisms
- Traditional and Medicinal Uses of Annonaceae
- Carbohydrate Chemistry and Synthesis
- Congenital Anomalies and Fetal Surgery
- Bioactive natural compounds
- Molecular spectroscopy and chirality
- Cellular transport and secretion
- Pharmacological Receptor Mechanisms and Effects
- Parkinson's Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Herbal Medicine Research Studies
- Alkaloids: synthesis and pharmacology
Brigham and Women's Hospital
2015-2022
Harvard University
2015-2021
Ligand Pharmaceuticals (United States)
2017
Harvard NeuroDiscovery Center
2015
Repligen (United States)
2000-2010
University College Dublin
2000-2005
University of Salford
1994-2001
The University of Texas at Austin
2000
Glutamatergic systems play a critical role in cognitive functions and are known to be defective Alzheimer’s disease (AD) patients. Previous literature has indicated that glial glutamate transporter EAAT2 plays an essential loss of protein is common phenomenon observed AD patients animal models. In the current study, we investigated whether restored function could benefit pathology APPSw,Ind mice, model AD. A transgenic mouse approach via crossing mice with APPSw,Ind. pharmacological using...
Parkinson disease (PD) has useful symptomatic treatments that do not slow the neurodegenerative process, and no significant disease-modifying are approved. A key therapeutic target in PD is α-synuclein (αS), which both genetically implicated accumulates Lewy bodies rich vesicles other lipid membranes. Reestablishing αS homeostasis a central goal PD. Based on previous lipidomic analyses, we conducted mouse trial of stearoyl-coenzyme desaturase (SCD) inhibitor ("5b") prevented αS-positive...
[reaction: see text] Novel and highly efficient syntheses of oxazolo[4,5-c]quinoline-4(5H)-ones (1) thiazolo[4,5-c]quinoline-4(5H)-ones (2) from ethyl 2-chlorooxazole-4-carboxylate (4) 2-bromo-5-chlorothiazole-4-carboxylate (13), respectively, are described.
[reaction: see text] By using a sequence of regiocontrolled halogenation and palladium-catalyzed coupling reactions, the synthesis variously substituted oxazoles from ethyl 2-chlorooxazole-4-carboxylate (2) was accomplished. The methodology applied to series 2,4-disubstituted, 2,5-disubstituted, 2,4,5-trisubstituted oxazoles.
The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a nonselective channel that can be activated by wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade TRPV1 activation selective antagonists under investigation in an attempt to identify novel agents for pain treatment. design synthesis series with variety different 6,6-heterocyclic cores described, extensive evaluation the pharmacological pharmacokinetic properties number these compounds...
Abstract Synucleinopathy (Parkinson’s disease (PD); Lewy body dementia) disease-modifying treatments represent a huge unmet medical need. Although the PD-causing protein α-synuclein (αS) interacts with lipids and fatty acids (FA) physiologically pathologically, targeting FA homeostasis for therapeutics is in its infancy. We identified PD-relevant target stearoyl-coA desaturase: inhibiting monounsaturated synthesis reversed PD phenotypes. However, lipid degradation also generates pools. Here,...
The dopaminergic receptor profile of a series trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal identifying compound having affinities for D2 and D4 receptors in ratio similar to that observed atypical neuroleptic clozapine. compounds (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dichlorophenyl)piperazine (5m) (1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine (5t) selected...
Abstract Targeted delivery of drugs to tumor cells, which circumvent resistance mechanisms and induce cell killing, is a lingering challenge that requires innovative solutions. Here, we provide two bioengineered strategies in nanotechnology blended with cancer medicine preferentially target distinct drug resistance. In the first ‘case study’, demonstrate use lipid–drug conjugates molecular signaling pathways, result from taxane-induced tolerance via surface lipid raft accumulations. Through...
Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification compounds act transcriptionally, enhance exon recognition, or stabilize SMN protein. describe optimization and characterization analog suitable for in vivo testing. Initially, we identified 4m had good vitro properties but low plasma brain exposure mouse PK experiment due to short stability; this was...
The design, synthesis, and structure−activity relationships of a novel series pyrazines, acting as corticotropin releasing factor-1 (CRF-1) receptor antagonists, are described. Synthetic methodologies were developed to prepare number substituted pyrazine cores utilizing regioselective halogenation chemoselective derivatization. Noteworthy, an efficient 5-step synthesis was for the lead compound 59 (NGD 98−2), which required no chromatography. Compound characterized orally bioavailable, brain...