Rational Design of a Novel AMPA Receptor Modulator through a Hybridization Approach

Caldwell, Nicola; Harms, Jonathan E.; Partin, Kathryn M.; Jamieson, Craig

doi:10.1021/ml5004553

Cited by 9 publications

(5 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A compilation of structures of fluorinated pyrazoles, their activities, and the corresponding references during the last 5 years are provided in Figure . − …”

Section: Applications Of Fluorinated Pyrazolesmentioning

confidence: 99%

Fluorinated Pyrazoles: From Synthesis to Applications

2020

View full text Add to dashboard Cite

Fluorinated pyrazoles play an important role in medicinal chemistry, drug discovery, agrochemistry, coordination chemistry, and organometallic chemistry. Since the early 1990s, their popularity has grown exponentially. Moreover, more than 50% of all contributions on the topic have been published in the last 5 years. In this review, analysis of novel synthetic approaches to fluorinated pyrazoles that appeared in recent years is performed. A particular emphasis is devoted to a detailed consideration of reaction mechanisms. In addition, the reasons that have led to the ever-increasing popularity of fluorinated pyrazoles in various areas of science are discussed. At the end of the review, several potentially interesting but yet mostly unknown classes of fluorinated pyrazoles are outlined.

show abstract

“…A compilation of structures of fluorinated pyrazoles, their activities, and the corresponding references during the last 5 years are provided in Figure . − …”

Section: Applications Of Fluorinated Pyrazolesmentioning

confidence: 99%

Fluorinated Pyrazoles: From Synthesis to Applications

2020

View full text Add to dashboard Cite

show abstract

“…Pfizer researchers also revealed a class of compounds known as dihydroisoxazoles (DHI), particularly hit 67 (Figure ), with apparent favorable physicochemical and ADME properties . Studies involving a hybridization strategy revealed structures such as compound 68 (Figure ), which showed significant in vivo biological activity against GluA2 …”

Section: Ampa Receptorsmentioning

confidence: 99%

“…[232] Studies involvingah ybridization strategy revealed structuress uch as compound 68 (Figure 7), which showeds ignificant in vivo biological activitya gainst GluA2. [233] Many more have been discovered in this context,a nd they are reviewed elsewhere. [217,226,234] What we stress herei st hat the evolution of studies relatedt ot argetingt he AMPAr eceptor is ag ood example of learning from failure.…”

Section: Ampar Eceptorsmentioning

confidence: 99%

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

et al. 2019

View full text Add to dashboard Cite

Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β‐amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.

show abstract

“…A recent publication from one of the Organon authors currently working at the University of Strathclyde described another hybridisation strategy, [130] in which the hydroxymethyl pyrazole used in the design of 77 is combined with a template related to those previously described by Cortex to produce hybrid 79. Only in vitro activity data is de-scribed in an electrophysiology assay with compounds being tested on both flip and flop isoforms of GluA2.…”

Section: Optimization Of An Hts-derived Hit By Or-ganon Using Sbddmentioning

confidence: 99%

AMPA Receptor Positive Allosteric Modulators: Potential for the Treatment of Neuropsychiatric and Neurological Disorders

Reuillon

Ward²,

Beswick³

2016

CTMC

View full text Add to dashboard Cite

The neurotransmitter glutamate and its receptors have long been of interest to scientists involved in pharmaceutical research since dysfunction of the glutamatergic signalling pathway has been associated with the pathophysiology of several psychiatric and neurological disorders. The research on AMPAR positive allosteric modulators offers opportunities to modulate fast excitatory synaptic transmission and identify new potential therapeutic agents for a range of neurodiseases. The field of AMPAR modulators continues to be a dynamic area of drug discovery with a pronounced diversification of the chemotypes explored in recent years. This article reviews literature published in this area in the last 6 years, focusing on the new core templates, some derived from high-throughput screens, with an emphasis on structure-activity relationships, drug metabolism and pharmacokinetics properties, and pharmacological profiles of these series.

show abstract

Rational Design of a Novel AMPA Receptor Modulator through a Hybridization Approach

Cited by 9 publications

References 25 publications

Fluorinated Pyrazoles: From Synthesis to Applications

Fluorinated Pyrazoles: From Synthesis to Applications

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

AMPA Receptor Positive Allosteric Modulators: Potential for the Treatment of Neuropsychiatric and Neurological Disorders

Contact Info

Product

Resources

About