Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors

Hamblin, J. Nicole; Angell, Tony D.; Ballantine, Stuart P.; Cook, Caroline M.; Cooper, Anthony W. J.; Dawson, John A.; Delves, C. J.; Jones, Paul S.; Lindvall, Mika K.; Lucas, Fiona; Mitchell, Charlotte; Neu, Margarete; Ranshaw, Lisa E.; Solanke, Yemisi; Somers, Don O.; Wiseman, Joanne O.

doi:10.1016/j.bmcl.2008.05.052

Cited by 66 publications

(14 citation statements)

References 8 publications

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“…Further, smaller standard deviation value (SD = 0.56) and root mean square error (RMSE = 0.69) and P value of fourth PLS indicate that the developed AAHPRR.15 model was stable for predicting unknown compounds in the test set. To evaluate the efficacy, model AAHPRR.15 was further validated with the external 27 test set 46 , 47 . The scatter plots for the experimentally observed and estimated fit values for the training set and the test set molecules is plotted in Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay

Jang

Yadav

Subedi

et al. 2018

Sci Rep

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In this study, pharmacophore based 3D QSAR models for human acetylcholinesterase (AChE) inhibitors were generated, with good significance, statistical values (r2training = 0.73) and predictability (q2training = 0.67). It was further validated by three methods (Fischer’s test, decoy set and Güner-Henry scoring method) to show that the models can be used to predict the biological activities of compounds without costly and time-consuming synthesis. The criteria for virtual screening were also validated by testing the selective AChE inhibitors. Virtual screening experiments and subsequent in vitro evaluation of promising hits revealed a novel and selective AChE inhibitor. Thus, the findings reported herein may provide a new strategy for the discovery of selective AChE inhibitors. The IC50 value of compounds 5c and 6a presented selective inhibition of AChE without inhibiting butyrylcholinesterase (BChE) at uM level. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds studies to explain high affinity.

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Section: Resultsmentioning

confidence: 99%

Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay

Jang

Yadav

Subedi

et al. 2018

Sci Rep

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“…Furthermore, pyrazolopyridines ( 96 ), as novel PDE4 inhibitors, have the capacity to treat chronic obstructive pulmonary disease, chronic bronchitis and emphysema.…”

Section: Inhibitors and Activators Involved In Camp Signaling Pathmentioning

confidence: 99%

The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review)

Yan

Gao

Cui

et al. 2016

Molecular Medicine Reports

154

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During development of disease, complex intracellular signaling pathways regulate an intricate series of events, including resistance to external toxins, the secretion of cytokines and the production of pathological phenomena. Adenosine 3′,5′-cyclic monophosphate (cAMP) is a nucleotide that acts as a key second messenger in numerous signal transduction pathways. cAMP regulates various cellular functions, including cell growth and differentiation, gene transcription and protein expression. This review aimed to provide an understanding of the effects of the cAMP signaling pathway and the associated factors on disease occurrence and development by examining the information from a new perspective. These novel insights aimed to promote the development of novel therapeutic approaches and aid in the development of new drugs.

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“…[17][18][19] Using some previous results as starting point, [20][21][22] we successfully synthesized novel triaza-indacene and triaza-cyclopentanaphthalene derivatives 11,14{3} and 11,14{4} respectively, and tetrahydropyrazolopyridines 12{1}, 13{2} and 15{1} in acceptable to good yields, from the reaction of benzotriazolylmethylaminopyrazoles 8 and 9 with the representative terminal alkenes 10{1-4}, following the benzotriazole methodology in solvent-free conditions, under the presence of p-toluenesulfonic acid (PTSA) as catalyst. 23 In our protocol, pyrazolo-benzotriazolyl derivatives 8 and 9 [24][25] were initially prepared as depicted in Scheme 2.…”

Section: Synthesis Of Novel Hydropyrazolopyridine Derivatives Under Smentioning

confidence: 99%

Recent contributions to the Diversity-Oriented Synthesis (DOS) mediated by iminium ions through multicomponent Mannich-type reactions

Abonı́a¹,

Castillo²,

Kotali³

2017

Arkivoc

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This short account summarizes the most recent contributions of the author and his collaborators to the Diversity Oriented Synthesis (DOS) mediated, at least in a step of the process, by Mannich-type reactions (MTR) and using formaldehyde as common starting material in all cases. Through this strategy, diverse nitrogen-containing acyclic and heterocyclic systems were synthesized, whether in straightforward or multicomponent approaches.

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Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors

Cited by 66 publications

References 8 publications

Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay

Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay

The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review)

Recent contributions to the Diversity-Oriented Synthesis (DOS) mediated by iminium ions through multicomponent Mannich-type reactions

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