Novel N-thiazolyl piperazine-1-carboxamide CCR2 antagonists – investigation of an unexpected reaction with glutathione

Cumming, John G.; MacFaul, Philip A.; Leach, Andrew G.

doi:10.1039/c5md00362h

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…A few promising drug candidates are shown in Figure . Compound 1 , also known as AZ12567889, has been reported by AstraZeneca to stand out because of its highly potent rodent affinity as well as good pharmacokinetic properties including CNS penetration . Furthermore, it has been used in a preclinical model of neuropathic pain to reverse hyperalgesia .…”

Section: Resultsmentioning

confidence: 68%

“…Compound 1, also known as AZ12567889, has been reported by AstraZeneca to stand out because of its highly potent rodent affinity as well as good pharmacokinetic properties including CNS penetration. 40 Furthermore, it has been used in a preclinical model of neuropathic pain to reverse hyperalgesia. 41 Compounds 2 (INCB8761/PF-4136309) 42 and 3 (INCB3284) 43 both exhibited potent hCCR2 activity, combined with high selectivity over other chemokine receptors and GPCRs and reasonable oral bioavailability.…”

Section: Antagonist Selectionmentioning

confidence: 99%

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Synthesis, ³H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Artelsmair

Miranda-Azpiazu

Kingston

et al. 2019

Labelled Comp Radiopharmac

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The immune system is implicated in the pathology of neurodegenerative disorders. The C‐C chemokine receptor 2 (CCR2) is one of the key targets involved in the activation of the immune system. A suitable ligand for CCR2 could be a useful tool to study immune activation in central nervous system (CNS) disorders. Herein, we describe the synthesis, tritium radiolabelling, and preliminary in vitro evaluation in post‐mortem human brain tissue of a known potent small molecule antagonist for CCR2. The preparation of a tritium‐labelled analogue for the autoradiography (ARG) study gave rise to an intriguing and unexpected side reaction profile through a novel amination of ethanol and methanol in the presence of tritium. After successful preparation of the tritiated radioligand, in vitro ARG measurements on human brain sections revealed nonspecific binding properties of the selected antagonist in the CNS.

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Section: Resultsmentioning

confidence: 68%

Section: Antagonist Selectionmentioning

confidence: 99%

Synthesis, ³H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Artelsmair

Miranda-Azpiazu

Kingston

et al. 2019

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

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Pd(OAc)2-catalyzed synthesis of benzyl phenyl ether derivatives with H2O2 as an oxidant in neat water

Chen

Zhang

Yang

2019

Catalysis Communications

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Novel N-thiazolyl piperazine-1-carboxamide CCR2 antagonists – investigation of an unexpected reaction with glutathione

Abstract: A series of CCR2 antagonists containing halothiazoles were found to undergo an unexpected reaction with glutathione.

Cited by 2 publications

References 14 publications

Synthesis, ³H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Synthesis, ³H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Pd(OAc)2-catalyzed synthesis of benzyl phenyl ether derivatives with H2O2 as an oxidant in neat water

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Novel N-thiazolyl piperazine-1-carboxamide CCR2 antagonists – investigation of an unexpected reaction with glutathione

Abstract: A series of CCR2 antagonists containing halothiazoles were found to undergo an unexpected reaction with glutathione.

Cited by 2 publications

References 14 publications

Synthesis, 3H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Synthesis, 3H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Pd(OAc)2-catalyzed synthesis of benzyl phenyl ether derivatives with H2O2 as an oxidant in neat water

Contact Info

Product

Resources

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Synthesis, ³H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2

Synthesis, ³H‐labelling and in vitro evaluation of a substituted dipiperidine alcohol as a potential ligand for chemokine receptor 2