2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists

Ryu, Hyung-Chul; Seo, Sejin; Kim, Myeong Seop; Kim, Mi Yeon; Kim, Ho Shin; Ann, Jihyae; Tran, Phuong Thao; Hoang, Van-Hai; Byun, Jieun; Cui, Minghua; Son, Karam; Sharma, Pramod Kumar; Choi, Sun; Blumberg, Peter M.; Frank-Foltyn, Robert; Bahrenberg, Gregor; Koegel, Babette Yvonne; Christoph, Thomas; Frormann, Sven; Lee, Jeeyeon

doi:10.1016/j.bmcl.2014.05.072

Cited by 16 publications

(5 citation statements)

References 23 publications

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“…Within the 2‐arylsubstituted pyridine, propanamide analogs such as 48 (Fig. ) showed antiallodynia in a mouse neuropathic pain model and blocked capsaicin‐induced hypothermia in a dose‐dependent manner . In this study, the SARs of 2‐alkyl/alkenyl pyridine derivatives, as hTRPV1 antagonists, were also investigated.…”

Section: Medicinal Chemistry Of Trpv1 Antagonistsmentioning

confidence: 96%

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Tabrizi

Baraldi

et al. 2016

Medicinal Research Reviews

129

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Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury. TRPV1 activation has been associated to chronic inflammatory pain and peripheral neuropathy. Its expression is also detected in nonneuronal areas such as bladder, lungs, and cochlea where TRPV1 activation is responsible for pathology development of cystitis, asthma, and hearing loss. This review offers a comprehensive overview about TRPV1 receptor in the pathophysiology of chronic pain, epilepsy, cough, bladder disorders, diabetes, obesity, and hearing loss, highlighting how drug development targeting this channel could have a clinical therapeutic potential. Furthermore, it summarizes the advances of medicinal chemistry research leading to the identification of highly selective TRPV1 antagonists and their analysis of structure-activity relationships (SARs) focusing on new strategies to target this channel.

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Section: Medicinal Chemistry Of Trpv1 Antagonistsmentioning

confidence: 96%

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Tabrizi

Baraldi

et al. 2016

Medicinal Research Reviews

129

View full text Add to dashboard Cite

show abstract

“…This family of transmembrane receptors (TRPV1 to TRPV6) is found in several tissues and mediates the influx of Ca 2+ into the cytosol [ 199 ]. The TRPV receptors can be activated by many stimuli such as proton (H + ), heat, and natural substances such as 28 , 77, and resiferatoxin [ 200 , 201 , 202 ]. In sensory neuronal fibers, the activation of TRPV1 by 77 triggers a rapid increase in Ca 2+ flux, causing neuronal depolarization and the characteristic burning sensation [ 203 , 204 , 205 , 206 ].…”

Section: Literature-related Cytotoxic Compoundsmentioning

confidence: 99%

Peppers: A “Hot” Natural Source for Antitumor Compounds

et al. 2021

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Piper, Capsicum, and Pimenta are the main genera of peppers consumed worldwide. The traditional use of peppers by either ancient civilizations or modern societies has raised interest in their biological applications, including cytotoxic and antiproliferative effects. Cellular responses upon treatment with isolated pepper-derived compounds involve mechanisms of cell death, especially through proapoptotic stimuli in tumorigenic cells. In this review, we highlight naturally occurring secondary metabolites of peppers with cytotoxic effects on cancer cell lines. Available mechanisms of cell death, as well as the development of analogues, are also discussed.

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“…We next examined this simple arylation protocol in the synthesis of biaryl-containing compounds of valuable biological and pharmacological properties (Scheme ). For example, key precursors of TRPV1 antagonists, 3ca , 3cd , and 3ce , were readily obtained using economical nicotinonitrile 1c by this one-pot arylation protocol with iodonium salts under standard conditions. Biaryl 3aq , a key intermediate of AT1 receptor antagonists, was readily prepared from nicotinonitrile 1a in one step (Scheme b).…”

mentioning

confidence: 92%

Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts

Liu

Wang

2016

Org. Lett.

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Arylation, vinylation, and alkynylation of electron-deficient arenes and heteroarenes have been achieved by chemoselective C-H zincation followed by copper-catalyzed coupling reactions using iodonium salts. This approach offers a direct and general access to a wide scope of (hetero)biaryls as well as alkenylated and alkynylated heteroarenes under mild conditions. It is particularly useful and valuable for the rapid and modular synthesis of diverse (hetero)aryl compounds, as demonstrated in the synthesis of transient receptor potential vanilloid 1 (TRPV1) antagonists and angiotensin II receptor type 1 (AT1 receptor) antagonists.

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2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists

Cited by 16 publications

References 23 publications

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Peppers: A “Hot” Natural Source for Antitumor Compounds

Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts

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