Discovery of piperidine carboxamide TRPV1 antagonists

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 16; pp. 4569 - 4572
• Main Authors: Cheung, Wing S., Calvo, Raul R., Tounge, Brett A., Zhang, Sui-Po, Stone, Dennis R., Brandt, Michael R., Hutchinson, Tasha, Flores, Christopher M., Player, Mark R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-08-2008; Elsevier
• Subjects: Amides - chemistry; Analgesics; Benzoxazines - chemistry; Benzoxazines - pharmacology; Biological and medical sciences; Capsaicin; Capsaicin - chemistry; Carrier Proteins - antagonists & inhibitors; Chemistry, Pharmaceutical - methods; Drug Design; Humans; Inhibitory Concentration 50; Medical sciences; Models, Chemical; Molecular Conformation; Neuropharmacology; Pharmacology. Drug treatments; Piperidines - chemistry; Protein Binding; Quantitative Structure-Activity Relationship; Structure-Activity Relationship; TRPV Cation Channels - antagonists & inhibitors; TRPV1; VR1; VR1; Capsaicin; TRPV1; Rat; Lactam; Hyperalgesia; TRPV1 vanilloid receptor; Structure activity relation; Bicyclic compound; Aromatic compound; Antagonist; Chemical synthesis; Oxygen nitrogen heterocycle; Human; Rodentia; Benzene derivatives; Oral administration; In vitro; In vivo; Vertebrata; Chemotherapy; VR1 vanilloid receptor; Mammalia; Treatment; Analgesic; TRP ion channel; Animal; Affinity; Carboxamide; Fluorine Organic compounds
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.07.035

A series of piperidine carboxamides were developed as potent antagonists of the transient receptor potential receptor vanilloid 1 (TRPV1), an emerging target for the treatment of pain. A focused library of polar head groups led to the identification of a benzoxazinone amide that afforded good potency in cell-based assays. Synthesis and a QSAR model will be presented.
A series of piperidine carboxamides were developed as potent antagonists of the transient receptor potential vanilloid-1 (TRPV1), an emerging target for the treatment of pain. A focused library of polar head groups led to the identification of a benzoxazinone amide that afforded good potency in cell-based assays. Synthesis and a QSAR model will be presented.