Skin- and airway-deliverable TRPA1 inhibitor.
Bioorg Med Chem
; 110: 117812, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38941887
ABSTRACT
This study explored the potential of perfumery compounds as sources of transient receptor potential ankyrin 1 (TRPA1) inhibitors that could be formulated for effective delivery to the skin and airways. A highly potent, small, and selective TRPA1 inhibitor, 2-methyl-4-phenyl-1-pentanol (1), was discovered in perfumery compounds. Compound 1 demonstrated promising inhibitory activity against a broad range of TRPA1 agonists. A single stereoisomer of 1 was identified as the most effective TRPA1 inhibitor, indicating the potential for stereoselective synthesis to enhance its potency. Additionally, the structure-activity relationship of 1 was evaluated to elucidate the structural features of TRPA1 inhibitors within the fragrance-like compounds. Notably, the topical application of 1 alleviated sensory irritation in individuals with sensitive skin, while the inhalation of 1 resulted in a significant reduction in ammonia irritation, underscoring its efficacy in both skin and airway applications.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Canal de Cátion TRPA1
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article