Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl carbamates as potent and long acting muscarinic antagonists

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• 作者：Maria Prat^a ; ^{maria.prat@almirall.com"" rel=""nofollow} ; Marí ; a Antonia Buil^a ; Maria Dolors Ferná ; ndez^b ; Jordi Castro^a ; Juan Manuel Monle&#xf3 ; n^a ; Laia Tort^a ; Gaspar Casals^a ; Manuel Ferrer^a ; Josep Maria Huerta^a ; S&#xf2 ; nia Espinosa^a ; Manuel L&#xf3 ; pez^a ; Victor Segarra^a ; Amadeu Gavaldà ; ^a ; Montserrat Miralpeix^a ; Israel Ramos^a ; Dolors Vilella^a ; Marisa Gonzá ; lez^a ; M&#xf2 ; nica C&#xf3 ; rdoba^a ; Alvaro Cá ; rdenas^c ; Francisca Ant&#xf3 ; n^d ; Jorge Beleta^a ; Hamish Ryder^e
• 关键词：(3R)-Quinuclidinyl carbamates ; M₃ Muscarinic antagonists ; Long acting bronchodilators ; Low systemic exposure ; COPD
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 June 2011
• 年：2011
• 卷：21
• 期：11
• 页码：3457-3461
• 全文大小：425 K

文摘

Novel quaternary ammonium derivatives of N,N-disubstituted (3R)-quinuclidinyl carbamates have been identified as potent M₃ muscarinic antagonists with long duration of action in an in vivo model of bronchoconstriction. These compounds have also presented a high level of metabolic transformation (human liver microsomes). The synthesis, structure–activity relationships and biological evaluation of these compounds are reported.