Novel quinuclidinyl heteroarylcarbamate derivatives as muscarinic receptor antagonists.
Herein, we describe the synthesis and pharmacological profiles of novel quinuclidinyl heteroarylcarbamate derivatives. Among them, the quinuclidin-4-yl thiazolylcarbamate derivative ASP9133 was identified as a promising long-acting muscarinic antagonist (LAMA) showing more selective inhibition of bronchoconstriction against salivation and more rapid onset of action in a rat model than tiotropium bromide.
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: shinya.nagashima@astellas.com.
Shinya
S
Nagashima
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Yuji
Y
Matsushima
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Hisao
H
Hamaguchi
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Hiroshi
H
Nagata
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Toru
T
Kontani
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Ayako
A
Moritomo
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Tadatsura
T
Koshika
Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Makoto
M
Takeuchi
D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011812:Quinuclidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D002219:Carbamates; D011812:Quinuclidines; D043587:Receptor, Muscarinic M3
ASP9133; COPD; In vivo selectivity; Long acting muscarinic receptor antagonist