Discovery of a muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors among 2-[(1S,3S)-3-sulfonylaminocyclopentyl]phenylacetamide derivatives.

  title={Discovery of a muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors among 2-[(1S,3S)-3-sulfonylaminocyclopentyl]phenylacetamide derivatives.},
  author={Morihiro Mitsuya and Yoshio Ogino and Kumiko Kawakami and Minaho Uchiyama and T. Kimura and Tomoshige Numazawa and Takuro Hasegawa and Norikazu Ohtake and Kazuhito Noguchi and Toshiaki Mase},
  journal={Bioorganic \& medicinal chemistry},
  volume={8 4},
Stereoselective synthesis of oxazolidinonyl-fused piperidines of interest as selective muscarinic (M1) receptor agonists: a novel M1 allosteric modulator.
The bicyclic system with a 2-furyl substituent at C2 was identified as an important target and the (1RS,2SR,6SR) nonan-8-ones with substituents at C1 that could facilitate C2 deprotonation were unstable with respect to oxazolidinone ring-opening and this restricted both the synthetic approach and choice of 2-heteroaryl substituENT.
Medicinal chemistry and therapeutic potential of muscarinic M3 antagonists
The introduction of selective M3 antagonists has not improved clinical efficacy compared with the old non‐selective antimuscarinics but has reduced the rate of adverse events mediated by the blockade of cardiac M2 receptors (tachycardia) and central M1 receptors (cognitive impairment).
All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain microvascular endothelium
All muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells and it is argued that research on drug development should especially focus on the allosteric binding sites of the M1 and M3 receptors.
Cycloaddition reaction of schiff bases with ketenes generated by pyrolysis of 2‐aryl‐substituted 1,5,7‐trioxaspiro[2.5]octane‐4,8‐diones
The α-oxo ketenes 6 which are generated by the pyrolysis of the 2-aryl-substituted 1,5,7-trioxaspiro[2.5]octane-4,8-diones 1, were reacted with Schiff bases 2 to give spiro compounds constructed
Changes in Cyclooxygenase-2’s Expression, and PGE2 ’s and 6-keto-PGF1α’s Levels in the Presence of the Muscarinic Acethylcholine Receptor Antibody in Primary Sjögren Syndrome
The levels and the generation of PGE2, 6-keto-PGF1α by Enzyme-linked immunoabsorbent assay (ELISA), cyclic AMP (cAMP) by cAMPc-RIA kit and COX-2 mRNA gene’s expression at Real Time PCR in rat


Muscarinic receptor subtypes.
The aim of this review is to discuss the structure, function, and binding properties of the different muscarinic receptor species, attempting where possible to coordinate the diverse experimental data into a uniform picture.
Distinct primary structures, ligand‐binding properties and tissue‐specific expression of four human muscarinic acetylcholine receptors.
Differences among subtypes in the affinities and proportions of such sites suggest the capacity of mAChR subtypes to interact differentially with the cellular effector‐coupling apparatus.
Identification of a family of muscarinic acetylcholine receptor genes.
Analysis of human and rat genomic clones indicates that there are at least four functional muscarinic receptor genes and that these genes lack introns in the coding sequence.
Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor
Cloning and sequence analysis of DNA complementary to porcine cerebral messenger RNA encoding the muscarinic acetylcholine receptor predict the complete amino-acid sequence of this protein.