J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors.

  title={J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors.},
  author={Morihiro Mitsuya and Toshiaki Mase and Yoshimi Tsuchiya and Kumiko Kawakami and Hanae Hattori and K. Kobayashi and Yoshio Ogino and Toru Fujikawa and Atsushi Satoh and T. Kimura and Kazuhito Noguchi and Norikazu Ohtake and K Tomimoto},
  journal={Bioorganic \& medicinal chemistry},
  volume={7 11},
Discovery of 2-aminothiazole-4-carboxamides, a novel class of muscarinic M(3) selective antagonists, through solution-phase parallel synthesis.
In the course of searching for a muscarinic M(3) antagonist with a structure distinct from those of the 2-(4,4-difluorocyclopentyl)-2-phenylacetamide derivatives, a thiazole-4-carboxamide derivative was identified as a lead compound in the in-house chemical collection.
A new series of M3 muscarinic antagonists based on the 4-amino-piperidine scaffold.
Novel, highly selective, muscarinic M3 receptor antagonists
  • Biology, Chemistry
  • 2001
A series of muscarinic receptor antagonists based upon a polyamide backbone linking a trityl group and a N-alkylpiperidine, or N,N-dialkylpiperidinium group, are claimed. The linking group may be
1,5-Benzodioxepin derivatives as a novel class of muscarinic M3 receptor antagonists.
Functional activation of G-proteins coupled with muscarinic acetylcholine receptors in rat brain membranes.
All of the data suggest that functional activation of Gi/o proteins coupled to mAChRs, especially the M4 subtype, is detectable by means of CCh-stimulated [(35)S]GTPγS binding assay in rat discrete brain regions.
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).


Synthesis and antimuscarinic activity of some 1-cycloalkyl-1-hydroxy-1-phenyl-3-(4-substituted piperazinyl)-2-propanones and related compounds.
Results of this study are consistent with the proposition that the described piperazinylpropanones interact with muscarcinic receptors in a hydrogen-bonded form that presents a conformation similar to that apparently adopted by classical antimuscarinic agents.
18F-labeled benzamides for studying the dopamine D2 receptor with positron emission tomography.
Results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors and are suitable candidates for further evaluation in positron emission tomography imaging studies.
Agents for the treatment of overactive detrusor. VI. Synthesis and pharmacological properties of acetamide derivatives bearing cyclic amines in N-substituents.
With the aim of improving of the efficacy and decreasing the side effects of oxybutynin (1), N-[(tetrahydro-3- or 4-pyridyl)methyl]-, N-(4-piperidyl)-, and N-(3- or
Synthesis and angiotensin converting enzyme inhibitory activity of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. I.
The most prolonged activity in vivo was observed with (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2, 3, 4, 5-tetrahydro-1, 5,benzothiazepine-5-acetic acid (8c : CV-5975) on i.v. and p.o. administrations.
Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography.
The high-yield preparation and specificity and selectivity of high specific activity [125I]IQNP for muscarinic receptors suggest that this is an attractive new agent for potential imaging of cerebral receptors using single photon tomographic imaging (SPECT).
Agents for the treatment of overactive detrusor. III. Synthesis and structure-activity relationships of N-(4-amino-2-butynyl)acetamide derivatives.
A series of N-(4-amino-2-butynyl)acetamides were synthesized and examined for their inhibitory activity on detrusor contraction and mydriatic activity as an index of anticholinergic side effect and showed equipotent inhibitoryactivity on detrousor contraction to oxybutynin.
Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs.
(R)OXY may offer no significant pharmacological advantage over (R/S)O XY in terms of its principal therapeutic and side effect profile, and it appears that (R)/S OXY resides predominantly in the (R)-enantiomer.
Parasympatholytic (anticholinergic) esters of the isomeric 2-tropanols. 1. Glycolates.
Several esters had significantly greater activity in both the peripheral and central nervous systems than did the reference compounds and were more potent than either its epimer (-)-2beta-tropanol or its optical isomer(-)-2alpha- Tropanol.