Kathryn L. Chapman

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L-745,870,(3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H- pyrollo[2,3-b] pyridine, was identified as a selective dopamine D4 receptor antagonist with excellent oral bioavailability and brain penetration. L-745,870 displaced specific binding of 0.2 nM [3H] spiperone to cloned human dopamine D4 receptors with a binding affinity (Ki) of 0. 43 nM which was 5-(More)
In the present study we have described an ex vivo binding assay in mice to measure the central nervous system (CNS) activity of systemically administered CCKB receptor antagonists. This assay incorporated a transcardiac perfusion step to remove the residual blood from the brain, which otherwise may result in an overestimation of CNS activity. The(More)
In rat isolated perfused tail arteries, dose-response curves were established for the vasopressor effects of phenylephrine (alpha 1-adrenoceptor agonist), clonidine (alpha 1- and alpha 2-adrenoceptor agonist), clonidine in the presence of 10(-7) mol/l prazosin (alpha 2-agonist), and BHT-920 (alpha 2-agonist). The ED50 values were: phenylephrine 1.85 X(More)
Histone lysine methyltransferases (HKMTs) are an important class of targets for epigenetic therapy. 1 (chaetocin), an epidithiodiketopiperazine (ETP) natural product, has been reported to be a specific inhibitor of the SU(VAR)3-9 class of HKMTs. We have studied the inhibition of the HKMT G9a by 1 and functionally related analogues. Our results reveal that(More)
A novel series of 5-amino-1,4-benzodiazepin-2-one derivatives (amidines), which contain a cationic solubilizing group and which are antagonists for the cholecystokinin (CCK)-B receptor, have been identified. Optimization of this series led to the identification of an azabicyclononane amidine, L-740,093(More)
Many pharmacological studies have demonstrated two distinct types of alpha adrenoceptor in the vasculature; these receptors have been named alpha-1 and alpha-2. In the present study, using isolated perfused tail arteries from normotensive Sprague-Dawley rats, we have demonstrated two types of alpha adrenoceptor but neither of these could be classified as an(More)
Melanocortin-4 receptor (MC4R) has an important regulatory role in energy homeostasis and food intake. Peptide agonists of the MC4R are characterized by the conserved sequence His(6)-Phe(7)-Arg(8)-Trp(9), which is crucial for their interaction with the receptor. This investigation utilized the covalent attachment approach to identify receptor residues in(More)
Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the(More)
The design, synthesis, and biological activity of a novel series of CCK-B receptor antagonists (1) which incorporate a tetrazol-5-ylamino functionality attached to the phenyl ring of the arylurea moiety of L-365,260 are described. In these compounds, the acidity of the tetrazole was gradually modified by utilization of simple conformational constraints, and(More)