Kosuke Kanuma

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Melanin-concentrating hormone (MCH) is a cyclic peptide produced in the lateral hypothalamus. It has been implicated in a number of physiological processes including feeding behavior, energy balance, and the regulation of emotional states. Here, we report in vitro and in vivo profiles of ATC0065(More)
The analgesic activity and side effect liabilities of a novel NR2B antagonist, 7-hydroxy-6-methoxy-2-methyl-1-(2-(4-(trifluoromethyl)phenyl)ethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (HON0001) were investigated. HON0001 inhibited [3H]MK-801 binding to rat brain membranes in a biphasic manner, with IC50 values of 54.68+/-4.96 nM and 46.48+/-5.85 muM(More)
The glutamate hypothesis of schizophrenia suggests that hypofunction of N-methyl-D-aspartate (NMDA) receptors may be critical for schizophrenic symptoms; therefore, pharmacological approaches that enhance NMDA function may be beneficial for the treatment of schizophrenia. Several lines of evidence indicate that NMDA and metabotropic glutamate (mGlu) 5(More)
Melanin-concentrating hormone receptor 1 (MCH1 receptor) is known to be involved in the control of mood and stress, in addition to the regulation of feeding. Here, we report further evidence that the blockade of the MCH1 receptor exhibits antidepressant and anxiolytic-like effects in a variety of animal models using TASP0382650 and TASP0489838, newly(More)
The optimization of the distance between two key pharmacophore features within our first hit compounds 1a and 2a led to the identification of a new class of potent non-peptidic antagonists for the MCH-R1, based around 4-amino-2-cyclohexylaminoquinazolines. In particular, ATC0065 (2c),(More)
The optimization of a series of 4-(dimethylamino)quinazoline antagonists of the melanin-concentrating hormone receptor 1 (MCH-R1) is described. The combination of the elaboration of both the linker portion and the terminal phenyl ring provided N-(cis-4-{[4-(dimethylamino)quinazolin-2-yl]amino}cyclohexyl)-3,4-difluorobenzamide hydrochloride 28 (ATC0175),(More)
A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic(More)
A series of 4-(dimethylamino)quinazoline based antagonists of the melanin-concentrating hormone receptor 1 (MCH-R1) is described. This series was derived from a lead compound, AR129330, identified by HTS of a GPCR-directed library using a functional assay with a constitutively activated (CART) form of the receptor. The preliminary optimization resulted in(More)
Isolated rat hepatocytes possess a saturable glucocorticoid uptake system with high affinity (Kd value = 2.8 +/- 0.7 x 10(-8) M; 318,000 +/- 80,000 binding sites per cell; 317 fmol/mg protein). The initial rates of uptake decrease by about 30-40% if the cells are incubated simultaneously with [3H]corticosterone and either SH-reagents (N-ethylmaleimide and(More)
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