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Enkoji T

Bio: Enkoji T is an academic researcher. The author has an hindex of 1, co-authored 1 publications receiving 41 citations.

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TL;DR: Preliminary mechanism studies indicated that the 3,4-dihydroxyphenylguanidines act at least partially by a direct alpha-adrenergic mechanism.
Abstract: A series of aromatic guanidines and several 1-phenylbiguanides was prepared and tested for cardiovascular (CV) effects in anesthetized dogs measuring heart rate, blood pressure, carotid artery blood flow, and myocardial force changes. The predominant CV effect at minimally effective dose was vasoconstriction unassociated with cardiac stimulation. The structure-activity relationships of the compounds were discussed comparing their structural similarities to the beta-phenylethylamines. The most potent members of the series were phenylguanidines substituted in the 3 and 4 positions on the aromatic nucleus with hydroxy or chloro groups. Preliminary mechanism studies indicated that the 3,4-dihydroxyphenylguanidines act at least partially by a direct alpha-adrenergic mechanism

42 citations


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TL;DR: Molecular docking studies were conducted in an attempt to enhance the understanding of the observed structure-activity relationship and led to the discovery of [1,3,5]triazine-pyridine as a new series of potent CDK inhibitors.
Abstract: On the basis of previous studies, we identified pyrazine-pyridine A as a potent vascular endothelial growth factor inhibitor and pyrimidine-pyridine B as a moderately potent cyclin dependent kinase (CDK) inhibitor. A proposed combination of CGP-60474 and compound B led to the discovery of [1,3,5]triazine-pyridine as a new series of potent CDK inhibitors. Palladium-catalyzed C-C bond formation reactions, particularly the Negishi coupling reaction, were used to assemble various triazine-heteroaryl analogues effectively. Among them, compound 20 displayed high inhibitory potency at CDK1 (IC(50) = 0.021 microM), CDK2, and CDK5 and submicromolar potency at CDK4, CDK6, and CDK7. Compound 20 also displayed high potency at GSK-3beta. It demonstrated potent antiproliferative activity on various tumor cell lines, including HeLa, HCT-116, U937, and A375. When 20 was administered intraperitoneally at 150 and 125 mg/kg to nude mice bearing human A375 xenografts, the compound produced a significant survival increase. Molecular docking studies were conducted in an attempt to enhance the understanding of the observed structure-activity relationship.

94 citations

Journal ArticleDOI
TL;DR: The syntheses of three new amphiphilic porphyrin derivatives, containing a guanidine, a biguanidine, or an MLS peptide, that were designed to target the cell mitochondria showed low dark toxicity toward human carcinoma HEp2 cells.

87 citations

Journal ArticleDOI
TL;DR: Although curious similarities exist between the structure-activity relationships of the arylpiperazines, arylbiguanides, and aRYlguanidines, it cannot be concluded that all three series of compounds are binding in the same manner.
Abstract: Arylpiperazines are nonselective agents that bind at 5-HT3 serotonin receptors with moderate to high affinity, whereas 1-phenylbiguanide is a low-affinity but more selective 5-HT3 agonist. In an at...

69 citations

Journal ArticleDOI
TL;DR: For a series of monosubstituted arylguanidines, 5-HT3 receptor affinity was found generally related to the electron withdrawing nature of the substituent at the aryL 3-position and the lipophilicity of the 4-position substituents.

47 citations

Journal ArticleDOI
TL;DR: Both 2-aminoimidazoline derivatives and 18b and 26b showed antagonistic properties over alpha(2)-ARs not only in vitro [(35)S]GTPgammaS binding but also in vivo microdialysis experiments and can be considered as potential antidepressants.
Abstract: The efficient preparation and pharmacological characterization of different families of (bis)guanidine and (bis)2-aminoimidazoline derivatives ("twin" and "half" molecules) as potential alpha(2)-adrenoceptor antagonists for the treatment of depression is presented. The affinity toward the alpha(2)-adrenoceptor of all the compounds prepared was measured in vitro in human brain tissue. Additionally, the activity as agonist or antagonist of those compounds with a pK(i) larger than 7 was determined in functional [(35)S]GTPgammaS binding assays in human brain tissue. Finally, the activity of the most promising compounds was confirmed by means of in vivo microdialysis experiments in rats. Compounds 1, 2b, 3b, 12b, 13b, 17b, 18b, 22b, 25b, 26b, 28b, and 30 showed a good affinity toward the alpha(2)-ARs. In general, the 2-aminoimidazoline derivatives displayed higher affinities than their guanidine analogues. Finally and most importantly, compounds 18b and 26b showed antagonistic properties over alpha(2)-ARs not only in vitro [(35)S]GTPgammaS binding but also in vivo microdialysis experiments. Moreover, both compounds have shown to be able to cross the blood-brain barrier and, therefore, they can be considered as potential antidepressants.

43 citations