Masataka Shoji

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Cilnidipine is a 1,4-dihydropyridine derived L/N-type calcium channel dual blocker possessing neuroprotective and analgesic effects which are related to its N-type calcium channel inhibitory activity. In order to find specific N-type calcium channel blockers with the least effects on cardiovascular system, we performed structure-activity relationship study(More)
Antiallergic drug cyproheptadine (Cyp) is known to have inhibitory activities for L-type calcium channels in addition to histamine and serotonin receptors. Since we found that Cyp had an inhibitory activity against N-type calcium channel, Cyp was optimized to obtain more selective N-type calcium channel blocker with analgesic action. As a consequence of the(More)
We report a set of strategies to develop novel ligands (Structure Based and Experimental Selection of Fragments: SbE-SF). First, a docking simulation utilizing DOCK3.5 is performed in order to screen the fragment database, which was generated with the in-house program FRAGMENT++ specifically for docking simulation purposes. Although the affinity of these(More)
A structure-activity relationship study of 6-unsubstituted-1,4-dihydropyridine and 2,6-unsubstituted-1,4-dihydropyridine derivatives was conducted in an attempt to discover N-type calcium channel blockers that were highly selective over L-type calcium channel blockers. Among the tested compounds,(More)
Cilnidipine is a 1,4-dihydropyridine-derived voltage-dependent calcium channel (VDCC) blocker and suppresses N-type VDCC currents in addition to L-type VDCC currents. An earlier investigation has suggested that intrathecally injected cilnidipine produces antinociception by blocking N-type VDCCs in mice. The present study using the rat formalin model(More)
In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the(More)
Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. We describe the discovery of APY0201, a unique small molecular IL-12/23 production inhibitor, from activated macrophages and(More)
A series of isoxazole derivatives were synthesized and their antagonistic activities against LPA stimulation on both LPA(1)/CHO cells and rHSC cells were evaluated. Among them, 3-(4-[4-[1-(2-chloro-cyclopent-1-enyl)-ethoxycarbonylamino]-isoxazol-3- y]]-benzylsulfanyl)-propionic acid (34) showed the most potent activities.
An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method,(More)
An inhibitor of the complex of factor VIIa and tissue factor (fVIIa/TF), 2-substituted-4-amidinophenylpyruvic acid 1a, was structurally modified with the aim of increasing its potency and selectivity. The lead compound 1a was originally found in our factor Xa (fXa) inhibitor library on the basis of structural similarity of the primary binding sites of fVIIa(More)