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We synthesized diaminobutane derivatives as potent Ca 2+ -permeable AMPA receptor antagonists with non-hypotensive activity. Compound 10c showed selective Ca 2+ -permeable AMPA receptor antagonist activity and neuroprotective effects in transient global ischemia models in gerbils.

A series of 2-(biphenylmethyl)glutaric acid amide derivatives were synthesized and evaluated for NEP inhibitory activity. The mode of inhibitor-enzyme interactions of the most potent compound 3a, with a thiazolylacetic acid group at the P2' position, was evaluated by a computer analysis.

A series of glutaric acid amide derivatives were synthesized and tested for NEP inhibitory activity. Compounds 14a, 14b, 16a and 22, with a biphenylmethyl group at P′1 position, showed potent inhibitory activity.

In the early 1990's, we reported on the low-molecular selective fXa inhibitor DX-9065a having two amidino groups. However, it had poor oral bioavailability due to its strong basic amidino groups. To obtain fXa inhibitors with improved oral bioavailability, we investigated various non-amidino fXa inhibitors and finally discovered cis-1,2-diaminocyclohexane derivative 4c to have potent fXa inhibition, promising anticoagulant activity, and good oral bioavailability, compared with amidino compound DX-9065a. In addition, we will discuss the influence of the third substituent on the cyclohexane ring on anti-fXa activity, anticoagulant activity, PK profile, and lipophilicity.

An enantioselective synthesis of (+)-brefeldin C has been achieved using Lewis acid mediated cyclization of a chiral epoxy-allylsilane as a key step.

The hydrindanol (2), a C/D-ring synthon of vitamin D3 metabolites, has been synthesized enantioselectively by the use of stereoselective epoxy alcohol-initiated polyalkene cyclisation as a key step.