Kikuo Sugimoto

Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo

The suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption was examined in vitro and in vivo. This synthetic peptidyl aldehyde was found to be a potent and selective cathepsin L inhibitor in our screening for cysteine protease inhibitors. In the pit formation assay with unfractionated rat bone cells, 1.5 nM of this compound markedly inhibited parathyroid hormone-stimulated osteoclastic bone resorption. In addition, intraperitoneal administration of this peptidyl aldehyde (2.5-10 mg/kg) for 4 weeks suppressed bone weight loss dose dependently in the ovariectomized mouse, experimental model of osteoporosis. Hydroxyproline measurement of the decalcified femurs from these ovariectomized mice suggested that this compound acts as a bone resorption suppressor through the inhibition of collagen degradation.

Peptidyl aldehyde derivatives as potent and selective inhibitors of cathepsin L

Abstract A series of peptidyl aldehyde derivatives were synthesized and tested for their inhibitory effects on several cysteine proteases and a serine protease. These componds showed no inhibition for α-chymotrypsin at the concentration less than 1000 ng/ml, while they exhibited prominent inhibition for calpain II and cathepsins, especially cathepsin L.

Sphingomyelin analogues as inhibitors of sphingomyelinase.

To search for neutral sphingomyelinase inhibitors we designed and synthesized hydrolytically stable analogues of sphingomyelin. The novel compounds 8 and 9 which were replaced the phosphodiester moiety of sphingomyelin with the carbamate moiety showed inhibitory activity with an IC(50) value of micro M on neutral sphingomyelinase in rat brain microsomes. Compound 8i showed a selective neutral sphingomyelinase inhibitory activity.

A new selective dichlorination of CC double bonds

Abstract A new dichlorination procedure of CC double bond was developed with hexachloroethane as chlorinating agent and RuCl2(PPh3)3 as catalyst. The reaction is highly selective for CC double bond; other functional groups are unaffected by these conditions.