Hiroshi Miyauchi

Fatty acid amide hydrolase substrate specificity.

Fatty acid amide hydrolase (FAAH), also referred to as oleamide hydrolase and anandamide amidohydrolase, is a serine hydrolase responsible for the degradation of endogenous oleamide and anandamide, fatty acid amides that function as chemical messengers. FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural fatty acid primary amide substrates using pure recombinant rat FAAH.

α-Keto heterocycle inhibitors of fatty acid amide hydrolase: carbonyl group modification and α-substitution

Two sets of novel analogues of the recently disclosed α-keto heterocycle inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for regulation of endogenous oleamide and anandamide, were synthesized and evaluated in order to clarify a role of the electrophilic carbonyl group and structural features important for their activity. Both the electrophilic carbonyl and the degree of α-substitution markedly affect inhibitor potency.

Synthesis and antifungal activity of new azole derivatives containing an oxathiane ring

Abstract A series of azole derivatives containing an oxathiane ring, which were designed to simulate the D ring of lanosterol, were synthesized and evaluated for their antifungal activity. 3,3-Dimethyl derivatives showed potent activity against murine systemic candidosis and aspergillosis, whereas (2R ∗ ,3R ∗ )-3- monomethyl derivatives showed only weak activity in both in vitro and in vivo.

Structure-activity relationships of sulfur-containing triazole antifungals

Abstract Alkylthio and alkylsulfonyl derivatives of antifungal SM-8668 ( 3 ) were synthesized and estimated for their activities in vitro and in vivo . Derivatives having pentylthio, heptylthio or nonylthio group showed potent activities against both candidiasis and aspergillosis. The introduction of hydroxyl group at the end of their alkyl chain made their activities stronger.

Synthesis and inhibitory effects of bivalent sialyl lewis X analogs at preventing cell adhesion

Abstract Several sialyl Lewis X (SLeX) dimers attached to symmetric linkers, 1,3-di(ω-hydroxyalkyl)-benzene, 1,3-di(ω-hydroxyalkoxy)benzene, and 1,3-di(ω-hydroxyalkoxy)cyclohexane, were synthesized and evaluated for their inhibitory activity against adhesion of HL-60 cells to recombinant soluble E-selectin. The SLeX dimers showed 4 to 6-fold higher inhibitory activity than the corresponding monomers.

Synthesis and inhibitory effect of a sialyl lewis X-acrylamide homopolymer at preventing cell adhesion

Abstract A novel glycopolymer, a homopolymer of conjugated SLeX-acrylamide, was synthesized and evaluated for its inhibitory activity against E-selectin mediated cell adhesion both in vitro and in vivo. The homopolymer showed approximately 10-fold higher activity per SLeX unit than the corresponding SLeX-acrylamide monomer in vitro and was significantly more effective in an LTA-induced murine pleurisy model.

SYNTHESIS AND ANTIFUNGAL ACTIVITIES OF OPTICALLY ACTIVE ISOMERS OF SM-8668

Abstract Synthesis and antifungal activities of optically active isomers of SM-8668 ( 1 ) are described. These isomers were prepared in eight steps from m -difluorobenzene. The crucial step was optical resolution of a synthetic intermediate dl - threo -2-(2,4-difluorophenyl)-2-(1-methylthio)ethyloxirane ( 2 ). Only (2R,3R)-isomer of 1 showed potent antifungal activities both in vitro and in vivo .

Synthesis and antifungal activity of alkylthio and alkylsulfonyl derivatives of SM-8668

Triazole analogues which contained alkylthio or alkylsulfonyl groups where synthesized as derivatives of antifungal SM-8668 and estimated for their in vitro and in vivo activity. Derivatives having pentylthio, heptylthio or nonylthio groups showed excellent efficacy against both candidiasis and aspergillosis. Introduction of a hydrophilic group at the end of their alkyl chain made their activity stronger. Especially, 5-hydroxypentylthio and 7-hydroxyheptylthio derivatives showed the strongest antifungal activity.

Stereoselective synthesis of lewis-associated trisaccharides as E-selectin inhibitors

Abstract Three types of Lewis-associated trisaccharides [the Le a analogs, their epimers with respect to the fucose residue (the 1 c-epi-Le a analogs), and the Le x analogs] were synthesized in a stereoselective manner. Not only the Le a analogs but also the 1 c-epi-Le a analogs inhibited E-selectin-mediated neutrophil accumulation into pleural cavity in lipoteichoic acid-treated mice, with the trend being Le a > 1 c-epi-Le a > Le x .