SYNTHESIS, CHEMICAL, AND BIOLOGICAL PROPERTIES OF VINYLOGOUS HYDROXAMIC ACIDS - DUAL INHIBITORS OF 5-LIPOXYGENASE AND IL-1 BIOSYNTHESIS

被引：19

作者：

WRIGHT, SW ^{[1
]}

HARRIS, RR ^{[1
]}

KERR, JS ^{[1
]}

GREEN, AM ^{[1
]}

PINTO, DJ ^{[1
]}

BRUIN, EM ^{[1
]}

COLLINS, RJ ^{[1
]}

DOROW, RL ^{[1
]}

MANTEGNA, LR ^{[1
]}

SHERK, SR ^{[1
]}

COVINGTON, MB ^{[1
]}

NURNBERG, SA ^{[1
]}

WELCH, PK ^{[1
]}

NELSON, MJ ^{[1
]}

MAGOLDA, RL ^{[1
]}

机构：

[1] DUPONT CO,DEPT CENT RES & DEV,WILMINGTON,DE

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 22期

关键词：

D O I：

10.1021/jm00100a011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.

引用

页码：4061 / 4068

页数：8

共 49 条

[1] NITROXIDES(AMINYL OXIDES) .39. FORMATION OF POLYCYCLIC DIMERS FROM VINYL NITROXIDES AND THEIR DISSOCIATION AND ISOMERIZATION [J].