-transparent.png){kind=logo}
The hydroxamic acid functionality can be incorporated in a variety of simple molecules to produce potent inhibitors of 5-lipoxygenase. As an example of this, the structure-activity relationships in a series of omega-phenylalkyl and omega-naphthylalkyl hydroxamic acids are presented. Among the features described are the influence of hydrophobicity, aryl substitution, and modifications of the hydroxamate group on enzyme inhibitory potency. To assist in the selection of more potent hydroxamic acid inhibitors, a simple hypothesis about the nature of enzyme-inhibitor binding was devised. In this hypothesis, the structures of compounds were matched to a proposed geometry of arachidonic acid when bound to the enzyme. Compounds that match best without extending into disfavored regions were predicted to be the best inhibitors. Three series of hydroxamates selected according to this approach are described. Within these series are some of the most potent inhibitors of 5-lipoxygenase reported to date.
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
April 1999,
Bioorganic & medicinal chemistry letters,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
June 1998,
Chemical & pharmaceutical bulletin,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
January 1997,
Advances in experimental medicine and biology,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
December 2020,
Journal of enzyme inhibition and medicinal chemistry,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
August 1990,
Journal of medicinal chemistry,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
August 1992,
Journal of medicinal chemistry,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
May 1993,
The Journal of antibiotics,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
January 1991,
Agents and actions. Supplements,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
March 2002,
Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti,
J B Summers, and
H Mazdiyasni, and
J H Holms, and
J D Ratajczyk, and
R D Dyer, and
G W Carter
February 2010,
Organic & biomolecular chemistry,
