Development of a series of phenyltetrazole leukotriene D4(LTD4) receptor antagonists

Abstract

A hypothetical model for receptor binding of leukotriene D4 (LTD4) was deduced from conformational analysis of LTD4 and from the structure-activity relationships (SAR) of known LTD4 receptor antagonists. A new structural series of LTD4 receptor antagonists exemplified by 5-[4-(4-phenylbutoxy)phenyl]-2-[4-(tetrazol-5-yl)butyl]-2H-t etrazole was designed in which a phenyltetrazole moiety was incorporated as a receptor binding equivalent of the triene unit of LTD4. A number of these phenyltetrazoles were prepared and found to possess LTD4 receptor antagonist activity. The structure-activity relationship (SAR) of this series is described.

Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation

“…HGF may mediate mitogenic action on the ovarian surface epithelium after ovulation. Early studies examining the action of HGF on ovarian surface epithelial cell proliferation have reported conflicting results [ 44 , 45 ]. This study showed that the ovarian surface epithelium expresses the HGF receptor MET, which responds to HGF in FF/PF with autophosphorylation and induces cell proliferation.…”

Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation

“…HGF may mediate mitogenic action on the OSE after ovulation. Early studies examining the action of HGF on OSE cell proliferation have reported conflicting results (Gubbay et al, 2004;Harper et al, 1992). This study showed that the OSE expresses the HGF receptor c-MET, which responds to HGF in FF/PF with autophosphorylation and induces cell proliferation.…”

5-Lipoxygenase, Leukotrienes Biosynthesis and Potential Antileukotrienic Agents

“…The hydroxyacetophenone pharmacophore of this compound became an important component in a series number of potential LT receptor antagonists [22,[66][67][68].…”