Synthesis, preliminary biological evaluation and molecular modeling of some new heterocyclic inhibitors of TACE.

Central heteroaryl ring analogues belonging to a series of potent hydroxamate TACE inhibitors were synthesized. The TACE inhibitory activities of these compounds were evaluated by in vitro WBA and in silico molecular modeling studies using crystal structure of human TACE. Compound 14 showed very good in vitro inhibition, supported by the in silico docking studies.

Preclinical efficacy and safety pharmacology of SUN-1334H, a potent orally active antihistamine agent.

Objective: These studies aimed to outline the in vitro and in vivo histamine H(1) receptor antagonistic activity and safety pharmacology of SUN-1334H, a new potent antihistamine agent under clinical development.

Methods: In vitro antihistamine activity and selectivity of SUN-1334H was evaluated in a panel of receptor and enzyme assays and functional assays using isolated tissues. In vivo antihistamine and antiallergy efficacy were assessed following oral administration of SUN-1334H in histamine-induced bronchoconstriction in guinea pigs, skin wheal in beagle dogs and ovalbumin-induced rhinitis (sneezing, vascular permeability and intranasal pressure) in guinea pigs.