151091-46-2

Upstream product

• 115-46-8 C₁₈H₂₁NO 
• 939-52-6 4-chloro-1-phenylbutan-1-one 
• 24070-52-8 4-bromo-1-phenyl-1-butanone 
• 65488-05-3 4-iodobutyrophenone 

Relevant academic research and scientific papers

METHODS AND COMPOSITIONS FOR TREATING INFECTION

Provided herein are compositions and methods for treating or preventing infection.

Repurposing the antihistamine terfenadine for antimicrobial activity against staphylococcus aureus

Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure-activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied through this round of optimization; however, given the overall improvement in activity of the set, terfenadine-based analogues provide a novel structural class of antimicrobial compounds with potential for further characterization as part of the continuing process to meet the current need for new antibiotics.

Identification of terfenadine as an inhibitor of human CD81-receptor HCV-E2 interaction: Synthesis and structure optimization

Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert- butylphenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27 % inhibition) of the CD81-LEL-HCV-E2 interaction. To increase the observed biological activity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilic substitution. The prepared compounds were tested for their inhibitory potency by means of a fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activity relationships could be derived. Optimization was successful, leading to 3g, identfied as the most potent compound (69 % inhibition). Experiments with viral particles revealed that there might be additional HCV infection reducing mechanisms.

Structure-activity relationships within a series of analogues of the histamine H1-antagonist terfenadine

A number of terfenadine derivatives including terfenadine enantiomers were synthesized and tested for histamine H1-receptor affinity. No significant differences in H1 activity were found between terfenadine enantiomers. Qualitative structure-activity relationship studies identified the α,α-diphenyl-4-piperidinomethanol moiety as the pharmacophore for the H1 activity of this group of compounds. The major role of the phenylbutanol moiety in terfenadine seems to be preventing the compound from crossing the blood-brain barrier.