Ethics and the Responsible Conduct of Research in the Chemical Community: The Unique Role and Challenges of the News Media.

Journalists who cover scientific research, including chemistry research, have an obligation to report on alleged cases of research misconduct when knowledge of these surface. New Government definitions of research misconduct, beginning in the late 1990s with the Clinton Administration, have helped scientists, policymakers, as well as journalists sort out and make sense of alleged research misconduct. Journalistic reporting on research misconduct includes many challenges: gathering information from sources who are intimidated or afraid to speak, strict adherence to journalist ethics that take on a new dimension when careers, reputations, and research funding are at stake; efforts by government and institutional bureaucrats to dampen or thwart legitimate news coverage. The Internet, blogging, and social media have added still more complexity and ethical quandaries to this blend. The author, News Editor of Chemical & Engineering News published by the American Chemical Society, provides examples from his own career and that of colleagues. He suggests that an enhanced spirit of understanding and cooperation between journalists and members of the scientific community can lead to avenues of open discussion of research misconduct--discussions that might prevent and mitigate the very real damage caused by bad actors in science who betray themselves, their peers, and the body of modern day scientific knowledge when they make the decision to march into the darkness of dishonesty, plagiarism, or falsification.

Synthesis and biological evaluation of a series of liver-selective phosphonic acid thyroid hormone receptor agonists and their prodrugs.

Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TRbeta(1), K(i) < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T(3), PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED(50) 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.