Heavy drugs draw heavy interest from pharma backers

  title={Heavy drugs draw heavy interest from pharma backers},
  author={A. Katsnelson},
  journal={Nature Medicine},
It’s an age-old problem in drug development: a compound that seems to exert its desired effects against cells in a Petri dish, but flops in vivo, either in animal models or, later, in humans. One common reason for such failures is how the body metabolizes drugs. Enzymes in the liver can break down molecules quickly, substantially limiting their potency. They might produce toxic metabolites in the process to boot. If you could fortify the chemical bonds that hold those drugs together, thereby… Expand

Paper Mentions

Iron-catalysed tritiation of pharmaceuticals
An iron-catalysed method for the direct 3H labelling of pharmaceuticals by hydrogen isotope exchange is described, using tritium gas as the source of the radioisotope. Expand
Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals
Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities of deuterated compounds they are evaluated for the treatment of human diseases. Expand
Deuterated drugs: where are we now?
  • G. Timmins
  • Chemistry, Medicine
  • Expert opinion on therapeutic patents
  • 2014
It would seem that the likelihood of obviousness rejections is increasing in this area, however, careful elucidation of metabolic outcomes from deuteration that would not be anticipated from the prior art, and are instead unexpected and unobvious, has enabled allowance. Expand
Effect of N-methyl deuteration on metabolism and pharmacokinetics of enzalutamide
ENT was mainly metabolized through the “parent→M2→M1” pathway based on in vitro and in vivo elimination behavior and the observed in vitro deuterium isotope effect translated into increased exposure of the deuterated analog in rats. Expand
Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer
Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines, while the CUR–BF2 adducts exhibited significantly higher cytotoxicity than CURs. Expand
Dissecting fibrosis: therapeutic insights from the small-molecule toolbox
The pharmacology and structural information for small molecules being evaluated for lung, liver, kidney and skin fibrosis is examined, and how these entities can inform, and probe, emerging insights into disease mechanisms, including the potential for future drug combinations are discussed. Expand
Effect of deuteration on metabolism and clearance of Nerispirdine (HP184) and AVE5638.
Examination of the metabolic behaviour of two molecules from the Sanofi portfolio in a range of in vitro and in vivo systems indicates that it could be of value to concentrate efforts in this area to molecules which are metabolised by a major pathway that involves enzymes of the amine oxidase family or other low-capacity enzyme families. Expand
Deuterated drugs; updates and obviousness analysis
  • G. Timmins
  • Medicine
  • Expert opinion on therapeutic patents
  • 2017
While the importance of §103 ‘obviousness’ rejections remains in patent applications under current prosecution, IPR of issued patents is developing and will affect likely affect §103 interpretations in this area. Expand
Photoredox-mediated Hydrogen Isotope Exchange Reactions of Amino-Acids, Peptides and Peptide-derived drugs.
A photoredox-initiated hydrogen atom transfer (HAT) protocol which efficiently and selectively introduces deuterium or tritium at C(sp 3 )-H bonds, utilizing heavy water as the hydrogen isotope source, and a guanidine base is reported. Expand
Synthesis of Deuterated Benzopyran Derivatives as Selective COX-2 Inhibitors with Improved Pharmacokinetic Properties.
A series of specifically deuterated benzopyran analogues as new COX-2 inhibitors showed pharmacodynamic efficacy in several murine models of inflammation and pain and possess improved pharmacokinetic profiles in rats compared to their nondeuterated congeners. Expand


A Randomized Phase I Evaluation of CTP‐499, a Novel Deuterium‐Containing Drug Candidate for Diabetic Nephropathy
The range of tolerated doses of CTP‐499 and the effects of food on exposure were identified, contributing to selection of the dose for Phase II development. Expand
Effect of Deuterium Substitution in Sympathomimetic Amines on Adrenergic Responses
It was discovered that replacement of the α-hydrogens of tyramine and tryptamine by deuterium produces a marked intensification of the blood pressure effects and nictitating membrane contractionExpand