MS Applications in Support of Medicinal Chemistry Sciences

Abstract

In the drug discovery process, medicinal chemistry plays a crucial role in the optimal design and synthesis (production) of new chemical entities (NCEs) or new biological entities (NBEs); this is true for a single entity as well as a complete compound library. A key requirement in this field of science is the optimization of both the chemical and the biological properties of these potential drug-like compounds. Important criteria are the design of efficient synthesis routes, the balancing of the physical chemical properties with optimal in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) processes, and a profound understanding of the pharmacodynamics in the appropriate pharmacological models. In the lead optimization stage, an important step is scaling up the synthesis route as needed for the execution of toxicology studies and the screening of suitable drug formulations. In summary, medicinal chemistry support includes participating in a large variety of activities and decision making processes that play a key role in the search for either a "first in class" new drug or a "best in class" new drug [1].These "drug discovery" processes are continuously under pressure, as the research and development (R&D) costs continue to increase and more data are requested before new drug candidates are taken into (pre-)clinical development. Hence, the choice of "targeted" high-throughput screening (HTS) libraries, the process of hit appraisal, and the understanding of target-ligand interactions can be considered the starting points for a new drug discovery program [2]. Next, the main focus is on the discovery of a lead compound; typically, this is a compound showing promising data regarding target affinity, reasonable efficacy in cellular models, good physical chemical parameters (i.e., a "drug-like" compound), and acceptable oral bioavailability in Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher.

Canolol Dimer, a Biologically Active Phenolic Compound of Edible Rapeseed Oil

“…In the edible oil extract, five phenolic compounds were detected at 280 nm with canolol dimer as the dominant compound making almost 97% of total phenol. The purity of the test compounds for the in vitro assays should be >95% (Honing et al, 2013) making our extracts suitable for determination of biological and antioxidant activity of canolol and canolol dimer. Phenolic extracts of crude and edible rapeseed oils were stored for 5 months at three different temperatures: a freezer temperature of −20 C, a fridge temperature of 4 C, and RT, which varied from 20 to 25 C. The canolol dimer showed significantly better stability during storage than the monomer at all three investigated temperatures (Fig.…”