Synthesis of Stable Isotope, Tritiated, and Carbon-14 Labeled Balcinrenone.

As part of a medicinal chemistry program aimed at discovering a mineralocorticoid receptor modulator for treatment of kidney and cardiovascular indications, multiple labeled versions of the lead compound, balcinrenone (AZD9977), were prepared. Four stable isotope labeled versions of the compound were prepared for clinical bioanalysis and biological investigations. Three of these stable isotope labeled compounds were tritiated as well as the parent for biology applications and DMPK investigations.

Automatic Cocrystal Detection by Raman Spectral Deconvolution-Based Novelty Analysis.

Cocrystals are important molecular adducts that have many advantages as a means of modifying the physicochemical properties of active pharmaceutical ingredients, including taste masking and improved solubility, bioavailability, and stability. As a result, the discovery of new cocrystals is of great interest to commercial drug discovery programs. Time-consuming manual analysis of the large volumes of data that emerge from large-scale cocrystal screening programs of up to 1000s of preparations poses a challenge.

Relationship between conformational flexibility and chelate cooperativity.

A family of four biscarbamates (AA) and four bisphenols (DD) were synthesized, and H-bonding interactions between all AA•DD combinations were characterized using (1)H NMR titrations in carbon tetrachloride. A chemical double mutant cycle analysis shows that there are no secondary electrostatic interactions or allosteric cooperativity in these systems, and the system therefore provides an ideal platform for investigating the relationship between chemical structure and chelate cooperativity. Effective molarities (EMs) were measured for 12 different systems, where the number of rotors in the chains connecting the two H-bond sites was varied from 5 to 20.