Preparation of Water-Soluble Compounds by Covalent Attachment of Solubilizing Moieties

Small Molecule Inhibitors Targeting the “Undruggable” Survivin: The Past, Present, and Future from a Medicinal Chemist’s Perspective

“…141 Such nitrogencontaining groups (NCGs) are one class of solubilizing moieties commonly adopted in medicinal chemistry to help address solubility issues of lead compounds. 157 NCGs in biologically active compounds usually exist in different forms including amine salt, neutral amide, or heterocyclic compounds. 158 It is estimated that nearly 75% of FDA-approved small molecule drugs contain at least one nitrogen atom, and ∼60% have a nitrogen-containing heterocyclic, suggesting that NCGs are prevalent in approved drugs.…”

“…Third, 2 does not contain a nitrogen atom while many of its ester or ether derivatives do (Figure B/C) . Such nitrogen-containing groups (NCGs) are one class of solubilizing moieties commonly adopted in medicinal chemistry to help address solubility issues of lead compounds . NCGs in biologically active compounds usually exist in different forms including amine salt, neutral amide, or heterocyclic compounds .…”

Molecular Switches—Tools for Imparting Control in Drug Delivery Systems

“…As discussed earlier, this is a significant challenge associated with many anticancer therapeutics. Poor solubility is especially the case in larger drugs molecules, where the introduction of solubilising bioisosteres does not significantly affect the drugs partition coefficient ( Wermuth and Lesuisse, 2015 ). A notorious example of an anticancer drug with poor water solubility is paclitaxel (PTX) ( Table 2 ); which has a water solubility of ∼0.5 μg/ml ( Liu et al, 2011 ).…”

Discovery of aurones bearing two amine functionalities as SHIP2 inhibitors with insulin-sensitizing effect in rat myotubes

“…In addition, the introduction of a basic, ionizable piperidine would in principle, provide an opportunity for formulation into watersoluble salts for improved oral absorption and other pharmacokinetic features. 22 In this study, 23 aurones were synthesized and investigated for their in vitro SHIP2 inhibitory activity. A recombinant human SHIP2 protein containing a C2 domain in addition to the phosphatase domain was used in our assay to better represent the enzyme in the cellular milieu.…”

“…In addition, the introduction of a basic, ionizable piperidine would in principle, provide an opportunity for formulation into water-soluble salts for improved oral absorption and other pharmacokinetic features. 22…”