Description

Medicinal Chemistry group focuses on the design and synthesis of new compounds, on the creation of molecule libraries and collections of building blocks. The aim of the group is the discovery of new chemotypes with potential biological activity (hits) towards therapeutic targets of interest. The skills and expertise include the design, organic chemistry and structural characterization of newly synthesized compounds, as well as the planning, development and optimization of new synthetic routes and scale up process. More general and multidisciplinary skills concern cell biology, pharmacology, toxicology. Structure-activity relationships (SAR) studies allow, through chemical manipulations, the exploration of the chemical space of biologically interesting compounds and helps to better define the pharmacokinetic profile in terms of potency and efficacy. This is essential for identifying new lead compounds that are actually introduced into the pre-clinical development phase (hit-to-lead). Within the multidisciplinary context of Ri.MED Foundation Drug Discovery area, the group supports screening programs, with the following activities: i) confirmation of the structures of preliminary actives (quality control of commercial batches), ii) synthesis of preliminary actives where necessary, iii) expansion of the chemical series of the most interesting hits during the earlier stages. In later stages, the platform works on the structural optimization of most promising compounds and SAR exploration for the identification of one or more potential lead compounds.

Expertise

• Pharmaceutical and organic chemistry
• Drug discovery campaigns
• Small molecules, peptides and peptidomimetics chemistry
• Synthesis in solution, on solid support, in parallel, microwave-assisted
• Synthetic routes planning, development, optimization and scale-up
• Purification of complex mixture (normal and reverse phase)
• Isolation of compounds of interest
• Analytical characterization of newly synthesized molecules (NMR and mass spectrometry)
• Purity grade assessment

Facilities & Equipment

• Flash chromatography (Isolera One, Biotage): Automated system for compounds purification and isolation (normal and reverse phase) starting from complex reaction mixtures.
• Ultra-High resolution liquid chromatography (uHPLC, Nexera Series Shimadzu): Automated system for semi-preparative applications (separation of analytes in reverse phase) and purity standard assessment.
• Liquid Chromatography coupled with Single Quadrupole: (LCMS 2020, Shimadzu): Automated system for monitoring chemical reactions and analyzing complex reaction mixtures.
• Microwave reactor (Discover 2.0, CEM): Chemical transformations in homogeneous and heterogeneous phase irradiated with microwaves.
• Centrifugal evaporator (H4T, Genevac): Evaporation system under high vacuum and mild heat avoiding compound degradation.
• Water purification system (Milli-Q, Merck): Production of distilled water (for glassware cleaning) and ultra-pure water, necessary for analytical applications.
• Lyophilizer (Lyo-200, Büchi). The system is used to remove water from samples, by sublimation, with the advantage of using low temperature and vacuum, thus preserving the molecule’s integrity.