Skip to Content
Merck
  • CNS drug design: balancing physicochemical properties for optimal brain exposure.

CNS drug design: balancing physicochemical properties for optimal brain exposure.

Journal of medicinal chemistry (2014-12-17)
Zoran Rankovic
ABSTRACT

The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to prevent injury from external insults and toxins. Designing molecules that can overcome this protection system and achieve optimal concentration at the desired therapeutic target in the brain is a specific and major challenge for medicinal chemists working in CNS drug discovery. Analogous to the now widely accepted rule of 5 in the design of oral drugs, the physicochemical properties required for optimal brain exposure have been extensively studied in an attempt to similarly define the attributes of successful CNS drugs and drug candidates. This body of work is systematically reviewed here, with a particular emphasis on the interplay between the most critical physicochemical and pharmacokinetic parameters of CNS drugs as well as their impact on medicinal chemistry strategies toward molecules with optimal brain exposure. A summary of modern CNS pharmacokinetic concepts and methods is also provided.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethanolamine, puriss. p.a., ACS reagent, ≥99.0% (GC/NT)
Sigma-Aldrich
Ethanolamine, purified by redistillation, ≥99.5%
Sigma-Aldrich
Ethanolamine, ACS reagent, ≥99.0%
Sigma-Aldrich
Quinuclidine, 97%
Supelco
Ethanolamine, analytical standard
Supelco
Aucubin, analytical standard
Sigma-Aldrich
Ethanolamine, ≥98%
Sigma-Aldrich
Ethanolamine, liquid, BioReagent, suitable for cell culture, ≥98%
Aucubin, primary reference standard
Sigma-Aldrich
Ethanolamine, ≥99%
Sigma-Aldrich
Quinidine, crystallized, ≥98.0% (dried material, NT)
Sigma-Aldrich
Quinine, suitable for fluorescence, anhydrous, ≥98.0% (dried material, NT)
Sigma-Aldrich
Pyridine, ≥99%
Sigma-Aldrich
Benzimidazole, 98%
Sigma-Aldrich
Quinine, 90%
Sigma-Aldrich
Quinidine, anhydrous
Supelco
Pyridine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Pyridine, analytical standard
Sigma-Aldrich
Pyridine, suitable for HPLC, ≥99.9%
Trolamine impurity A, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Pyridine, ACS reagent, ≥99.0%
Sigma-Aldrich
Pyridine, biotech. grade, ≥99.9%
Supelco
Quinine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland