The Bioisosteric Concept Applied to Cannabinoid Ligands

Abstract

Bioisosterism is widely used in medicinal chemistry as an approach aimed at either rationally modifying a hit compound into a more potent and/or selective molecule or a lead compound into a more drug-like one. Two different cannabinoid receptors have been cloned from mammalian tissues, the CB1 receptor, mostly expressed in brain, and the CB2 receptor, mostly expressed in the immune system, both regulating a variety of physiological functions. Synthetic cannabinoids have been developed that act as highly selective agonists or antagonists/inverse agonists at one or other of these receptor types with the ultimate goal of modulating the endocannabinoid system. This review takes into account the use of the bioisosteric substitution in the field of cannabinoid ligands as a tool for improving both their pharmacodynamic and pharmacokinetic properties.

Influence of Bio-Isosteric Replacement on the Formation of Templating Methanol and Acetonitrile Solvates in Lophines

“…by using neutron diffraction. Crystal size (mm 3 The powder X-ray diffractograms of all four TPI derivatives show certain similarities ( Figure 5). Whilst Br-TPI and I-TPI can be regarded as isostructural, which can be detected as a shift of the peak positions without changing the overall pattern, there is no similarity between these two, F-TPI and Cl-TPI.…”

“…1,2 This enables the medicinal chemist to improve specific properties, such as solubility, crystallinity, metabolic stability etc., which subsequently will improve the overall processability of the new drug compound. This concept has been applied to as diverse drug classes as cannabinoids 3 and HIV antivirals. 4 The selection of replacement groups is nowadays heavily helped by in silico studies and property predictions.…”

“…One of the tools used in the area of medicinal chemistry is bio-isosteric replacement, which is the replacement of substituents of a lead molecule with other chemical groups without changing the overall biological activity. , This enables the medicinal chemist to improve specific properties, such as solubility, crystallinity, and metabolic stability, which subsequently will improve the overall processability of the new drug compound. This concept has been applied to such diverse drug classes as cannabinoids and HIV antivirals . The selection of replacement groups is nowadays heavily helped by in silico studies and property predictions. − …”