Citation

Morales P, Goya P, Jagerovic N. Anales de la Real Academia Nacional de Farmacia 2018; 84(2): 164-184.

Copyright

(Copyright © 2018)

DOI

unavailable

PMID

unavailable

Abstract

The endogenous cannabinoid system (ECS) has been recognized as one of the most important neuromodulatory systems. This system plays a crucial role in the regulation of numerous pathophysiological conditions such as pain, cancer, or neurodegeneration. Despite the vast effort focused on the development of drugs targeting the ECS, thus far, the clinical use of synthetic and phytogenic cannabinoids has been limited to pain, emesis and appetite due to their undesirable psychoactive properties. Therefore, novel strategies to therapeutically exploit the cannabinoids need to be developed to overcome these side-effects. Moreover, novel chemical tools to study the role of possible additional cannabinoid missing receptors, such as GPR55, need to be addressed to fully unravel the pharmacology of this complex system. In this scenario, the chromenopyrazole scaffold was recently discovered as a privileged structure in drug discovery targeting the ECS. In this review, the development of novel modulators of the ECS based on the chromenopyrazole scaffold will be thoroughly discussed. Pharmacological avenues for this novel chemotype, as well as future perspectives will be analyzed.

Language: en

Keywords

human; cognition; Review; depression; suicide attempt; pain; vomiting; controlled study; pathophysiology; unclassified drug; headache; anxiety disorder; psychotropic agent; drug mechanism; drug structure; appetite; nonhuman; mouse; prostate cancer; histopathology; multiple sclerosis; traditional medicine; in vitro study; nonhodgkin lymphoma; in vivo study; binding site; receptor binding; daunorubicin; endocannabinoid; advanced cancer; doxorubicin; antineoplastic activity; drug targeting; mitoxantrone; dronabinol; structure activity relation; pyrazole derivative; rimonabant; cannabinoid receptor; mitomycin; nerve degeneration; cannabinoid derivative; neuromodulation; nabilone; IC50; nabiximols; malignant neoplasm; metastatic breast cancer; acute myeloid leukemia; 5 dimethylheptyl 2 (1h pyrazol 5 yl)benzene 1,3 diol; 5 pentyl 2 (1h pyrazol 5 yl)benzene 1,3 diol; androgen deprivation therapy; beta lapachone; chromenopyrazole; drug development; hydrazine; photosensitizing agent; procaspase 3; quinone derivative; Rac1 protein; RhoA guanine nucleotide binding protein; triple negative breast cancer