Related Experiment Video
Updated: Jun 4, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
2-Substituted 5,6-dimethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines: new series of highly potent and specific
Alexandre V Ivachtchenko1, Elena S Golovina, Madina G Kadieva
1Department of Organic Chemistry, Chemical Diversity Research Institute, 141400 Khimki, Moscow Reg, Russia.
Abstract:
Syntheses, biological evaluation, and structure-activity relationships for a series of novel 2-substituted 3-benzenesulfonyl-5,6-dimethyl-pyrazolo[1,5-a]pyrimidines are disclosed. In spite of a wide, four orders of magnitude, SAR range (K(i) varied from 260 pM to 2.96 μM), no significant correlation of 5-HT(6)R antagonistic potency was observed with major physiochemical characteristics, such as molecular weight, surface polar area, cLogP, or number of rotatable bonds. Statistically significant trend was only observed for size of substitute group, which was not enough to explain the deep SAR trend. Besides with the substitute group size, another factor that presumably plays a role in defining the compound potencies is a relative position of the heterocycle and sulfophenyl moieties. Among all synthesized derivatives, (3-benzenesulfonyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 18 is the most potent (K(i) = 260 pM) and extremely selective, 5000 to >50,000-fold relative to 55 therapeutic targets, antagonist of the 5-HT(6) receptor.
More Related Videos
08:49Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
10:42Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Related Concept Videos
Antidepressant Drugs: MAOIs and Other Agents
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Antipsychotic Drugs: Typical and Atypical Agents
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...