Synthesis of cycloalkane-annelated 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines and their evaluation as 5-HT6 receptor antagonists

Alexandre V Ivachtchenko; Dmitri E Dmitriev; Elena S Golovina; Elena S Dubrovskaya; Madina G Kadieva; Angela G Koryakova; Volodymyr M Kysil; Oleg D Mitkin; Sergey E Tkachenko; Ilya M Okun; Anton A Vorobiov

doi:10.1016/j.bmcl.2010.02.046

Synthesis of cycloalkane-annelated 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines and their evaluation as 5-HT6 receptor antagonists

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2133-6. doi: 10.1016/j.bmcl.2010.02.046. Epub 2010 Feb 14.

Authors

Alexandre V Ivachtchenko¹, Dmitri E Dmitriev, Elena S Golovina, Elena S Dubrovskaya, Madina G Kadieva, Angela G Koryakova, Volodymyr M Kysil, Oleg D Mitkin, Sergey E Tkachenko, Ilya M Okun, Anton A Vorobiov

Affiliation

¹ Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Region, Russia.

PMID: 20207539
DOI: 10.1016/j.bmcl.2010.02.046

Abstract

Synthesis and biological evaluation of 1 ('angular') and 2 ('linear') cycloalkane-annelated 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines as novel ligands of the 5-HT(6) receptors are disclosed. The new compounds 1 and 2 are highly selective antagonists of the receptor with sub-nanomolar affinities (K(i)<1 nM). In its structure, this new chemotype lacks a basic ionizable side chain, which is considered as the characteristic feature of the 5-HT(6) receptor antagonists pharmacophore model.

MeSH terms

Animals
CHO Cells
Cell Line
Cricetinae
Cricetulus
Ether-A-Go-Go Potassium Channels / metabolism
Humans
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology*
Receptors, Serotonin / metabolism*
Serotonin Antagonists / chemical synthesis
Serotonin Antagonists / chemistry*
Serotonin Antagonists / pharmacology*

Substances

Ether-A-Go-Go Potassium Channels
Pyrimidines
Receptors, Serotonin
Serotonin Antagonists
serotonin 6 receptor