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环烷并[1,3]二氧戊环-3-苯磺酰基吡唑并[1,5-a]嘧啶的合成及其作为 5-HT6 受体拮抗剂的评价。

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

机构信息

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

出版信息

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

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

摘要

合成并评价了 1（角型）和 2（线型）环己烷并环合的 3-苯磺酰基-吡唑并[1,5-a]嘧啶类化合物作为 5-HT（6）受体的新型配体。新化合物 1 和 2 对该受体具有高度选择性拮抗作用，亲和力在纳摩尔以下（K(i)<1 nM）。在结构上，这种新的化学类型缺乏一个碱性可离子化的侧链，这被认为是 5-HT（6）受体拮抗剂药效团模型的特征。

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