Synthesis of N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides as new selective ligands for sigma receptors.
Synthesis of N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides as new selective ligands for sigma receptors.
复制标题
合成 N-苯基-N-(3-(哌啶-1-基)丙基)苯并呋喃-2-甲酰胺作为 σ 受体的新选择性配体。
DOI：
10.1016/j.bmc.2012.09.044
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发表时间：
2012
影响因子：
3.5
通讯作者：
Stewart,LeonardE
中科院分区：
文献类型：
--
作者：
Marriott,Karla-SueC;Morrison,AndrewZ;Moore,Misty;Olubajo,Olarongbe;Stewart,LeonardE
通过微波辅助Perkin重排反应和改进的Finkelstein卤素交换促进n-烷基化，合成了对sigma受体具有选择性的新型苯并呋喃-2-羧酰胺配体。合成的配体为3-甲基- n-苯基- n-（3-（胡椒碱-1-基）丙基）苯并呋喃-2-羧酰胺（KSCM-1、KSCM-5和KSCM-11）。苯并呋喃-2-羧酰胺结构分别被N-芳基化和N-烷基化，分别包含N-苯基和N-(3-（胡椒苷-1-基）丙基取代基。这些新的羧酰胺对sigma-1受体具有很高的亲和力，其基值在7.8 ~ 34nM之间。配体KSCM-1在苯并呋喃环的C-5和C-6上有两个甲氧基取代基，在sigma-1上Ki=27.5nM，对sigma-1的选择性优于sigma-2。
Novel benzofuran-2-carboxamide ligands, which are selective for sigma receptors, have been synthesized via a microwave-assisted Perkin rearrangement reaction and a modified Finkelstein halogen-exchange used to facilitate N-alkylation. The ligands synthesized are the 3-methyl-N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides (KSCM-1, KSCM-5 and KSCM-11). The benzofuran-2-carboxamide structure was N-arylated and N-alkylated to include both N-phenyl and N-(3-(piperidin-1-yl)propyl substituents, respectively. These new carboxamides exhibit high affinity at the sigma-1 receptor with Kivalues ranging from 7.8 to 34nM. Ligand KSCM-1 with two methoxy substituents at C-5 and C-6 of the benzofuran ring, and Ki=27.5nM at sigma-1 was found to be more selective for sigma-1 over sigma-2.