Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3704-7. doi: 10.1016/j.bmcl.2011.04.080. Epub 2011 May 4.
A series of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes were prepared and evaluated as potential allosteric modulators of the A(1) adenosine receptor (AR). The structure-activity relationships of the 3-position were explored along with varying the size of the cycloalkyl ring. 2-Aminothiophenes with amide and hydrazide groups in the 3-position were completely inactive in an A(1)-AR-mediated ERK1/2 phosphorylation assay, yet most of the 3-benzoyl substituted compounds exhibited allosteric effects on responses mediated by the orthosteric agonist, R-PIA. Despite finding an increase in both agonistic and allosteric activities by going from a cyclopentyl ring to a cyclohexyl ring in the 3-benzoyl series, decreases were observed when further increasing the ring size. Varying the substituents on the phenyl ring of the 3-benzoyl group also affected the activity of these compounds.
一系列 2-氨基-4,5,6,7,8,9-六氢环辛[b]噻吩被制备并评估为 A(1)腺苷受体 (AR) 的潜在别构调节剂。还探索了 3-位的结构-活性关系，同时改变环烷基环的大小。3-位具有酰胺和酰肼基团的 2-氨基噻吩在 A(1)-AR 介导的 ERK1/2 磷酸化测定中完全没有活性，但大多数 3-苯甲酰取代的化合物对正位激动剂 R-PIA 介导的反应表现出别构效应。尽管在 3-苯甲酰系列中，从环戊基环变为环己基环会增加激动剂和别构活性，但当进一步增加环的大小时，活性会降低。3-苯甲酰基苯环上取代基的变化也会影响这些化合物的活性。
