The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c] pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-pyrrolidinol analogue 17 (IC50 = 2.7 nM) was found to be approximately 5-fold more potent than the corresponding pyrrolidine analogue 16 (IC50 = 15 nM). In the rat and hamster vasa deferentia (mu-specific and delta-specific tissues, respectively), 17 showed only weak antagonist activity (pKB > 5.5), underlining its selectivity for the kappa-opioid receptor. The major activity for 17 is resident in the 4S,3'S-isomer 26 (rabbit vas deferens IC50 = 1.1 nM). Compound 26 displays excellent antinociceptive activity, as determined in the mouse acetylcholine-induced abdominal constriction test (ED50 = 0.001 mg/kg, sc).

中文翻译：

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4-[（烷基氨基）甲基]呋喃[3,2-c]吡啶：一系列新的选择性κ受体激动剂。

描述了5-（芳基乙酰基）-4-[（烷基氨基）甲基]呋喃[3,2-c]吡啶（16-23、26、27）的合成及其作为κ阿片受体激动剂的活性。κ-激动剂效力对碱性部分的性质特别敏感。特别地，在兔输精管（κ特异性组织）中，发现3-吡咯烷醇类似物17（IC50 = 2.7 nM）比相应的吡咯烷类似物16（IC50 = 15 nM）强约5倍。在大鼠和仓鼠输精管中（分别为mu特异组织和delta特异组织），17只显示弱的拮抗剂活性（pKB> 5.5），突显了其对κ阿片受体的选择性。17的主要活性存在于4S，3'S-异构体26中（兔输精管IC50 = 1.1 nM）。化合物26具有出色的抗伤害感受活性，