2,3-Dihydro-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine]s and 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,3'-pyrrolidine]s: novel antihypertensive agents

Abstract

A series of 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine]s (IV) and 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,3'-pyrrolidine]s (V) was synthesized and evaluated for cardiovascular activity. The majority of the compounds displayed good antihypertensive activity in the spontaneous hypertensive rat model at 50 mg/kg po. Compounds 5 (2,3-dihydro-1'-methyl-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine] ) and 12a (2,3-dihydro-1'-ethyl-3-(1-pyrryl)-spiro[benzofuran-2,4'-piperidine] ) were selected for a more detailed cardiovascular evaluation in the renal hypertensive rat and for standard cardiovascular challenges in anesthetized dogs and the sinoaortic-deafferented dog.

Palladium‐Catalyzed Tandem Reaction of Alkyne‐Based Aryl Iodides and Salicyl N‐Tosylhydrazones to Construct the Spiro[benzofuran‐3,2′‐chromene] Skeleton

“…For example, spiro[[2]benzofuran‐1,4′‐piperidine] derivatives serve as novel σ 1 receptor ligands and promising agents for labeling σ 1 receptors intracellularly 2. Other spirocyclic compounds containing the benzofuran moiety show antifungal,3 anticonvulsant,4 antihypertensive,5 and antiviral activities 6…”

Synthesis and derivatisation of a novel spiro[1-benzofuran-2,4′-piperidin]-3-one scaffold

“…IR spectra were recorded on a Nicolet Impact 400 spectrometer. 1 H-NMR and 13 C-NMR were recorded in CDCl 3 solution using a Bruker DPX400 (400 and 100 MHz respectively) unless otherwise stated. Chemical shifts are reported in d units with CHCl 3 being used as an internal standard.…”

“…1). 13 The spirocyclic ring system may be particularly important since its rigidity serves to position the required functional groups appropriately in 3-dimensional space, whilst minimising the number of rotatable bonds and thus increasing the potential for oral bioavailability. 5,14 With this in mind, we reasoned that the furan-3-one containing spiropiperidine 6 would provide an attractive conformationally constrained scaffold possessing a capacity for selective single, double, or triple substitution with appropriate reagents to provide a host of derivatised spirocycles (Fig.…”

Recent Advances in the Microwave Assisted Synthesis of Benzofuran and Indole Derivatives

“…Benzofuran is a heterocyclic compound consisting of fused benzene and furan rings. This heterocycle is well known for its anti-inflammatory, 11 anti-hypertensive, 12 anti-tubercular 13 and anti-hyperglycaemia 14 activities. Benzofurans are important moiety present in polymers and natural products.…”