Investigation of piperidine derivatives in ex vivo models of pain and platelet aggregation

Abstract

Piperidine derivatives are known to exhibit analgesic activities and are likely to possess the ability to block the effects of prostaglandins through inhibition of downstream signaling pathways. The present study investigated the activity of five derivatives (PD2-6) of 4-(4'-bromophenyl)-4-piperidinol (PD1), against pain and platelet aggregation mediated by the release of prostaglandins and thromboxane A2, respectively. The results showed that compound PD1 and its two phenacyl derivatives PD3 and PD5 exhibited a highly significant analgesic effect (p < 0.01), whereas PD4 and PD6 also showed significant activity. PD3, the most active analgesic compound when docked to the opioid receptor, had interactions between the oxygen of its nitro group and the amino group of ARG 573, indicating a distance of 1.2563 Å. The antiplatelet data showed that compound PD5 (4-(4'-bromo-phenyl)-4-hydroxy-1-[2-(2″,4″-dimethoxyphenyl)-2-oxo-ethyl]-piperidinium bromide) had an IC(50) = 0.06 mM, which was the most active compound, whereas PD3 was the second most active compound against platelet aggregating factor-induced aggregation with an IC(50) = 80 mM. Acetyl salicylic acid (IC(50) = 150 μM) was used as a positive control.

Synthetic bacteriochlorins with integral spiro-piperidine motifs

“…The nitrogen of the piperidine motif is conveniently derivatized by mono-or dimethylation, acetylation, or sulfonylation, and in principle, by a wide variety of other procedures. 63,64 To our knowledge, the closest analogues of diamino-bacteriochlorins BCpip and MeOBCpip appear to be the annulated cis-and transdiaminobacteriochlorins I and II (Chart 2). 14,20 In both types of architectures (BCpipMe 2 I, MeOBCpipMe 2 I; I, II) the amino groups are embedded in rings that are integral to the pyrrolines of the bacteriochlorin, thereby leaving the mesoand b-pyrrolic sites of the macrocycle open for other types of substituents.…”

Microwave‐Assisted Nanocatalysed Synthesis of Phenacyl Halides as Future Anti‐Platelet Agents

“…Recent studies show that derivatives of phenacyl halides possess moderate to good antiplatelet activities . Phenacyl halides are valuable synthons in the synthetic organic chemistry, these are used as key intermediate for the synthesis of various heterocyclic skeleton of biological importance .…”