Pakistan Research Repository

SYNTHESIS OF SOME PHENACYL DERIVATION OF PYRROLINDINE AND PIPERIDINE HAVING POTENTIAL BIOLOGICAL ACTIVITIES

Mushtaq, Nousheen (2004) SYNTHESIS OF SOME PHENACYL DERIVATION OF PYRROLINDINE AND PIPERIDINE HAVING POTENTIAL BIOLOGICAL ACTIVITIES. PhD thesis, University of Karachi, Karachi.

[img]HTML
18Kb

Abstract

Synthesis of piperidine and pyrrolidine derivatives, which led to the development of biologically active compounds, has major contribution in the field of medicine and therapeutics. The present work is another approach in this line of research work. Analogues of piperidine and pyrrolidine moieties were obtained by N-alkylation of 4-Pyrrolidin-1-yl-Pyridine (III), and 4-(1-Pyrrolidinyl) Piperidine (IV) with phenacyl halides having nitro, methoxy and hydroxyl substitutions on the aromatic ring. Structures of compounds were confirmed by using HNMR, IR, Mass and UV spectrophotometer techniques All the compounds were examined for analgesic, antiplatelet, antioxidant and cytotoxic activities, while 4-(1-Pyrrolidinyl) Piperidine (IV) and its derivatives (XXI, XXII, XXIV, XXV) were also evaluated for their effects on behavior, on the concentration of biogenic amines and plasma glucose level 4-(1-Pyrrolidinyl) Piperidine (IV) (50, 100 and 200 mg/kg) and its derivatives (XXI, XXII, XXIV and XXV) (100mg/kg) showed variable results when tested for the open field activity. Compounds XXI and XXII, found to be active in this experimental model are nitro derivatives of compound (IV) with the only change in position of nitro group (ortho and meta) in phynyl ring. While methoxy and hydroxyl derivatives were evaluated to their effects on the concentration of catecholamine and indoleamine neurotransmitters. 4-(1-Pyrrolidinyl) Piperidine (IV) in doses (50, 100, 200mg/kg) produced variable effects on Dopamine (DA), 5-Hydroxytryptamine (5-HT) and 5-Hydroxy indoleacetic acid (5-HIAA). All the derivatives (100mg/kg) did not show any significant effects on DA but decreased the concentration of DOPAC (3,4-dihydroxy phenyl acetic acid), HVA (Homovanilic acid), 5-HT, and 5HIAA Parent compound 4-(1-Pyrrolidinyl) Piperidine (IV) did not affect plasma glucose level and among its analogues only nitro derivative XXI markedly reduced glucose level Most of the analogues of 4-(4-Chlorophenyl)-4-piperidinol (1) showed significant analgesic activity by thermal method (tail immersion). 4-(4-Bromophenyl)-4-piperidinol (II) was the only parent compound, which showed profound analgesia. Derivatives of compound (1) and (II) showed significant results while those of 4-Pyrrolidin-1-yl-Pyridine (III) have not displayed encouraging results In case of antiplatelet activity nitro phenacyl derivatives of parent compounds (I-III) were found active, while methoxy phenacyl derivative of Compound (II) was found to be the most potent of all the active agents with IC50=0.03mg/ml. All the derivatives exhibited anti-platelet activity at very low doses as compared to Aspirin used as standard When evaluated for antioxidant activity, only analogues of 4-(4-Chlorophenyl)-4-Piperidinol (I) and 4-(4-Bromophenyl)-4-piperidinol (II) showed better results as compared to the derivatives of 4-Pyrrolidin-1-yl-Pyridine (III) and 4-(1-Pyrrolidinyl) Piperidine (IV) All the parent compounds and their analogues were examined for cytotoxic activity and with the exception of one compound (XXI) (LD50=8.98 μg/ml) all were found inacitive against Artemia salina Among the substituted derivatives of compounds (I-IV), nitro phenacyl analogues showed promising results as compared to methoxy and hydroxyl phenacyl derivatives. Over all, it is clear that not the piperidine and pyrrolidine moieties, but also the functional groups and their positions in the phenacyl ring are equally important for the biological activity. Some of the compounds can be selected for further studies because of their promising results

Item Type:Thesis (PhD)
Uncontrolled Keywords:pyrrolindine, piperidine, cyotoxic activity, antioxidant activity, plasma glucose, antiplatelet activity, analgesic activity
Subjects:Biological & Medical Sciences (c) > Medical Sciences (c2) > Pharmacy(c2.5)
ID Code:1218
Deposited By:Mr. Muhammad Asif
Deposited On:04 Jan 2007
Last Modified:04 Oct 2007 21:05

Repository Staff Only: item control page