I= SYNTHESIS OF SOME PHENACYL DERIVATION OF PYRROLINDINE AND PIPERIDINE HAVING POTENTIAL BIOLOGICAL ACTIVITIES
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Title of Thesis
SYNTHESIS OF SOME PHENACYL DERIVATION OF PYRROLINDINE AND PIPERIDINE HAVING POTENTIAL BIOLOGICAL ACTIVITIES

Author(s)
Nousheen Mushtaq
Institute/University/Department Details
University of Karachi/ Department of Pharmaceutical Chemistry
Session
2004
Subject
Pharmacy
Number of Pages
211
Keywords (Extracted from title, table of contents and abstract of thesis)
pyrrolindine, piperidine, cyotoxic activity, antioxidant activity, plasma glucose, antiplatelet activity, analgesic activity

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

Download Full Thesis
1911.93 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents 0
86.7 KB
2 1 introduction 7
432.68 KB
3 2 Section-A-Synthesis Of Some Phenacyl Derivatives Of Pyrrolidine And Piperidine 58
229.37 KB
  2.1 Experimental 58
  2.2 Results 73
  2.3 Discussion 84
4 3 Section-B- Biological Studies Of Synthesized Derivatives / Behavioural Study (Open Field Activity) Experimental Results And Discussion 85
80.08 KB
5 4 Neurochemical Study Experimental Results And Discussion 92
314.22 KB
6 5 Analgesic Activity Results And Discussion 116
351.49 KB
7 6 Antiplatelet Activity Experimental Results And Discussion 139
111.96 KB
8 7 Effect On Plasma Glucose Concentration Experimental Results And Discussion 152
47.39 KB
9 8 Antioxidant Activity Experimental Results And Discussion 157
96.26 KB
10 9 Cyotoxic Activity Experimental Results And Discussion 167
61.11 KB
11 10 References 174
371.78 KB
  10.1 Appendix 202