الفهرس 
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Abstract
The present thesis comprises the following chapters:
Chapter I (Introduction):
An introductory part describing the chemistry of the synthesized compounds
(indole derivatives) and the different approaches for their synthesis. Another
introductory part describing Alzheimer’s disease (AD), and the role of beta-secretase
enzyme in the pathogenesis of this disease with the beneficial effect of this
enzymatic activity inhibition.
Chapter II (Research Objectives):
In this project, the main aim is to develop novel, potent and selective
betasecretase enzyme inhibitors with enhanced blood-brain barrier penetration used
for the treatment of Alzheimer`s disease.
According to the published pharmacophore models, 3D-molecular docking and
structure similarity algorithms for betasecretase receptor ligands, four common
features are identified: one hydrogen bond donor group, one positive ionizable
group, one aromatic ring and two hydrophobic groups. Hence, to accomplish our
aim, we will synthesize novel N-containing heterocyclic compounds which maintain
the four common features essential for the biological activity.
Chapter III (Results and discussion):
A theoretical discussion of synthetic pathways that have been followed to obtain
final novel compounds and their mechanisms and spectral data.
Chapter IV (Experimental):
Targeted series (Products 1-12 & 13-24) discussed in this work were synthesized
following the strategies depicted on Scheme I, 2-(1H-indol-3-yl) acetohydrazide
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Abstract
(III), was prepared by the dropwise addition of hydrazine hydrate to a solution of
ethyl 2-(1H-indol-3-yl)acetate (indole 3’ acetic acid ethyl ester) (II) in ethanol under
reflux. Subsequently reaction of (III) with different aromatic aldehydes with the
addition of few drops of acetic acid in refluxing ethanol to obtain products (1-12),
All Products (1-12) were subsequently reacted with thioglycolic acid in the presence
of Zinc Chloride under refluxing conditions of dry Dimethylformamide (DMF) to
furnish products (13-24). Generally, products (1-12) were obtained in relatively
higher yields than products (13-24). Final synthesized compounds were analyzed by
1H-NMR, 13C- NMR and LC-MS.
The present investigation involves the synthesis of the following intermediates:
1. ethyl 2-(1H-indol-3-yl)acetate (II)
2. 2-(1H-indol-3-yl)acetohydrazide (III)
In addition to the synthesis of the following final new compounds:
1. (E)-N’-(4-chlorobenzylidene)-2-(1H-indol-3-yl)acetohydrazide (1).
2. (E)-N’-benzylidene-2-(1H-indol-3-yl)acetohydrazide (2).
3. (E)-N’-(4-hydroxybenzylidene)-2-(1H-indol-3-yl)acetohydrazide (3).
4. (E)-N’-(3-hydroxybenzylidene)-2-(1H-indol-3-yl)acetohydrazide (4).
5. (E)-N’-(4-hydroxy-3,5-dimethoxybenzylidene)-2-(1H-indol-3-yl)acetohydrazide (5).
6. (E)-N’-(4-(dimethylamino)benzylidene)-2-(1H-indol-3-yl)acetohydrazide (6).
7. (E)-2-(1H-indol-3-yl)-N’-(3-nitrobenzylidene)acetohydrazide (7).
8. (E)-2-(1H-indol-3-yl)-N’-(4-nitrobenzylidene)acetohydrazide (8).
9. (E)-2-(1H-indol-3-yl)-N’-(4-methoxybenzylidene)acetohydrazide (9).
10. (E)-N’-(2-chlorobenzylidene)-2-(1H-indol-3-yl)acetohydrazide (10).
11. (E)-N’-(4-bromobenzylidene)-2-(1H-indol-3-yl)acetohydrazide (11).
12. (E)-N’-(furan-2-ylmethylene)-2-(1H-indol-3-yl)acetohydrazide (12).
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Abstract
13. N-(2-(4-bromophenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (13).
14. N-(2-(4-chlorophenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (14).
15. 2-(1H-indol-3-yl)-N-(4-oxo-2-phenylthiazolidin-3-yl)acetamide (15).
16. N-(2-(4-hydroxyphenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (16).
17. N-(2-(3-hydroxyphenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (17).
18. N-(2-(4-hydroxy-3,5-dimethoxyphenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (18).
19. N-(2-(4-(dimethylamino)phenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (19).
20. 2-(1H-indol-3-yl)-N-(2-(4-nitrophenyl)-4-oxothiazolidin-3-yl)acetamide (20).
21. 2-(1H-indol-3-yl)-N-(2-(3-nitrophenyl)-4-oxothiazolidin-3-yl)acetamide (21).
22. 2-(1H-indol-3-yl)-N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)acetamide (22).
23. N-(2-(2-chlorophenyl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (23).
24. N-(2-(furan-2-yl)-4-oxothiazolidin-3-yl)-2-(1H-indol-3-yl)acetamide (24).
Chapter V (References):
A list of references which were used and their arrangement according to their order
in the thesis.