الفهرس 
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Abstract
Thesis submitted by Rasha Mohamed Mohamed Hassan, for the partial fulfillment of the degree of MSc. of Pharmaceutical Sciences (Pharmaceutical Chemistry), Ain Shams University.
In this work design and synthesis of 1-(4-(3-substituted benzyloxy) benzylamino) cyclohexanecarboxamides (XVa-e), 1-(4-(3- substituted benzyloxy) benzylamino) cycloheptanecarboxamides (XVIa-e)and 1-(4-
(3-substitutedbenzyloxy)benzylamino)-2,3-dihydro-1H-indene-1- carboxamides series (XVIIa-e) have been accomplished. The aim of their preparation is to evaluate their anticonvulsant activity.
This thesis contains the following sections :
I- Introduction:
This part includes the mechanism of action of antiepileptic drugs and
review on different classes of antiepileptic and anticonvulsant agents.
II- Basis of the present investigation:
This part gives the pharmacological basis on which the synthesized compounds were chosen, molecular modeling approaches carried out in this work and the schemes followed in the synthesis.
Abstract
III- Theoretical discussion:
This part shows the reactions followed in the synthesis of the new target compounds in addition to different methods of preparation that are reported in literature and are used for the synthesis of intermediates.
IV- Experimental part:
This includes the detailed procedures for the synthesis of the new compounds and intermediates in addition to their microanalytical and spectral data.
Published compounds:
• (3-Chlorophenyl)methanol (IIc)
• (3-Methoxyphenyl)methanol (IId)
• (3-Nitrophenyl)methanol (IIe)
• 1-(Bromomethyl)-3-chlorobenzene (IIIc)
• 1-(Bromomethyl)-3-methoxybenzene (IIId)
• 1-(Bromomethyl)-3-nitrobenzene (IIIe)
• 4-(3- Benzyloxy) benzaldehyde (Va)
• 4-(3-Fluorobenzyloxy) benzaldehyde (Vb)
• 4-(3-Chlorobenzyloxy) benzaldehyde (Vc)
• 4-(3-Methoxybenzyloxy) benzaldehyde (Vd)
• 4-(3-Nitrobenzyloxy) benzaldehyde (Ve)
• 1-Aminocyclohexanecarbonitrile (VIIa)
• 1-Aminocycloheptanecarbonitrile (VIIb)
• 1-Aminocyclohexanecarboxamide (VIIIa)
• 1-Aminocycloheptanecarboxamide (VIIIa)
• S -spiro(Imidazolidine- 4, 1`- indane)2,5-dione (X)
• S -1-Amino-2,3-dihydro-1H-indene-1-carboxylic acid (XI)
Abstract
• S-1-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-1-carboxylic acid (XII)
• S -1-Amino-2,3-dihydro-1H-indene-1-carboxamide (XIV)
• S-2-(tert-Butoxycarbonylamino)propanoic acid (XIX)
• S-tert-Butyl 1-amino-1-oxopropan-2-ylcarbamate (XX)
• S-2-Aminopropanamide hydrochloride (XXI)
• S-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamide
methanesulfonate (XXII) (Safinamide)
New intermediate:
S-tert-Butyl- 1-carbamoyl-2,3-dihydro-1H-inden-1-ylcarbamate (XIII)
New target compounds:
1-[4-(Benzyloxy)benzylamino]cyclohexanecarboxamide ( XVa) 1-[4-(3-Fluorobenzyloxy)benzylamino]cyclohexanecarboxamide
( XVb)
1-[4-(3-Chlorobenzyloxy)benzylamino]cyclohexanecarboxamide
( XVc)
1-[4-(3-Methoxybenzyloxy)benzylamino]cyclohexanecarboxamide
(XVd)
1[4-(3-Nitrobenzyloxy)benzylamino]cyclohexanecarboxamide
(XVe)
1-[4-(Benzyloxy)benzylamino]cycloheptanecarboxamide (XVIa)
1-[4-(3-Fluorobenzyloxy)benzylamino]cycloheptanecarboxamide
( XVIb)
1-[4-(3-Chlorobenzyloxy)benzylamino]cycloheptanecarboxamide
( XVIc)
Abstract
1-[4-(3-Methoxybenzyloxy)benzylamino]
cycloheptanecarboxamide ( XVId)
1-[4-(3- Nitrobenzyloxy)benzylamino]cycloheptanecarboxamide
(XVIe)
S-1-[4-(Benzyloxy)benzylamino]-2,3-dihydro-1H-indene-1- carboxamide( XVIIa)
S-1-[4-(3-Fluorobenzyloxy)benzylamino]-2,3-dihydro-1H-indene- 1-carboxamide (XVIIb)
S-1-[4-(3-Chlorobenzyloxy)benzylamino]-2,3-dihydro-1H-indene- 1-carboxamide (XVIIc)
S-1-[4-(3-Methoxybenzyloxy)benzylamino]-2,3-dihydro-1Hindene- 1-carboxamide (XVIId)
S-1-[4-(3-Nitrobenzyloxy)benzylamino]-2,3-dihydro-1H-indene-1- carboxamide (XVIIe)
V- Molecular modeling:
This part discusses the lignad based pharmacophore modeling to obtain a qualitative common feature hypothesis for sodium channel blockers having anticonvulsant activity. Also it includes docking studies of the target compounds in the branched – chain aminoteransferase enzyme.
VI- Biological evaluation:
All of the above mentioned newly synthesized compounds were tested for their anticonvulsant activity. In addition the compounds which will display the maximum protection will be selected for and the neurotoxicity
screening.