الفهرس 
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Abstract
from the present study, the following conclusions could be drawn:In the present study, 52 newly synthesized derivatives have been prepared and confirmed by 1H, 13C NMR and elemental analysis.
1. N-alkyl-2-(substitutedbenzamido) benzamides6-7(a-b) andmethyl [(2-(substitutedbenzamido)benzamido)] alkanoate derivatives 8-9(a-c) were prepared applying both DCC/HOSuand benzoxazine (method B) procedures.
2. The benzoxazine procedure showedslight improvement in the % yields compared to DCC/HOSu method.
3. The DCC/HOSu procedure has the advantage of making this chemical transformation under mild conditions using some specific expensive chemicals.
4. The benzoxazine method has the advantage of making this chemical transformation using a simple workup procedure, no isolated by products as well as using low cost available simple reagents.
5. Methyl (2-(3-chlorobenzamido)benzamido) alkanoates8a-c proved to be an excellent precursors for the structure modification of these benzamide derivatives by an attachment of amines and amino acid through a peptide bond via DCC and azide.
6. Three derivatives ofN-(2-(benzylamino)-2-oxoalkyl)-2-(3-chlorobenzamido)benzamides13a-cwere obtained from thecorresponding carboxylic acids and hydrazidesviaDCC and azide coupling methods.
7. Fifteen derivatives of methyl ((2-(3-chlorobenzamido)benzamido)alkanamido) alkanoates 14-16(a-e)were obtained from thecorresponding carboxylic acids and hydrazidesviaDCC and azide coupling methods.
8. The azide coupling method (method A) for the preparation of 13a-c and 14-16(a-e)gaveslight better % yields compared to DCC/HOSu(method B).
9. The azide coupling method has the advantage of absence of byproducts from low cost available simple reagents under mild conditions.
10. Molecular docking study revealed an excellent binding affinity for the tested derivatives as human σ1 receptor which plays a significant role in cancer biology.
11. The study of structure-activity relationship using the molecular docking tool for elucidation the binding interactions of the synthesized derivatives, which might justify their higher potency agonist for human sigma-1 receptor bound to 4-IBP (PDB: 5HK2) using (MOE 2008-10).
12. The efficiency of binding affinity of the docked compounds derivatives as an agonist for human σ1 receptor (PDB: 5HK2) is dependent on type of interaction between them.
13. The strongest binding affinity is showed for methyl 2-[2-(2-(3-chlorobenzamido)benzamido)acetamido] acetate (14a) showing two hydrogen bond with Glu 172 and one arene-arene interaction with Tyr 103 interactions between ligands and interactive residues.
14. Compounds 6a, 12c, 15a, 16b also showed strong binding affinity due to one hydrogen bond with Glu 172 and one arene-arene interaction with Tyr 103.
15. Compounds 8c, 9a, 9c, 13a, 13c, 14c, 14e, 15c, and 16e exhibited moderate binding affinity (with docking score from -5.36 to - 9.87 Kcal/mol) by forming only one hydrogen bond with Glu 172.
16. Compound 8a formed only one arene-arene interaction with Tyr 103 without hydrogen bond formation, so it exhibited low binding affinity (with docking score -4.32 Kcal/mol).
17. Thecytotoxic activity of the synthesized derivatives3a, 8c,11a, 12a, 13b with high affinity was tested against breast (MCF-7), lung (A549) cell lines by measuring the percentage of cell survival against their serial dilutions (1, 10, 100, and 1000 µM).
18. A potent cytotoxic activity of the tested derivatives with low IC50 values, especially for 14a (5.3 µM) in comparative with the standard drug 5-FU (5.8 µM).
19. Meanwhile, the tested derivatives were not found to be active against the A549 cell line, they exhibited high IC50 values compared to the 5-FU, except 14a (6.53 µM), so we concluded the selective cytotoxic activity of the tested compounds.
20. The classical preparation of the target compoundN-alkyl 2-aryl quinazolin-4-amines 23a-d and 24b from 4-chloro-2-(substituted-chlorophenyl) quinazolines22a-d by the reaction with amines; benzyl and allyl amines occurs in a six-step sequential reactions.
21. The alternative method for the preparation of N-benzyl 2-aryl quinazolin-4-amines 23a-d, N-allyl-2-arylquinazolin-4-amines 24b and methyl 4-((2-arylquinazolin-4-yl)amino) butanoates 28a-d in 51-70% yield was formed by the reaction of the insitu generated free benzimidoyl chlorides 27a-d with alkyl amines; benzyl amine, allyl amine and γ-amino butyric acid methyl ester hydrochloride in an interesting one-pot Domino reaction strategy.
22. The major advantages of this protocol are short reaction time, mild condition, simple work up, high yields, pure products based on one-pot domino reaction.
23. Four compounds of the complex structures; 6-aryl-2,3-dihydro-4H-pyrimido[1,2-c]quinazolin-4-ones 29a-d, were obtained by the reaction of the insitu generated free benzimidoyl chlorides 27a-d with-alanine methyl ester hydrochloride in an interesting one-pot Domino reaction strategy.
24. Four compounds of the complex structures; 5-arylimidazo[1,2-c]quinazolin-3(2H)-ones 30a-d, were obtained by the reaction of the insitu generated free benzimidoyl chlorides 27a-d with glycine methyl ester hydrochloride in an interesting one-pot Domino reaction strategy in excellent yields.
25. Four compounds of the complex structures; 5-aryl-2-methylimidazo[1,2-c]quinazolin-3(2H)-ones31a-d, were obtained by the reaction of the insitu generated free benzimidoyl chlorides 27a-d with L-alanine methyl ester hydrochloride in an interesting one-pot Domino reaction strategy in excellent yields.
26. The insitu generated free benzimidoyl chlorides 27a-d was prepared in a one-pot strategy by the reaction ofN-(2-cyanophenyl)-substitutedbenzamides26a-d with thionyl chloride under reflux for 12h.
27. The unsubstitutedbenzamides or chloro-substituted benzamides26a-d were selected carefully to facilitate the Dimroth rearrangement.
28. The rational mechanism of the interesting Domino reaction involveinstantaneous reactions that include Dimroth rearrangement and cyclocondensations multi step reactions of unisolated active intermediates.