SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS
Ziedan, N., El-Shanawani, A., El-Adl, S., Sakr, S. (2006). SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS. EKB Journal Management System, 15(2), 19-28. doi: 10.21608/zjps.2006.169423
Noha Ziedan; Abdalla El-Shanawani; Sobhy El-Adl; Samy Sakr. "SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS". EKB Journal Management System, 15, 2, 2006, 19-28. doi: 10.21608/zjps.2006.169423
Ziedan, N., El-Shanawani, A., El-Adl, S., Sakr, S. (2006). 'SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS', EKB Journal Management System, 15(2), pp. 19-28. doi: 10.21608/zjps.2006.169423
Ziedan, N., El-Shanawani, A., El-Adl, S., Sakr, S. SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS. EKB Journal Management System, 2006; 15(2): 19-28. doi: 10.21608/zjps.2006.169423

SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS

Zagazig Journal of Pharmaceutical Sciences
Article 3, Volume 15, Issue 2, December 2006, Page 19-28  XML PDF (2.78 MB)
Document Type: Original Article
DOI: 10.21608/zjps.2006.169423
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Authors
Noha Ziedan email 1; Abdalla El-Shanawani1; Sobhy El-Adl2; Samy Sakr1
1Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
2Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazige University, Zagazig, Egypt
Abstract
A series of 1,2,4-triazolo4,3-cJquinazoline-3-thiol was synthesized by reacting isatoic anhydrides (Ia, Ib) with thiosemicarbazide to yield the appropriate 2-acylhydrazinocarbothioamides (IIab ,IIb) which were cyclized to afford 5-(2- substituted aminophenyl)-1,2,4-triazol-3-thiols (IIIab ,IIIb) using sodium hydroxide. The triazol derivatives (IIIab,IIIb) were cyclized to the new 1,2,4-riazolo4,3-cquinazoline-3-thiol (IV) upon condensation with aromatic aldehydes. Whereas, cyclization of (IIIab,IIIb) with formaldehyde unexpectedly afforded 3-hydroxymethyl-1,2,4-triazolo1,5-cquinazolin-2-thione (VIa, VIb). The last reaction is the role-play to the formation of a series of 1,2,4-triazolo 1,5-cquinazoline-2-thiol (VLc, VId, VII) upon boiling of the appropriate 1,2,4-triazolo4,3-cquinazoline-3-thiol in ethanol with acidified formaldehyde. Also, alkylation of 3-thiol derivatives (IV) with the appropriate alkyl halide in alkaline medium afforded a new series of 3-alkyl (or 3-aralkyl) thio-1,2,4-triazolo4,3-cquinazolines (Va-b). Otherwise, alkylation of 5-(2-methylaminophenyl)-1,2,4-triazol-3-thiol (IIIa) was affected firstly and followed by condensation with either carbon disulfide or hydroxybenzaldehyde to produce 3-alkylthio-6- methyl-1,2,4-triazolo(4,3-cquinazolin-5(6H)-thione (IX) or 3-alkylthio-5-(hydroxyphenyl)-6-methyl-1,2,4-triazolo4,3- c]quinazoline (V1-1) respectively. Oxo-desulfuration was the key-procedure for preparation of 3-hydroxy-6-methyl-5-(4- nitrophenyl)-1,2,4-triazolo4,3-cquinazoline (X) from its thione analogue. The new triazoloquinazoline derivatives were subjected to preliminary pharmacological screening, where compounds (VIf, Vb, VIa, VIb, VId, X) produced a moderate to high CNS stimulant effect when tested on mice. Furthermore, compound (VIa) was tested by recording the electroencephalographic changes induced by its intravenous injection in conscious rabbits which gave noticeable results.
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