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Synthesis of Pyridotriazolopyrimidines as Antitumor Agents
Author(s) -
Abdallah Magda A.,
Gomha Sobhi M.,
Morad Mahmoud A.,
Elaasser Mahmoud M.
Publication year - 2017
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.2699
Subject(s) - chemistry , pyrimidinones , triethyl orthoformate , hydrazone , ethyl chloroformate , anticancer drug , proton nmr , carbon 13 nmr , combinatorial chemistry , medicinal chemistry , cancer cell lines , stereochemistry , organic chemistry , drug , cancer cell , cancer , medicine , catalysis , psychology , psychiatry
2‐Hydrazino‐5,7‐di‐ p ‐tolylpyrido[2,3‐ d ]pyrimidin‐4(3 H )‐one ( 4 ) was prepared and condensed with different aldehydes 5a , 5b , 5c , 5d , 5e , 5f , 5g to give the corresponding hydrazone derivatives 6a , 6b , 6c , 6d , 6e , 6f , 6g . Oxidative cyclization of the latter compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g gave the corresponding pyrido[2,3‐ d ][1,2,4]triazolo[4,3‐ a ]pyrimidin‐5(1 H )‐ones 7a , 7b , 7c , 7d , 7e , 7f , 7g . Furthermore, compound 4 reacted with benzoyl chloride, triethyl orthoformate, acetyl chloride , ethyl chloroformate, and carbon disulphide in alcoholic KOH solution to afford the corresponding pyrido[2,3‐ d ][1,2,4]triazolo[4,3‐ a ]pyrimidinones ( 7a , 8 , 9 , 10 , 11 ). The reaction of thione 3 or its 2‐methylthio derivative 16 with hydrazonoyl halides 12a , 12b , 12c , 12d , 12e , 12f , 12g , 12h , 12i , 12j , 12k , 12l , 12m yielded the corresponding pyrido[2,3‐ d ][1,2,4]triazolo[4,3‐ a ]pyrimidinones 15a , 15b , 15c , 15d , 15e , 15f , 15g , 15h , 15i , 15j , 15k , 15l , 15m . The structures of all the products were confirmed by elemental and spectral analyses ( 1 H NMR, 13 C NMR, IR, and MS). In addition, the anticancer activity of 20 pyridotriazolopyrimidinones against two cancer cell lines namely MCF‐7 and HepG2 was evaluated, and the results revealed that compounds 7d and 9 have promising activity , compared with doxorubicin, which used as standard reference drug.