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Abstract

Design, synthesis and evaluation of new 2,6-dihydroimidazo[1,2-c]pyrimido[5,4-e]-pyrimidine-5(3H)-thiones as possible antihistaminic/antiasthmatic agents?

Author(s): K Sirisha1, G Achaiah2, A Raghu Ram Rao2
1Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Ramnagar, Warangal-506 001, India 2University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506 009, India

Correspondence Address:
A Raghu Ram Rao Medicinal Chemistry Research Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506 009 India E-mail: [email protected]


A series of new 10-(alkylamino)-8-methyl-2,6-dihydroimidazo[1,2-c]pyrimido[5,4-e]pyrimidine-5(3H)-thiones (4a-g) were subjected to molecular property prediction (drug-likeness, lipophilicity and solubility parameters) using Osiris Property Explorer, ALOGPS 2.1, Molinspiration and ACD/Chemsketch 12.0 software programmes. The calculated drug-related properties of the designed molecules were similar to those found in most marketed drugs. Amongst the proposed analogues, four promising candidates were chosen (4a-d) for synthesis on the basis of Lipinski's 'Rule of Five' and drug-likeness scores. The significant biological activity of the test compounds in two in vitro modes (isolated guinea pig tracheal chain preparation, isolated guinea pig ileum) supports the promise and accuracy of the prediction. Among them, 4a was the most potent antihistaminic (IC 50 value of 30.2 μM; standard, chlorpheniramine maleate showed an IC 50 of 14.1 μM).



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