Novel pyrimidine-pyridine hybrids: Synthesis,cyclooxygenase inhibition,anti-inflammatory activity and ulcerogenic liability |
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| Institution: | 1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;2. Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf 2014, Saudi Arabia;3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;1. Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research (Formerly, Faculty of Pharmacy), Jamia Hamdard, New Delhi 110062, India;2. Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Mehrauli-Badarpur Road, Pushp Vihar, Sector-3, New Delhi 110017, India;1. Department of Chemistry, UGC-Centre for Advanced Studies-II, Guru Nanak Dev University, Amritsar 143005, India;2. Department of Chemistry, South African Medical Research Council Drug Discovery and Development Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt;2. Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;2. Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;3. Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;4. Biochemistry Lab, Cairo General Hospital, Cairo, Egypt;5. Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62514, Egypt |
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| Abstract: | Some derivatives containing pyrido2,3-d:6,5d′]dipyrimidine-4,5-diones (9a-f), tetrahydropyrido2,3-d]pyrimidine-6-carbonitriles (11a-c) and 6-(4-acetylphenyl)-2-thioxo-2,3,5,6,7,8-hexahydro-1H-pyrimido4,5-d]pyrimidin-4-one (12) were synthesized from 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (8). The anti-inflammatory effect of these candidates was determined and the ulcer indices were calculated for active compounds. 7-Amino-5-(3,4,5-trimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrido2,3-d] pyrimidine-6-carbonitrile (11c) exhibited better edema inhibition than celecoxib. Moreover, compounds 9b, 9d and 11c revealed better COX-2 inhibitory activity in a range (IC50 = 0.25–0.89 µM) than celecoxib (IC50 = 1.11 µM). Regarding ulcerogenic liability, all of the compounds under the study were less ulcerogenic than indomethacin. Molecular docking studies had been carried on active candidates 9d and 11c to explore action mode of these candidates as leads for discovering other anti-inflammatory agents. |
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| Keywords: | Pyrimidine derivatives Pyridine derivatives Anti-inflammatory activity Cox isoforms Ulcerogenic studies |
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