Design, synthesis and anticonvulsant potential of (E)-3-(5-(substituted aminomethyl)-1,3,4-thiadiazol-2-yl)-2-substituted styrylquinazolin-4-(3H)-one
Abstract
Objective: The prime objective of the paper was to design and synthesize new derivatives of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one and evaluated for their anticonvulsant potential.
Material and methods: Various derivatives of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one derivatives has been synthesized by reacting 2-substituted benzoxazin-4-one with (E)-2-(4-Substituedstyryl)-4H-benzo[d][1,3]oxazin-4-one. All synthesized compounds have been characterized by the IR, NMR and mass spectral analysis. Proposed compounds have been evaluated for anticonvulsant potential by subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock seizure (MES) model and compared with the reference drug phenytoin &carbamazepine.
Result and discussion: The subcutaneous pentylenetetrazoles (scPTZ) model denotes that compounds SB-6, SB-12, SB-14 and SB-18 were found most active at anticonvulsant screening when compared with phenytoin and carbamazepine (standard drug).The most active compound of the series was SB-1, SB-4, SB-6, SB-9, SB-12, SB-14, SB-14 and SB-18. In most of the Cl and nitro group phenyl ring in position of the 1,3,4-thiadiazoles nucleus and Cl on phenyl ring of 4(3H)-quinazolinone has shown the potent activity.
Keywords: quinazolinone, anticonvulsant, maximal electroshock seizure, phenytoin, carbamazepine
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References
1. Serban G, Stanasel O, Serban E, Bota S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Design Development and Therapy 2018; 12:1545-1566.
2. Rivas FM, Stables JP, Murphree L, Edwankar RV, Edwankar CR, Huang S, Jain HD, Zhou H, Majumder S, Sankar S, Roth BL, Ramerstorfer J, Furtmüller R, Sieghart W, Cook JM. Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models. Journal of Medicinal Chemistry 2009; 52(7):1795-8.
3. Raja AS, Pandeya SN, PandaJ SS, Stables P. Synthesis and anticonvulsant evaluation of semicarbazones of acetophenone mannich bases. Pharmaceutical Chemistry Journal, 2007; 41(6):302–307.
4. Pester RJ, Cereghino JJ, Gladding GD, Hessie BJ, Kupferberg HJ, Seoville B, White B. Antiepileptic Drug Development Program. Cleveland Clinic Journal of Medicine 1984; 51: 293-305.
5. Narayana BN, Bhushan B, Madhavan V. Synthesis and Biological activity of some Novel 1,3,4-Thiadiazole derivatives. International Journal of ChemTech Research 2012; 4(1):74-78
6. Mohamed M. Abdel-Daim, Khaled Abo-EL-Sooud, LotfiAleya, Simona G. Bungǎu, Agnieszka Najda and Rohit Saluja. Alleviation of Drugs and Chemicals Toxicity: Biomedical Value of Antioxidants. Oxidative Medicine and Cellular Longevity. 2018;12;135-140
7. Mishra P, Jatav V, Kashaw SK. Some Novel 2‐Methyl‐3‐(1′,3′,4′‐thiadiazoyl)‐4‐(3H) quinazolinone with Anticonvulsant and CNS Depressant Activity. Chemical Information 2007; 38(34).
8. Mandhane SN, Aavula K, Rajamannar T. Timed pentylenetetrazol infusion test: a comparative analysis with s.c.PTZ and MES models of anticonvulsant screening in mice. Seizure. 2007; 16(7):636-44.
9. Kumar A, Kashaw V, Irchhiaya R, Kashaw SK, Shukla SK. Synthesis and biological screening of some novel 2-amino-5-aryl-1,3,4-oxadiazole analogues. Medicinal Chemistry Research 2010; 19:S46-S46.
10. Kashaw SK, Kashaw V, Mishra P, Jain NK. Design, synthesis and potential CNS activity of some novel 1-(4-substituted-phenyl)-3-(4-oxo-2-propyl-4Hquinazolin-3-yl)-urea. Arkivoc 2008; 14:17-26.
11. Kashaw SK, Kashaw V, Mishra P, Jain NK, Stables JP. Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea. European Journal of Medicinal Chemistry 2009; 44(11):4335-43.
12. Kashaw SK, Kashaw V, Mishra P, Jain NK, Stables JP. Design, synthesis, and potential CNS activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl-4H-quinazolin-3-yl)-urea. Medicinal Chemistry Research 2011; 20(6):738-45.
13. Kashaw SK, Gupta V, Kashaw V, P. Mishra, Stables JP, N.K. Jain. Medicinal Chemistry Research 2010; 19:250- 261.
14. Jatav V, Mishra P, Kashaw S, Stables JP. Synthesis and CNS depressant activity of some novel 3-[5-substituted 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. European Journal of Medicinal Chemistry 2008; 43(1):135-41.
15. Jatav V, Mishra P, Kashaw S, Stables JP. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. European Journal of Medicinal Chemistry 2008; 43(9):1945-54.
16. Jatav V, Kashaw S, Mishra P. Synthesis, antibacterial and antifungal activity of some novel 3-[5-(4-substituted phenyl) 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. Medicinal Chemistry Research 2008; 17(2-7):169-81.
17. Jatav V, Jain SK, Kashaw SK, Mishra P. Synthesis and anti-microbial activity of novel 2-Methyl-3-(1'3'4'-Thiadiazoyl)-4-(3h) Quinazolinones. Indian Journal of Pharmaceutical Sciences 2006; 68(3):360-363.
18. Gatadi S, Lakshmi TV, Nanduri S. 4(3H)-Quinazolinone derivatives: Promising antibacterial drug leads. European Journal of Medicinal Chemistry 2019; 170:157-172.
19. Chaudhari PS, Chitlange SS, Nanda RK. Synthesis and Biological Evaluation of Novel 2-(4-acetyl-3-methyl- 5-(arylamino) thiophen-2-yl)-3-arylquinazolin-4(3H)-one derivatives as potential anti-inflammatory and antioxidant agents. Medicinal Chemistry 2018; 17(2):102-114.
20. Al-Salahi R, Anouar EH, Marzouk M, Abuelizz HA. Anti-HAV evaluation and molecular docking of newly synthesized 3-benzyl(phenethyl)benzo[g]quinazolines. Bioorganic Medicinal Chemistry Letter 2019; 12: 134-139.
21. Akerbladh L, Chow SY, Odell LR, Larhed M. Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by carbonylation Cyclization Domino Reaction of ortho-Halo phenols and Cyanamide. Chemistry Open. 2017; 6(5):620-628.
22. Aggarwal N, Mishra P. Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for anticonvulsant activity. J Zhejiang University Science B, 2005; 6(7): 617-21.
2. Rivas FM, Stables JP, Murphree L, Edwankar RV, Edwankar CR, Huang S, Jain HD, Zhou H, Majumder S, Sankar S, Roth BL, Ramerstorfer J, Furtmüller R, Sieghart W, Cook JM. Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models. Journal of Medicinal Chemistry 2009; 52(7):1795-8.
3. Raja AS, Pandeya SN, PandaJ SS, Stables P. Synthesis and anticonvulsant evaluation of semicarbazones of acetophenone mannich bases. Pharmaceutical Chemistry Journal, 2007; 41(6):302–307.
4. Pester RJ, Cereghino JJ, Gladding GD, Hessie BJ, Kupferberg HJ, Seoville B, White B. Antiepileptic Drug Development Program. Cleveland Clinic Journal of Medicine 1984; 51: 293-305.
5. Narayana BN, Bhushan B, Madhavan V. Synthesis and Biological activity of some Novel 1,3,4-Thiadiazole derivatives. International Journal of ChemTech Research 2012; 4(1):74-78
6. Mohamed M. Abdel-Daim, Khaled Abo-EL-Sooud, LotfiAleya, Simona G. Bungǎu, Agnieszka Najda and Rohit Saluja. Alleviation of Drugs and Chemicals Toxicity: Biomedical Value of Antioxidants. Oxidative Medicine and Cellular Longevity. 2018;12;135-140
7. Mishra P, Jatav V, Kashaw SK. Some Novel 2‐Methyl‐3‐(1′,3′,4′‐thiadiazoyl)‐4‐(3H) quinazolinone with Anticonvulsant and CNS Depressant Activity. Chemical Information 2007; 38(34).
8. Mandhane SN, Aavula K, Rajamannar T. Timed pentylenetetrazol infusion test: a comparative analysis with s.c.PTZ and MES models of anticonvulsant screening in mice. Seizure. 2007; 16(7):636-44.
9. Kumar A, Kashaw V, Irchhiaya R, Kashaw SK, Shukla SK. Synthesis and biological screening of some novel 2-amino-5-aryl-1,3,4-oxadiazole analogues. Medicinal Chemistry Research 2010; 19:S46-S46.
10. Kashaw SK, Kashaw V, Mishra P, Jain NK. Design, synthesis and potential CNS activity of some novel 1-(4-substituted-phenyl)-3-(4-oxo-2-propyl-4Hquinazolin-3-yl)-urea. Arkivoc 2008; 14:17-26.
11. Kashaw SK, Kashaw V, Mishra P, Jain NK, Stables JP. Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea. European Journal of Medicinal Chemistry 2009; 44(11):4335-43.
12. Kashaw SK, Kashaw V, Mishra P, Jain NK, Stables JP. Design, synthesis, and potential CNS activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl-4H-quinazolin-3-yl)-urea. Medicinal Chemistry Research 2011; 20(6):738-45.
13. Kashaw SK, Gupta V, Kashaw V, P. Mishra, Stables JP, N.K. Jain. Medicinal Chemistry Research 2010; 19:250- 261.
14. Jatav V, Mishra P, Kashaw S, Stables JP. Synthesis and CNS depressant activity of some novel 3-[5-substituted 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. European Journal of Medicinal Chemistry 2008; 43(1):135-41.
15. Jatav V, Mishra P, Kashaw S, Stables JP. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. European Journal of Medicinal Chemistry 2008; 43(9):1945-54.
16. Jatav V, Kashaw S, Mishra P. Synthesis, antibacterial and antifungal activity of some novel 3-[5-(4-substituted phenyl) 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. Medicinal Chemistry Research 2008; 17(2-7):169-81.
17. Jatav V, Jain SK, Kashaw SK, Mishra P. Synthesis and anti-microbial activity of novel 2-Methyl-3-(1'3'4'-Thiadiazoyl)-4-(3h) Quinazolinones. Indian Journal of Pharmaceutical Sciences 2006; 68(3):360-363.
18. Gatadi S, Lakshmi TV, Nanduri S. 4(3H)-Quinazolinone derivatives: Promising antibacterial drug leads. European Journal of Medicinal Chemistry 2019; 170:157-172.
19. Chaudhari PS, Chitlange SS, Nanda RK. Synthesis and Biological Evaluation of Novel 2-(4-acetyl-3-methyl- 5-(arylamino) thiophen-2-yl)-3-arylquinazolin-4(3H)-one derivatives as potential anti-inflammatory and antioxidant agents. Medicinal Chemistry 2018; 17(2):102-114.
20. Al-Salahi R, Anouar EH, Marzouk M, Abuelizz HA. Anti-HAV evaluation and molecular docking of newly synthesized 3-benzyl(phenethyl)benzo[g]quinazolines. Bioorganic Medicinal Chemistry Letter 2019; 12: 134-139.
21. Akerbladh L, Chow SY, Odell LR, Larhed M. Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by carbonylation Cyclization Domino Reaction of ortho-Halo phenols and Cyanamide. Chemistry Open. 2017; 6(5):620-628.
22. Aggarwal N, Mishra P. Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for anticonvulsant activity. J Zhejiang University Science B, 2005; 6(7): 617-21.
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Bhattacharya S, Kashaw V. Design, synthesis and anticonvulsant potential of (E)-3-(5-(substituted aminomethyl)-1,3,4-thiadiazol-2-yl)-2-substituted styrylquinazolin-4-(3H)-one. JDDT [Internet]. 15Mar.2019 [cited 18Aug.2022];9(2):591-02. Available from: http://jddtonline.info/index.php/jddt/article/view/2705
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