Abstract Article


Synthesis of 1,8-Napthyridine derivatives and their evaluation as possible antiepileptic agents

Brijeshkunvar J Mishra*

ONLINE ISSN : 2456-8244



Aminopropyloxy derivatives of 1,8-naphthyridines have been synthesized using the principle of Conrad-Limpach synthesis of quinolines. The hydroxy group at 2- position of the naphthyridine ring was converted to the corresponding epoxypropane ether derivative by etherification with epichlorhydrin. The epoxy ether was then aminated in presence of KOH with the corresponding amines to obtain the aminopropyloxy derivatives. The compounds were tested for anti convulsant action at dose of 150mg/Kg relative to diazepam (5mg/Kg) by prevention of PTZ-induced seizures in mice.


Naphthyridine, anticonvulsant, Pentylenetetrazole, tonic clonic, aminopropyloxy



Agrawal SK, Saxena AK, Jain PC, Anand N, Sur RN, Srimal RC, and Shawan BN (1990) Synthesis and structure activity relationship in aryloxyalkylamines. Indian J Chem 29B: 80-84. Bouzard D, Cesare PD, Essiz M, Jacquet J, Ledoussal B, Remuzon P, Kessler R, and Tomc JF (1992) Fluoronaphthyridines as antibacterial agents. 4. Synthesis and structure-activity relationships of 5-substituted-6-fluoro-7-(cycloamino)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids. J Med Chem 35(3): 518-525. Drug Discovery and Evaluation: Pharmacological Assays (Ed. H. G. Vogel), Springer-Verlag, Berlin Heidelberg (2002), pp. 385-593. Ferrarini P, Manera C, Mori C, Badawneh M, and Saccomanni G (1998) Synthesis and evaluation of antimycobacterial activity of 4-phenyl-1,8-naphthtyridine derivatives Farmaco 53(12): 741-746. Ferrarini P, Mori C, and Tellini N (1990) Synthesis and local anesthetic activity of (E)- and (Z)-diethylaminoethyl-iminoethers of 1,8-naphthyridine. Farmaco 45(3): 385-389. Ferrarini PL, Badawneh M, Franconi F, Manera C, Miceli M, Mori C, and Saccomani G (2001) Synthesis and antiplatelet activity of some 2,7-di(N-cycloamino)-3-phenyl-1,8-naphthyridine derivatives. Farmaco 56(4): 311-318. Kuo S, Tsai S, Li H, Wu C, Ishii K, and Nakamura H (1988) Studies on heterocyclic compounds. IX. Synthesis and antiallergic activity of furo [2,3-b] [1,8] naphthyridine-3,4 (2H, 9H)-diones, and 4H-furo [2,3-d] pyrido [1,2-alpha]-pyrimidine-3,4 (20-diones). Chem Pharm Bull 36(11): 4403-4407. Scotese SA, Bauer R, and Bell S (1987) 2-Oxo-1,8-naphthyridine-3-carboxylic acid derivatives with potent gastric antisecretory properties J Med Chem 30(12): 2270-2277. Settimo AD, Primofiore G, Settimo FD, Simorini F, Barili P, Senatore G, Martini C, and Luccacchini A (1994) Synthesis and benzodiazepine receptor activity of some 4,5-dihydro-1H-pyrazolo [4,3-c] [1,8] naphthyridine derivatives. Drug Des Discov 11(40): 307-328. Sur RN, Shanker G, Rathore RSK, Chak IM, Agrawal SK, and Jain PC (1980) Pharmacological studies on 1-(p-aminophenoxy)-3-[N1-(O-methoxypheynyl)-N4-piperazinyl]propane dihydrochloride. Indian J Exp Biol 18: 1190-1191. Takeshi K, Fumio K, and Tadafumi T (1992) A novel synthesis and potent anti-inflammatory activity of 4-Hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3-carboxamides, J Med Chem 35(6): 1130-1135. Thomas LJ, Gangadhar R, Kishore SG, Ramchandran S, Saravanan M, and Sridhar SK (2003) Synthesis and pharmacological activities of 1,8-naphthyridine derivatives. Indian Drugs 40(6): 320-327. Zhang SX, Bastow KF, Tachibana Y, Kuo SC, Hamel E, Mauger A, Narayana VL, and Lee KH (1999) Antitumor Agents. 196. Substituted 2-Thienyl-1,8-naphthyridin-4-ones: Their synthesis, cytotoxicity, and inhibition of Tubulin Polymerization 1. J Med Chem 42(20): 4081-4087.