Indian J Physiol Phannacol 1992; 36(4): 247-250 PHARMACOLOGICAL SCREENING OF FEW NEW 2-(SUBSTITUTED ACETYL) AMINO-5-ALKYL-l,3,4-0XADIAZOLES PRADEEP MISHRA*, GOPAL K. JOSHI, ASHOK K. SHAKYA, R. K. AGRAWAL AND G. K. PATNAIK** Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar - 470 003 (M.P.) and ** Division of Pharmacology. Central Drug Research Institute. Lucknow - 226 001 (u.P.) ( Received on August 10, 1991 ) Abstract: Nine new 2-(substituted acetyl) amino-5-alkyl-I,3,4-oxadiazoles were synthesised and confinned on the basis of IR and nitrogen analysis. These were screened for spasmolytic. anti-inflammatory and their effects on blood pressure after detennining ALD",. Compounds GK-4 i.e. 2-(dielhylaminoacetyl)- amino-5-methyl-l.3,4-oxadiazole and GK-8 i.e. 2-(din- propylamino acelyl)- amino-5-ethyl-I,3,4-oxadiawle were found to be spasmolytic. Compound GK-6 i.e. 2-(diethylaminoacelyl)- amino-5-n-propyl-I.3.4-oxadiawle was found to be a potent hypotensive agent with the effect lasting for more than two hours. Key words: 1,3,4-oxadiazole spasmolytic hypotensive N-t:>J H N:::I<" q IT .. Q., R KF 0 3 " It INfRODUCTION Our studies on 2 - (substituted acetyl)-amino-5- alkyl 1,3,4-thiadiazoles showed some of them to be CNS depressant (1) and anti-inflammatory agents (2) in addition to their being antihistaminics. Various biological activities like analgesic, anti-inflammatory (3), oral hypoglycemic (4), fungitoxic (5) and hypo- tensive (6) reported with 1,3,4,- oxadiazo1'es promoted us to synthesise a series of new 2-(substituted acetyl) amino-5-alkyl 1,3,4-oxadiazoles. Their pharma-cological screening for antiinflammatory, spasmolytic and effect on cardiovascular system were done to find out whether oxadiazoles too have parallel activities to thiadiazoles. METHODS Synthesis : The synthesis involved the following sequence. RCOOH N-N H2NHNCNH2 H-C:::O » )L R 1 c-' R 0 }c...,cOCI N-N 3 ·Corresponding Author Synthesis of 2-amino -5-alkyl - 1.3.4-oxadiazole (2) : Semicarbazide HCI (0.15 mole) was added to 100 ml of the fatty acid and maintained at 70-80°C for 2 hr. Concentrated sulphuric acid Analar (specific gravity 1.84, 10 ml) was added and the contents were heated to 90-100°C for another 3 hr. After cooling the reaction mixture was poured on crushed ice with constant stir- ring. It was made alkaline with potassium bicarbonate. The crude product thus separated was filtered and recrystallised from 70% aqueous methanol. Yield: 2a (R=methyl) (72%), m.p. 212-15°C, 2b (R=ethyl) (80%), m.p.-230-33°C, 2c (R=n-propyl) (85%), m.p.2oo-03°C. 2-chloroacetylamino-5-alkyl-I.3.4-oxadiazole (3) : Chloroacetyl chloride (0.11 mole) was added dropwise to compound (2) (0.10 mole) in'dioxane (40 ml). The reaction mixture was refluxed for 3 hours. After cool- ing the mixture was poured on crushed ice. The crude product thus precipitated was recrystallized from metha- nol (95% vjv). Yield: 3 a(R=methyl) (80%), m.p. 210- l2°C. 3b (R=ethyl) (85%), m.p_ 232-35°, 3c (R=n- propyl) (90%), m.p. 240-43°C. 2(substituted acetyl)-amino-5-alkyl-l ,3 .4-oxadia- zoles (4): A mixture of (3) (0.02 mole), appropriate secondary amine (0.04-0.05 mole), potassium carbonate