pharmaceutically acceptable salts of the compounds of formula ( i ) include acid addition salts formed with inorganic acids , e . g ., hydrochloric acid , sulfuric acid , nitric acid , etc ., or organic acids , e . g ., fumaric acid , tartaric acid , maleic acid , succinic acid , oxalic acid , etc ., and salts formed from a carboxyl group and an alkali metal , e . g ., sodium , potassium , etc ., or an alkaline earth metal , e . g ., calcium , magnesium , etc . the compounds of formula ( i ) and salts thereof proved highly safe on examination of acute toxicity ( ld 50 ) in oral administration or intravenous injection to rats . the compounds of formula ( i ) or a salt thereof can be formulated into various pharmaceutical preparations , such as tablets , powders , capsules , and injectable solutions , according to known pharmaceutical techniques and is usually administered orally or intravenously . the dose level of the compounds of formula ( i ) or a salt thereof generally ranges from 50 to 1000 mg / day for an adult ( body weight : about 50 to 60 kg ) in oral administration . the compounds of formula ( i ) or a salt thereof experimentally exhibited excellent antidiabetic effects such as hypoglycemic activity and improvement of glucose tolerance in a diabetic model such as streptozotocin - induced diabetic spontaneous hypertensive rats , and also exhibited no significant side effects in case of long term oral administration . therefore , the compounds of formula ( i ) or a salt thereof are useful as an diabetic agent . the present invention is now illustrated in greater detail with reference to the following test example and reference example , but it should be understood that the present invention is not limited thereto . 5 - week old spontaneous hypertensive male rats ( shr ), available from nippon charles river , were used . streptozotocin ( stz ) was dissolved in a 0 . 1m citrate buffer solution ( ph 4 . 5 ) and injected into the tail vein of the rats at a dose level of 50 mg / kg to prepare diabetic rats . for control , rats received 1 ml / kg of the citrate buffer solution alone through administration to the tail vein . after one week from the stz administration , blood was taken from the tail vein of the unanesthetized rats , and the blood sugar level was determined . those rats having a blood sugar level of 300 mg / dl or higher were used as diabetic rats . 6 -( 1 - imidazolylmethyl )- 5 , 6 , 7 , 8 - tetrahydronaphthalene - 2 - carboxylic acid hydrochloride hemihydrate ( hereinafter referred to as compound a ) was dissolved in distilled water and administered orally to the test animals at a dose level of 1 mg / kg / day or 10 mg / kg / day for 5 consecutive months from one week after the administration of stz or a citrate buffer solution . just before the administration of compound a , blood was sampled from the tail vein of the rats without any restriction of diet to determine the blood sugar level using a commercial glucose assay kit ( trade name : new blood sugar test , produced by boehringer mannheim co ., ltd ., west germany ). the results are shown in table 1 , expressed as mean ± s . e . after 3 months from the start of the administration of compound a , the rats were fasted for 18 hours . glucose was administered orally to the rats at a dose level of 2 g / kg . blood was sampled from the tail vein of the rats just before the administration of glucose and at 1 hour and 2 hours after the administration to determine the blood sugar lever using the above method . the result was shown in table 2 , expressed as mean + s . e . table 1______________________________________hypoglycemic activity adminis - blood sugar level ( mg / dl ) tration dosage of compound a term ( mg / kg / day ) ( weeks ) 0 1 10______________________________________shr 0 103 . 8 ± 100 . 7 ± 108 . 0 ±( n = 8 ) 2 . 5 1 . 6 3 . 2 2 96 . 6 ± 95 . 4 ± 90 . 9 ± 2 . 6 2 . 8 1 . 5 8 94 . 2 ± 94 . 5 ± 93 . 2 ± 1 . 5 1 . 5 1 . 8diabetic 0 356 . 1 ± 374 . 6 ± 361 . 4 ± shr ( n = 7 ) 9 . 6 17 . 3 10 . 6 2 481 . 5 ± 406 . 3 ± 365 . 2 ± 36 . 4 39 . 9 40 . 9 * 8 544 . 2 ± 445 . 0 ± 277 . 3 ± 30 . 0 57 . 6 44 . 7 ** ______________________________________ n : number of test animals * p & lt ; 0 . 05 compared with the control group ( not administered compound a ) ** p & lt ; 0 . 01 compared with the control group as is apparent from table 1 , compound a exhibited a tendency to lower the high blood sugar level of the diabetic shr from 2 weeks after the start of the administration of compound a , and significantly lowered the blood sugar level at 8 weeks after the start of the administration of compound a . however , the blood sugar level in shr was not affected by the administration of compound a . therefore , it was confirmed that compound a lowered the high blood sugar level in diabetic animals . table 2______________________________________effect on glucose tolerance blood sugar level ( mg / dl ) dosage of compound a ( mg / kg / day ) 0 1 10sampling time ( n = 7 ) ( n = 7 ) ( n = 8 ) ______________________________________just before the 178 . 5 ± 136 . 8 ± 105 . 1 ± glucose load 32 . 8 19 . 0 5 . 71 hour after 329 . 5 ± 255 . 4 ± 202 . 4 ± glucose load 34 . 9 19 . 7 15 . 7 * 2 hours after 280 . 8 ± 167 . 3 ± 137 . 1 ± glucose load 41 . 9 17 . 5 5 . 9______________________________________ * p & lt ; 0 . 05 compared with the control group as is apparent from table 2 , compound a improved the glucose tolerance in the diabetic shr . acute toxicities of compound a in rats through oral administration or intravenous injection were as follows . table 3______________________________________acute toxicity in ratsld . sub . 50 ( mg / kg ) male female______________________________________2438 1994 ( p . o .) 807 783 ( i . v . ) ______________________________________reference example______________________________________compound a 20 mglactose 50 mgcorn starch 25 . 5 mghydroxypropyl cellulose 4 mgmagnesium stearate 0 . 5 mgtotal 100 mg per one tablet______________________________________ according to the above formulation , the tablet containing compound a was prepared by usual pharmaceutical techniques . while the invention has been described in detail and with reference to specific embodiments thereof , it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof .
an antidiabetic agent is disclosed , which comprises a compound represented by formula : ## str1 ## wherein r represents an imidazolyl group , a thiazolyl group or a pyridyl group ; n represents 1 or 2 ; and m represents an integer of from 1 to 4 , or a pharmaceutically acceptable salt thereof as an active ingredient .