3-Substituted-ureido-N-pyridyl benzamides

Abstract

Benzamide derivatives of the formula: ##STR1## wherein R.sub.1 is a hydrogen atom, a methyl group or a methoxy group; R.sub.2 is a straight-chain or branched-chain alkyl group having 2 to 8 carbon atoms, a substituted phenyl group, or group --NHR.sub.4, R.sub.4 being a hydrogen atom, a straight-chain or branched-chain or cyclic alkyl group having 1 to 6 carbon atoms, or a phenyl group that may have a substituent on the nucleus; R.sub.3 is a hydrogen atom or one or two alkyl groups having 1 to 4 carbon atoms and n is 0 or 1, a process for preparing these derivatives, and pharmaceutical compositions containing the same are provided.The compounds of the above formula have the action to reduce the blood glucose level and, therefore, are useful as medicines.

Description

The present invention relates to benzamide derivatives of the formula: ##STR2## (wherein R.sub.1 is a hydrogen atom, a methyl group or a methoxy group; R.sub.2 is a straight-chain or branched-chain alkyl group having 2 to 8 carbon atoms, a substituted phenyl group, or group --NHR.sub.4, R.sub.4 being a hydrogen atom, a straight-chain or branched-chain or cyclic alkyl group having 1 to 6 carbon atoms, or a phenyl group that may have a substituent on the nucleus; R.sub.3 is a hydrogen atom or one or two alkyl groups having 1 to 4 carbon atoms, and n is 0 or 1), a process for preparing these derivatives, and pharmaceutical compositions containing them. Examples of the substituent of the phenyl group of R.sub.2 and R.sub.4 in the formula (I) are a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.

The compounds of the present invention that are represented by formula (I) are useful as medicines since they have the ability to reduce the blood glucose level.

One method of producing the compounds of the present invention comprises the steps of reacting 3-nitrobenzoyl chloride with amines in the presence of a base to form 3-nitrobenzamide derivatives and reducing them by a conventional technique to form 3-aminobenzamide derivatives, and reacting them with a carboxylic acid chloride or an isocyanate. This method is illustrated by the following reaction scheme wherein X is a halogen atom and the other symbols have the same meanings as defined above: ##STR3##

Compound (II) is reacted with aminopyridines under the conditions conventionally used for the reaction of forming acid amides; for example, the two compounds are reacted in a solvent such as acetone, tetrahydrofuran or dioxane, preferably in the presence of a base such as triethylamine or pyridine, at a temperature between 0.degree. and 30.degree. C. for a period of 1 to 5 hours.

Compound (III) can be readily converted to compound (IV) by catalytic reduction using a catalyst such as palladium-carbon, Raney's nickel or platinum dioxide.

Compound (IV) can be converted to the end compound (I) by reacting it with a reactive derivative of carboxylic acid or an isocyanate in the presence of a solvent such as tetrahydrofuran, dioxane, benzene or toluene, in the presence of a base such as triethylamine, pyridine dimethylanilin or picoline, at a temperature between 0.degree. and 100.degree. C. for a period of 1 to 48 hours.

The compound (I) so obtained is highly capable of reducing the blood glucose level and can be used as a medicine to treat diabetes.

The pharmaceutical composition containing the compound (I) of the present invention can be administered to human beings orally or parenterally by intramuscular, subcutaneous or intravenous injection or in the form of a suppository. The composition can be formulated in a suitable dosal form by any of the conventional drug-making techniques, and among the suitable drug forms are tablets, slow-release agents, powders, capsules, suspensions, injections and suppositories.

The present invention is now described in greater detail by reference to the following examples and experiments to which the scope of the invention is by no means limited.

EXAMPLE 1

To a mixture of 2-aminopyridine (28.2 g), triethylamine (45 ml) and acetone (600 ml), 3-nitrobenzoyl chloride (55.8 g) was gradually added with stirring under ice cooling. The mixture was stirred for 30 minutes under the same condition, then for one hour at room temperature. Thereafter, the reaction solution was poured into 3 liters of water, and the resulting crystal was collected by filtration, washed with water, and recrystallized from methanol to provide 58.5 g of 3-nitro-N-2-pyridylbenzamide as a colorless acicular crystal (yield: 80%, m.p. 156.degree.-157.degree. C.). Hydrogen was bubbled into a mixture of the 3-nitro-N-2-pyridylbenzamide (15.9 g), 10% palladium-carbon (1.5 g) and ethanol (300 ml). After a stoichiometric amount of hydrogen was absorbed, the catalyst was removed, the reaction mixture was concentrated under vacuum, and the residue was recrystallized from ethanol to provide 7.2 g of a colorless acicular crystal of 3-amino-N-2-pyridylbenzamide (yield: 52%, m.p. 113.degree.-115.degree. C.). To a mixture of the 3-amino-N-2-pyridylbenzamide (6.4 g), triethylamine (4.5 ml) and acetone (60 ml), propionic acid chloride (2.8 g) was gradually added with stirring at room temperature. After one hour of stirring, the reaction mixture was poured into 200 ml of water which was then made weakly alkaline by gradually adding a 10% solution of sodium hydroxide. The resulting crystal was collected by filtration, washed with water and recrystallized from methanol to provide 7.0 g of 3-propionyl-N-2-pyridylbenzamide as a colorless acicular crystal (compound 1) (yield: 87%, m.p. 128.degree.-129.degree. C.).

Elemental analysis: Calculated for C.sub.15 H.sub.15 N.sub.3 O.sub.2 (%): C, 66.90; H, 5.61; N, 15.61; Found (%): C, 66.97; H, 5.65; N, 15.52.

EXAMPLES 2-36

Compounds 2 to 36 having the characteristics shown in Table 1 below were prepared as in Example 1.

TABLE 1__________________________________________________________________________ ##STR4## No. R.sub.1 R.sub.2 n ##STR5## formulamolecular m.p. (.degree.C.) (%)yield CHNelemental analysis__________________________________________________________________________2 H C.sub.2 H.sub.5 0 ##STR6## C.sub.15 H.sub.15 N.sub.3 O.sub.2 197-199 83 cal'd (%) found 66.90 66.94 5.61 5.56 15.61 15.58 3 " " 1 ##STR7## C.sub.16 H.sub.17 N.sub.3 O.sub.2 108-109 74 cal'd (%) found 67.82 67.85 6.05 6.02 14.83 14.87 4 " " 1 ##STR8## " 140-141 78 cal'd (%) found 67.82 67.76 6.05 6.57 14.83 14.88 5 " " 0 ##STR9## " 60-61 71 cal'd (%) found 67.82 67.78 6.05 6.59 14.83 14.84 6 " " 0 ##STR10## C.sub.17 H.sub.19 N.sub.3 O.sub.2 81-82 85 cal'd (%) found 68.66 68.62 6.44 6.45 14.13 14.19 7 " n-C.sub.3 H.sub.7 1 ##STR11## " 155-156 81 cal' d (%) found 68.66 68.63 6.44 6.49 14.13 14.10 8 " " 0 ##STR12## " 84-85 82 cal'd (%) found 68.66 68.67 6.44 6.47 14.13 14.08 9 " i-C.sub.3 H.sub.7 0 " " 201-202 88 cal'd (%) 68.66 6.44 14.13 found (%) 68.69 6.43 14.17 10 " n-C.sub.4 H.sub.9 1 ##STR13## C.sub.18 H.sub.21 N.sub.3 O.sub.2 97-98 68 cal'd (%) found 69.43 69.38 6.80 6.77 13.50 13.55 11 " " 0 ##STR14## " 133-134 75 cal'd (%) found 69.43 69.45 6.80 6.79 13.50 13.54 12 " i-C.sub.4 H.sub. 9 0 " " 90-91 79 cal'd (%) 69.43 6.80 13.50 found (%) 69.41 6.83 13.5213 " n-C.sub.5 H.sub.11 0 " C.sub.19 H.sub.23 N.sub.3 O.sub.2 87-88 86 cal'd (%) 70.13 7.12 12.91 found (%) 70.19 7.06 12.8514 " n-C.sub.6 H.sub.13 0 " C.sub.20 H.sub.25 N.sub.3 O.sub.2 94-95 82 cal'd (%) 70.77 7.43 12.38 found (%) 70.72 7.48 12.4415 " n-C.sub.7 H.sub.15 0 " C.sub.21 H.sub.27 N.sub.3 O.sub.2 97-98 75 cal'd (%) 71.36 7.70 11.89 found (%) 71.31 7.65 11.95 16 " n-C.sub.8 H.sub.17 0 ##STR15## C.sub.22 H.sub.29 N.sub.3 O.sub.2 100-101 81 cal'd (%) found 71.90 71.96 7.95 7.99 11.44 11.48 17 " ##STR16## 0 ##STR17## C.sub.20 H.sub.17 N.sub.3 O.sub.2 229-231 91 cal'd (%) found 72.49 72.53 5.17 5.14 12.68 12.67 18 " " 1 " C.sub.21 H.sub.19 N.sub.3 O.sub.2 225-227 84 cal'd (%) 73.02 5.55 12.17 found (%) 73.10 5.51 12.22 19 " " 0 ##STR18## " 176-177 86 cal'd (%) found 73.02 73.03 5.55 5.53 12.17 12.14 20 " ##STR19## 0 " C.sub.21 H.sub.19 N.sub.3 O.sub.3 183-185 80 cal'd (%) found 69.79 69.84 5.30 5.33 11.63 11.67 21 CH.sub.3 C.sub.2 H.sub.5 1 ##STR20## C.sub.17 H.sub.19 N.sub.3 O.sub.2 188-200 87 cal'd (%) found 68.66 68.64 6.44 6.41 14.13 14.18 22 " " 0 ##STR21## " 157-158 88 cal'd (%) found 68.66 68.62 6.44 6.45 14.13 14.16 23 " n-C.sub.3 H.sub.7 1 ##STR22## C.sub.18 H.sub.21 N.sub.3 O.sub.2 179-180 76 cal'd (%) found 69.43 69.49 6.80 6.88 13.50 13.45 24 " " 0 ##STR23## " 151-152 78 cal'd (%) found 69.43 69.48 6.80 6.82 13.50 13.52 25 " i-C.sub.3 H.sub.7 1 ##STR24## " 140-141 73 cal'd (%) found 69.43 69.40 6.80 6.85 13.50 13.54 26 " " 0 ##STR25## " 200-201 89 cal'd (%) found 69.43 69.47 6.80 6.86 13.50 13.55 27 " n-C.sub.4 H.sub.9 1 ##STR26## C.sub.19 H.sub.23 N.sub.3 O.sub.2 177-178 72 cal'd (%) found 70.13 70.09 7.12 7.18 12.91 12.93 28 " " 0 ##STR27## " 152-153 71 cal'd (%) found 70.13 70.14 7.12 7.15 12.91 12.98 29 OCH.sub.3 C.sub.2 H.sub.5 1 ##STR28## C.sub.17 H.sub.19 N.sub.3 O.sub.3 86-87 74 cal'd (%) found 65.16 65.19 6.11 6.14 13.41 13.37 30 " " 0 ##STR29## " 142-143 78 cal'd (%) found 65.16 65.18 6.11 6.08 13.41 13.44 31 " n-C.sub.3 H.sub.7 1 ##STR30## C.sub.18 H.sub.21 N.sub.3 O.sub.3 139-140 76 cal'd (%) found 66.03 66.06 6.47 6.42 12.84 12.81 32 " " 0 ##STR31## " 77-78 84 cal'd (%) found 66.03 66.01 6.47 6.41 12.84 12.89 33 " i-C.sub.3 H.sub.7 1 ##STR32## " 174-175 75 cal'd (%) found 66.03 66.07 6.47 6.51 12.84 12.87 34 " " 0 ##STR33## " 150-151 82 cal'd (%) found 66.03 66.09 6.47 6.43 12.84 12.80 35 " n-C.sub.4 H.sub.9 1 ##STR34## C.sub.19 H.sub.23 N.sub.3 O.sub.3 130-131 73 cal'd (%) found 66.84 66.89 6.79 6.82 12.31 12.34 36 " " 0 ##STR35## " 102-103 79 cal'd (%) found 66.84 66.87 6.79 6.84 12.31__________________________________________________________________________ 12.28

EXAMPLE 37

A mixture of the 3-amino-N-2-pyridylbenzamide (6.4 g), acetone (60 ml), methyl isocyanate (1.8 ml) and a catalytic amount of triethylamine were stirred at room temperature for 24 hours. The resulting crystal was collected by filtration and recrystallized from acetone to provide 6.9 g of 3-(3-methylureido)-N-2-pyridylbenzamide as a colorless acicular crystal (compound 37) (yield: 85%, m.p. 163.degree.-164.degree. C.).

Elemental analysis: Calculated for C.sub.14 H.sub.14 N.sub.4 O.sub.2 (%): C, 62.21; H, 5.22; N, 20.73; Found (%): C, 62.18; H, 5.27; N, 20.78.

EXAMPLES 38-75

Compounds 38 to 75 having the characteristics shown in Table 2 below were prepared as in Example 37.

TABLE 2__________________________________________________________________________ ##STR36## No. R.sub.1 R.sub.2 n ##STR37## formulamolecular m.p. (.degree.C.) (%)yield CHNelemental analysis__________________________________________________________________________38 H NHC.sub.2 H.sub.5 0 ##STR38## C.sub.15 H.sub.16 N.sub.4 O.sub.2 154-155 81 cal'd (%) found 63.36 63.39 5.67 5.62 19.71 19.78 39 " NHn-C.sub.3 H.sub.7 0 " C.sub.16 H.sub. 18 N.sub.4 O.sub.2 158-159 83 cal'd (%) 64.41 6.08 18.78 found (%) 64.44 6.13 18.8240 " NHi-C.sub.3 H.sub.7 0 " " 173-174 88 cal'd (%) 64.41 6.08 18.78 found (%) 64.45 6.06 18.73 41 " ##STR39## 0 " C.sub.19 H.sub.22 N.sub.4 O.sub.2 191-193 91 cal'd (%) found 67.43 67.39 6.55 6.57 16.56 16.52 42 " NHC.sub.2 H.sub.5 0 ##STR40## C.sub.15 H.sub.16 N.sub.4 O.sub.2 209-210 85 cal'd (%) found 63.36 63.30 5.67 5.62 19.71 19.75 43 " NHi-C.sub.3 H.sub.7 1 ##STR41## C.sub.17 H.sub.20 N.sub.4 O.sub.2 165-166 82 cal'd (%) found 65.36 65.33 6.45 6.41 17.94 17.98 44 " NHCH.sub.3 0 ##STR42## C.sub.15 H.sub.16 N.sub.4 O.sub.2 186-187 73 cal'd (%) found 63.36 63.32 5.67 5.61 19.71 19.76 45 " NHC.sub.2 H.sub.5 0 " C.sub.16 H.sub.18 N.sub.4 O.sub.2 185-186 79 cal'd (%) 64.41 6.08 18.78 found (%) 64.37 6.06 18.7246 " NHn-C.sub.3 H.sub.7 0 " C.sub.17 H.sub.20 N.sub.4 O.sub.2 149-150 81 cal'd (%) 65.36 6.45 17.94 found (%) 65.34 6.49 17.9947 " NHi-C.sub.3 H.sub.7 0 " " 183-184 80 cal'd (%) 65.36 6.45 17.94 found (%) 65.31 6.42 17.9848 " NHn-C.sub.4 H.sub.9 0 " C.sub.18 H.sub.22 N.sub.4 O.sub.2 157-158 74 cal'd (%) 66.23 6.79 17.17 found (%) 66.28 6.85 17.21 49 " ##STR43## 0 " C.sub.20 H.sub.24 N.sub.4 O.sub.2 193-194 88 cal'd (%) found 68.16 68.12 6.86 6.83 15.90 15.94 50 " ##STR44## 0 " C.sub.20 H.sub.18 N.sub.4 O.sub.2 182-183 89 cal'd (%) found 69.35 69.37 5.24 5.22 16.18 16.14 51 " ##STR45## 0 " C.sub.20 H.sub.17 ClN.sub.4 O.sub.2 216-217 83 cal'd (%) found 63.07 63.04 4.50 4.58 14.71 14.76 52 " NHCH.sub.3 0 ##STR46## C.sub.16 H.sub.18 N.sub.4 O.sub.2 139-140 76 cal'd (%) found 64.41 64.36 6.08 6.05 18.78 18.74 53 " NHC.sub.2 H.sub.5 0 " C.sub.17 H.sub.20 N.sub.4 O.sub.2 202-204 84 cal'd (%) 65.36 6.45 17.94 found (%) 65.39 6.44 17.8854 " NHn-C.sub.3 H.sub.7 0 " C.sub.18 H.sub.22 N.sub.4 O.sub.2 192-193 82 cal'd (%) 66.23 6.79 17.17 found (%) 66.27 6.72 17.2455 " NHi-C.sub.3 H.sub.7 0 " " 172-173 88 cal'd (%) 66.23 6.79 17.17 found (%) 66.26 6.76 17.21 56 " ##STR47## 0 " C.sub.21 H.sub.26 N.sub.4 O.sub.2 148-150 89 cal'd (%) found 68.83 68.87 7.15 7.17 15.29 15.24 57 CH.sub.3 NHCH.sub.3 0 ##STR48## C.sub.15 H.sub.16 N.sub.4 O.sub.2 218-220 86 cal'd (%) found 63.36 63.31 5.67 5.62 19.71 19.76 58 " NHC.sub.2 H.sub.5 0 " C.sub.16 H.sub.18 N.sub.4 O.sub.2 210-212 75 cal'd (%) 64.41 6.08 18.78 found (%) 64.48 6.06 18.7359 " NHn-C.sub.3 H.sub.7 0 " C.sub.17 H.sub.20 N.sub.4 O.sub.2 220-221 77 cal'd (%) 65.36 6.45 17.94 found (%) 65.33 6.42 17.9960 " NHi-C.sub.3 H.sub.7 0 " " 238-240 71 cal'd (%) 65.36 6.45 17.94 found (%) 65.30 6.41 17.98 61 " NHCH.sub.3 0 ##STR49## C.sub.16 H.sub.18 N.sub.4 O.sub.2 214-215 79 cal'd (%) found 64.41 64.48 6.08 6.03 18.78 18.75 62 " NHC.sub.2 H.sub.5 0 " C.sub.17 H.sub.20 N.sub.4 O.sub.2 217-219 80 cal'd (%) 65.36 6.45 17.94 found (%) 65.34 6.48 17.9763 " NHn-C.sub.3 H.sub.7 0 " C.sub.18 H.sub.22 N.sub.4 O.sub.2 178-179 86 cal'd (%) 66.23 6.79 17.17 found (%) 66.27 6.75 17.1264 " NHi-C.sub.3 H.sub.7 0 " " 180-181 82 cal'd (%) 66.23 6.79 17.17 found (%) 66.28 6.79 17.1865 " NHn-C.sub.4 H.sub.9 0 " C.sub.19 H.sub.24 N.sub.4 O.sub.2 189-190 75 cal'd (%) 67.03 7.11 16.46 found (%) 67.07 7.18 16.42 66 " ##STR50## 0 " C.sub.21 H.sub.26 N.sub.4 O.sub.2 192-193 92 cal'd (%) found 68.83 68.88 7.15 7.13 15.29 15.24 67 " ##STR51## 0 " C.sub.21 H.sub.19 ClN.sub.4 O.sub.2 235-237 88 cal'd (%) found 63.87 63.84 4.85 4.89 14.19 14.25 68 OCH.sub.3 NHCH.sub.3 0 " C.sub.16 H.sub.18 N.sub.4 O.sub.3 203-204 75 cal'd (%) 61.13 5.77 17.83 found (%) 61.17 5.74 17.8769 " NHC.sub.2 H.sub.5 0 " C.sub.17 H.sub.20 N.sub.4 O.sub.3 165-166 72 cal'd (%) 62.18 6.14 17.06 found (%) 62.24 6.19 17.0270 " NHn-C.sub.3 H.sub.7 0 " C.sub.18 H.sub.22 N.sub.4 O.sub.3 164-165 80 cal'd (%) 63.14 6.48 16.36 found (%) 63.18 6.42 16.3071 " NHi-C.sub.3 H.sub.7 0 " " 144-145 88 cal'd (%) 63.14 6.48 16.36 found (%) 63.17 6.44 16.3872 " NHn-C.sub.4 H.sub.9 0 " C.sub.19 H.sub.24 N.sub.4 O.sub.3 147-148 76 cal'd (%) 64.02 6.79 15.72 found (%) 64.09 6.72 15.76 73 " ##STR52## 0 " C.sub.21 H.sub.26 N.sub.4 O.sub.3 183-184 85 cal'd (%) found 65.95 65.91 6.85 6.89 14.65 14.63 74 " ##STR53## 0 " C.sub.21 H.sub.19 ClN.sub.4 O.sub.3 191-192 82 cal'd (%) found 61.39 61.32 4.66 4.60 13.64 13.59 75 H NH.sub.2 0 " C.sub.14 H.sub.14 N.sub.4 O.sub.2 205-207 75 cal'd (%) 62.21 5.22 20.73 found (%) 62.19 5.25 20.70__________________________________________________________________________

EXPERIMENTS

Groups each consisting of five male DDY mice (5 weeks old and weighing 25-30 g) were fasted 16 hours and given an intravenous injection of 75 mg/kg of alloxan. Forty-eight hours later, aqueous solutions or suspensions containing 200 mg/kg of the compounds indicated in Table 3 were orally administered to the mice, and 150 minutes later, blood was drawn from their hearts and the glucose level was measured by the glucose oxidase method. The results are shown in Table 3 and Table 4, wherein the compound numbers are keyed to those used in Examples 1 to 75.

TABLE 3______________________________________ blood blood glucose level glucose levelCompound (mg/dl) Compound (mg/dl)No. mean .+-. S.D. No. mean .+-. S.D.______________________________________none 485 .+-. 28 19 396 .+-. 29**(control) 20 390 .+-. 25*** 1 389 .+-. 35** 21 421 .+-. 38* 2 371 .+-. 29*** 22 424 .+-. 34* 3 392 .+-. 36** 23 419 .+-. 27** 4 403 .+-. 31** 24 405 .+-. 31** 5 368 .+-. 40*** 25 390 .+-. 29*** 6 379 .+-. 33*** 26 378 .+-. 36*** 7 411 .+-. 29** 27 384 .+-. 28*** 8 415 .+-. 34** 28 391 .+-. 33** 9 420 .+-. 25** 29 412 .+-. 38*10 399 .+-. 19*** 30 418 .+-. 25*11 385 .+-. 38** 31 390 .+-. 31***12 392 .+-. 25*** 32 385 .+-. 40**13 393 .+-. 25*** 33 369 .+-. 29***14 385 .+-. 31*** 34 396 .+-. 28**15 411 .+-. 28** 35 418 .+-. 33**16 379 .+-. 33*** 36 405 .+-. 29**17 407 .+-. 40**18 405 .+-. 31**______________________________________ *P < 0.05 **P < 0.01 ***P < 0.001 TABLE 4______________________________________ blood blood glucose level glucose levelCompound (mg/dl) Compound (mg/dl)No. mean .+-. S.D. No. mean .+-. S.D.______________________________________none 468 .+-. 31 56 388 .+-. 31**(control) 57 325 .+-. 29***37 394 .+-. 28** 58 415 .+-. 26*38 331 .+-. 41*** 59 388 .+-. 32**39 368 .+-. 32** 60 337 .+-. 24***40 392 .+-. 33** 61 369 .+-. 35**41 401 .+-. 27** 62 386 .+-. 42**42 383 .+-. 31** 63 363 .+-. 50**43 349 .+-. 25*** 64 392 .+-. 37**44 377 .+-. 35** 65 354 .+-. 36***45 365 .+-. 28*** 66 381 .+-. 29**46 351 .+-. 35*** 67 399 .+-. 27**47 311 .+-. 30*** 68 331 .+-. 29***48 390 .+-. 29** 69 362 .+-. 31***49 403 .+-. 34* 70 375 .+-. 34**50 411 .+-. 27* 71 344 .+-. 36***51 385 .+-. 40** 72 366 .+-. 39**52 378 .+-. 21*** 73 321 .+-. 36***53 395 .+-. 33** 74 347 .+-. 38***54 342 .+-. 29*** 75 341 .+-. 33***55 365 .+-. 26***______________________________________ *P < 0.05 **P < 0.01 ***P < 0.001

Claims

1. A benzamide derivative of the formula: ##STR54## wherein R.sub.1 is a hydrogen atom, a methyl group or a methoxy group; R.sub.2 is a hydrogen atom, a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms or a cyclic alkyl group having 5 or 6 carbon atoms or an unsubstituted phenyl group or a phenyl group substituted with a halogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms on the nucleus; and R.sub.3 is a hydrogen atom or one or two alkyl groups having 1 to 4 carbon atoms.

2. 3-(3-n-Propylureido)-N-(6-methyl-2-pyridyl)benzamide according to claim 1.

3. 3-(3-Isopropylureido)-N-(6-methyl-2-pyridyl)benzamide according to claim 1.

4. 3-(3-n-Butylureido)-N-(6-methyl-2-pyridyl)benzamide according to claim 1.

5. 3-(3-n-Butylureido)-4-methyl-N-(6-methyl-2-pyridyl)benzamide according to claim 1.

6. 3-(3-n-Butylureido)-4-methoxy-N-(6-methyl-2-pyridyl)benzamide according to claim 1.

7. 3-(3-Isopropylureido)-N-(4,6-dimethyl-2-pyridyl)benzamide according to claim 1.

8. 3-Ureido-N-(6-methyl-2-pyridyl)benzamide according to claim 1.