Cyanoguanidine derivatives

Abstract

Novel cyanoguanidine derivatives, and acid addition salts thereof useful as medicines which have pharmacological actions such as anti-secretory effect, local anesthesia action and the like; and process for the preparation thereof.

Description

This invention relates to novel cyanoguanidine derivatives, acid addition salts thereof having excellent actions as medicines and to the process for the preparation thereof, wherein the cyanoguanidine derivatives are represented by the general formula: ##STR1## wherein A represents a substituted or unsubstituted phenyl, furyl, thienyl or cycloalkyl group;

B represents pyridyl, phenyl, or pyridine-N-oxide group; R represents a lower alkyl group, a lower alkenyl group, or a group of the formula: ##STR2## wherein R.sub.1 and R.sub.2 are the same or different, and each represent a lower alkyl group, or together form nitrogen-containing heterocycle with the nitrogen atom to which they bond, and n is an integer of 1-3, or R represents a group of the formula: ##STR3## wherein R.sub.3 is a lower alkyl group, n is an integer of 1-3 and m is an integer of 4-5; X represents an alkylene or an alkylene group containing the terminal sulfur atom; and p is 0 or 1, with the proviso that (i) when A is unsubstituted phenyl and B is pyridyl, p is 1 and R is a group of the formula: ##STR4## or a group of the formula: ##STR5## and (ii) when A is unsubstituted phenyl and B is phenyl or pyridine-N-oxide, p is 0; and intermediate therefor represented by the general formula: ##STR6## wherein Y represents a lower alkoxy or a lower alkylthio group, and A, B, X and p have the same meanings as defined above.

Illustrative substituents on the substituted phenyl groups mentioned for the definition of A in the general formula (I) include, practically, a lower alkyl, lower alkenyl, halogen, lower alkoxy, lower alkylthio, lower alkylsulfonyl, halogen substituted lower alkyl groups and the like. The term "lower" used in the above illustration is meant for any straight or branched carbon chains containing 1-6 carbon atoms. Illustrative said lower alkyl groups may include, for example, methyl, ethyl, n-propyl, isopropyl, isobutyl, 1-methylpropyl, tert-butyl, n-pentyl, 1-ethylpropyl, isoamyl, n-hexyl and the like, and lower alkenyl groups may include isopropenyl, allyl, crotyl, methallyl and the like.

The lower alkoxy or a lower alkylthio group mentioned for the definition of Y in the general formula (V) has also 1-6 carbon atoms.

The term "halogen" means practically fluoro, chloro, iodo or bromo group.

The cycloalkyl group means practically a cycloalkyl group containing 5-6 carbon atoms. The lower alkyl and lower alkenyl groups shown in the definitions of R, R.sub.1 and R.sub.2 have the same meanings as those defined above.

Further, illustrative nitrogen-containing heterocycles formed by the groups R.sub.1 and R.sub.2, with nitrogen atom to which they bond, include, for example, pyrrolidine, piperidine, piperazine, morpholine and the like.

Alkylene represented by X means lower alkylene groups, such, for example, as methylene, ethylene, propylene, and the like, which may contain a terminal sulfur atom. The pyridyl group represented by B may be combined at any one of the 2, 3 and 4 positions on the pyridine ring.

There are some tautomers of the compound (I) of this invention, and these tautomers are, of course, included in this invention.

The compound (I) of this invention may be easily converted into the pharmacologically acceptable acid addition salt by reacting it with an inorganic or organic acid. Illustrative inorganic acids include hydrochloric, hydrobromic, hydroiodic, sulfuric acids and the like, and illustrative organic acids include maleic, fumaric, succinic, acetic, malonic, citric, benzoic acids and the like.

The compounds to be provided according to this invention are all novel compounds which have not as yet been reported in the literature. Said compounds have very excellent and broad pharmacological actions as medicine, such as, very intensively, gastric juice secretion inhibitory or antisecretory, antidepressant, local anesthesia, antidiarrheal, antiedema, diuretic, hypertensive, hypotensive, vasoconstrictive, antiserotonin, smooth muscle relaxing, coronary vasodilative, and bradycardia actions and the like. Thus, the compounds (I) of this invention are useful as various medicines due to such pharmacological actions. Illustrative medicines include antipeptic ulcer drug, antidepressant, local anesthetics, anti-inflammatory agents, diuretics, antiallergic agents, antidiarrheal, hypertensive, hypotensive, anti-arrhythmic agent, muscle relaxants, coronary vasodilator and the like.

Since the inhibitory action of the compounds according to this invention to gastric juice secretion is not based on the anticholine action, the compound of this invention do not exhibit the side effect due to the anticholine action. This is a great characteristic of the compounds according to this invention, and therefore the compounds are particularly expected as a new type antipeptic ulcer drug among the various medicines mentioned above.

The compounds (I) of this invention can be prepared through various processes. Among these processes, the following shows one process which may be usually employed. ##STR7## wherein Y represnts a lower alkoxy or a lower alkylthio group, and A, B, R, X and p have the same meanings as defined above.

Process (1) for the Preparation

The compounds (I) of this invention are produced, in one step, by reacting the amine derivative represented by the above formula (II) with an isothiourea derivative or an isourea derivative represented by the above formula (III). This reaction may be effected in the presence or absence of solvent.

An excess amount of the amine derivative may be used as a solvent. However, it is desirable to use, for example, methanol, ethanol, isopropanol, acetonitrile, chloroform and the like as solvent. The reaction is effected at room temperature or elevated temperature. The reaction may be effected under reflux, when solvent is used.

Process (2) for the Preparation

The compounds represented by the general formula (I) of this invention are produced, through two steps, by reacting the amine derivative represented by the general formula (II) with a compound represented by the general formula (IV) to produce a compound represented by the general formula (V), followed by reacting the latter compound (V) with an amine represented by the general formula (VI). According to this process, both reactions of said two steps may be effected with the similar procedures as the reaction between the amine derivative (II) and the isothiourea derivative or isourea derivative (III) as described above. This reaction may be also effected without separating the compound (V) from the reaction vessel after the reaction of the amine derivative (II) with the compound (IV).

The excellent pharmacological actions of the compounds of this invention are illustrated hereinafter with respect to typical compounds of this invention.

1. Anti-secretory effect

Inhibitory ratio to the gastric juice serection was determined by the Shay rat 4 hr method [H. Shay et al.; Gastroentrogy, vol. 5, P. 43 (1945)]. Results are shown in Table 1.

TABLE 1______________________________________ Oral dosage InhibitoryCompound (mg/Kg) ratio (%)______________________________________Known Cimetidinecompound (control) 50 85.8 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)benzyl] guanidine (control) 100 69.3Compound N--cyano-N'--ethyl-N--of this [.alpha.-(2-pyridyl)ortho-invention methylbenzyl] guanidine 50 93.5 N--cyano-N'--allyl-N-- [.alpha.-(2-pyridyl)ortho- methylbenzyl] guanidine 50 79.0 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)ortho- methoxybenzyl] guanidine 50 91.6 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)ortho- methoxybenzyl] guanidine 50 96.7 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)metha- chlorobenzyl] guanidine 50 79.2 N--cyano-N'--(3-diethyl- aminopropyl)-N--[.alpha.-(2- pyridyl)benzyl] guanidine 100 81.0 N--cyano-N'--(1-ethyl pyrrolyl-2)-methyl-N-- [.alpha.-(2-pyridyl)benzyl] guanidine 100 86.0______________________________________

2. Anti-depressant efficacy

Anti-depressant efficacy was determined using mouse by the method as described in G. Chen and B. Bohner: J. Pharmac. Exptl. Therap. 131, 179 (1961).

Results are shown in Table 2.

TABLE 2______________________________________ Minimum effective dose (mouse, oral Compound dosage mg/Kg)______________________________________Known Imipraminecompound (control) 10 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)benzyl/ guanidine (control) 25Compound N--cyano-N'--ethyl-N--of this [.alpha.-(2-pyridyl)ortho-invention methylbenzyl] guanidine 1 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)metha- methylbenzyl] guanidine 10 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)ortho- methoxybenzyl] guanidine 10 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)ortho- chlorobenzyl] guanidine 10 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)metha- chlorobenzyl] guanidine 2.5______________________________________

3. Local anesthesia action

Local anesthesia action was determined by the method as described in M. R. A. Chance et al., J. Pharmac. Exptl. Therap. 82, 203 (1944). Results are shown in Table 3.

TABLE 3______________________________________ Minimum effective Compound concentration (%)______________________________________Known Dibucainecompound (control) 0.1 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)benzyl] guanidine (control) >3Compound N--cyano-N'--(1-ethyl-of this pyrolidyl-2)methyl-N--invention [.alpha.-(2-pyridyl)para- methylbenzyl] guanidine 0.5 N--cyano-N'--(3-dimethyl- aminopropyl)-N--[.alpha.-(2- pyridyl)paramethylbenzyl] guandine 0.5 N--cyano-N'--(1-ethylpyro- lidyl-2)methyl-N--[.alpha.-(2- pyridyl)orthomethoxy- benzyl]guanidine 0.25______________________________________

4. Antidiarrheal action

TABLE 4______________________________________ Minimum effective dose (mouse, oral Compound dosage, mg/Kg)______________________________________Known Atropinecompound (control) 60 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)benzyl] guanidine (control) 50Compound N--cyano-N'--ethyl-N--of this [.alpha.-(2-pyridyl)ortho-invention methylbenzyl] guanidine 1 N--cyano-N'--allyl-N-- [.alpha.-(2-pyridyl)ortho- methylbenzyl] guanidine 10 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)ortho- chlorobenzyl] guanidine 5 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)metha- chlorobenzyl] guanidine 10 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)metha- trifluoromethylbenzyl] guanidine 25______________________________________

5. Antiedema action

Antiedema action was determined using rat by the method as described C. A. Winter, et al.: Proc. Soc. Exp. Biol. Med. 111, 544 (1962). Results are shown in Table 5.

TABLE 5______________________________________ Minimum effective dose (rat, oral Compound dosage, mg/Kg)______________________________________Known Indomethacincompound (control) '- N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)benzyl] guanidine (control) >100Compound N--cyano-N'--methyl-N--of this [.alpha.-(2-pyridyl)ortho-invention methylbenzyl] guanidine 2.5 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)ortho- methylbenzyl] guanidine 2.5 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)ortho- methoxybenzyl] guanidine 2.5______________________________________

6. Diuretics action

Diuretics action was determined by the method as described in E. Cornish: J. Pharm. Pharmacol. 18, 65 (1966). Results are shown in Table 6.

TABLE 6______________________________________ Minimum effective dose (oral dosage Compound mg/Kg)______________________________________Known Hydrofulumethiazidecompound (control) 2.0 N--cyano-N'--methyl-N-- [.alpha.-(2-pyridyl)benzyl] guanidine (control) 5.0Compound N--cyano-N'--ethyl-N--of this [.alpha.-(2-pyridyl)ortho-invention methylbenzyl] guanidine 0.1 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)metha- methylbenzyl] guanidine 0.25 N--cyano-N'--ethyl-N-- [.alpha.-(2-pyridyl)metha- chlorobenzyl] guanidine 0.5 N--cyano-N'--methyl-N-- [.alpha.(2-pyridyl)metha- trifluoromethylbenzyl] guanidine 0.5 N--cyano-N'--allyl-N-- [.alpha.-(2-pyridyl)ortho- methoxybenzyl] guanidine 1.0______________________________________

As apparently seen from the results of the above pharmacological experiments, the guanidine derivatives provided according to this invention exhibit very intense pharmacological actions, as compared with the known compounds.

This invention will be more particularly illustrated by the following examples. However, it should be understood that this invention is not limited to only those examples.

EXAMPLE 1

N-cyano-N'-methyl-N-[.alpha.-(2-pyridyl)-o-methylbenzyl]guanidine

(1) (a) Dimethylcyanodithioimido carbonate in amount of 11.4 g (0.1 mol) and .alpha.-(2-pyridyl)-o-methylbenzylamine in amount of 18.4 g (0.1 mol) were dissolved in 300 ml of ethanol. The whole was allowed to react at room temperature overnight. Crystals deposited were separated by filtration. The filtrate was concentrated to deposit an additional amount of crystals. These crystals were combined and recrystallized from ethyl acetate to produce 17.7 g (yield: 66.4%) of N-cyano-S-methyl-N-[.alpha.-(2-pyridyl)orthomethylbenzyl]isothiourea.

Melting point: 162.degree.-4.degree. C.

Elementary analysis of the compound having the presumed formula C.sub.16 H.sub.16 N.sub.4 S gave:

______________________________________ C H N______________________________________Calculated (%): 64.83 5.44 18.90Found (%): 65.03 5.31 18.79______________________________________

(b) A mixture consisting of 5.9 g (0.02 mol) of N-cyano-S-methyl-N-[.alpha.-(2-pyridyl)orthomethylbenzyl]isothiourea prepared in (a), 30 ml of 20% solution of methylamine in ethanol and 70 ml of ethanol was prepared and reacted at room temperature overnight. The reaction solution was concentrated under a reduced pressure. The residue was recrystallized from ethyl acetate to produce 4.7 g of the subject material, N-cyano-N'-methyl-N-[.alpha.-(2-pyridyl)orthomethylbenzyl]guanidine (yield: 85.0%).

Melting point: 187.degree.-9.degree. C.

Elementary analysis of the compound having the presumed formula C.sub.16 H.sub.17 N.sub.5 gave:

______________________________________ C H N______________________________________Calculated (%): 68.78 6.13 25.07Found (%): 68.83 6.01 25.26______________________________________

(2) Alpha-(2-pyridyl)orthomethylbenzylamine in amount of 1.8 g (0.01 mol) and N-cyano-S,N'-dimethylisothiourea in amount of 1.3 g (0.01 mol) were dissolved in 50 ml of acetonitrile. The whole was reacted under heating for 10-15 hours. The reaction solution was then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to produce 1.6 g of the subject material, N-cyano-N'-methyl-N-[.alpha.-(2-pyridyl)orthomethylbenzyl]guanidine (yield: 59.0%).

Melting point: 187.degree.-9.degree. C.

Elementary analysis of the compound having the presumed formula C.sub.16 H.sub.17 N.sub.5 gave:

______________________________________ C H N______________________________________Calculated (%): 68.78 6.13 25.07Found (%): 68.81 6.05 25.20______________________________________

EXAMPLES 2-107

Examples 2-107 were achieved according to the process for the preparation as described in Example 1 (1) via isothiourea derivatives. Tables 7 and 8 show respectively melting point, yield (%) and elementary analysis of the resulting isothiourea derivatives and the compounds of this invention.

In Table 7, the general formula: ##STR8## represents the formula wherein p is 0 and Y is methylthio group in the formula (V) hereinbefore mentioned.

In Table 8, the general formula: ##STR9## represents the formula wherein p is 0 in the formula (I).

TABLE 7__________________________________________________________________________ ##STR10## Elementary Analysis Melting Upper line: Calcd. Point Molecular Lower line: FoundEx. A B (.degree.C.) Yield Formula C H N__________________________________________________________________________ ##STR11## 2-pyridyl 166-168 63.5 C.sub.16 H.sub.16 N.sub.4 S 64.83 64.87 5.44 5.26 18.90 19.013 ##STR12## 2-pyridyl 148-149 76.7 C.sub.16 H.sub.16 N.sub.4 S 64.83 65.05 5.44 5.36 18.90 18.914 ##STR13## 2-pyridyl 119-120 71.7 C.sub.15 H.sub.13 N.sub.4 SCl 56.87 56.60 4.10 4.09 17.69 17.055 ##STR14## 2-pyridyl 205-206 80.1 C.sub.15 H.sub.13 N.sub.4 SCl 56.87 56.65 4.10 3.94 17.69 17.456 ##STR15## 2-pyridyl 121-122 85.5 C.sub.15 H.sub.13 N.sub.4 SCl 56.87 56.79 4.10 4.06 17.69 17.507 ##STR16## 2-pyridyl 118-119 55.3 C.sub.15 H.sub.12 N.sub.4 SCl.sub.2 51.28 51.09 3.42 3.29 15.95 15.628 ##STR17## 2-pyridyl 126-128 64.5 C.sub.16 H.sub.16 N.sub.4 OS 61.53 61.43 5.16 4.98 17.94 17.479 ##STR18## 2-pyridyl 162-163 84.0 C.sub.16 H.sub.16 N.sub.4 OS 61.53 61.90 5.16 5.03 17.94 17.7910 ##STR19## 2-pyridyl 151-152 70.0 C.sub.16 H.sub.16 N.sub.4 OS 61.53 61.60 5.16 5.05 17.94 18.0811 ##STR20## 2-pyridyl 155-156 88.0 C.sub.17 H.sub.18 N.sub.4 O.sub.2 S 59.64 59.76 5.30 5.24 16.37 16.7712 ##STR21## 2-pyridyl 117-118 86.5 C.sub.17 H.sub.18 N.sub.4 OS 62.56 63.05 5.56 5.42 17.17 17.2313 ##STR22## 2-pyridyl 138-139 87.5 C.sub.18 H.sub.20 N.sub.4 OS 63.51 63.54 5.92 5.84 16.46 15.9614 ##STR23## 2-pyridyl 103-104 68.8 C.sub.16 H.sub.16 N.sub.4 S.sub.2 58.53 58.71 4.91 4.69 17.07 17.4115 ##STR24## 2-pyridyl 139-140 71.1 C.sub.16 H.sub.16 N.sub.4 O.sub.2 S.sub.2 53.33 53.14 4.48 4.19 15.55 15.4316 ##STR25## 2-pyridyl 163-164 68.1 C.sub.16 H.sub.13 N.sub.4 F.sub.3 S 54.86 54.88 3.74 3.76 16.00 16.1217 ##STR26## ##STR27## 182-183 65.5 C.sub.15 H.sub.14 N.sub.4 OS 60.40 60.73 4.70 4.58 18.79 18.8218 ##STR28## 2-pyridyl 116-118 70.0 C.sub.13 H.sub.12 N.sub.4 OS 57.33 57.50 4.44 4.18 20.57 20.5419 ##STR29## 2-pyridyl 104-106 56.0 C.sub.13 H.sub.12 N.sub.4 S.sub.2 54.13 54.43 4.19 4.18 19.43 19.7220 ##STR30## 2-pyridyl 140-143 73.3 C.sub.15 H.sub.20 N.sub.4 S 62.46 62.82 6.98 6.99 19.43 19.2021 ##STR31## ##STR32## 150-152 46.3 C.sub.16 H.sub.15 N.sub.3 S 68.29 68.30 5.38 5.52 14.94 14.8722 ##STR33## 2-pyridyl 152-153 60.1 C.sub.17 H.sub.18 N.sub.4 OS 62.56 62.90 5.56 5.57 17.17 17.11__________________________________________________________________________ TABLE 8__________________________________________________________________________ ##STR34## Elementary Analysis Melting Upper line: Calcd. Point Molecular Lower line: FoundEx. A B R (.degree.C.) Yield Formula C H N__________________________________________________________________________ 2 ##STR35## 2-pyridyl C.sub.2 H.sub.5 132-133 81.0 C.sub.17 H.sub.19 N.sub.5 69.59 69.98 6.52 6.53 23.87 23.76 3 ##STR36## 2-pyridyl CH.sub.2 CHCH.sub.2 147-149 79.5 C.sub.18 H.sub.19 N.sub.5 70.79 71.21 6.27 6.16 22.93 22.96 4 ##STR37## 2-pyridyl ##STR38## 115-117 86.0 C.sub.22 H.sub.30 69.80 70.12 7.99 8.09 22.20 22.30 5 ##STR39## 2-pyridyl ##STR40## 171-172 55.5 C.sub.22 H.sub.28 N.sub.6 70.17 70.58 7.49 7.56 22.32 22.54 6 ##STR41## 2-pyridyl CH.sub.3 172-174 76.0 C.sub.16 H.sub.17 N.sub.5 68.78 69.09 6.13 6.14 25.07 25.07 7 ##STR42## 2-pyridyl C.sub.2 H.sub.5 145-147 83.1 C.sub.17 H.sub.19 N.sub.5 69.59 69.46 6.52 6.63 23.87 23.68 8 ##STR43## 2-pyridyl CH.sub.2 CHCH.sub.2 112-114 75.5 C.sub.18 H.sub.19 N.sub.5 70.79 70.78 6.27 6.38 22.93 22.81 9 ##STR44## 2-pyridyl ##STR45## 100-102 47.4 C.sub.22 H.sub.28 N.sub.6 70.19 70.38 7.49 7.67 22.32 22.4310 ##STR46## 2-pyridyl CH.sub.3 171-172 95.9 C.sub.16 H.sub.17 N.sub.5 68.78 68.97 6.13 6.30 25.07 24.9511 ##STR47## 2-pyridyl C.sub.2 H.sub.5 153-154 87.5 C.sub.17 H.sub.19 N.sub.5 69.59 69.81 6.52 6.50 23.87 23.8512 ##STR48## 2-pyridyl CH.sub.2 CHCH.sub.2 144-145 88.0 C.sub.18 H.sub.19 N.sub.5 70.79 70.83 6.27 6.44 22.93 22.8313 ##STR49## 2-pyridyl ##STR50## 84-85 67.7 C.sub.22 H.sub.30 N.sub.6 69.80 69.78 7.99 8.06 22.20 22.0914 ##STR51## 2-pyridyl ##STR52## 113-115 87.4 C.sub.22 H.sub.28 N.sub.6 70.17 69.94 7.49 7.54 22.32 22.2915 ##STR53## 2-pyridyl CH.sub.3 210-211 89.3 C.sub.15 H.sub.14 N.sub.5 60.10 60.15 4.67 4.56 23.40 23.3416 ##STR54## 2-pyridyl C.sub.2 H.sub.5 176-177 84.9 C.sub.16 H.sub.16 N.sub.5 61.24 61.28 5.10 4.89 22.33 22.4317 ##STR55## 2-pyridyl CH.sub.2 CHCH.sub.2 144-145 81.7 C.sub.17 H.sub.16 N.sub.5 62.27 62.54 4.92 4.72 21.51 21.7418 ##STR56## 2-pyridyl ##STR57## 103-104 90.1 C.sub.21 H.sub.27 N.sub.6 63.24 63.16 6.77 6.88 21.08 21.0119 ##STR58## 2-pyridyl ##STR59## 169-172.5 70.3 C.sub.21 H.sub.25 N.sub.6 63.56 63.56 6.30 6.20 21.18 21.2420 ##STR60## 2-pyridyl CH.sub.3 194-195 84.2 C.sub.15 H.sub.14 N.sub.5 60.10 60.05 4.67 4.62 23.40 23.4021 ##STR61## 2-pyridyl C.sub.2 H.sub.5 153-155 92.9 C.sub.16 H.sub.16 N.sub.5 61.24 61.11 5.10 5.14 22.33 22.2522 ##STR62## 2-pyridyl CH.sub.2 CHCH.sub.2 136-137 87.5 C.sub.17 H.sub.16 N.sub.5 62.27 61.90 4.92 4.80 21.51 20.8723 ##STR63## 2-pyridyl ##STR64## 80-84 69.8 C.sub.21 H.sub.27 N.sub.6 63.24 63.30 6.77 6.79 21.08 21.2224 ##STR65## 2-pyridyl ##STR66## 117-118 63.9 C.sub.21 H.sub.25 N.sub.6 63.56 63.76 6.30 6.55 21.18 20.8925 ##STR67## 2-pyridyl CH.sub.3 180-181 96.2 C.sub.15 H.sub.14 N.sub.5 60.10 59.85 4.67 4.67 23.40 23.4026 ##STR68## 2-pyridyl C.sub.2 H.sub.5 159-160 98.6 C.sub.16 H.sub.16 N.sub.5 61.24 61.04 5.10 5.16 22.33 21.9827 ##STR69## 2-pyridyl CH.sub.2 CHCH.sub.2 177 87.5 C.sub. 17 H.sub.16 N.sub.5 62.27 62.43 4.92 4.84 21.51 21.3628 ##STR70## 2-pyridyl ##STR71## 157-161 66.1 C.sub.21 H.sub.25 N.sub.6 63.56 63.66 6.30 6.54 21.18 20.9829 ##STR72## 2-pyridyl CH.sub.3 217-218 81.5 C.sub.15 H.sub.13 N.sub.5 Cl.sub.2 53.89 54.04 3.89 4.13 20.96 20.3230 ##STR73## 2-pyridyl C.sub.2 H.sub.5 137-139 88.1 C.sub.16 H.sub.15 N.sub.5 Cl.sub.2 55.17 55.09 4.31 4.30 20.11 19.9131 ##STR74## 2-pyridyl CH.sub.2 CHCH.sub.2 142-144 70.7 C.sub.17 H.sub.15 N.sub.5 Cl.sub.2 56.67 56.57 4.17 4.12 19.44 19.3532 ##STR75## 2-pyridyl ##STR76## 85-90 44.6 C.sub.17 H.sub.26 N.sub.6 Cl.sub.2 58.20 58.26 6.00 5.97 19.39 19.3533 ##STR77## 2-pyridyl ##STR78## 130-136 75.5 C.sub.21 H.sub.24 N.sub.6 Cl.sub.2 58.47 58.65 5.57 5.62 19.49 19.3634 ##STR79## 2-pyridyl CH.sub.3 173-174 78.2 C.sub.16 H.sub.17 N.sub.5 65.06 65.36 5.80 5.81 23.72 23.7035 ##STR80## 2-pyridyl C.sub.2 H.sub.5 121-122 64.6 C.sub.17 H.sub.19 N.sub.5 66.00 66.17 6.19 6.34 22.64 22.6336 ##STR81## 2-pyridyl CH.sub.2 CHCH.sub.2 118-119 72.0 C.sub.18 H.sub.19 N.sub.5 67.27 67.21 5.96 6.02 21.79 21.7437 ##STR82## 2-pyridyl ##STR83## 73-74 41.2 C.sub.22 H.sub.30 N.sub.6 66.97 66.91 7.67 7.84 21.30 21.2238 ##STR84## 2-pyridyl ##STR85## 136-138 54.1 C.sub.22 H.sub.28 N.sub.6 67.32 67.56 7.19 7.43 21.41 21.2039 ##STR86## 2-pyridyl CH.sub.3 149-150 71.9 C.sub.16 H.sub.17 N.sub.5 65.06 65.27 5.80 5.79 23.72 23.9140 ##STR87## 2-pyridyl C.sub.2 H.sub.5 115-116 74.9 C.sub. 17 H.sub.19 N.sub.5 66.00 66.22 6.19 6.17 22.64 22.8741 ##STR88## 2-pyridyl CH.sub.2 CHCH.sub.2 99-100 60.3 C.sub.18 H.sub.19 N.sub.5 67.27 67.72 5.96 5.85 21.79 21.9442 ##STR89## 2-pyridyl ##STR90## 85-86 64.9 C.sub.22 H.sub.30 N.sub.6 66.97 67.04 7.67 7.74 21.30 21.3843 ##STR91## 2-pyridyl ##STR92## 142-143 22.0 C.sub.22 H.sub.28 N.sub.6 67.32 67.40 7.19 7.14 21.41 21.5444 ##STR93## 2-pyridyl CH.sub.3 187-188 74.0 C.sub.16 H.sub.17 N.sub.5 65.06 65.59 5.80 6.03 23.72 23.4845 ##STR94## 2-pyridyl C.sub.2 H.sub.5 144-145 84.9 C.sub.17 H.sub.19 N.sub.5 66.00 66.05 6.19 6.12 22.64 22.5246 ##STR95## 2-pyridyl CH.sub.2 CHCH.sub.2 139-140 70.0 C.sub.18 H.sub.19 N.sub.5 67.27 67.22 5.96 5.67 21.79 21.8347 ##STR96## 2-pyridyl ##STR97## 74-75 58.6 C.sub.22 H.sub.30 N.sub.6 66.97 67.22 7.67 7.68 21.30 21.3548 ##STR98## 2-pyridyl ##STR99## 134-135 46.2 C.sub.22 H.sub.28 N.sub.6 67.32 67.61 7.19 7.15 21.41 21.4249 ##STR100## 2-pyridyl CH.sub.3 161-162 86.3 C.sub.17 H.sub.19 N.sub.5 O.sub.2 62.75 62.44 5.89 5.52 21.53 21.5150 ##STR101## 2-pyridyl C.sub.2 H.sub.5 154-155 80.7 C.sub.18 H.sub.21 N.sub.5 O.sub.2 63.70 63.79 6.24 6.20 20.14 20.5851 ##STR102## 2-pyridyl CH.sub.2 CHCH.sub.2 102-103 64.3 C.sub.19 H.sub.21 N.sub.5 O.sub.2 64.94 65.22 6.02 6.12 19.93 19.9252 ##STR103## 2-pyridyl ##STR104## 103-104 49.4 C.sub.23 H.sub.32 N.sub.6 O.sub.2 65.07 65.39 7.60 7.64 19.80 20.1353 ##STR105## 2-pyridyl ##STR106## 141-143 29.2 C.sub.23 H.sub.30 N.sub.6 O.sub.2 65.38 65.81 7.16 7.18 19.89 20.3054 ##STR107## 2-pyridyl CH.sub.3 149-150 73.8 C.sub.17 H.sub.19 N.sub.5 66.00 66.32 6.19 6.07 22.64 22.3755 ##STR108## 2-pyridyl C.sub.2 H.sub.5 139-140 80.7 C.sub.18 H.sub.21 N.sub.5 66.85 66.35 6.55 6.59 21.66 21.3756 ##STR109## 2-pyridyl CH.sub.2 CHCH.sub.2 112-113 73.9 C.sub.19 H.sub.21 N.sub.5 68.04 68.34 6.31 6.16 20.88 20.3557 ##STR110## 2-pyridyl ##STR111## 84-85 59.0 C.sub.23 H.sub.32 N.sub.6 67.62 68.00 7.90 8.09 20.57 20.7258 ##STR112## 2-pyridyl ##STR113## 121-123 70.6 C.sub.23 H.sub.30 N.sub.6 67.85 68.34 7.44 7.48 20.67 20.8059 ##STR114## 2-pyridyl CH.sub.3 148-149 69.5 C.sub.18 H.sub.21 N.sub.5 66.85 67.25 6.55 6.52 21.66 21.8860 ##STR115## 2-pyridyl C.sub.2 H.sub.5 141-142 72.6 C.sub.19 H.sub.23 N.sub.5 67.63 67.55 6.87 6.75 20.76 20.3961 ##STR116## 2-pyridyl CH.sub.2 CHCH.sub.2 120-121 62.4 C.sub.20 H.sub. 23 N.sub.5 68.74 68.59 6.63 6.56 20.04 20.0062 ##STR117## 2-pyridyl ##STR118## 100-101 83.7 C.sub.24 H.sub.34 N.sub.6 68.21 68.33 8.11 8.35 19.89 20.1063 ##STR119## 2-pyridyl ##STR120## 134-136 45.3 C.sub.24 H.sub.32 N.sub.6 68.54 69.15 7.67 7.76 19.99 20.4964 ##STR121## 2-pyridyl CH.sub.3 206-207 65.4 C.sub.16 H.sub.17 N.sub.5 61.72 62.01 5.50 5.39 22.50 22.5265 ##STR122## 2-pyridyl C.sub.2 H.sub.5 132-133 66.6 C.sub.17 H.sub.19 N.sub.5 62.75 62.55 5.89 5.66 21.53 21.3866 ##STR123## 2-pyridyl CH.sub.2 CHCH.sub.2 111-112 68.1 C.sub.18 H.sub.19 N.sub.5 64.08 64.28 5.68 5.59 20.76 20.6667 ##STR124## 2-pyridyl ##STR125## 88-89 52.8 C.sub.22 H.sub.30 N.sub.6 64.36 64.68 7.37 7.61 20.47 20.2668 ##STR126## 2-pyridyl ##STR127## 132-133 64.3 C.sub.22 H.sub.28 N.sub.6 64.68 64.81 6.91 6.82 20.58 20.5569 ##STR128## 2-pyridyl CH.sub.3 152-153 67.2 C.sub.16 H.sub.17 N.sub.5 O.sub.2 S 55.97 55.76 4.99 4.74 20.40 20.2770 ##STR129## 2-pyridyl C.sub.2 H.sub.5 109-110 62.5 C.sub.17 H.sub.19 N.sub.5 O.sub.2 S 57.13 57.18 5.36 5.65 19.60 19.6871 ##STR130## 2-pyridyl CH.sub.2 CHCH.sub.2 124-125 64.5 C.sub.18 H.sub.19 N.sub.5 O.sub.2 S 58.53 58.75 5.19 5.08 18.96 18.9772 ##STR131## 2-pyridyl ##STR132## 127-129 28.2 C.sub.22 H.sub.30 N.sub.6 O.sub.2 S 57.37 57.36 7.00 7.11 18.25 18.0573 ##STR133## 2-pyridyl ##STR134## 155-156 29.2 C.sub.22 H.sub.28 N.sub.6 O.sub.2 S 59.98 60.17 6.41 6.53 19.08 18.6974 ##STR135## 2-pyridyl CH.sub.3 175-176 63.0 C.sub.16 H.sub.14 N.sub.5 F.sub.3 57.65 57.54 4.23 4.25 21.01 21.0075 ##STR136## 2-pyridyl C.sub.2 H.sub.5 158-159 70.7 C.sub.17 H.sub.16 N.sub.5 F.sub.3 58.78 58.58 4.64 4.64 20.16 20.2076 ##STR137## 2-pyridyl CH.sub.2 CHCH.sub.2 115-116 64.3 C.sub.18 H.sub.16 N.sub.5 F.sub.3 60.16 60.07 4.49 4.50 19.49 19.5377 ##STR138## 2-pyridyl ##STR139## 74-75 39.6 C.sub.22 H.sub.27 N.sub.6 F.sub.3 61.09 61.28 6.29 6.08 19.43 19.5678 ##STR140## 2-pyridyl ##STR141## 137-138 60.6 C.sub.22 H.sub.25 N.sub.6 F.sub.3 61.38 61.36 5.84 5.87 19.52 19.6079 ##STR142## ##STR143## CH.sub.3 178-181 84.9 C.sub.15 H.sub.15 N.sub.5 64.06 63.80 5.34 5.08 24.91 24.7780 ##STR144## ##STR145## C.sub.2 H.sub.5 97-98 58.6 C.sub.16 H.sub.17 N.sub.5 65.08 64.92 5.76 5.60 23.73 23.4981 ##STR146## ##STR147## CH.sub.2 CHCH.sub.2 167-168 67.9 C.sub.17 H.sub.17 N.sub.5 66.45 66.80 5.54 5.38 22.80 22.7682 ##STR148## ##STR149## ##STR150## 128-129 70.6 C.sub.21 H.sub.28 N.sub.6 66.32 66.35 7.37 7.44 22.11 22.0183 ##STR151## ##STR152## ##STR153## 185-187 34.9 C.sub.21 H.sub.26 N.sub.6 66.64 66.31 6.92 6.93 22.21 21.9184 ##STR154## 2-pyridyl CH.sub.3 141-143 72.8 C.sub.13 H.sub.12 N.sub.5 61.40 61.49 4.75 5.03 27.54 27.7685 ##STR155## 2-pyridyl C.sub.2 H.sub.5 131-133 72.6 C.sub.14 H.sub.15 N.sub.5 62.43 62.74 5.61 5.66 26.00 26.3086 ##STR156## 2-pyridyl CH.sub.2 CHCH.sub.2 129-130 87.0 C.sub.15 H.sub.15 N.sub.5 64.03 64.30 5.37 5.66 24.90 25.3587 ##STR157## 2-pyridyl CH.sub.3 137-139 66.0 C.sub.13 H.sub.13 N.sub.5 57.53 57.87 4.82 4.85 25.81 25.7788 ##STR158## 2-pyridyl C.sub.2 H.sub.5 161-163 64.9 C.sub.14 H.sub.15 N.sub.5 58.91 58.95 5.29 5.16 24.54 24.2689 ##STR159## 2-pyridyl CH.sub.2 CHCH.sub.2 123-125 73.9 C.sub.15 H.sub.15 N.sub.5 60.57 60.90 5.08 4.97 23.55 23.2490 ##STR160## 2-pyridyl ##STR161## 112-114 53.1 C.sub.19 H.sub.24 N.sub.6 61.92 61.91 6.56 6.23 22.81 22.6191 ##STR162## 2-pyridyl CH.sub.3 195-197 76.1 C.sub.15 H.sub.21 N.sub.5 66.38 66.23 7.80 7.90 25.81 25.7492 ##STR163## 2-pyridyl C.sub.2 H.sub.5 153-155 78.5 C.sub.16 H.sub.23 N.sub.5 67.33 67.48 8.12 8.18 24.54 24.5693 ##STR164## 2-pyridyl CH.sub.2 CHCH.sub.2 100-102 53.6 C.sub.17 H.sub.23 N.sub.5 68.65 68.89 7.79 8.07 23.55 23.7294 ##STR165## 2-pyridyl ##STR166## 148-151 41.9 C.sub.21 H.sub.32 N.sub.6 68.43 68.28 8.75 8.90 22.80 22.6595 ##STR167## ##STR168## CH.sub.3 147-150 78.5 C.sub.16 H.sub.16 N.sub.4 72.70 73.01 6.10 6.05 21.20 21.0696 ##STR169## ##STR170## C.sub.2 H.sub.5 145- 146 82.2 C.sub.17 H.sub.18 N.sub.4 73.34 73.47 6.53 6.73 20.13 20.1397 ##STR171## ##STR172## CH.sub.2 CHCH.sub.2 149-150 78.8 C.sub.18 H.sub.18 N.sub.4 74.45 74.78 6.25 6.11 19.30 19.2098 ##STR173## ##STR174## ##STR175## 122-124 82.6 C.sub.22 H.sub.29 N.sub.5 72.69 73.21 8.04 7.95 19.27 19.2299 ##STR176## ##STR177## ##STR178## 176-178 71.2 C.sub.22 H.sub.27 N.sub.5 73.09 73.29 7.53 7.49 19.38 19.24100 ##STR179## 2-pyridyl CH.sub.3 192-193 71.7 C.sub.17 H.sub.19 N.sub.5 66.00 6.19 6.11 22.64 22.56101 ##STR180## 2-pyridyl C.sub.2 H.sub.5 136-137 79.8 C.sub.18 H.sub.21 N.sub.5 66.85 67.12 6.55 6.53 21.66 21.72102 ##STR181## 2-pyridyl CH.sub.2 CHCH.sub.2 131-132 71.3 C.sub.19 H.sub.21 N.sub.5 68.04 68.21 6.31 6.25 20.88 20.62103 ##STR182## 2-pyridyl n-C.sub.3 H.sub.7 119-120 87.3 C.sub.18 H.sub.21 N.sub.5 66.85 67.30 6.55 6.63 21.66 21.64104 ##STR183## 2-pyridyl ##STR184## 105-106 46.6 C.sub.21 H.sub.28 N.sub.6 66.29 66.60 7.42 7.55 22.99 22.39105 ##STR185## 2-pyridyl ##STR186## 122-123 74.4 C.sub.20 H.sub.26 N.sub.6 68.54 68.95 7.48 7.47 23.98 23.89106 ##STR187## 2-pyridyl n-C.sub.4 H.sub.9 175-176 89.0 C.sub.18 H.sub.20 N.sub.5 63.25 63.40 5.86 5.98 20.50 20.45107 ##STR188## 2-pyridyl ##STR189## 92-95 84.2 C.sub.20 H.sub.25 N.sub.5 68.34 68.41 7.18 7.17 19.93 19.86__________________________________________________________________________

EXAMPLE 108

Five grams (0.018 mol) of N-cyano-N'-[.alpha.-(2-pyridyl)benzyl]-S-methylisothiourea and 5 g (0.057 mol) of N,N-dimethylethylenediamine were dissolved in 100 ml of ethanol, and the whole was reacted under reflux for 10-15 hours. The reaction solution was concentrated under a reduced pressure. The residue was washed with water, followed by recrystalizing from ethyl acetate to produce 3.4 g of N-cyano-N'-(2-dimethylamino)ethyl-N-[.alpha.-(2-pyridyl)benzyl]guanidine (yield: 58.7%).

Melting point: 142.degree.-4.degree. C.

Elementary analysis (%) for C.sub.18 H.sub.22 N.sub.6 :

______________________________________ C H N______________________________________Calculated: 67.04 6.89 26.07Found: 67.09 6.97 25.96______________________________________

EXAMPLES 109-123

The following Table 9 shows the compounds which were prepared using the procedures similar to Example 108.

In Table 9 Part I, the general formula: ##STR190## represents the formula wherein A is phenyl, B is pyridyl, and p is 0 in the formula (I) hereinbefore mentioned.

In Table 9 Part II, the general formula: ##STR191## represents the formula wherein A is phenyl, B is pyridyl, and p is 1 in the formula (I).

TABLE 9__________________________________________________________________________ Elementary Analysis Melting Upper line: Calcd. Point Molecular Lower line: FoundEx. B R X (.degree.C.) Yield Formula C H N__________________________________________________________________________ ##STR192##109 2-pyridyl ##STR193## 151-152 82.5 C.sub.20 H.sub.26 N.sub.6 68.53 68.76 7.49 7.56 23.98 23.97110 2-pyridyl ##STR194## 143 86.0 C.sub.19 H.sub.24 N.sub.6 67.83 67.87 7.19 7.47 24.98 24.11111 2-pyridyl ##STR195## 84-85 58.0 C.sub.21 H.sub.28 N.sub.6 69.18 69.21 7.76 7.81 23.06 22.89112 2-pyridyl ##STR196## 136-137 67.5 C.sub.21 H.sub.26 N.sub.6 69.58 70.15 7.23 7.44 23.19 23.17113 2-pyridyl ##STR197## 142-143 75.8 C.sub.21 H.sub.26 N.sub.6 O 66.64 67.07 6.92 6.97 22.21 22.72114 3-pyridyl ##STR198## 97-98 64.8 C.sub.21 H.sub.28 N.sub.6 69.19 69.24 7.74 7.70 23.06 23.12115 3-pyridyl ##STR199## 148-150 53.1 C.sub.21 H.sub.21 N.sub.6 69.58 69.36 7.23 7.22 23.19 23.51116 4-pyridyl ##STR200## 133-135 51.1 C.sub.21 H.sub.28 N.sub.6 69.19 69.12 7.74 7.87 23.06 23.01117 4-pyridyl ##STR201## 166-168 44.05 C.sub.21 H.sub.21 N.sub.6 69.58 69.80 7.23 7.12 23.19 23.24118 2-pyridyl ##STR202## 155-158 73.0 C.sub.20 H.sub.24 N.sub.6 68.92 69.36 6.96 7.02 24.12 24.12119 2-pyridyl ##STR203## 99-101 72.6 C.sub.23 H.sub.30 N.sub.6 70.72 70.87 7.76 7.58 21.52 21.11 ##STR204##120 2-pyridyl ##STR205## CH.sub.2 104-105 41.0 C.sub.22 H.sub.30 N.sub.6 69.81 69.75 7.99 7.90 22.20 22.08121 2-pyridyl ##STR206## CH.sub.2 136-138 40.8 C.sub.22 H.sub.23 N.sub.6 70.18 70.38 7.50 7.63 22.32 22.46122 2-pyridyl ##STR207## (CH.sub.2).sub.2 S 94-95 47.1 C.sub.23 H.sub.32 N.sub.6 S 65.06 65.23 7.60 7.54 19.79 19.85123 2-pyridyl ##STR208## (CH.sub.2).sub.2 S 130-131 41.9 C.sub.23 H.sub.30 N.sub.6 S 65.37 65.48 7.16 7.36 19.89 19.11__________________________________________________________________________

Claims

1. A compound of the formula ##STR209## wherein B is 2-, 3- or 4-pyridyl, R represents a group of the formula: ##STR210## wherein R.sub.1 and R.sub.2 are the same or different, and each represent a lower alkyl group, or together form a nitrogen-containing heterocycle of 5-member ring or 6-member ring which ring may also contain oxygen as hetero atom, and n is an integer of 1-3, or R represents a group of the formula ##STR211## wherein R.sub.3 is a lower alkyl group, n is an integer of 1-3, and m is an integer of 4-5.

2. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR212##

3. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR213##

4. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR214##

5. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR215##

6. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR216##

7. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR217##

8. A compound according to claim 1 wherein B is 3-pyridyl and R is ##STR218##

9. A compound according to claim 1 wherein B is 3-pyridyl and R is ##STR219##

10. A compound according to claim 1 wherein B is 4-pyridyl and R is ##STR220##

11. A compound according to claim 1 wherein B is 4-pyridyl and R is ##STR221##

12. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR222##

13. A compound according to claim 1 wherein B is 2-pyridyl and R is ##STR223##