JPS5936630B2 - 2-imino-1,3-diazacycloalkane derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula (1) ra0, uni'-h (wherein R1 is a hydrogen atom or a phenyl group, R2 and R3
each independently represents a hydrogen atom, a lower alkyl group or a lower hydroxyalkyl group, and n represents an integer of 2 to 4.

However, regarding new compounds represented by (excluding those where n is 2 and R1, R2 and R3 are hydrogen atoms), 2-imino-1,3-diazacycloalkane derivatives or acid addition salts thereof, compounds of formula (1) exhibits a strong hypoglycemic effect. Formula (1
) can be produced by the following method.

(In the above formula, R4 is a cyano group, a lower alkanoyl group or a lower alkoxycarbonyl group, R5 is a lower alkyl group, X is a halogen atom, and R1, R2, R3 and n are the same as above). According to this, the desired product can be obtained almost quantitatively by adding amines represented by the formula () to an organic solvent in which a halogen cyanide is dissolved.

Organic solvents used in this reaction include alcohols such as methanol and ethanol, chloroform, benzene, etc.
A general organic solvent is used, and the reaction temperature ranges from room temperature to about 6
A range of 0°C is preferred. When using guanidine hydrochloride instead of halogen cyanide, the target compound can be prepared by heating directly with the compound represented by the formula () at 120 to 200°C, preferably 160 to 180°C for several hours without using a solvent. I can do it. According to method 5, the target compound is obtained by reacting the starting compound of formula () with an alkyl halide in dimethylformamide in the presence of a deoxidizing agent such as sodium hydride or sodium alcolade at a temperature from room temperature to about 150°C. It can be obtained by letting

According to method 5, a compound of formula () is dissolved in tert-butanol with 2
The target compound is obtained by heating for 5 to 8 hours in the presence of ~3 times the mole of hydrochloric acid.

According to method 4, the raw material compound of formula (V) and the alkylamines are heated in an alcohol solvent for about 60 to more than ten hours.
The target compound is obtained by heating to 100°C.
The compound of the present invention thus produced has a benzyl group or benzhydryl group at the 1-position of the 1,3-diazacycloalkane derivative, and has structural specificity fundamentally different from that of conventional hypoglycemic drugs. and has a strong hypoglycemic effect.

More specifically, the compounds of the present invention exhibit superior effects on normal fasting movements compared to sulfonylurea and biguanide compounds, which are conventionally frequently used hypoglycemic drugs.

The results of comparing the hypoglycemic effects of several examples of the compounds of the present invention with those of commercially available tolbutamide and fenformine are shown below.

Example 1 6.0 y of 1-benzylamino-2-aminoethane is added to a solution of 4.45 y of bromine cyanide in 150 d of benzene while stirring so that the reaction temperature does not rise above 50°C.

After 2 to 4 hours, the precipitated crystals were collected and 1-benzyl-2
- Hydrobromide of iminoimidazolidine is obtained quantitatively.

Melting point: 200-202°C. The compounds shown in Table 2 were obtained in the same manner.

Example 4 6.56 r of 1-benzylamino-3-aminopropane and 3.807 r of guanidine hydrochloride were heated to 160-180°C for 6 hours, cooled, and crystallized by rubbing in isopropanol and ether to obtain 1-benzyl-2-imino. 6.0 r (67%) of -1,3-diazacyclohexane hydrochloride is obtained.

Melting point: 160-164°C. Example 5 1-benzhydryl-2-imino-imidazolidine 1.
Dissolve 0t in 15ml of dimethylformamide and dilute to 50%
After adding 0.22 y of oily sodium hydride and stirring at room temperature for 1 hour, 0.69 t of ethyl iodide was added.

It reacts by gradually foaming. After stirring for 4 hours,
The solvent is distilled off under reduced pressure, water and chloroform are added to the residue, and the mixture is thoroughly shaken.

The organic layer is separated, thoroughly washed with water, dried, and chloroform is distilled off. Ethanol was added to the residue to dissolve it, concentrated hydrochloric acid was added to adjust the pH to 2, and the mixture was concentrated to dryness under reduced pressure. The residue crystallizes when rubbed with acetone. 0.367 (29%) of 1-benzhydryl-2-imino-3-ethylimidazolidine hydrochloride was obtained.

Melting point 236-237°C. The compounds shown in Table 3 were obtained in the same manner.

Example 10 1-benzhydryl-2-cyanoimino-1 0.58 V of 3-diazacyclohexane was dissolved in tert-butanol 10
ml and 0.6 ml of concentrated hydrochloric acid and heated under reflux for 6 hours.

After cooling, the residue was concentrated to dryness under reduced pressure, and acetone was added to the residue, which crystallized by rubbing.
3-Diazacyclohexane 0.34V (58%)
was gotten. Melting point 218-22°C. A compound of formula (I) was obtained from a compound of formula () as shown in Table 4 in a similar manner.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ 2-imino-1,3-diazacycloalkane derivatives or their acids, where n is an integer from 2 to 4 (excluding those where n is 2 and R_1, R_2, and R_3 are hydrogen atoms) Added salt. 2. The compound according to claim 1, which is 1-benzhydryl-2-imino-3-methylimidazolidine. 3. The compound according to claim 1, which is 1-benzhydryl-2-imino-3-ethylimidazolidine. 4. The compound according to claim 1, which is 1-benzhydryl-2-methyliminoimidazolidine.