DE2009738A1 - Substituted biguanides with anti-hyperglycemic effects - Google Patents

Description

FARBENFABRIKENBAYERAG

LEVERKUSEN-Biyerwetk March 2nd, 1970 . Patent department Si / AS

Substituted biguanides with antihyperglycemic effects

It is known that a number of substituted biguanides have a blood sugar lowering effect. Phenäthy1-biguanid, Butylbiguanid and N, N-Dimethylbiguanid are commercially available as antidiabetic agents. On the other hand, N ₁ -aryl-N (- alkyl-biguanides are considered to have only weak antidiabetic activity / ** B. EIper η, Ann. NY Acad. Sci. U8, 577 (1968) J. So for the N ₁ -P -ChIOrphenyl-Nc-isopropylbiguanid ("Proguanilhydrochlorid ¹¹ ) a slight hypoglycemic effect, which only occurs in toxic doses, described /" κ.Κ. Chen and R, C-. Anderson, J * Pharmacol. Exp. Therap. <31_, 157 ( 1947) y. It has now surprisingly been found that N-aryl-N ^ -alkyl-biguanides of the general formula ■

vv — wtT-r! -wpr_n_

and their salts with non-toxic acids, wherein R is hydrogen, chlorine or bromine,

R _{1 stands} for an alkyl or alkenyl radical with 5 to 12, preferably 4 to 8 carbon atoms, which, if it contains more than three carbon atoms, can also be branched, or a cycloalkyl, cycloalkylalkyl or alkoxyalkyl radical with 3 to 12 carbon atoms and

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109 83871B67

R _{2 can have} the same meanings as R ₁ , where ^ R .. and Rg can be the same or different and where R _{2 can} also stand for hydrogen

have a good antihyperglycemic effectiveness, even that of the mentioned commercial biguanides ζ. Τ. far exceeds.

Since the effect of the commercially available biguanides only occurs in high doses, there is a risk of long-term treatment Incompatibility / "see. H. Mehnert and H.S. Sadow in" Oral. Hypoglykaemic Agents ", page 281, Academic Press, London, 1969./· The use according to the invention of biguanides, the are effective in a much smaller dose with approximately the same toxicity, therefore represents an important advantage. .

These compounds, some of which are known, are produced by known methods / "pHS Curd, JA Hendry, TS Kenny, AG Murray and PL Rose, Soc. 1948 , 1630; FHS Curd and FL Rose, Soc. 1946 , 729 J ·

The following table compares the antihyperglycemic effects of some BT ₁ -aryl-N ₁ -alkyl biguanides with that of proguanil hydrochloride (compound 15). This antihyperglycemic effect can be demonstrated in the following experiment: - '· "" - "_; i

Fasted rats received after multiple oral-appli- _: '% _r ^~: \ cation of the active ingredient in physiological saline dissolved glucose administered per os. The blood glucose level ν of the animals treated with an effective biguanide increases less strongly than in untreated animals as a function of the dose. The measurement is carried out 30 and / or 60 minutes after the administration of glucose. * The indicated dose is the single dose administered in each case, which is one compared to the untreated

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COPY 109838/1687

2009730

th control group significant (P <£ 0.05) reduction in Causes hyperglycaemia after administration of glucose.

NH NH II II -NH-C-NH-C-N

PP of Hydrochloride

dose

> CHaite) in. Mg / kg

1 4-Cl UC ₅ H ₇ . H (the known
Proguanil hydrochloride) 213-214 ° 2.5 120 2 4-Cl Allyl H 194-196 ° 3
4th 4-Cl
4-Cl S ₄ H ₉ H
H 211-212 °
239-240 ° 2.5
5 320 5 4-Cl UC ₅ H ₁₁ ; H 218-220 ° 2.5 452 6th 4-Cl UC ₆ H ₁ 3 H 207 ° 7th 4-Cl UC ₈ H ₁₇ H 190-191 ° 8th 4-Cl -CH ₂ -CH ₂ OCH ₅ H 165-167 ° 9 4-Cl UC ₅ H ₇ , nC, H ₇ 173-175 ° 10 3-Cl IsO-C ₄ H ₉ H 212-214 ° 11 - H - UC ₅ H ₇ H 207-209 ° 12th H Allyl . H 195-197 ° 13th H > -c ₄ V H 206, -208 ° 4th 256 14th , IsO-C ₄ H ₉ H; 221-223 ° 5 * 656. 15th 4-Cl 4SO-C ₅ H ₇ H 250-251 ° 10 114

16 4-Cl

2.5

(as naphthalene-1,5 disulfonate.
P. 169-171 °)

71

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- 3 ■ -8 3871 £ 67

GOPY

Claims (3)

Claims 1) Medicinal products, characterized by a content of a compound of the general formula NH NH _p
Cx V -NH-C-NH-CN ^ Xl Rp and their salts with non-toxic acids, in which j R is hydrogen, chlorine or bromine, WR ₁ for an alkyl or alkenyl radical with 3 to 12, preferably 4 to 8 carbon atoms, which, if it contains more than three carbon atoms, can also be branched, or a cycloalkyl, cycloalkylalkyl or alkoxyalkyl radical with 3 to 12 carbon atoms stands and Rp can have the same meanings as R ₁ , where R ₁ and Rp can be identical or different and where Ro can also stand for hydrogen. 2) Agent with antihyperglycemic effect, characterized by a content of a compound of the specified in claim 1 general formula. 3) Orally applicable agents with antihyperglycemic effect, characterized by a content of a compound the general formula given in claim 1. Le A 12 828 - 4 - 109838/1667