SU503853A1 - Butane fatty aromatic aminoamides or their salts exhibiting anesthetic activity - Google Patents

Description

fatty amino amines of the bucket variety, formula

but

C, ", -C - (CH,),, G

well

where I am; and CH, 5 R - -BHg with H, (3) - CHj 6tH, (1),

-CH-DHjCa)

H - CH, 0NH | - (, ft-fll. -T, k -), H- “H5 | C“ 4-7), M-OasbH4- (c).

These compounds can be obtained in a trivial way, namely, the interaction of amino alcohols with nitriles in the presence of an ACID catalyst according to the scheme:

fzcrf

((

(CHfOOOH)

miso / g

,) ZMK;

physico-chemical characteristics of the compounds of formula I are presented in table. one.

The pharmacological activity of the compounds was tested on amino-tmid chlorohydrates.

The anesthetic effect of these compounds has been studied in the following types: terminal, infiltration and conduction anesthesia.

Hermine / anesthesia myiolmide has been tested on the cornea of the eye of rabbits, tyiltrative — on my pigs, conductors — on l thick bushes.

Conductor anesthesia was tested by exposure of the test drug solution to the exposed sciatic nerve according to Bulbringai-Wade method. The activity of the compounds is determined by the lowest concentration at which tissue anesthesia begins to appear, the rate at which anesthesia develops; the lowest concentration at which comes full tissue anesthesia and the duration of complete anesthesia (see table 2).

For comparison, Table 2 shows the known compounds of general formulas:

f

WH-C-d

, -c - (CHA-N

i) R

de H.I. RebiH,:

.7

Y “C, N (9) g“ s, n U

J R

. YN

 n 7

-SH, And

and

R

 and H

.N 1 fn, v

to

: Ci ", J

R

Data on the pharmacological) activity of compounds of general formula I in comparison

L

Research institutes with compounds of general formula D are given in Table. 1, 2 and 3.

The characteristics of the anesthetic activity of these substances in comparison with the medical standard, dikain, according to the values of the Valet index are given in the B table. 3,

but

a c h f f b

Oh see

0)

with

about

R

Si S S

S

o s: o

g

yo

and about

w o

D. C

01 S

with sh o

s

S

-, g i

but

X

with; Yu

03

s

f

S

ABOUT)

h o s (

with

about.

with

O.L

§§

2 (Y

2, o

aio

00

Yu

GCD

-c) A little more than zero, as is well known, is also of great importance to the breadth of the therapeutic effect of npenajiaTOB, which op () is toxic to the compound and its actinch (to: c1. C-ednsh, toxic) Table2

Table3

The doses for intravenous administration and calculated according to the Litchfield-Wea Coxon 1Ds- / method, intraperitoneal dissection are shown in Table. 4 as for vK.i.i.iiinyh substances, and for dikainp. Room; Formula: Flying dose of drugs :: injections, mg / kg As can be seen from the above figures (see Table 1-4), the proposed amio amides are quite strong local remedies that cause all types of local anesthesia: terminal intracranial and conductive. Compared with the substances of general formula II 01. And they act faster, stronger and longer. The toxicity of aminoamides is less than that of dicain used in medicine. Example, 4.25 g of 1 - D1. Methylamino-4-phenyl-4 (p-toluyl) -aminobutane is a solution of yut in 50 ml of absolute methanol and potentiometrically titrated with 0.2 M solution of HC t in methanol (potentiometer pI 340) to the equivalence point . After distilling off the solvent in vacuo, the product is washed with benzene, ether, and recrystallized from acetone. 3.88 g (82%) of 1-dimethylomyl-4-phonyl-4 - (p-toluyl) aminobutane hydrochloride are obtained. Found,%: CE 8.95 and 8.92; N 7.51, and 7.44, ipfsi Calculated,%: Ct 9.65; N 7.65.

Table for intravenous administration: 1DI for intra-abdominal: nominal administration, mg / kg. Example 2 4.8 g of 1-dimethylamino-4-phenylbutanol — 4, 3.7 g of nitrile to -togylic acid and 1Olc ice-acetic acid are added to 9 ml of 100% - oh sulfuric acid at a temperature of 6 ° –7 ° C dropwise with stirring. The reaction mass is stirred at room temperature for 4 hours and kept at room temperature for 24 hours. I Then the reaction mass is poured into a mixture of {and uvor ammonia with ice, the product is salted out with potash and extracted with ether: ethyl acetate 1: 1 (3 X 150) ml. The extract is dried over calcined magnesium sulfate, the solvent is distilled off,. the product is distilled under vacuum; 4.25 g (54.2%) of 1-dimethylamino-4-phenyl-4 (p-toluyl) amnobutane crawl, b.p. 184-185 C at O, O6 mm, I 5 O, 73 (MuO degree I activity in the solvent system ether: ethanol 2O; 1); Rj.g 0.64 (in the solvent system ether: this-