CS242022B1 - Substituted 3-benzyl-5-chlorosalicylic anilides - Google Patents

Abstract

Substituted anilides of 3-benzyl-5-chlorosalicylic acid of the general formula I where R* 1 is a hydrogen atom or a chlorine atom, R2 is a nitro group. These new, previously undescribed substances exhibit anthelmintic activity against the helminth Hymenolepis nana. They can be easily prepared by the reaction of 3-benzyl-5-chlorosalicylic acid with 4-nitroaniline or 2-chloro-4-nitroaniline in xylene in the presence of phosphorus trichloride at elevated temperature

Description

Substituted 3-benzyl-5-chlorosalicylic acid anilides of formula I

wherein R ^{* 1} is hydrogen or chlorine, R ² is nitro.

These novel, yet undescribed substances exhibit anthelmintic activity against Hymenolepis nana helminth. They can be readily prepared by reacting 3-benzyl-5-chlorosalicylic acid with 4-nitroaniline or 2-chloro-4-nitroaniline in xylene in the presence of phosphoric chloride at elevated temperature.

The present invention relates to substituted 3-benzyl-5-chlorosalicylic acid anilides of formula (I)

wherein R ¹ is hydrogen or chlorine, R ² is nitro.

These novel substances, which have not yet been described, exhibit useful anthelmintic activity, in particular against the model helminth of Hymenolepis nana.

The compounds of the formula I according to the invention can be prepared by reacting the known 3-benzyl-5-chlorosalicylic acid (No. AO No. 177 663) with 4-nitroaniline or 2-chloro-4-nitroaniline in the presence of phosphorotrichloride in an inert solvent. elevated temperatures, preferably with 0.4 moles of phosfortrichloride in xylene at a temperature of 130 to 140 degrees Celsius.

Evaluation of anthelmintic efficacy against model helminth Hymenolepis nana

The tests were performed on male H strain mice weighing 10-13 g in groups of 6 each. Two of the three control groups were invaded, untreated, the third was invadivated, treated with a standard formulation - niclosamide piperazine salt - against which the efficacy of the compounds was compared.

Invasion was performed by probing orally with 300 mature Hymenolepis nana eggs in a volume of 0.25 ml / mouse.

Compounds of formula I were administered orally by gavage at 150 mg / kg body weight on days 13 and 14 after invasion. hm. The standard was also applied on days 13 and 14 after invasion at 150 mg / kg b.w. %, which, calculated as niclosamide, represents a dose of 4.58. . 10 mol / kg bw hm.

The anthelmintic activity of the compounds of formula I, expressed as a percentage by the Steward indirect activity method, is given below.

The substituents in formula I dose mol / kg bw. R ¹ R ²

H NO2 3.9. ΙΟ ⁴

Cl NO2 3.6. 10 ~ ⁴

The process for preparing the compounds of the invention is simple and provides the desired products in satisfactory yields. Further details are given in the following examples. The examples given are merely illustrative and not limiting.

He did

4-Nitroanilide acid

-3-benzyl-5-chlorosalicyl

A mixture of 26.2 g of 3-benzyl-5-chlorosalicylic acid (0.1 mol) and 13.8 g of 4-nitroaniline (0.1 mol) and 500 ml of xylene was heated to boiling and 5.5 g of fosfortrichloride were added dropwise to the boiling solution. (0.04 mol). The reaction mixture was heated at 130 to 140 ° C for 8 h under reflux and then separated from the undissolved inorganic residue while still hot. The crystallized solid was filtered off with suction and washed with xylene, 5% aqueous bicarbonate. efficiency in% Example of indirect activity method

80.9 1

62.0 2 sodium methane and water. Recrystallization of the crude material from acetone gave 35.51 g (92.8% w / w) of m.p. 191 ° C.

Example 2

2-Chloro-4-nitroanilide acid

3-benzyl-5-chlorosalicyl

A mixture of 17.3 g of 3-benzyl-5-chlorosalicylic acid (66 mmol) and 11.4 g of 2-chloro-4-nitroaniline (66 mmol) and 140 ml of xylene was heated to boiling and 3.15 g of fosfortrichloride added dropwise to the boiling solution. (23 mmol). The reaction mixture was heated at 130-140 ° C for 7 h under reflux and then, after cooling, shaken with 5% aqueous sodium bicarbonate. The organic layer was freed from the organic solvent by distillation at 50 mbar and the residue was recrystallized from chloroform-petroleum ether. It was obtained

24.9 g (90%), mp 129-130 ° C.

Claims (1)

The object of the invention Substituted 3-benzyl-5-chlorosalicylic acid anilides of formula I wherein R ¹ is hydrogen or chlorine, R ² is nitro.