CS261293B1 - Substituted 2-benzamido-3-cyanopyrimido [1,2-a] benzimidazoles - Google Patents

Abstract

The solution relates to substituted 2-benzamido-3-cyanopyrimido[1,2-a]benzimidazoles of the general formula I NHCO CN (I), where R1 and R2 are hydrogen and R2 are nitro or R1 is chlorine and R2 is nitro and R2 is hydrogen or R1 is pentyloxy and R2 is hydrogen and R4 is chlorine or R2 is isopropyloxy and R2 is hydrogen and R2 is bromine. These new, yet undescribed substances exhibit anthelmintic activity against the model helminth Hymenolepis nana.

Description

wherein R and R are H and R ² is nitro and Ri is chloro and R ² is nitro and R ² is. is H and R is a pentyloxy group, and R ² is H and R 4 is chloro and R is isopropoxy and R ² is hydrogen and R ² is bromo. These novel substances, which have not been described yet, exhibit anthelmintic activity against the model helminth of Hymenolepis nana.

The present invention relates to substituted 2-benzamido-3-cyanopyrimido [1,2-a] benzimidazoles of formula I

CN |

R ³

2 1 2 where R and R are hydrogen and R is nitro or R is chlorine and R is nitro

1 2 3 and R is hydrogen or R is pentyloxy and R is hydrogen and R is chlorine

Or R is isopropyloxy and R is hydrogen and R is bromo.

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

The compounds of the formula I according to the invention can be prepared by the reaction of the known 2-amino-3-cyanopyrimido [1,2-a] benzimidazole (de Cat A., van Dormael A .: Bull. Soc. Chim. Belges 60, 69 (1951)). l) with 4-nitrobenzoic acid chloride or 2-chloro-4-nitrobenzoic acid or 2-pentyloxy-5-chlorobenzoic acid or 2-isopropyloxy-5-bromobenzoic acid in pyridine at 20 to 80 ° C.

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 invaded, treated with a standard formulation - niclosamide piperazine salt - against which the efficacy of the substances was compared.

Invasion was performed by probing orally with 500 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 ^-1 body weight (w / w) at 13 and 14 days after invasion as a homogenate in Dorfman's reagent.

Mice were sacrificed on day 3 post-application and anthelmintic efficacy was determined by calculation of Steward's indirect activity method after total taseranic colloquial counts at complete helmintological necropsy of the small intestine of mice. The standard was also applied 11 and 14 days after invasion at a dose of 150 mg.kg ^-1 body weight, which, calculated as niclosamide, means the dose

4,58.10 ⁴ mol.kg ^- ! bw

The anthelmintic activity of the compounds of formula I against the model helminth of Hymenolepis nana, expressed as a percentage by the Steward indirect activity method, is shown below.

Fabric according to an exemplary embodiment Dose mol.kg ”1 bw Efficiency in% method indirect activities 1 4,18.10 ^-4 66 2 4,18.10 ^-4 66 3 3,45.10 ^-4 84 4 3,33.10 ^-4 62

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.

Example 1

2- (4-nitrobenzamido) -3-kyanopyrimido / l, 2-a / benzimidazole

To a suspension of 6.27 g (0.03 mol) of 2-amino-3-cyanopyrimido [1,2-a] benzimidazole in 60 ml of pyridine was added 7.4 g (0.04 mol) of 4-nitrobenzoyl chloride and the mixture heated with stirring 6 h at 80 ° C. The cold reaction mixture was poured into 400 ml of water and the precipitate after pouring the solution was still decanted with water and aspirated. Recrystallization from 90% DMF afforded 9 g (83.7%) of the substance does not melt up to 360 ° C a composition ^c X 8 ^H 10 ^N 6 ° 3 '

Example 2

2- (2-chloro-4-nitrobenzamido) -3-kyanopyrimido / l, 2-a / benzimidazole

As described in Example 1, from 6.27 g (0.03 mol) of 2-amino-3-cyanopyrimido [1,2-a] benzimidazole and 8.8 g (0.04 mol) of 2-chloro-4-nitrobenzoyl chloride The crude material was recrystallized from 80% 2-ethoxyethanol. Afforded 6.7 g (56.9%) of material melting at 293-294 ° C of the composition C ₁₈ H ₉ ClNgOj.

Example 3

2- (2-pentyloxy-5-chlorobenzamide) -3-kyanopyrimido / l, 2-a / benzimidazole

As described in Example 1, 2-amino-3-cyanopyrimido [1,2-a] benzimidazole (6.27 g, 0.03 mol) and 2-pentyloxy-5-chlorobenzoyl chloride (10.5 g, 0.04 mol) were used. The crude product was recrystallized from ethanol. 8.6 g (66.2%) of a substance melting at 248-249 [deg.] C. with C ₂₃ H ₂ gClNgO _{2 was obtained} .

Example 4

2- (2-isopropoxy-5-bromobenzamido) -3-kyanopyrimido / l, 2-a / benzimidazole

As described in Example 1, from 2-amino-3-cyanopyrimido [1,2-a] benzimidazole (6.27 g, 0.03 mol) and 2-isopropyloxy-5-bromobenzoyl chloride (11.1 g, 0.04 mol) The crude product was recrystallized from ethanol. 7.26 g (53.8%) of a substance melting at 255-256 ° C with a composition of ^C 21 ^H 16 ^BrN 5 ° 2 'was obtained.

Claims (3)

substituted 2-Benzamido-3-cyanopyrimido [1,2-a] benzimidazoles of formula (I) IN CN (I) NHCO ² R R ³ And R is hydrogen and R is nitro or R is chlorine and R is nitro 19 R ¹ and R ^J is hydrogen and R 'is nitro or R is chlorine and R * is nitro o 2 R @ 3 is hydrogen or R is pentyloxy and R is hydrogen and R is chlorine 1 '2 3 R is isopropyloxy and R is hydrogen and R is bromo.