N6-(ferrocene methyl) quinazolin-2,4,6-triamine (h2) and the derivatives and prodrugs thereof as antimicrobial, antiparasitic, antiprotozoal and antileishmania agents

Abstract

The invention relates to the use of compound N 6 -(ferrocenmethyl)quinazolin-2,4,6-triamin (H2) and the derivatives and prodrugs thereof having an antimicrobial (antibiotic, microbicidal), antiparasitic (parasiticidal), antiprotozoal (protozoacidal), antileishmanial (leishmanicidal) activity, and to the use thereof as a drug for (human and animal) vertebrates.

Description

Background technique

[0001] Still no N 6 -(Methylferrocene)quinazoline-2,4,6-triamine for use as an antibacterial, antibiotic, bactericide, bacteriostatic, bacteriostatic, antiparasitic, antiprotozoal or antileishmaniatic Reports on insecticide use.

[0002] Since the appearance of leishmaniasis in 1885, basically no agents have been reported for the treatment of this disease, and these agents have different potencies and efficiencies. Treatment options are few and include expensive drugs that are difficult to obtain, lack uniform registration, and may be toxic or ineffective. For example, antimony-containing agents (including meglumine antimonate) introduced in 1940, although this treatment was longer than 20 days and caused pancreatitis (the most common cause of treatment discontinuation) and severe ECG changes, the drug still Continued use as a treatment option for cutaneous leishmaniasis. Amphotericin B, which is harmful to the kidneys and causes hypercalcemia, is stil...

Examples

Embodiment Construction

[0039] 1) synthesis

[0040]Using a 50ml flat-bottomed flask equipped with magnetic stirring, a Vigreux fractionating column and under a nitrogen atmosphere, 0.31g of ferrocene formaldehyde (0.00143), 0.3g of N,N'-(6-aminoquinazoline- 2,4-diyl) diacetylamine (1 equiv), 1 ml of DMF and one drop of acetic acid were mixed. The mixture was stirred at 85°C for 45 minutes. The mixture was then cooled to 0°C using an ice-water bath, and 0.0671 g (2 equiv) of NaBH was added slowly 4 . The ice bath was removed and stirring was continued at room temperature for 12 hours. DMF was evaporated in a rotary evaporator, and Na 2 CO 3 Saturated solution was added to the residue. The yellow precipitate formed was isolated by filtration and washed several times with water. After drying at room temperature, the solid was washed several times with diisopropyl ether to afford 0.3239 g of HA in 48% yield, R f =0.76(CHCl 3 / MeOH80:20), p.f.=218–220°C. HA2 was hydrolyzed with one normal metha...

Background technique

[0001] Still no N 6 -(Methylferrocene)quinazoline-2,4,6-triamine for use as an antibacterial, antibiotic, bactericide, bacteriostatic, bacteriostatic, antiparasitic, antiprotozoal or antileishmaniatic Reports on insecticide use.

[0002] Since the appearance of leishmaniasis in 1885, basically no agents have been reported for the treatment of this disease, and these agents have different potencies and efficiencies. Treatment options are few and include expensive drugs that are difficult to obtain, lack uniform registration, and may be toxic or ineffective. For example, antimony-containing agents (including meglumine antimonate) introduced in 1940, although this treatment was longer than 20 days and caused pancreatitis (the most common cause of treatment discontinuation) and severe ECG changes, the drug still Continued use as a treatment option for cutaneous leishmaniasis. Amphotericin B, which is harmful to the kidneys and causes hypercalcemia, is stil...

Examples

Embodiment Construction

[0039] 1) synthesis

[0040]Using a 50ml flat-bottomed flask equipped with magnetic stirring, a Vigreux fractionating column and under a nitrogen atmosphere, 0.31g of ferrocene formaldehyde (0.00143), 0.3g of N,N'-(6-aminoquinazoline- 2,4-diyl) diacetylamine (1 equiv), 1 ml of DMF and one drop of acetic acid were mixed. The mixture was stirred at 85°C for 45 minutes. The mixture was then cooled to 0°C using an ice-water bath, and 0.0671 g (2 equiv) of NaBH was added slowly 4 . The ice bath was removed and stirring was continued at room temperature for 12 hours. DMF was evaporated in a rotary evaporator, and Na 2 CO 3 Saturated solution was added to the residue. The yellow precipitate formed was isolated by filtration and washed several times with water. After drying at room temperature, the solid was washed several times with diisopropyl ether to afford 0.3239 g of HA in 48% yield, R f =0.76(CHCl 3 / MeOH80:20), p.f.=218–220°C. HA2 was hydrolyzed with one normal metha...

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