Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1994-12-07
1997-08-19
Wilson, James O.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514297, 514931, 536 41, 546103, A61K 3170
Patent
active
056588860
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The invention relates to medicinally useful bioactive substances manufactured by chemical techniques. Particularly, the invention relates to new derivatives of acridanones having the general formula /1/ ##STR2## which possess a wide range of bioactivities such as interferonogenic, anti-viral (including anti-HIV), anti-parasitic, anti-promotive, and radioprotective activities.
BACKGROUND OF THE INVENTION
Compounds of acridanone class occur in nature and acridanone derivatives have been synthesized by chemical means. Acridanone derivatives have been reported to have anti-tumor and anti-viral activities. See Japanese Published Patent Application Nos. 64-40426 of Feb. 10, 1989 and 63-310826 of Dec. 19, 1988. Naturally occurring compounds of the same class have been described as having anti-protozoal and anti-herpetic activities. See U.S. Pat. No. 4,244,954 of Jan. 13, 1978 and European Publication No. 110 298 of Jun. 13, 1984.
A structural analog of the acridanone cycloferone, namely 10-carboxymethyl-9-acridone dimethyl-aminoethylether chlorhydrate, of the general formula /2/ ##STR3## (where R is hydrogen) has been reported to have interferonogenic activity. The analog is distinguished from cycloferone by a substitution in position 10 of the acridone cycle. See Polish Patent 139 805 of Jul. 31, 1984. The cycloferone analog exhibits lower interferonogenic activity when compared to the compound of the present invention and exhibits the same level of toxicity.
SUMMARY OF THE INVENTION
The goal of the invention was to obtain a new acridanone derivative possessing a wide range of biological activities, low toxicity, and superior chemotherapeutic properties.
The goal was accomplished in the synthesis of compounds of general formula /1/, obtained through the interaction of the compound of general formula /3/ ##STR4## (where R.sub.1 is a hydrogen, alkyl group, metal or ammonium cation) with derivatives of L,D-glucopyranosilamine of general formula /4/ ##STR5## (where R.sub.2 is a methyl group).
The presently preferred derivative is N-methyl-N-.alpha.-D-glucopyranosil-ammonium-2-acridone-9-on-10-yl-acetate , having the formula ##STR6## The derivative has interferonogenic, anti-viral (including anti-HIV), anti-parasitic, anti-promotive, and radioprotective activities and is designated CYCLOFERONE herein. The name CYCLOFERONE has been registered as a trademark in Russia.
Due to its low toxicity, it is contemplated that CYCLOFERONE (N-methyl-N-.alpha.-D-glucopyranosil-ammonium-2-acridone-9-on-10-yl-acetat e) be formulated as a medication for parenteral, oral, and topical application.
DETAILED DESCRIPTION
Example 1
Preparation of CYCLOFERONE
Case 1 99.6 grams of N-methyl-N-.alpha.,D-glucopyranosilamine was dissolved in 200 milliliters of distilled water. Then, gradually, 125 grams of carefully fragmented 2-/acridone-9-on-10-yl/acetic acid was added with stirring. Stirring continued at room temperature until solids were completely dissolved, and then 1 liter of ethyl alcohol was added. The resulting precipitate was filtered, washed in 100 ml ethyl alcohol, re-filtered, and dried for 1 hour at 60.degree. C. 224 grams of 100% pure N-methyl-N-.alpha.-D-glucopyranosil-ammonium-2-acridone-9-on-10-yl-acetate (CYCLOFERONE) of formula C.sub.22 H.sub.26 N.sub.2 O.sub.8 were thus obtained in yellow crystals upon re-crystallization using low-grade alcohols. The melting point of CYCLOFERONE was 129.degree.-132.degree. C.
CASE 2 276 grams of sodium 2-/acridone-9-on-10-yl/acetate were dissolved by stirring in 400 milliliters of distilled water. Concentrated hydrochloric acid was added to pH 3. The resulting precipitate was filtered, washed in 100 milliliters of distilled water, and re-filtered. The precipitate was recrystallized from dimethylformamide and water mixed at a ratio of 3:1. The 2-/acridone-9-on-10-yl-/acetic acid precipitate was dried for 3 hours at 105.degree. C. before proceeding as indicated in Case 1. The process yield was 398 grams of 89% pure CYCLOFERONE with a melting point upon being recry
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Alekseeva Ljudmila Evgenievna
Borisova Margarita Alekseevna
Chizhov Novomir Pavlovich
Kovalenko Aleksei Leonidovich
Kupchinsky Roald Antonovich
Limited Liability Partnership "POLYSAN"
Wilson James O.
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