IL33942A - 1-phenyl-5-amino-1,2,3-triazole-4-carboxylic acid esters,their preparation and pharmaceutical compositions containing them - Google Patents

Description

acid their preparation pharmaceutical eontainiag them This invention relates to new triazole The invention also relates to a process for preparing compounds of this According to a feature of the present invention there are provided new triazole derivatives having the general formula I wherein A stands for an containing from 1 to 5 carbon and the one from the 1 and R2 stands for hydrogen atom and the other stands for a group having the general formula II fluorine wherein X is a chlorine or atom in or Compounds of similar but wherein 2 always stands for a hydrogen atom and X stands for a hydrogen a or group are known from the literature 2001 These known compounds an antipyretic effect and the derivative has a bacteriostatic effect Suitable representatives of the compounds of formula I are the following derivatives lic acid ethyl lic acid ethyl oxylic acid ethyl acid ethyl lic acid ethyl acid ethyl acid ethyl acid ethyl The new compounds according to the invention can be conveniently prepared by reacting a acid ester of the formula III C COOALk has the same meanings as with a azide of formula wherein has the same meanings as and if the is a acid alkyl in which stands for a hydrogen if this ester is subjected to a rearrangement 183 44 The Dimroth rearrangement is preferably carried out in pyridine5 while The new compounds of formula I possess valuable pharmacological They have an effect which is especially strong in the case of Bnchytraeus albidus and Tubifex The anthelmintic effect of some compounds according to the invention is shown in Table The vermicidal activity was investigated with method in Table 1 Designation of the Minimum concentration for Z 24 acid ethyl este acid ethyl ester acid ester lic acid ethyl lic acid ethyl ester HC1 acil chloride for comparison purposes and having excellent anthelmintic The compounds 2 to 5 show a good anthelmintic effect also in connection with Candida According to a further feature of the present invention there are provided pharmaceutical compositions comprising as active ingredient at least one compound of formula in admixture with suitable pharmaceutical carriers These pharmaceutical compositions can be coated or such as or jectable The compositions can be suitable for rectal or parenteral The carriers can be conventional organic or inorganic such as magnesium polyalkylene magnesium carbonate The pharmaceutical compositions may contain such as disintegrating and watting agents The preparation may comprise in addition to the compound of formula I further therapeutically active compounds as The pharmaceutical compositions of the present invention be prepared by usual methods known per se of the industry by admixing the active ingredient with suitable solid or liquid organic or inorganic tical carriers excipients if wit other therapeutically active The daily dose of the compounds according to the vention for adults amounts from 60 to 400 The invention is further illustrated by the aid of the following which are given for the purpose of illustration only and are not to be construed as limiting the Example 1 g of metafluorophenyl azide and of cyanacetic acid ethyl ester are dissolved in 90 ml of absolute ethanol and in a provided a mixer and a tube containing calcium chloride against the moisture content of a sodium ethylate solution pared from of sodium and 90 of ethanol is dropped to while keeping the temperature below 10 by the aid of outer After finishing the the cooling is ceased and the mixture is stirred for a further hour at room Thereafter the mixture is poured into 1500 of icy The crystals precipitated are washed with water and In this way of acid ethyl ester are obtained with a melting point of After recrys from 220 of colourless crystals weighing 11 are obtained with a melting point of Example 2 8 of acid ethyl ester are dissolved in 24 of pyridine and the solution is boiled under reflux 3 whereafter it is poured into 300 of icy filtered The white crystalline precipitate is washed with cold water and In this way 7 of acid ethyl ester are obtained with a melting point of After crystallizing from acetic 75 of product are obtained a melting point of 139 to 141 Analysis data for 9 ST F ΕΓ Example 3 of acid and of cyanacetic acid ethyl eater are dissolved in 100 ml of absolute and in a flask provided with a mixer and a tube containing calcium chloride against the moisture content of the a sodium ethylate solution pared from of sodium and 50 of added absolute ethanol are to while keeping the temperature external 0 with cooling below 10 After finishing the addition the cooling is ceased and the mixture 13 stirred for a further hour at room then it is poured into filtered 15OO of The crystals precipitated are washed with water and In this way of acid ethyl ester are obtained with a meltin point of to 137 After recrystallizing from 500 of 62 of crystals needles are obtained with a melting poin of 139 Analysis data for P 59 P 7 Example 4 of acid ethyl ester are dissolved in 24 of absolute The solution is boiled for 8 hours under reflux and then poured into 300 of icy The filtered crystalline precipitate formed is washed witk cold water and In this way of lic acid ester are obtained with a melting point of After recrystallizing from of acetic of product are obtained with a melting point of 141 Analysis data for t P N P Example 5 of azide and of cyanacetic acid ethyl ester are dissolved in 100 of absolute and in a provided with a stirrer and a tube containing calcium chloride against the moisture content of the air a sodium ethylate solution prepared from of sodium and ml of ethanol is dropped to while the temperature o below 10 C with outer After the addition is the cooling is the mixture is stirred for further 2 hours at room temperature and then it is poured into 1500 of icy The crystals precipitated filtered are washed with water and In this way of acid ethyl ester are obtained with a melting point of 1fter recrystallizing from 400 of of colourless crystal needles are obtained with a melting point of Analysis data for Cl N ti t Cl Example 6 o of acid ethyl ester are dissolved in 21 of absolute The solution is boiled for 3 hours under reflux and then it is poured into of icy The white filtered crystals obtained are washed with cold water and In this way acid ethyl ester are obtained with a melting point of 15 After recrystallizing from 2 0 of 50 acetic of product is obtained with a melting point of Analysis data for N Example of azide and of cyanacetic acid ethyl ester are dissolved in 100 of absolute and in a flask provided a stirrer and a tube filled with calcium chloride against the moisture of a sodium ethylate solution pared from of sodium and of ethanol is dropped to while keeping the temperature outer cooling below 10 After finishing the addition and ceasing the the mixture is stirred for a further hour at room temperature and then it is poured into filtered 1500 of The crystals precipitated are washed with cold water and In this way of acid ethyl ester are obtained with a melting point of After recrystallizing from of o of colourless crystals are Analysis data for fo 01 Example of acid ethyl ester are dissolved in 24 ml of absolute The solution is boiled under reflux for 8 hours and then it is poured into 300 of icy filtered The white crystals separated are sucked washed with cold water In this way fo of acid ethyl ester are obtained with a melting point of After from of 50 acetic fo of product are obtained with a melting point of 162 Analysis data for fo 01 N insufficientOCRQuality

Claims (12)

What we claim is:

1. ETe¾r compound of the general formula I wherein Alk stands for an alkyl group containing from 1 to 5 carbon atoms, and the one from the substituents R 2 and ¾ stands for hydrogen atom and the other stands for a group having the general formula II fluorine wherein X is a chlorine or bromine atom, in m- or p-position,

2. A compound selected from the group consisting of 5-m-fluorophenyl-5-aminotriazole-4-carboxylic acid ethyl ester, 5-m-fluo*^nilino~triazole-4-carboxylic acid ethyl ester, 1-p-fluorophenyl-5-aminotriazole-4-carboxylic acid ethyl ester, 5~P~fluor^.nilino-triazole-4-carboxylie acid ethyl ester, l- -chlo^phenyl-5-aminotriazole—4-carbox lie acid ethyl ester, ^m-chlar/^nilino—triazole~4-carboxylic acid ethyl ester, l-p-chlorophenyl-5~aminotriazole-4- -carboxylic acid ethyl ester and 5_P~chlo^anilino-triazole- -4-carboxylic acid ethyl ester.

3. A process for preparing the new compounds of formula I B½H COO-illk wherein Alk stands for an alkyl-group containing from 1 to 5 carbon atoms, and the one from the substituents Ή1 and H' stands for hydrogen atom and the other stands for a group having the general formula II fluorine wherein X is a chlorine or/bromfpnrc atom in m- or p-position comprising the steps of reacting a cyanacetic acid alkyl ester of formula III ΓΓ - CH2 - GOOAlk (ill) wherein Alk has the same meanings as above, with a halophen azide of formula IV wherein X has the same meanings as above, and if the product is a halophenyl™5~amino-l , »3-triazole-4-carboxylic acid alkyl ester, in which E1 is a hydrogen atom, then, if desired, subjecting this ester to a Dimroth rearrangement. *

4. » A process as claimed in claim 3, in which the reaction between the compounds of formulas ΓΙΧ and IV is carried out in an alcoholic medium at a temperature between -10°C and +40 °C.

5. 5. A process as claimed in claim 3, in which the Dimroth rearrangement is carried out while boiling in a medium containing pyridine.

6. A process as claimed in claim 3» substantially as herein described, with reference to the Examples. ιο

7. Compounds as claimed in claim 1, whenever prepared by a process as claimed in any of claims 3 to 6.

8. Pharmaceutical compositions comprising as active ingredient at least one compound of formula I, in admixture with suitable solid or liquid pharmaceutical carriers and/or 15 excipients .

9. Pharmaceu ical compositions as claimed in claim 8 , in the form of tablets, pills, coated pills, suppositories, capsules, solutions, emulsions, suspensions or injectable preparations. 20

10. Pharmaceutical compositions as claimed in claim 8 or 9, comprising in addition to the compound of formula I at least one further therapeutically active compound.

11. A process for preparing pharmaceutical compositions as claimed in any of claims 8 to 10, comprising admixing one or more compound of formula I and optionally therapeutically active compounds with suitable solid or liquid organic or inorganic pharmaceutical carriers and/or excipients. a

12. Pharmaceutical compositions whenever prepared by y process as claimed in claim 11. nts