Aromatic derivatives substituted by a ribose, their preparation process and their use as medicaments

A subject of the invention is the compounds of formula (I): ##STR1## having antibiotic properties.

The present invention relates to new aromatic derivatives substituted by a 
ribose, their preparation process and their use as medicaments. 
A subject of the invention is the compounds of formula (I): 
##STR2## 
in which: R.sub.1 represents a hydrogen or halogen atom, 
R.sub.2 represents a hydrogen atom or an alkyl radical containing up to 4 
carbon atoms, 
R.sub.3 represents an alkyl radical containing up to 4 carbon atoms, or a 
halogen atom, 
R.sub.4 represents a hydrogen atom, a halogen atom, a linear, branched or 
cyclic alkyl, alkenyl or alkynyl radical containing up to 12 carbon atoms, 
R.sub.5 represents a hydrogen atom, an OH or O-alkyl radical, containing up 
to 12 carbon atoms, 
R.sub.a and R.sub.b identical or different represent a hydrogen atom, an 
alkyl radical containing up to 4 carbon atoms, either R.sub.a and R.sub.b 
form with the nitrogen atom to which they are linked a mono- or polycyclic 
heterocycle, optionally containing another heteroatom chosen from 
nitrogen, sulphur or oxygen, or R.sub.a and/or R.sub.b represent a 
radical: 
##STR3## 
in which n is an integer varying from 0 to 6, alk.sub.1 and alk.sub.2 
representing an alkyl radical containing up to 8 carbon atoms and their 
salts in all their possible stereoisomer forms as well as their mixtures. 
As examples of salts there can also be mentioned the salts formed with the 
following acids: acetic, propionic, trifluoroacetic, maleic, tartaric, 
methanesulphonic, benzenesulphonic, p-toluenesulphonic, hydrochloric, 
hydrobromic, hydroiodic, sulphuric, phosphoric and especially stearic, 
ethylsuccinic or laurylsulphonic acids. 
In the definition of the substituents: 
the alkyl, alkenyl or alkynyl radical is preferably a methyl, ethyl, 
propyl, isopropyl, n-butyl, isobutyl, terbutyl, decyl or dodecyl, vinyl, 
allyl, ethynyl, propynyl, cyclobutyl, cyclopentyl or cyclohexyl radical, 
the halogen is preferably fluorine or chlorine, or bromine, 
the aryl radical is preferably the phenyl radical, 
the heterocyclic radical is preferably the pyrrolyl, pyrrolidinyl, pyridyl, 
pyrazinyl, pyrimidyl, piperidinyl, piperazinyl, quinuclidinyl, oxazolyl, 
isoxazolyl, morpholinyl, indolyl, imidazolyl, benzimidazolyl, triazolyl, 
thiazolyl, azetidinyl, aziridinyl radical. 
Among the preferred compounds of the invention, there can be quite 
particularly mentioned the compounds of formula (I) in which R.sub.1 
represents a hydrogen or fluorine atom, those in which R.sub.2 represents 
a methyl radical or a hydrogen atom, those in which R.sub.3 represents a 
methyl radical, a hydrogen or chlorine atom, those in which R.sub.4 
represents a hydrogen or chlorine atom, those in which R.sub.5 represents 
a hydrogen atom, those in which R.sub.a and R.sub.b represent an alkyl 
radical containing up to 4 carbon atoms, and in particular a methyl 
radical, those in which R.sub.a and R.sub.b form with the nitrogen atom to 
which they are linked a heterocyclic radical optionally containing another 
heteroatom, and which can be optionally substituted, and in particular 
those in which R.sub.a and R.sub.b form together a 
##STR4## 
radical in which X represents an oxygen atom or an NH, or NCH.sub.3 
radical, the heterocyclic radical thus formed can be optionally 
substituted. 
A more particular subject of the invention is the compounds the preparation 
of which is given hereafter in the experimental part and quite especially 
the compounds of Example 1 and 2. 
The products of general formula (I) have a very good antibiotic activity on 
gram.sup.3/4 bacteria such as staphylococci, streptococci, pneumococci 
enterococci, listeria, anaerobes. 
The compounds of the invention can therefore be used as medicaments in the 
treatment of infections caused by susceptible germs and in particular, in 
that of staphylococcia, such as staphylococcal septicemias, malignant 
staphylococcia of the face or skin, pyodermatitis, septic or suppurating 
wounds, boils, anthrax, phlegmons, erysipelas and acne, staphylococcia 
such as acute primary or post-influenzal angina, bronchopneumonia, 
pulmonary suppuration, streptococcia such as acute angina, otitis, 
sinusitis, scarlet fever, pneumococcia such as pneumonia, bronchitis and 
diphtheria. The products of the present invention are also active against 
infections caused by germs such as Haemophilus influenzae. 
Therefore a subject of the invention is the compounds of formula (I) as 
medicaments. 
A more particular subject of the invention is as medicaments the compounds 
indicated above as preferred compounds. 
A subject of the invention is also the pharmaceutical compositions 
containing at least one of the medicaments defined above as active 
ingredient. 
These compositions can be administered by buccal, rectal, parenteral route 
or by local route as a topical application on the skin and mucous 
membranes, but the preferred administration route is the buccal or 
injectable route. 
They can be solid or liquid and be presented in the pharmaceutical forms 
commonly used in human medicine, such as for example, plain or 
sugar-coated tablets, capsules, granules, suppositories, injectable 
preparations, ointments, creams, gels; they are prepared according to the 
usual methods. The active ingredient or ingredients can be incorporated 
with excipients usually employed in these pharmaceutical compositions, 
such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa 
butter, aqueous or non-aqueous vehicles, fatty substances of animal or 
vegetable origin, paraffin derivatives, glycols, various wetting, 
dispersing or emulsifying agents, preservatives. 
These compositions can also be presented in the form of a powder intended 
to be dissolved extemporaneously in an appropriate vehicle, for example 
apyrogenic sterile water. 
The dose administered is variable accoring to the illness treated, the 
patient in question, the administration route and the product considered. 
It can be, for example, comprised between 50 mg and 3000 mg per day by 
oral or injectable route, in an adult for the preferred products. 
A subject of the invention is also a process characterized in that a 
compound of formula (II): 
##STR5## 
in which R.sub.3, R.sub.4, R.sub.5, R.sub.a and R.sub.b retain their 
previous meaning, is subjected to the action of a compound of formula 
(III): 
##STR6## 
in which R.sub.2 retains its previous meaning and R.sub.7 represents a 
radical 
##STR7## 
in which R.sub.1 retains its previous meaning, in order to obtain the 
corresponding compound of formula (I) which is modified if desired. 
A subject of the invention is also a variant of the process characterized 
in that a compound of formula (IV): 
##STR8## 
in which R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 retain their 
previous meaning and R represents a parting group is subjected to the 
action of an amine 
##STR9## 
in which R.sub.a and R.sub.b retain their previous meaning in order to 
obtain the corresponding compound of formula (I) which is modified if 
desired. 
The compounds of formulae (II) and (IV) are new products, their preparation 
is given hereafter in the experimental part, and are themselves a subject 
of the present invention. 
The compounds of formula (II) can be prepared according to the process 
described in the experimental part, for example according to the following 
operating method: 
##STR10## 
As parting groups R there can be mentioned the remainder of a tosylate, a 
mesylate, a triflate. 
The compounds of formula (IV) can be prepared according to the processes 
described in the experimental part: 
##STR11## 
In the above R has the same value as the preceding parting groups.

EXAMPLE 1 
(4-(dimethylamino)-8-methyl-2-oxo-2H-1-benzopyran-7-yl) 
6-deoxy-5-C-methyl-4-O-methyl-3-O-(5-methyl-1H-pyrrol-2-yl) carbonyl) 
alpha-L-lyxo-hexopyranoside 
5.3 ml of a 0.1 N solution of cobalt chloride in acetonitrile is introduced 
at 100.degree. C. into a solution containing 210 mg of 
7-(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl) 
oxy-4-(dimethylamino)-8-methyl-2H-1-benzopyran-2-one and 124 mg pyrrolic 
anhydride. Agitation is carried out at 100.degree. C. for 15 minutes, the 
reaction medium is left to cool down and concentrated under reduced 
pressure. A product is obtained which is purified by chromatography on 
silica eluting with a methylene chloride-acetone mixture (80-20). 56.2 mg 
of sought product is obtained. rf=0.25, M.p.&gt;300.degree. C. 
Preparation 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl) 
oxy]-4-(dimethylamino)-8-methyl-2H-1-benzopyran-2-one 
Stage A 
7-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-4-hydroxy-8-methyl-2H-1-benzopyra 
n-2-one 
85 ml of triethylamine is agitated in a suspension containing 50 g of 
4,7-dihydroxy-8-methyl-2H-1-benzopyran-2-one and 400 ml of 
tetrahydrofuran. A solution of 76 ml of terbutyldiphenylchlorosilane in 50 
ml of tetrahydrofuran is added. The reaction mixture is agitated for 20 
hours, then it is poured into a buffer solution of sodium hydrogen 
phosphate. Extraction is carried out with ethyl acetate, the organic phase 
is washed with water, dried and brought to dryness. A product is obtained 
which is taken up in methanol, agitation is carried out for 4 hours, 
followed by separating, washing and drying. 84,5 g of sought product is 
obtained. 
Stage B 
7-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-8-methyl-4-[[(trifluoromethyl)sul 
phonyl]oxy]-2H-1-benzopyran-2-one 
7.3 ml of triethylamine is introduced at 0.degree. C. into a suspension of 
15 g of the product of Stage A in 150 ml of methylene chloride. A solution 
of 7.1 ml trifluoromethyl sulphonic anhydride and 7 ml of methylene 
chloride are added. The reaction mixture is maintained under agitation for 
30 minutes at 0.degree. C., then for 1 hour at ambient temperature. The 
reaction medium is poured into 150 ml of a 1M solution of sodium acid 
phosphate, followed by extraction with methylene chloride, washing, drying 
and concentrating under reduced pressure. A product is obatined which is 
chromatographed on silica eluting with a hexane-ethyl acetate mixture 
(8-2). In this way 17.1 g of sought product is obtained. rf=0.49. 
Stage C 
4-(dimethylamino)-7-hydroxy-8-methyl-2H-1-benzopyran-2-one 
11.3 ml of a 0.6 M solution of dimethylamine in THF is introduced into a 
solution of 1.05 g of the product prepared in Stage B and 10 ml of THF. 
The reaction medium is maintained under agitation overnight. Nitrogen is 
bubbled through, the reaction is cooled down using an ice bath then 1.9 ml 
of n-tetrabutylammonium fluoride (1.1 M solution in THF) is poured in. 
Agitation is carried out for 15 minutes at OEC. The reaction medium is 
poured into 20 ml of a 1M solution of sodium acid phosphate. Extraction is 
carried out with methylene chloride. The organic phases are washed, dried 
and concentrated. A product is obtained which is taken up in 
methylethylketone, followed by separating, washing with methylethylketone 
and drying. The filtrate is concentrated, taken up in ethyl acetate, 
separated and dried. 350.4 mg of sought product is obtained. rf=0.18 
methylene chloride/acetone (9-1). 
Stage D 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-4-(dimeth 
ylamino)-8-methyl-2H-1-benzopyran-2-one 
1.2 g of triphenylphosphine and 796 .mu.l of DEAD (diethylazodicarboxylate) 
are introduced into a suspension containing 830 mg of the product of the 
previous stage and 804 mg of 
6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranose and 20 ml of 
methylene chloride. Agitation is carried out for one hour at ambient 
temperature and two additions of 0.6 then 0.4 equivalents of triphenyl 
phosphine and DEAD are carried out at a one hour interval. Concentration 
is carried out followed by chromatography on silica eluting with a 
methylene chloride/acetone mixture (80-20). After treatment with acetone 
the sought product is obtained rf=0.29 (methylene chloride-acetone (6-4)). 
EXAMPLE 2 
(8-methyl-4-(4-methyl-1-piperazinyl)-2-oxo-2H-1-benzopyran-7-yl) 
6-deoxy-5-C-methyl-4-O-methyl-3-O-(5-methyl-1H-pyrrol-2-yl)carbonyl)alpha- 
L-lyxo-hexopyranoside 
354 mg of triphenylphosphine and 224 .mu.l of DEAD are introduced into a 
dispersion containing 500 mg of 
7-hydroxy-8-methyl-4-(4-methyl-1-piperazinyl)-2H-1-benzopyran-2-one and 
370 mg of 6-deoxy-5-C-methyl-4-O-methyl-L-lyxohexopyranose 
3-(5-methyl-1H-pyrrole-2-carboxylate). After reaction for 2 hours, 354 mg 
of triphenylphosphine and 224 .mu.l of DEAD are added. Agitation is 
carried out for 2 hours and 283 mg of triphenylphosphine and 180 .mu.l of 
DEAD are added. Agitation is carried out for another 2 hours, and 142 mg 
of triphenylphosphine and 90 .mu.l of DEAD are added. Agitation is 
continued for 2 hours, followed by concentration and chromatography on 
silica, eluant MeOH--CH.sub.2 Cl.sub.2 (5-95). rf=0.21. In this way 373 mg 
of sought product is isolated. M.p.=150.degree. C. 
Preparation 
7-hydroxy-8-methyl-4-(4-methyl-1-piperazinyl)-2H-1-benzopyran-2-one 
Stage A 
7-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-8-methyl-4-(4-methyl-1-piperaziny 
l)-2H-1-benzopyran-2-one 
1.25 ml of N-methyl piperazine is added to a solution containing 2.53 g of 
7-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-8-methyl-4-[[(trifluoromethyl)su 
lphony]oxy]-2H-1-benzopyran-2-one and 22 ml of THF. The reaction medium is 
maintained under agitation for 1 hour, poured into a 1M aqueous solution 
of sodium acid phosphate, and extraction is carried out with ethyl 
acetate. The organic phases are combined, washed, dried and concentrated 
under reduced pressure. Chromatography is carried out on silica eluting 
with a methanol-methylene chloride mixture (6-94). 2.31 g of sought 
product is isolated. rf=0.3. 
Stage B 
7-hydroxy-8-methyl-4-(4-methyl-1-piperazinyl)-2H-1-benzopyran-2-one 
5.10 ml of a 1.1 M solution of n-tetrabutyl ammonium fluoride is added at 
0.degree. C. to THF. The reaction medium is maintained under agitation for 
1 hour at 0.degree. C. and 270 .mu.l of acetic acid is added, followed by 
concentrating, chromatography on silica eluting with a methanol-methylene 
chloride mixture 5-95 then 10-90, taking up in methylene chloride, 
separating and 0.88 g of product is isolated. rf=0.26 methanol-methylene 
chloride 10-90. 
EXAMPLE 3 
(4-(4,4-dimethylpiperazinium)-8-methyl-2-oxo-2H-1-benzopyran-7-yl)6-deoxy-5 
-C-methyl-4-O-methyl-3-O-(5-methyl-1H-pyrrol-2-yl)carbonyl)alpha-L-lyxo-hex 
opyranoside iodide 
8.5 .mu.l of iodomethane is added to a dispersion of 50 mg of the product 
of the preceding example in 1 ml of acetonitrile. The reaction mixture 
obtained is maintained under agitation at 60.degree. C., cooled down and 
concentrated under reduced pressure. After taking up in methylene chloride 
and separation, 52 mg of sought product is obtained. M.p.=230.degree. C. 
EXAMPLE 4 
N-(7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl) 
oxy)-8-methyl-2-oxo-2H-1-benzopyran-4-yl-2-(dimethylamino)acetamide5-methy 
l-1H-pyrrole-2-carboxylic-acid 3'-ester 
152 mg of 
2-(dimethylamino)-N-(7-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-4-yl)acetami 
de, 106 mg of triphenylphosphine and 67 .mu.l of DEAD are added to a 
dispersion containing 118 mg of 
6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranose 
5-methyl-1H-pyrrole-2-carboxylic acid ester and 3.5 ml of methylene 
chloride. The reaction medium is maintained under agitation for 2 hours at 
ambient temperature and another 106 mg of triphenylphosphine and 67 .mu.l 
of DEAD are added. After an additional 2 hours of reaction, another 42 mg 
of triphenylphosphine and 27 .mu.l of DEAD are added. Agitation is 
maintained for 2 hours and the product obtained is chromatographed, 
firstly eluting with a methanol-methylene chloride mixture (5-95) then 
with an acetone-methylene chloride mixture (20-80). In this way 72 mg of 
sought product is isolated. M.p.=260.degree. C. 
Preparation 
2-(dimethylamino)-N-(7-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-4-yl)acetamid 
e 
Stage A 
4-amino-7-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]-8-methyl-2-oxo-2H-1-benz 
opyran-4-yl]-acetamide 
783 mg of imidazole then 1.43 ml of tBuPh.sub.2 SiCl is added to a 
dispersion containing 1 g of 
4-amino-7-hydroxy-8-methyl-2H-1-benzopyran-2-one and 25 ml of anhydrous 
DMF. The reaction medium is agitated for 16 hours at ambient temperature, 
poured into an aqueous solution (1M) of sodium acid phosphate and 
extraction is carried out with THF. The aqueous phase is decanted and 
extraction is carried out with ethyl acetate. The organic phases are 
combined, washed with water, dried and concentrated under reduced 
pressure. The product obtained is chromatographed on silica eluting with a 
methanol-methylene chloride mixture (5-95). The product obtained is taken 
up in ether and separated. 1.01 g of sought product is obtained. rf=0.33, 
methanol-methylene chloride (5-95). 
Stage B 
2-chloro-N-[7-[[(1,1-dimethylethyl)diphenylsilyl] 
oxy]-8-methyl-2-oxo-2H-1-benzopyran-4-yl]-acetamide 
752 .mu.l of TEA and 430 .mu.l of chloroacetyl chloride is added at 
0.degree. C. to a solution containing 885 mg of the product of the 
preceding stage and 18 ml of THF. Agitation is carried out for 38 hours 
and the reaction medium is poured into an aqueous solution of sodium acid 
phosphate (1M) and extraction is carried out twice with ethyl acetate. The 
organic phases are combined, washed, dried and concentrated under reduced 
pressure. The product obtained is chromatographed on silica eluting with 
an ethyl acetate-methylene chloride mixture (2-98). In this way 453 mg of 
sought product is isolated. 
Stage C 
2-(dimethylamino)-N-(7-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-4-yl)acetamid 
e 
A few drops of dimethylamine are added at 0.degree. C. to a solution 
containing 351 mg of the product of the preceding stage and 7 ml of THF. 
The reaction medium is maintained under agitation for 2 hours at ambient 
temperature and concentrated under reduced pressure. The residue obtained 
is impatsed in acetone and separation is carried out, followed by washing 
with methylene chloride, then with pentane. After drying, 110 mg of 
product is isolated. The filtrate is chromatographed on silica eluting 
with a methanol-methylene chloride mixture (5-95). In this way an 
additional 32 mg of sought product is isolated rf=0.27. 
EXAMPLE 5 
7-(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-8-methyl-4 
-(4-morpholinyl)-2H-1-benzopyran-2-one 5-methyl-1H-pyrrole-2-carboxylic 
acid -3'-ester 
By operating as previously starting from 387 mg of 
7-hydroxy-8-methyl-4-(4-morpholinyl)-2H-1-benzopyran-2-one and 487 mg of 
6-deoxy-5-C-methyl-4-O-methyl-L-lyxohexo-pyranose 
3-(5-methyl-1H-pyrrole-2-carboxylate), 115.4 mg of sought product is 
obtained. M.p.&gt;260.degree. C. 
EXAMPLE 6 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-4-dimethy 
lamino)-8-methyl-2H-1-benzopyran-2-one 
4-fluoro-5-methyl-1H-pyrrole-2-carboxylic-acid 3'-ester 
213 mg of 4-fluoro-5-methyl-1H-pyrrole-2-carboxylic acid then 182 mg of 
DMAP, then 233 .mu.l of DIC are added to a dispersion containing 585 mg of 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-4-(dimet 
hylamino)-8-methyl-2H-1-benzopyran-2-one and 15 ml of methylene chloride. 
Agitation is carried out for 14 hours at ambient temperature and 222 .mu.l 
of DBU is added. Agitation is caried out for 2 hours at ambient 
temperature then the product obtained is chromatographed eluting with a 
methanol-methylene chloride mixture (5-95). The product obtained is taken 
up in acetone and separated. The product obtained is taken up in methanol 
and separated. 77 mg of sought product is isolated. M.p.&gt;260.degree. C. 
EXAMPLE 7 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-4-(2-dime 
thylamino)ethylmethylamino)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
The product was prepared by operating as previously, rf=0.15, CH.sub.2 
Cl.sub.2 --MeOH--NH.sub.3 (92-8-0.5). 
EXAMPLE 8 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-8-methyl- 
4-(1-piperazinyl)-2H-1-benzopyran-2-one 5-methyl-1H-pyrrole-2-carboxylic 
acid-3'-ester M.p.=190.apprxeq.200.degree. C. 
EXAMPLE 9 
8-methyl-4-(4-methyl-1-piperazinyl)-2-oxo-2H-1-(3-chlorobenzo pyran)-7-yl 
6-deoxy 
5-methyl-4-O-methyl-3-O-((5-methyl-1H-pyrrol-2-yl)carbonyl)-alpha-L-lyxo-h 
exopyranoside. 
By operating as previously starting from 
3-chloro-7-hydroxy-8-methyl-4-(4-methyl-1-piperazinyl)-2H-1-benzopyran-2-o 
ne, the sought product is obtained. M.p.=145.degree. C. 
EXAMPLE 10 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-4-(4-ethy 
l-1-piperazinyl)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
374 mg of 7-hydroxy 
8-methyl-4-(4-ethyl-1-piperazinyl)2H-1-benzopyran-2-one, 424 mg of 
6-deoxy-5-C-methyl-4-O-methyl-L-lyxohexopyranose 
3-(5-methyl-1H-pyrrole-2-carboxylate) and 408 mg of triphenylphosphine are 
suspended in 12 ml of methylene chloride. 275 .mu.l of DEAD is added. 
Agitation is carried out for 2 hours at ambient temperature and 408 mg of 
triphenyl-phosphine and 275 .mu.l of DEAD are added. Agitation is carried 
out for 1 hour 45 minutes and 170 mg of triphenylphosphine and 113 .mu.l 
of DEAD are added. The product obtained is chromatographed eluting with a 
methylene chloride-isopropanol mixture (9-1). The product is poured into 
30 ml of a molar solution of sodium dihydrogen phosphate and extraction is 
carried out with methylene chloride, followed by washing with a saturated 
solution of sodium chloride. The organic phases are combined and dried 
over magnesium sulphate. 2.61 g of product is isolated which is 
chromatographed on silica eluting with a methylene chloride-methanol 
mixture (90-10). The fraction with rf=0.10 is isolated, 350 mg of product 
is obtained which is impasted in acetonitrile, the product obtained is 
separated, the filtrate is brought to dryness, followed by taking up with 
acetonitrile, separating and combining with the first fraction obtained. 
In this way 170 mg of sought product is isolated. 
M.p.=246.apprxeq.248.degree. C. 
EXAMPLE 11 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-8-methyl- 
4-(4-(2-pyrimidyl)-1-piperazinyl)-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
By operating as previously starting with 
7-hydroxy-8-methyl-4-[4-(2-pyrimidinyl)-1-piperazinyl]-2H-1-benzopyran-2-o 
ne, the sought product was obtained. rf=0.25, methylene 
chloride-isopropanol (97-3). 
By operating as previously, the following products were obtained: 
EXAMPLE 12 
(4-(dimethylamino)-8-methyl-2-oxo-2H-1-benzopyran-7-yl 
6-deoxy-4-O-methyl-3-O-((5-methyl-1H-pyrrol-2-yl)carbonyl)-alpha-L-mannopy 
ranoside M.p.=225.degree. C. 
EXAMPLE 13 
(8-methyl-4-(4-morpholinyl)-2-oxo-2H-1-benzopyran-7-yl 
6-deoxy-4-O-methyl-3-O-((5-methyl-1H-pyrrol-2-yl)carbonyl)-alpha-L-mannopy 
ranoside M.p.=190.degree. C. 
EXAMPLE 14 
(8-methyl-4-(4-methyl-1-piperazinyl)-2-oxo-2H-1-benzopyran-7-yl 
6-deoxy-4-O-methyl-3-O-((5-methyl-1H-pyrrol-2-yl)carbonyl)-alpha-L-mannopy 
ranoside 
rf=0.31 acetone-ethyl acetate-water (5-4-1). 
EXAMPLE 15 
4,4-dimethyl-piperazinium-1-yl)-8-methyl-2-oxo-2H-1-benzopyran-7-yl 
6-deoxy-4-O-methyl-3-O-((5-methyl-1H-pyrrol-2-yl)carbonyl)-alpha-L-mannopy 
ranoside iodide 
By subjecting the product of the previous example to the action of methyl 
iodide, the sought product was obtained. rf=0 acetone-ethyl acetate-water 
(5-4-1). 
EXAMPLE 16 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-8-methyl- 
4-(3-methyl-1-piperazinyl)-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
By operating as previously, the sought product was obtained. 
M.p.=205.degree. C. 
EXAMPLE 17 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-8-methyl- 
4-(4-(2-piridinyl)-1-piperazinyl)-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
By operating as previously, the sought product was obtained. 
M.p.=228.apprxeq.230.degree. C. 
EXAMPLE 18 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-4-(4-dime 
tylamino)-1-piperidinyl)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
0.8 mmole of 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl 
-4-[[(4-methylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester is added at ambient 
temperature to a solution containing 2 mmole of 
4-dimethylamino-1-piperidine, in 2.5 ml of THF. Agitation is carried out 
for 2 hours. The reaction medium is poured into a saturated solution of 
sodium acid phosphate (1M). Extraction is carried out with ethyl acetate, 
followed by drying, concentrating and 87 mg of product is obtained to 
which 2 ml of acetonitrile is added; a product is obtained which is 
separated and dried. In this way 58 mg of product is obtained. 
M.p.=190.degree. C. 
Preparation 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl- 
4-[[(4-methylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
Stage A 
7-(hydroxy-8-methyl-4-[[(4-methylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-on 
e 
3.5 g of tosyl chloride is added at 0.degree. C., to a solution containing 
3.50 g of 4,7-dihydroxy 8-methyl-2H-1-benzopyran-2-one and 25 ml of 
pyridine. Agitation is carried out for 2 hours at 0.degree. C., the 
reaction medium is poured into a 1.2N aqueous solution of hydrochloric 
acid. Extraction is carried out with ethyl acetate, the organic phases are 
combined, dried and concentrated under reduced pressure. The product 
obtained is chromatographed on silica eluting with an acetone-methylene 
chloride mixture 5-95 and 3.88 g of a product is isolated which is 
impasted in ether and separated. The sought product is obtained. 
M.p.=206.degree. C. 
Stage B 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl- 
4-[[(4-methylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
1.4 g of triphenylphosphine and 886 .mu.l of DEAD are added to a solution 
of 1.87 g of the product of the preceding stage, 2 g of 
6-deoxy-5-C-methyl-4-O-methyl-L-lyxo-hexopyranose 
3,3-(5-methyl)-1H-pyrrole-2-carboxylate) and 50ml of methylene chloride. 
Agitation is carried out at ambient temperature for 1 hour, 0.5 
equivalents of triphenylphosphine and DEAD are added, agitation is carried 
out for 45 minutes, another 0.25 equivalents of triphenylphosphine and 
DEAD are added. Agitation is carried out for 30 minutes, followed by 
concentrating. After filtering, the product obtained is chromatographed on 
silica eluting with a methylene chloride-acetate mixture (95-5). 1.43 g of 
sought product is obtained. rf=0.25. 
EXAMPLE 19 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexanopyranosyl)oxy)-4-(4-hy 
droxy-1-piperidinyl)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
101.15 mg of 4-hydroxy 1-piperidine is added to a solution containing 216 
mg of 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl 
-4-[[(4-methylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester and 5 ml of THF. Agitation 
is carried out for 1 hour. A 1M solution of sodium acid phosphate. 
Extraction is carried out with ethyl acetate followed by drying and 
concentrating. A product is obtained which is chromatographed on silica 
eluting with a methylene chloride-acetone mixture (6-4). After 
concentrating, 53 mg of sought product is obtained. M.p.=230.degree. C. 
EXAMPLE 20 
(S) 
7-((6-deoxy-5-C-methyl-4-O-methylalpha-L-lyxo-hexopyranosyl)oxy)-4-[2-(hyd 
roxymethyl)-1-pyrrolidinyl]-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
240 .mu.l of 2-pyrrolidine methanol is introduced into a solution of 607 mg 
of 
7-((6-deoxy-5-C-methyl-4-O-methylalpha-L-lyxo-hexopyranosyl)oxy)-4-[[(4-me 
thylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester and 5 ml of THF. Agitation 
is carried out at ambient temperature for 30 minutes. The reaction medium 
is poured into 15 ml of a 1M solution of NaH.sub.2 PO.sub.4, followed by 
extraction with ethyl acetate, drying and concentrating. A product is 
obtained which is chromatographed on silica eluting with a methylene 
chloride-acetone mixture (7-3). After concentrating, 173 mg of product is 
obtained which is taken up in acetonitrile. After separating and drying, 
110 mg of sought product is obtained. M.p.&gt;240.degree. C. 
EXAMPLE 21 
7-((6-deoxy-5-C-methyl-4-O-methylalpha-L-lyxo-hexopyranosyl)oxy)-4-(2-hydro 
xymethyl)-4-morpholinyl]-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
By operating as previously starting with 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl 
-4-[[(4-(methylphenyl)-sulphonyl]oxy]-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester and 
2-(hydroxymethyl)-4-morpholine, the sought product is obtained. 
M.p.=260.degree. C. 
EXAMPLE 22 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-8-methyl- 
4-(methylamino)-2H-1-benzopyran-2-one 5-methyl-1H-pyrrole-2-carboxylic 
acid-3'-ester 
By operating as previously starting with 500 mg of 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl 
-4-[[(4-methylphenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester and methylamine, the sought 
product was obtained. rf=0.27 methylene chloride-isopropanol (9-1). 
EXAMPLE 23 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-4-(2-((di 
methylamino)methyl)-4-morpholinyl]-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
By operating as previously starting with 
2-(dimethylamino)methyl-4-morpholine and 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-8-methyl 
-4-[[(4-methyl phenyl)sulphonyl]oxy]-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester, the sought product was 
obtained. rf=0.18 methylene chloride-ethanol (8-2). 
By operating as previously the following products were obtained: 
EXAMPLE 24 
7-((6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy)-4-(3,5-di 
methyl-1-piperidinyl)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
M.p.=260.apprxeq.262.degree. C. 
EXAMPLE 25 
7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-4-(4-(2-h 
ydroxyethyl)1-piperazinyl)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester 
M.p.=230.apprxeq.232.degree. C. 
EXAMPLE 26 
(trans)7-[(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lyxo-hexopyranosyl)oxy]-4- 
(2,5-dimethyl-1-piperazinyl)-8-methyl-2H-1-benzopyran-2-one 
5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester (mixture of 
diastereoisomers) rf=0.1 methylene chloride-ethanol (90-10). 
Examples of Pharmaceutical Compositions 
Tablets were prepared containing: 
______________________________________ 
Product of Example 1 150 mg 
Excipient q.s.f. 1 g 
______________________________________ 
Detail of excipient: starch, talc, magnesium stearate 
______________________________________ 
Product of Example 2 150 mg 
Excipient q.s.f. 1 g 
______________________________________ 
Detail of excipient: starch, talc, magnesium stearate. 
Injectable solutions were also prepared from the salts. 
Pharmacological Study of the Products of the Invention 
A--Method of dilutions in liquid medium 
A series of tubes are prepared in which the same quantity of sterile 
nutritive medium is distributed. Increasing quantities of the product to 
be studied are distributed into each tube, then each tube is sown with a 
bacterial strain. After incubation for 24 hours in a heating chamber at 
37.degree. C., the growth inhibition is evaluated by transillumination, 
which allows the minimal inhibitory concentrations (M.I.C.) to be 
determined, expressed in micrograms/cm.sup.3. 
On the following strains: 
______________________________________ 
S. aureus 011HT3 
S. aureus 011UC4 
S. aureus 011HT28 
S. epidermidis 012GO20 
S. aureus 011CB20 
S. aureus 011HT26 
S. epidermidis 012GO39 
S. epidermidis 012HI1 
S. pyogenes 02A1UC1 
______________________________________ 
The following resultats were obtained: 
EQU 0.04&lt;MIC&lt;5 
B--Inhibition of gyrase B 
The products are inhibitors of gyrase B; the dose at 50% DNA supercoiling 
is less than 5:g/ml.