BE896592A - NOVEL CONDENSED CYCLOALIPHATIC DERIVATIVES OF PYRIDO [1,2-a] PYRIMIDINES SUBSTITUTED - Google Patents

Description

       

  New cycloaliphatic derivatives

  
  <EMI ID = 1.1>

  
The present invention relates to new derivatives

  
  <EMI ID = 2.1>

  
useful especially as antiallergic, anti-inflammatory drugs and in the prevention or treatment of gastrointestinal ulcers and a process for their preparation.

  
The new compounds of the invention correspond to the general formula (I)

  

  <EMI ID = 3.1>


  
n are t 1 or 2;

  
  <EMI ID = 4.1>

  
dense to the pyrido cycle;

  
R is a) a furyl, thienyl or pyridyl radical; or b) a radical of formula
  <EMI ID = 5.1>
 or

  
  <EMI ID = 6.1>
  <EMI ID = 7.1>
  <EMI ID = 8.1>

  
  <EMI ID = 9.1>

  
The invention also includes all possible isomers, for example stereoisomers and optical isomers and their mixtures and metabolites and metabolic precursors of the compounds of formula (I).

  
The numbering used to identify the positions in the compounds of formula (I) is conventional, as illustrated in the following examples:
A) when n = 1
  <EMI ID = 10.1>
  <EMI ID = 11.1>

  
It follows from the above definition of the meanings of the symbol A that, whatever the meanings of

  
  <EMI ID = 12.1>

  
bond between the carbon atoms 7 and 8 of the compounds where n is 1 or between the carbon atoms 8 and 9 of the compounds where n is 2,

  
  <EMI ID = 13.1>

  
The alkyl, alkoxy, alkanoyl and alkanoyloxy radicals can be branched or straight.

  
  <EMI ID = 14.1>

  
if killed, it is preferably a methyl, ethyl, isopropyl, hexyl or n-butyl radical.

  
  <EMI ID = 15.1>

  
is a halogen atom, it is preferably a chlorine or bromine atom.

  
  <EMI ID = 16.1>

  
is a halogen atom, it is preferably a fluorine or chlorine atom.

  
  <EMI ID = 17.1>

  
The preferred alkanoyloxy radicals are acetoxy and propionyloxy.

  
The preferred alkanoyl radicals are the acetyl and propionyl radicals.

  
The preferred compounds of the invention are the

  
  <EMI ID = 18.1>

  
carbonyl unsubstituted or substituted by a 2-N, N-di-alkyl- radical
(C.-C-) amino; R2 is a hydrogen atom; R3 is a hydrogen or chlorine atom or a methyl or methoxy radical; R4 is a hydrogen atom; A forms a bond thus creating a double bond, or, when R1 is a free carboxy radical, A can represent equally

  
  <EMI ID = 19.1>

  
dense to the pyrido cycle; n. is 1 or 2; R is a) a furyl, thienyl or pyridyl radical; or b) a radical of formula
  <EMI ID = 20.1>
 or

  
  <EMI ID = 21.1>

  
together form a methylenedioxy radical; and their pharmaceutically acceptable salts.

  
Examples of pharmaceutically acceptable salts are those formed with mineral bases such as sodium, potassium, calcium and aluminum hydroxides or with organic bases such as lysine, triethylamine, triethanol
-amine, dibenzylamine, lamethylbenzylamine, di- (2-ethylhexyl &#65533;

  
  <EMI ID = 22.1>
-amine, N-ethylmorpholine, 2-phenethylamine, N-benzyl--phenethylamine, N-benzyl-N, N-dimethylamine and other acceptable amines as well as the salts formed with mineral acids, for example for example hydrochloric, hydrobromic, nitric and sulfuric acids or with organic acids, for example citric, tartaric, maleic, malic, fumaric, methanesulfonic and ethanesulfonic acids. The preferred salts are the sodium and potassium salts as well as the hydrochlorides of the basic esters, for example diethylaminoethyl and dimethylaminoethyl esters.

  
Examples of particularly preferred compounds of the invention are:

  
  <EMI ID = 23.1>

  
[1,2-a] pyrimidine-7-carboxylic acid,

  
3- (2-methyl-benzylidene) -1,2,3,10-tetrahydro-10-oxo-cyclopenta [d] pyrido [l, 2-a] pyrimidine-7-carboxylic acid,

  
3- (2,5-dimethoxy-benzylidene acid) -1,2,3,10-tetrahydro-10-oxocyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylic acid 3- (2,3 -dimethoxy-benzylidene) -1,2,3,10-tetrahydro-10-oxocyclopenta [d] pyrido [l, 2-a] pyrimidine-7-carboxylic,

  
  <EMI ID = 24.1>

  
oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylic,

  
3- (3-methyl-benzylidene) -1,2,3,10-tetrahydro-10-oxo-cyclo- acid

  
  <EMI ID = 25.1>

  
3- (2-methoxy-benzylidene) -1,2,3,10-tetrahydro-10-oxo-cyclopenta [d] pyrido [l, 2-a] pyrimidine-7-carboxylic acid,

  
  <EMI ID = 26.1>

  
quinzoline-8-carboxylic,

  
4- (2-methyl-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido- acid

  
  <EMI ID = 27.1>

  
[2, l-b] quinazoline-8-carboxylic,

  
4- (2-methoxy-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H- acid

  
  <EMI ID = 28.1> <EMI ID = 29.1>

  
pyrido [2,1-b] quinazoline-8-carboxylic,

  
4- (4-ethoxy-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H- acid

  
  <EMI ID = 30.1>

  
4- (4-fluoro-benzylidene) -1,2,3,4,4-tetrahydro-ll-oxo-llHpyrido [2, l-b] quinazoline-8-carboxylic acid,

  
  <EMI ID = 31.1> <EMI ID = 32.1>

  
and their pharmaceutically acceptable salts, in particular sodium salts and hydrochlorides, basic esters (for example those formed with 2-diethylaminoethanol) and alkyl esters thereof.

  
  <EMI ID = 33.1>

  
liques, n-butyl and hexyl.

  
The compounds of the invention can be prepared according to a process which comprises:
a) the reaction of a compound of formula (II)
  <EMI ID = 34.1>
  <EMI ID = 35.1>

  
laying, with an aldehyde of formula (III)

R-CHO (III)

  
or

  
R is as defined above, to obtain compounds of formula (I) where A is a bond; or b) cyclopropylation of a compound of formula (IV)
  <EMI ID = 36.1>
 or

  
  <EMI ID = 37.1>

  
and / or, if desired, the conversion of a compound of formula (I)

  
into another compound of formula (I) and / or, if desired, the conversion of a compound of formula (I) into a pharmaceutically acceptable salt and / or, if desired the conversion of a salt into a free compound and / or, if desired, the separation of a mixture of isomers into the isolated isomers.

  
The preferred salts of a compound of formula (II) are for example those formed with mineral bases such as the sodium, potassium and calcium salts as well as the salts formed with mineral acids such as hydrochloric, hydrobromic and sulfuric.

  
The reaction of a compound of formula (II) is preferably carried out with an aldehyde of formula (III) in the presence of basic condensing agents such as sodium ethylate, sodium methylate, sodium hydride, sodium aids or potassium tert-butoxide in a solvent such as methanol, ethanol, <EMI ID = 38.1> preferably taken between around 0 [deg.] C and around 120 [deg.] C.

  
The preferred salts of a compound of formula (IV) are, for example, those formed with mineral bases, such as the sodium, potassium and calcium salts.

  
The cyclopropylation of a compound of formula (IV) can be carried out for example by reaction with dimethylsulfoxonium methylide (prepared for example according to the method described in J. Chem. Soc., 1967, 2495) by operating in an inert organic solvent such as dimethylformamide, dimethylacetamide,

  
  <EMI ID = 39.1>

  
tion is generally less than 5 hours, preferably less than 2 hours. Preferably 1 to 3 moles are used, in particular 1

  
1.5 moles of the reacting compound per mole of the compound of formula (IV).

  
A compound of formula (I) can be transformed as indicated above, into another compound of formula (I) according to known methods; for example we can transform the compound of formula

  
  <EMI ID = 40.1>

  
mule (I) where R is a carboxy radical by hydrolysis, for example basic hydrolysis, using for example sodium or potassium hydroxide in a solvent such as water or a lower aliphatic alcohol and operating at a temperature included between room temperature and 150 [deg.] C; the same reaction can for example also be carried out by treatment with lithium bromide in the

  
  <EMI ID = 41.1>

  
with hydrochloric, hydrobromic, hydroiodic or sulfuric acid in acetic acid at a temperature above 50 [deg.] C.

  
  <EMI ID = 42.1>
-COOH can be transformed into a compound of formula (I) where R. is a radical -CONH-, for example by reaction of the compound of formula (I) <EMI ID = 43.1>

  
presence of triethylamine in a solvent such as benzene, toluene, dioxane, tetrahydrofuran or dichloroethane to

  
  <EMI ID = 44.1>

  
corresponding mixed which is reacted in turn with gaseous ammonia in the same solvents at a temperature between

  
  <EMI ID = 45.1>

  
-CN radical, by dehydration of the amide, for example with p-toluenesulfonyl chloride in pyridine and dimethylformamide at a temperature between ordinary temperature and about 100 [deg.] C,

  
  <EMI ID = 46.1>

  
is a carboxy radical in a compound of formula (I) where R, is an esterified carboxy radical, for example an alkoxycarbonyl radical unsubstituted or substituted by a lower dialkylamino radical, according to conventional methods, for example by reaction of an alkaline salt acid with an appropriate alkyl halide in an inert solvent such as acetone, dioxane, dimethylformamide or hexamethylphosphorotriamide at a temperature between

  
  <EMI ID = 47.1>

  
Otherwise, a compound of formula (I) where R1 is a radical

  
  <EMI ID = 48.1>

  
an esterified carboxy radical, as defined above, by reaction with thionyl chloride in a solvent such as dioxane or dichloroethane at reflux temperature to obtain the corresponding chlorocarbonyl derivative which is reacted in turn with an alkanol suitable in a solvent such as benzene, toluene, dioxane, dichloroethane, methylene chloride or chloro-

  
  <EMI ID = 49.1>

  
It is possible, for example, to etherify the free hydroxy radicals substituting a phenyl ring by reaction with an appropriate alkyl halide in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, carbonate of potassium, sodium hydride, sodium amide, sodium methylate or sodium ethylate in a solvent such as methanol ethanol, dioxane, acetone, dimethylformamide, hexamethylphosphorotriamide, tetrahydrofuran or water or their mixtures,

  
  <EMI ID = 50.1>

  
In addition, etherified hydroxy radicals can be transformed into free hydroxy radicals, for example by treatment with pyridine hydrochloride or with a strong acid such as hydrochloric acid, hydrobromic acid or hydroiodic acid or with an acid of Lewis such as aluminum trichloride or boron tribromide.

  
In addition, it is possible, for example, to transform a free hydroxy or amino radical respectively into an alkanoyloxy radical into

  
  <EMI ID = 51.1>

  
known in organic chemistry.

  
A nitro radical substituting the phenyl ring can be transformed into an amino radical by treatment for example with stannous chloride in concentrated hydrochloric acid by using, if necessary, an organic co-solvent such as acetic acid, dioxane or tetrahydrofuran at a temperature between ordinary temperature and about 100 [deg.] C.

  
Also, the optional salification of a compound of formula (I) as well as the conversion of a salt into the free compound and the separation of a mixture of isomers into the isolated isomers can be carried out according to conventional methods.

  
For example, the separation of a mixture of optical isomers into the isolated isomers can be carried out by salification with an optically active base and then fractional crystallization.

  
One can for example prepare the compounds of formula
(II) by reaction of a compound of formula (V)

  

  <EMI ID = 52.1>


  
or

  
  <EMI ID = 53.1>

  
formula (VI)

  

  <EMI ID = 54.1>


  
or

  
  <EMI ID = 55.1>

  
the reaction between a compound of formula (V) and a compound of formula (VI) in the presence of an acidic condensing agent such as polyphosphoric acid (polyphosphoric acid means a

  
  <EMI ID = 56.1>

  
organic solvent such as dimethylformamide, dimethylacetamide, acetic acid, formic acid, benzene, toluene, xylene, or the monomethyl ether of ethylene glycol, but it is preferably carried out in the absence of solvent .

  
One can for example prepare the compounds of formula (IV) by reaction of a compound of formula (VII)

  

  <EMI ID = 57.1>


  
  <EMI ID = 58.1>

  
of formula (III) using the same experimental conditions as those previously defined for the reaction between a compound of formula (II) and an aldehyde of formula (III).

  
One can for example prepare the compounds of formula
(VII) by reaction of a compound of formula (VIII)

  

  <EMI ID = 59.1>


  
  <EMI ID = 60.1>

  
formula (VI) using the same experimental conditions as those previously defined for the reaction between a compound of formula (V) and a compound of formula (VI).

  
The compounds of formula (III), (V), (VI) and (VIII) are known compounds and can be prepared according to conventional methods: in some cases they are marketed products.

  
The compounds of the invention are useful for the prevention and treatment of all diseases in which inflammatory and / or anaphylactic mediators intervene, for example allergic conditions and inflammatory diseases.

  
Therefore the compounds of the invention are useful in the prevention and treatment for example of allergic rhinitis, hay fever, hives, dermatitis and they are in particular effective for the prevention and treatment of asthma allergic.

  
In addition, the compounds of the invention are also useful for the treatment for example of rheumatoid arthritis and osteoarthrosis.

  
The activity of the compounds of the invention is apparent, for example, from the fact that they are active in the following biological tests:

  
in vitro

  
1) SRS production test caused by

  
A 23187 from rat peritoneal cells, according to M.K. Bach and J.R. Brashler (J. Immunol., 113, 2040, 1974);

  
2) test of the production of SRS provoked by an antigen from ground lung of guinea pig, according to W.E. Brocklehurst (J. Physiol., 151, 416, 1960); and

  
in vivo

  
3) IgG-mediated passive peritoneal anaphylaxis test in rats according to H.C. Morse, K.J. Bloch and

  
K.F. Austen (Journal Immunology, 101, 658, 1968); and

  
4) IgE-mediated passive cutaneous anaphylaxis test in rats according to A.M.J.N. Blair (Immunology, 16, 749,
1969).

  
The results of these biological tests show that the compounds of the invention are active for example as inhibitors of the immunological release of mediators, for example histamine, from mast cells, and as inhibitors of the production and / or of the release anaphylactic mediators such as the "slow reacting substance" (SRS) in the peritoneal and pulmonary system, under the effect of a provocation by an ionophore or an antigen.

  
As a preferred example of a compound having antiallergic activity, there may be mentioned:

  
4-benzylidene-1,2,3,4-tetrahydro-ll-oxo-11H-pyrido [2, l-b] quinazoline-8-carboxylic acid (internal code. FCE 21273).

  
Table I below shows for example the in vitro inhibition obtained with compound FCE 21273 from the production of SRS

  
from rat peritoneal cells and guinea pig lungs.

TABLE I

  

  <EMI ID = 61.1>


  
In addition, the compounds of the invention are effective

  
  <EMI ID = 62.1>

  
inverted which is a model of an inflammatory reaction induced by an immune complex initiated by the interaction of an antigen and an antibody causing the formation of an immune complex followed by complement fixation and an accumulation of neutrophilic leukocytes in the focal site (DK Gemmell, J. Cottney and AJ Lewis, Agents and Actions 9/1 page 107, 1979).

  
For example in the above test carried out on the rat, the compound FCE 21273 causes an inhibition of approximately 30%

  
passive Arthus phenomenon reversed when administered orally at a dose of 100 mg / kg.

  
In addition, the compounds of the invention are active

  
on the gastrointestinal system in particular they are endowed with an antiulcerogenic and antisecretory activity and are therefore useful in therapy, for example for the prevention and treatment of peptic, for example duodenal, gastric and esophageal ulcers and for inhibiting the secretion of stomach acid. The antiulcerogenic activity of the compounds of the invention is manifested, for example, by the fact that they are active in the test for inhibition of stress ulcers in rats according to the method of Bonfils et al.

  
  <EMI ID = 63.1>

  
Table II below shows, for example, the approximate DE__ of the antiulcerogenic activity in the rat obtained with one of the compounds of the invention after oral administration.

TABLE II

  

  <EMI ID = 64.1>


  
The test compound was administered per hour one hour before immobilization.

  
Six male Sprague-Dawley rats (100-120 g) have been fasted for 24 hours for the experiment: a piece of fine flexible mesh is used for immobilization and four hours after immobilization, the rats are sacrificed, remove the stomachs and count the lesions with a dissecting microscope.

  
The compounds of the invention also have anti-secretory activity as shown by the fact that after intraduodenal administration, they effectively inhibit the gastric secretion of rats according to the method of H. Shay et al.
(Gastroenter., 1945, 43, 5).

  
One of the preferred compounds of the invention having an antisecretory activity is for example 3- (2-methyl-ben-

  
  <EMI ID = 65.1>

  
pyrimidine-7-carboxylic which has an approximate ED25 of 10 mg / kg in the above test in rats after intraduodenal administration. Due to their high therapeutic index, the compounds of the invention can be used safely in medicine. By

  
  <EMI ID = 66.1> 7-carboxylic and 4-benzylidene-1,2,3,4-tetrahydro-ll-oxo-llH-pyrido [2, lb] quinazoline-8-carboxylic, in mice, determined by single administration increasing doses and measured the seventh

  
  <EMI ID = 67.1>

  
Analogous toxicity values have been established for the other compounds of the invention.

  
The dosage depends on the age, weight, condition of the patient and the route of administration; for example, the dosage adopted for oral administration to adult humans may be between approximately 50 and approximately 200 mg per dose one to five times a day. The invention includes pharmaceutical compositions containing a compound of the invention in association with an excipient.
(which can be a support or a diluent) acceptable in pharmacies.

  
The pharmaceutical compositions containing the compounds of the invention are generally prepared according to conventional methods and they are administered in a suitable pharmaceutical form, for example in the form of aqueous or oily solutions or suspensions, aerosols and powders, tablets, pills , gelatin capsules, syrup, drops, suppositories or cream or lotions for local use.

  
Therefore, for oral administration, the pharmaceutical compositions containing the compounds of the invention are

  
preferably tablets, pills or gelatin capsules which contain the active substance with diluents such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose; lubricants, for example silica, talc, stearic acid, magnesium or calcium stearate and / or polyethylene glycols; or which may also contain binders such as starches, gelatin, methylcellulose, carboxymethylcellulose, gum arabic, gum tragacanth, polyvinylpyrrolidone; disintegrants such as starches, alginic acid, alginates, sodium starch glycolate; effervescent mixtures; dyes; sweeteners; wetting agents such as lecithin, polysorbates and laurylsulfates; and in general non-toxic substances and

  
without pharmacological activity used in pharmaceutical compositions.

  
These pharmaceutical preparations can be manufactured in a known manner, for example by mixing, granulation, shaping into tablets, coating or coating with a film.

  
For the treatment of allergic asthma, the compounds of the invention are also administered by inhalation. The compositions suitable for this use can be made up

  
of a suspension or solution of the active ingredient, preferably in the form of a salt such as the sodium salt or the triethanolamine or tris- (hydroxymethyl) -aminomethane salt, in water, for administration with a conventional nebulizer.

  
Otherwise, the compositions can consist of a suspension or a solution of the active ingredient in a conventional liquid propellant such as dichlorodifluoromethane.

  
or dichlorotetrafluoroethane for administration by means

  
a pressure container, for example an aerosol dispenser. When the drug is not soluble in the propellant, it may be necessary to add to the composition a cosolvent such as ethanol, dipropylene glycol, isopropyl myristate and / or

  
a surfactant to suspend the drug in

  
the propellant medium and such surfactants can be

  
any of those commonly used for this purpose such as

  
non-ionic surfactants, for example lecithin.

  
The compounds of the invention can also

  
be administered in the form of powders by means of a suitable insufflator and in this case fine powders of the active ingredients can be mixed with a diluent material such as lactose.

  
In addition, the compounds of the invention can also be administered by intradermal or intravenous injection in a conventional manner.

  
In addition to internal administration, the compounds of the invention may be useful in compositions for local application such as creams, lotions or pastes

  
for use in dermatological treatments.

  
For these compositions, the active ingredients can be mixed with conventional oil or emulsifying excipients.

  
The invention is illustrated by the following nonlimiting examples.

  
EXAMPLE 1

  
3.8 g of 2-amino-5-chloro-pyridine are reacted with 9.2 g of ethyl 2-oxo-cyclopentanecarboxylate in the presence of polyphosphoric acid (38 g, obtained from 18.1 g of

  
  <EMI ID = 68.1>

  
After cooling, the reaction mixture is diluted with ice water and neutralized to pH 6 using 35% sodium hydroxide.

  
The precipitate is filtered and crystallized

  
  <EMI ID = 69.1>

  
which is reacted with 6.7 g of benzaldehyde in 140 ml of methanol in the presence of 3.38 g of sodium methylate with stirring at reflux temperature for 68 h.

  
After cooling, the precipitate is separated by filtration, washed with water until neutral and crystallized from a mixture of methylene chloride / acetone to

  
  <EMI ID = 70.1>

  
C-2), 7.39 (m) (6H, phenyl and methine protons), 8.27 (d) (1H, C-5 proton), 8.50 (dd) (1H, C-6 proton), 9.47 (d) (1H, proton C-8).

  
By following a similar procedure starting from the appropriate halogenated 2-amino-pyridines, the following composites are prepared:

  
  <EMI ID = 71.1>

  
[1,2-a] pyrimidine-10-one.

  
EXAMPLE 2

  
4 g of 7-chloro-1,2,3,10-tetrahydro-cyclopenta [d] pyrido [1,2-a] pyrimidine-10-one (prepared according to

  
  <EMI ID = 72.1>

  
160 ml of methanol in the presence of 1.65 g of sodium methylate at reflux temperature for 140 h. After cooling, the precipitate is filtered off, washed with water until neutral and crystallized from a mixture of methylene chloride and

  
  <EMI ID = 73.1>

  
one, F. 222-223 [deg.] C.

  
  <EMI ID = 74.1>

  
3.95 (s) (9H, -OCH3), 6.82 (s) (2H, phenyl protons), 7.42 (s) (1H, = CH-), 7.58 (d) (2H , protons C-5 and C-6), 9.02 (t)

  
(1H, proton C-8).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 75.1>

  
pyrido [1,2-a] pyrimidine-10-one, <EMI ID = 76.1>

  
Example 1 with 3.4 g of 2-chlorobenzaldehyde in 150 ml of methanol in the presence of 1.73 g of sodium methylate with stirring at reflux temperature for 36 h.

  
After cooling, the precipitate is separated by filtration, washed with water until neutral and crystallized.

  
  <EMI ID = 77.1>

  
(3H, phenyl protons 3, 4 and 5), 7.70 (m) (1H, phenyl proton 6), 7.91 (m) (1H, = CH-), 8.25 (d) (1H, proton C-5), 8.50 (dd) (1H, proton C-6), 9.48 (d) (1H, proton C-8).

  
By operating in an analogous manner by reaction of

  
  <EMI ID = 78.1>

  
suitable with suitable substituted benzaldehydes, the following compounds are prepared:

  
  <EMI ID = 79.1>

  
pyrido [1,2-a] pyrimidine-10-one, F. 253-256 [deg.] C.

  
  <EMI ID = 80.1>

  
EXAMPLE 4

  
  <EMI ID = 81.1>

  
methyl oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylate, F. 153-154 [deg.] C, with 5.52 g of 3-methoxybenzaldehyde in 145 ml of methanol in the presence of 2.97 g of sodium methylate with stirring

  
at reflux temperature for 144 h. After cooling,

  
the precipitate is separated by filtration and treated with formic acid, then with water: the crude compound is collected by filtration, it is washed with water until neutral and it is crystallized from a mixture of methylene chloride and methanol for

  
  <EMI ID = 82.1>

  
hydro-10-oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylic, F. 310-312 [deg.] C.

  
  <EMI ID = 83.1>

  
4.11 (s) (3H, OCH3), 7.2-7.6 (m) (4H, phenyl protons), 7.61 (wide)
(1H, = CH-), 8.41 (d) (1H, proton C-5), 9.11 (d.d) (1H, proton C-6),
10.20 (d) (1H, proton C-8).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 84.1>

  
penta [d] pyrido [1,2-a] pyrimidine-7-carboxylic.

  
EXAMPLE 5

  
  <EMI ID = 85.1> F. 153-154 [deg.] C, in 300 ml of methanol containing 6.45 g of sodium methylate with 10.9 g of benzaldehyde, with stirring at reflux temperature for 96 h. After cooling and concentrating under vacuum to a small volume, the precipitate is separated by filtration and

  
it is treated with acetic acid and then with water; the crude product is recovered by filtration, washed with water until neutral and crystallized from a mixture of methylene chloride and methanol then in dioxane to obtain 3.25 g of 3-benzyli- acid

  
  <EMI ID = 86.1>

  
(6H, protons = CH- and phenyl), 8.44 (d) (1H, proton C-5), 9.15 (d.d)
(1H, proton C-6), 10.23 (d) (1H, proton C-8).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 87.1>

  
decomposition, and <EMI ID = 88.1>

  
10-oxo-cyclopenta [d] pyrido [l, 2-a] pyrimidine-7-carboxylic in

  
55 ml of methanol containing 2.9 g of sodium methylate with 4.86 g of 2-methylbenzaldehyde with stirring at reflux temperature for 144.h. After cooling and concentration in vacuo to a small volume, the precipitate is separated by filtration and treated with acetic acid and then with water; we recover

  
the crude compound by filtration, washing with water until neutral and crystallizing from a mixture of methylene chloride and methanol then in dioxane to obtain 1.9 g of 3- (2-

  
  <EMI ID = 89.1>

  
NMR (CF3COOD) 6 ppm: 2.49 (s) (3H, -CH3), 3.36 (s) (4H, cyclopentane protons), 7.42 (m) (3H, phenyl protons), 7.64 ( m) (1H, phenyl proton), 7.81 (broad s) (1H, = CH-), 8.40 (d) (1H, C-5 proton),

  
lique, prepared according to Example 4, with 54 ml of hydrochloric acid
37% in 54 ml of acetic acid with stirring at reflux temperature for 20 h. After cooling, the precipitate is separated by filtration, washed with water and then treated with aqueous sodium acetate with stirring: by filtration and crystallization of the precipitate in dimethylformamide, 1.85 g of acid are obtained. - (3-

  
  <EMI ID = 90.1>

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 91.1>

  
[d] pyrido [1,2-a] pyrimidine-7-carboxylic,

  
3- (3,4-methylenedioxy-benzylidene) -1,2,3,10-tetrahydro-10-oxocyclopenta [d] pyrido [l, 2-a] pyrimidine-7-carboxylic acid and

  
  <EMI ID = 92.1>

  
  <EMI ID = 93.1> <EMI ID = 94.1>

  
dehyde in 200 ml of methanol in the presence of 6.8 g of sodium methylate at reflux temperature for 96 h. After cooling and concentration under vacuum to a small volume, the precipitate is filtered and washed with water until neutral; by crystallization from a mixture of methylene chloride and methanol, 3-benzylidene-7-methyl-1,2,3,10-tetrahydro-cyclopenta [dlpyrido [1,2-a] pyrimidine-10-one is obtained, F. 197-199 [deg.] C.

  
  <EMI ID = 95.1>

  
Cl and C-2), 7.2-7.7 (m) (8H, protons = CH-, C-5, C-6 and phenyl), 8.80 (broad s) (1H, proton C-8 ).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 96.1>

  
pyrido [1,2-a] pyrimidine-10-one.

  
EXAMPLE 9

  
  <EMI ID = 97.1>

  
cyclopenta [d] pyrido [l, 2-a] pyrimidine-10-one, F. 212-214 [deg.] C, with 8 g

  
of benzaldehyde in 150 ml of methanol in the presence of 4 g of sodium methylate at reflux temperature for 150 h. After cooling and concentration in vacuo to a small volume, the precipitate is filtered and washed with water until neutral: by cris-tallization in dioxane, 2.5 g of 3-benzylidene-5 are obtained. -

  
  <EMI ID = 98.1>

  
one, F. 229-230 [deg.] C.

  
NMR (DMSO d6) S ppm: 3.26 (s wide) (4H, protons C-1 and C-2),

  
4.20 (s) (3H, OCH3), 7.5-7.9 (m) (8H, protons = CH, C-6, C-7 and phenyl; 8.90 (dd) (1H, proton C -8).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 99.1>

  
EXAMPLE 10

  
1.8 g of trimethylsulfoxonium iodide are reacted with 0.39 g of 50% sodium hydride in 30 ml of dimethylformamide with stirring at room temperature for 60 min and then

  
  <EMI ID = 100.1>

  
Methyl 10-oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylate, F. 248-250 "C, in 30 ml of dimethylformamide. The mixture is left to react at room temperature for 1 h then diluted with ice water and neutralized with acetic acid, the precipitate is separated by filtration and washed with water to obtain 2.55 g

  
  <EMI ID = 101.1>

  
methyl penta [d] pyrido [1,2-a] pyrimidine-7-carboxylate, F. 185-187 [deg.] C, which is treated with 90 ml of 0.5% potassium hydroxide solution

  
  <EMI ID = 102.1>

  
After cooling, the reaction mixture is acidified with acetic acid and diluted with water: the precipitate is separated by filtration, washed with water until neutral and crystallized from a mixture of methylene chloride and methanol to obtain 1.8 g of 3-benzylidene-7,8-methylene-1,2,3,10- acid

  
  <EMI ID = 103.1>

  
(1H, 7.8-methylene proton), 3.32 (broad s) (4H, cyclopentane protons), 3.51 (dd) (1H, C-8 proton), 7.01 (d) (1H, proton C-5), 7.45 (m) (1H, = CH-), 7.58 (broad s) (5H, phenyl protons), 8.26 (d) (1H, proton C-6).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 104.1>

  
oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylic. EXAMPLE 11

  
3.2 g of 3-benzylidene acid are suspended <EMI ID = 105.1> carboxylic in 70 ml of dioxane and 30 ml of tetrahydrofyran and

  
reacted with 4.55 g of ethyl chlorocarbonate in the presence

  
4.05 g of triethylamine with stirring at 15 [deg.] C for 2 h. The reaction mixture is then treated with 200 ml of dioxane saturated with gaseous ammonia for 30 min with stirring. After dilution with ice water and neutralization with hydrochloric acid, the precipitate is separated by filtration and purified by washing with dimethyl-

  
  <EMI ID = 106.1>

  
(6H, protons = CH- and phenyl), 8.42 (d) (1H, proton C-5), 9.03 (d.d)
(1H, proton C-6), 10.09 (d) (1H, proton C-8).

  
EXAMPLE 12

  
  <EMI ID = 107.1>

  
2.28 g of p-toluenesulfonyl chloride in 80 ml of dimethylformamide in the presence of 2 ml of pyridine with stirring at ordinary temperature for 24 h. Dilute with ice water to obtain a precipitate which is filtered and crystallized with a mixture of methylene chloride and isopropyl ether to obtain 1.25 g

  
  <EMI ID = 108.1>

  
7.52 (broad s) (6H, protons = CH- and phenyl), 8.45 (m) (2H, protons C-5 and C-6), 9.76 (broad s) (1H, proton C- 8).

  
EXAMPLE 13

  
1 g of 3-benzylidene-1,2,3,10- acid is reacted

  
  <EMI ID = 109.1>

  
for 72 h. After cooling and diluting with ice water, the precipitate is filtered off and washed with water until

  
  <EMI ID = 110.1>

  
F. 225-227 [deg.] C.

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 111.1>

  
ethyl pyrido [1,2-a] pyrimidine-7-carboxylate and <EMI ID = 112.1>

  
ethyl pyrido [1,2-a] pyrimidine-7-carboxylate.

  
EXAMPLE 14

  
  <EMI ID = 113.1>

  
10-oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylic with the stoichiometric amount of sodium methylate in methanol

  
at 60 [deg.] C for 10 min.

  
After concentration in vacuo to a small volume, the precipitate is filtered off and washed with a small amount of cold methanol and then hexane: 3-benzyli- is obtained.

  
  <EMI ID = 114.1>

  
sodium dine-7-carboxylate, F.> 300 [deg.] C.

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 115.1>

  
sodium pyrido [l, 2-a] pyrimidine-7-carboxylate, 3- (4-methoxy-benzylidene) -1,2,3,10-tetrahydro -10-oxo-cyclopenta [d] pyrido [l, 2- a] sodium pyrimidine-7-carboxylate,

  
  <EMI ID = 116.1>

  
Sodium 3-benzylidene-7,8-methylene-1,2,3,10-tetrahydro-10-oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylate,

  
  <EMI ID = 117.1>

  
sodium pyrido [1,2-a] pyrimidine-7-carboxylate. EXAMPLE 15

  
  <EMI ID = 118.1>

  
methyl pyrido [2, 1-b] quinazoline-8-carboxylate, F. 123-124 [deg.] C,

  
with 11 g of benzaldehyde in 250 ml of methanol in the presence of

  
7.3 g of sodium methylate with stirring at reflux temperature for 140 h. After cooling, the solution is concentrated in vacuo to a small volume: the precipitate is separated by filtration and washed with a little methanol and then dissolved in water.

JU

  
Acidification with acetic acid forms a precipitate which is separated by filtration, which is washed with water and which is dissolved in acetone: by treatment with a stoichiometric amount of hydrochloric acid at 37%, we form hydrochloride

  
  <EMI ID = 119.1>

  
poorly soluble quinazoline-8-carboxylic, F.> 300 [deg.] C, which is recovered by filtration and which is washed thoroughly with acetone.

  
It is treated with aqueous potassium carbonate to obtain the free compound which is crystallized with a mixture of methylene chloride and methanol to obtain 2.9 g of 4-benzylidene-1,2,3,4-tetrahydro- acid. 11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylic, F. 261-263 [deg.] C.

  
  <EMI ID = 120.1>

  
protons C1 and C-3), 7.55 (broad s) (5H, phenyl protons), 7.76 (broad s) (1H, = CH-), 8.39 (d) (1H, proton C-6 ), 9.06 (dd) (1H, proton C-7), 10.13 (d) (1H, proton C-9).

  
EXAMPLE 16

  
2.5 g of 1,2,3,4-tetrahydro-11-oxo- are reacted

  
  <EMI ID = 121.1>

  
4.3 g of potassium tert-butoxide, with stirring at reflux temperature for 8 h. After cooling, the solution is concentrated under vacuum to a small volume, the precipitate is filtered off, washed with a little methanol and then dissolved in

  
water containing sodium bicarbonate: the solution is acidified to pH 4 with 23% hydrochloric acid and the precipitate is separated by filtration and washed with water until neutral. By crystallization from acetone, 1.1 g of 4- (2-methoxy-

  
  <EMI ID = 122.1>

  
carboxylic, F. 300 [deg.] C (decomposition).

  
  <EMI ID = 123.1>

  
(dd) (1H, proton C-7), 9.73 (d) (1H, proton C-9).

  
EXAMPLE 17

  
By operating according to Examples 15 and 16, the following compounds are prepared:

  
  <EMI ID = 124.1>

  
[2,1-b] quinazoline-8-carboxylic,

  
4- (2-methyl-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylic acid, F. 295-300 [deg.] C, decomposition,

  
  <EMI ID = 125.1>

  
4- (3-chloro-benzylidene) -1,2,3,4,4-tetrahydro-ll-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylic, F. 285-293 [deg.] VS, <EMI ID = 126.1>

  
quinazoline-8-carboxylic, F. 296-299 [deg.] C,

  
4 - [(2-pyridyl) -methylene-1,2,3,4-tetrahydro-11-oxo-11H-pyrido acid [2, l-b] quinazoline-8-carboxylic acid,

  
  <EMI ID = 127.1>

  
pyrido [2,1-b] quinazoline-8-carboxylic,

  
4- (3-hydroxy-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylic acid,

  
4- (4-hydroxy-benzylidene) -1,2,3,4-tetrahydro-ll-oxo-11H-pyrido [2, l-b] quinazoline-8-carboxylic acid,

  
  <EMI ID = 128.1> <EMI ID = 129.1>

  
4- (2,6-dichloro-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11Hpyrido [2, lb] quinazoline-8-carboxylic acid, F. 320-330 [deg.] C, decomposition,

  
  <EMI ID = 130.1>

  
4- (3-isopropoxy-benzylidene) -1,2,3,4-tetrahydro-ll-oxo-llHpyrido [2,1-b] quinazoline-8-carboxylic acid,

  
4- (4-isopropoxy-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11Hpyrido [2, l-b] quinazoline-8-carboxylic acid,

  
  <EMI ID = 131.1>

  
4- (3-propoxy-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylic acid and

  
  <EMI ID = 132.1>

  
EXAMPLE 18

  
By operating according to example 15 from 1,2,3,10-

  
  <EMI ID = 133.1>

  
methyl and using the appropriate heterocyclic aldehydes, the following compounds are prepared:

  
  <EMI ID = 134.1>

  
3- (2-furfurylidene) -1,2,3,10-tetrahydro-10-oxo-cyclopenta [d] pyrido [1,2-a] pyrimidine-7-carboxylic acid.

  
EXAMPLE 19

  
By operating according to examples 15 and 16 from

  
  <EMI ID = 135.1>

  
The following compounds are prepared:
4-benzylidene-1,2,3,4-tetrahydro-11H-pyrido [2, l-b] quinazoline-ll-one,

  
  <EMI ID = 136.1>

  
pyrido [2, l-b] quinazoline-ll-one,

  
  <EMI ID = 137.1>

  
quinazoline-11-one, <EMI ID = 138.1>

  
[2,1-b] quinazoline-11-one

  
EXAMPLE 20

  
  <EMI ID = 139.1>

  
hydro-ll-oxD-11H-pyrido [2, lb] quinazoline-8-carboxylic with 1.25 g of methyl iodide and 1.15 g of anhydrous potassium carbonate in 40 ml of dimethylformamide with stirring at room temperature for 24 hours. Dilute with ice water to obtain a precipitate which is separated by filtration and which is washed with water until neutral: we obtain 0.9 g of 4-benzylidene-1,2,3,4tetrahydro -11-oxo-11H-pyrido [2,1-b] methyl quinazoline-8-carboxylate, F. 166-168 [deg.] C.

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 140.1>

  
Methyl 4- (2-methoxy-benzylidene) -1,2,3,4-tetrahydro-ll-oxo-11H-pyrido [2, l-b] quinazoline-8-carboxylate,

  
  <EMI ID = 141.1>

  
methyl quinazoline-8-carboxylate.

  
EXAMPLE 21

  
1.8 g of trimethylsulfoxonium iodide are reacted

  
  <EMI ID = 142.1>

  
mide with stirring at room temperature for 60 min, then a solution of 2.7 g of 4-benzylidene-1,2,3,4-tetrahydro- is added
Methyl 11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylate in
30 ml of dimethylformamide. The mixture is left to react at room temperature for 1 hour, then it is diluted with ice water and neutralized with acetic acid. The precipitate is separated by filtration and washed with water to obtain 2.25 g of 4-benzyli-

  
  <EMI ID = 143.1>

  
of a 0.5% solution of potassium hydroxide in ethanol to
95% at reflux temperature for 15 min. After cooling, the reaction mixture is acidified with acetic acid and diluted with water: the precipitate is separated by filtration, washed with water until neutral and crystallized with a mixture of methylene chloride and methanol to obtain 1.3 g of acid

  
  <EMI ID = 144.1>

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 145.1> <EMI ID = 146.1>

  
4- (2-thenylidene) -8,9-methylene-1,2,3,4-tetrahydro-11-oxo-11Hpyrido [2,1-b] quinazoline-8-carboxylic acid,

  
  <EMI ID = 147.1> <EMI ID = 148.1>

  
0.25 g of thionyl chloride in 250 ml of dioxane at reflux temperature for 2 h. After cooling, we evaporate

  
dry reaction mixture in vacuo and the residue is dissolved in
70 ml of dioxane then reacted with 3.5 g of 2- (N, N-diethylamino) -ethanol with stirring at room temperature for

  
8 p.m.

  
The reaction mixture is concentrated in vacuo to a small volume and then diluted with ice water: the precipitate is extracted with chloroform and the organic solution is evaporated to dryness under vacuum.

  
By crystallization of the residue with a mixture of methylene chloride and isopropyl ether, 2.9 g of 4- are obtained.

  
  <EMI ID = 149.1> 8.12 (s broad) (1H, = CH-), 9.50 (d) (1H, proton C-9).

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 150.1>

  
2- (N, N-diethylamino) -ethyl quinazoline-8-carboxylate, <EMI ID = 151.1>

  
2- (N, N-diethylamino) 4- (2-chloro-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylate - ethyl,

  
  <EMI ID = 152.1>

  
[2, 1-b] 2- (N, N-diethylamino) -ethyl quinazoline-8-carboxylate and <EMI ID = 153.1>

  
EXAMPLE 23

  
3.23 g of 4- (4-nitro-ber.zylidene) are reacted -

  
  <EMI ID = 154.1>

  
methyl with 17 g of stannic chloride dihydrate in 12.5 ml of 37% hydrochloric acid and 40 ml of acetic acid under agitation

  
  <EMI ID = 155.1>

  
methyl and washed with water and then dissolved in 60 ml

  
dimethylformamide and treated with 15 ml of 2N sodium hydroxide at room temperature for 3 h. After acidification with acetic acid and dilution with ice water, the precipitate formed is filtered off and washed with water: by crystallization from dimethylformamide, 2.1 g of acid are obtained.

  
  <EMI ID = 156.1>

  
quinazoline-8 -carboxylic.

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 157.1>

  
quinazoline-11-one.

  
EXAMPLE 24

  
One reacts 1 g of 4- (4-amino-benzylidene) acid -

  
  <EMI ID = 158.1>

  
ment and dilution with ice water, the precipitate is separated by filtration and washed with water: by crystallization from a mixture of dimethylformamide and ethanol, 0.7 g is obtained

  
  <EMI ID = 159.1>

  
By operating in a similar manner, the following compounds are prepared:

  
  <EMI ID = 160.1>

  
EXAMPLE 25

  
4-Benzylidene-1,2,3,4-tetrahydro- acid is treated

  
  <EMI ID = 161.1>

  
for 10 min.

  
After concentration under vacuum to a small volume, the precipitate is separated by filtration and washed with a small amount of cold methanol and then with hexane: the

  
  <EMI ID = 162.1>

  
By operating in an analogous manner, the following compounds are prepared:

  
  <EMI ID = 163.1>

  
sodium quinazoline-8-carboxylate,

  
Sodium sodium 4- (4-methoxy-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido [2,1-b] quinazoline-8-carboxylate,

  
  <EMI ID = 164.1>

  
EXAMPLE 26

  
Tablets weighing each are prepared as follows
200 mg and containing 100 mg of the active substance.

  
  <EMI ID = 165.1>

  

  <EMI ID = 166.1>


  
  <EMI ID = 167.1>

  
lique, lactose and half of the corn starch. The mixture is then forced through a sieve having openings of

  
0.5 mm. 18 g of corn starch are suspended in 180 ml of hot water. The paste obtained is used to granulate the powder. The granules are dried and fragmented on a sieve having 1.4 mm openings. The rest of the starch, talc and magnesium stearate are added, mixed thoroughly and formed into tablets with punches 10 mm in diameter.

  
EXAMPLE 27

  
Tablets each weighing 200 mg and containing 100 mg of the active substance are prepared as follows:
Composition (per 10,000 tablets)

  
  <EMI ID = 168.1>

  

  <EMI ID = 169.1>


  
4-Benzylidene-1,2,3,4-tetrahydro-11-oxo-HH-pyrido [2, 1-b] quinazoline-8-carboxylic acid, lactose and half of the corn starch are mixed. The mixture is then forced through a sieve having 0.5 mm openings. We put in suspension
18 g corn starch in 180 ml hot water. The paste obtained is used to granulate the powder. The granules are dried and on. fragments them on a sieve with 1.4 mm openings. Add the rest of the starch, talc and magnesium stearate, mix thoroughly and form into tablets using punches 8 mm in diameter.

  
Of course, various modifications can be made by those skilled in the art to the devices or methods which have just been described only by way of nonlimiting examples without departing from the scope of the invention.


    

Claims (7)

CLAIMS <EMI ID = 170.1> 1. New compounds, characterized in that they correspond to the general formula (I)  <EMI ID = 171.1> or n is 1 or 2;  <EMI ID = 172.1> condensed on the pyrido cycle; R is a) a furyl radical ,. thienyl or pyridyl, or b) a radical of formula  <EMI ID = 173.1>  <EMI ID = 174.1> of the adjacent radicals represented by two of the symbols  <EMI ID = 175.1> [2,1-b] quinazoline-8-carboxylic, 4- (4-chloro-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido- acid  <EMI ID = 187.1> quinazoline-8-carboxylic, acid 4 - [(2-pyridyl) -methylene] -1,2,3,4-tetrahydro-ll-oxo-llH-pyrido. [2, l-b] quinazoline-8-carboxylic,  <EMI ID = 188.1> <EMI ID = 189.1> pyrimidine-10-one, and their pharmaceutically acceptable salts. [2, l-b] quinazoline-8-carboxylic, <EMI ID = 185.1> pyrido [2, l-b] quinazoline-8-carboxylic, 4- (2,3-dimethoxy-benzylidene) acid-1,2,3,4-tetrahydro-ll-oxo-llH-  <EMI ID = 186.1> [2,1-b] quinazoline-8-carboxylic, 4- (4-c-ethyl-benzylidene) -1,2,3,4-tetrahydro-11-oxo-11H-pyrido [2, l-b] quinazoline-8-carboxylic acid,  <EMI ID = 184.1> 2. Compounds of formula (I) according to claim 1,  <EMI ID = 176.1> or substituted with a 2-N, N-alkyl (C.C) amino radical; R2 represents a hydrogen atom; R3 represents a hydrogen or chlorine atom or a methyl or methoxy radical; R4 represents a hydrogen atom; Forms a bond thus achieving a double bond or, when  <EMI ID = 177.1> in the pyrido cycle; n is 1 or 2; R is a) a furyl, thienyl or pyridyl radical; or b) a radical of formula  <EMI ID = 178.1>  <EMI ID = 179.1> together a methylenedioxy radical; and their pharmaceutically acceptable salts. 3. Compounds according to claim 1, characterized in that  <EMI ID = 180.1> 4. Compounds according to claim 1, characterized in that they consist of:  <EMI ID = 181.1> <EMI ID = 182.1> penta [d] pyrido [1,2-a] pyrimidine-7-carboxylic acid, 3- (2-methoxy-benzylidene) -1,2,3,10-tetrahydro-10-oxo-cyclo- acid  <EMI ID = 183.1> 5. A process for preparing a compound of formula (I) according to claim 1, characterized in that it comprises: a) the reaction of a compound of formula (II)  <EMI ID = 190.1>  or  <EMI ID = 191.1> corresponding salt, with an aldehyde of formula (III)  <EMI ID = 192.1> where R is as defined in claim 1, to obtain compounds of formula (I) where A is a bond, or b) cyclopropylation of a compound of formula (IV)  <EMI ID = 193.1>  <EMI ID = 194.1> pharmaceutically acceptable salts and / or, if desired, the conversion of a salt to a free compound and / or, if desired, the separation of a mixture of isomers into isomers isolated. 6. New drugs useful in particular as antiallergic, anti-inflammatory and in the prevention or treatment of gastrointestinal ulcers, characterized in that they contain as active product at least one of the compounds according to any one of claims 1 to 4 or their pharmaceutically acceptable salts. 7. Pharmaceutical compositions, characterized in that they contain as active component at least one of the compounds according to any one of claims 1 to 4 or their pharmaceutically acceptable salts.