Title of Invention	PHARMACEUTICAL COMPOUNDS
Abstract	Compounds or their salts having general formulas (I) and (II) wherein: s = is an integer equal to 1 or 2, preferably s = 2; b0 = 0 or 1; A is the radical of a drug and is such as to meet the pharmacological tests reported in the description, C and C¿1? are two bivalent radicals. The precursors of the radicals B and B¿1? are such as to meet the pharmacological test reported in the description.

Full Text

The present invention relates to new drugs for systemic use and non-systemic use, and the composition thereof, to be used in oxidative stress and/or endothelial dysfuntions cases. By oxidative stress it is meant the generation of free radicals or radicalic compounds, which causes injury both of the cell and that of the surrounding tissue (Pathophysiology: the biological basis for disease in adults and children, Mstance & Huether 1998 pages 48-54). By endothelial dysfunctions it is meant those relating to the vasal endothelium. The damage of the vasal endotheliuun is known as one of those important events that can cause a series of pathological processes affecting various organs and body apparatuses, as described hereinafter (Pathophysiology: The biological basis for disease in adults and children, Mstance & Huether 1998 page 1025). As known, the oxidative stress and/or the endothelial dysfunctions are associated to various pathologies as reported hereinafter. The oxidative stress can also be caused by toxicity of a great variety of drugs, which significantly affects their performances. Said pathological events are of a chronic, debilitating character and are very often typical of the elderly. As already said, in said pathological conditions the drugs used show a remarkably worsened performance. Examples of pathological situations caused by the oxidative stress and/or by the endothelial dysfunctions, or present in elderly, are the following: For the cardiovascular system: myocardial and vascular ischaemia in general, hypertension, stroke, arteriosclerosis, etc. For the connective tissue: rheumatoid arthritis and connected inflammatory diseases, etc. For the pulmonary system: asthma and connected inflammatory diseases, etc. For the gastrointestinal system: ulcerative and non ulcerative dyspepsias, intestinal inflammatory diseases, etc. For the central nervous system: Alzheimer disease, etc. For the urogenital system: impotence, incontinence. For the cutaneous system: eczema, neurodermatitis, acne. The infective diseases in general (ref. : Schwarz-KB, Brady "Oxidative stress during viral infection: A review" Free radical Biol. Med. 21/5, 641-649 1996). Further the ageing process can be considered as a true pathologic condition {ref. Pathophysiology: the biological basis for disease 5-n adults and children, pages 71-77). The known drugs when administered to patients having pathologies associated to oxidative stress and/or endothelial dysfunctions, show a lower activity and/or higher toxicity. This happens for example for drugs such as the anti-inflammatory, cardiovascular drugs, respiratory apparatus drugs, central nervous sisters drugs, bone system drugs, antibiotics, urogenital, endocrine drugs, etc. Drug research is directed to find new molecules having an improved therapeutic index (off icily/toxicity ratio) or a lower risk/benefit ratio, also for pathological conditions as those above mentioned, wherein the therapeutic index of a great number of drugs results lowered. In fact in the above mentioned conditions of oxidative stress and/or endothelial dysfunctions, many drugs show a lower activity and/or higher toxicity. For instance antiinflammatory drugs, such as NSAIDs and anticolitic drugs, such as 5 - aminosalicylic acid and its derivatives, show the following drawbacks. NSAIDs result toxic particularly when the organism is debilitated or affected by morbid conditions associated to oxidative stress. Said conditions are for example the following: age, pre-existing ulcer, pre-existing gastric bleeding, debilitating chronic diseases such as in particular those affecting cardiovascular, renal apparatuses, the haematic crasis, etc. {"Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving non-steroidal anti-inflammatory drugs. A randomized, double blind, placebo-controlled trial." F.E. Silverstein et Al., Ann. Intern. Med. 123/4, 241-9, 1995; Martindale 31a ed. 1996, pag. 73, Current Medical Diagnosis and Treatment 1998, pages 431 and 794). The administration of anti-inflammatory drugs to patients in the above mentioned pathological conditions can be made only at doses lower than those used in therapy in order to avoid remarkable toxicity phenomena. Thus anti-inflammatory activity results poor. Beta-blockers, us ed for the angina, hyper ends ion and cardiac arrhythmia treatment, show side effects towards the respiratory apparatus (dyspnoea, bronchoconstriction), and therefore they can cause problems in patients affected by pathologies to said organs (asthma, bronchitis). Therefore beta-blockers further worsen respiratory diseases such as asthma. Therefore in asthmatic patients doses of said drugs must be used reduced in order not to jeopardize even more the respiratory functionality. Thus the efficacy of the beta-blockers results very reduced. Antithrombotics, such as for example dipyridamole, aspirin, etc., used for the prophylaxis of thrombotic phenomena, have the same drawbacks. In patients affected by pathologies connected to oxidative stress and/or endothelial dysfunctions, the therapeutic action or the tolerability of these drugs, as in the case of aspirin, is greatly reduced. Bronchodilators for example salbutamol, etc., are used in the asthira and bronchitis treatment and drugs active on the cholinergic system are used in pathologies such as urinary incontinence. Their administration can produce similar side effects affecting the cardiovascular apparatus, causing problems both to cardiopathic and to hypertensive patients. Cardiopathies and hypertension are pathologies associated, as above said, to the oxidative stress and/or endothelial dysfunctions. Also these drugs show the same drawbacks as those above mentioned. Expectorant and mucolytic drugs, which are used in the therapy of inflammatory states of the respiratory organs, show drawbacks in patients affected by the above described conditions. Their administration can give rise to heartburn and gastric irritability, particularly in the elderly. Bone resorption inhibitors, such as diphosphonates (for example alendronate, etc.) are drugs showing high gastrointestinal toxicity. Therefore also these drugs can show the same drawbacks as those above mentioned. Phosphodiesterase inhibitors, such as for example sildenafil, zaprinast, used in the cardiovascular and respiratory system diseases, are charaterized by similar problems as to tolerability and/or efficacy in the mentioned pathological conditions of oxidative stress and/or endothelial dysfunctions. Ant allergic drugs, for example satirizing, montelukast, etc. show similar problems in the mentioned pathological conditions, particularly for that it concerns their efficacy. Anti-angiotensin drugs , f . i . ACE-inhibitors , for example enalapril, captopril, etc,, and receptor inhibitors, for example losartan, etc., are used in the cardiovascular disease treatment. Their drawback is to give side effects to the respiratory apparatus (i,e. cough, etc.) in the above mentioned pathological conditions. Antidiabetic drugs, both of the insulin-sensitizing and of hypoglycaemizing type, such as for example, sulphonylureas, tolbutamide, glypiride, glyclazide, glyburide, nicotinamide etc. , are ineffective in the prophylaxis of diabetic complications. Their administration can give side effects, such as for example gastric lesions. These phenomena become more intense in the pathological conditions above mentioned. Antibiotics, for example ampicillin, clarihtromycin, etc., and antiviral drugs, cycloid, etc., show problems as regards their tolerability, for example they cause gastro-intestinal irritability. Antitumoral drugs, for example doxorubicine, daunorubicin, cisplatinum, etc., have high toxicity, towards different organs, among which are stomach and intestine. Said toxicity is further worsened in the above mentioned pathologies of oxidative stress and/or endothelial dysfunctions. Ant dementia drugs for example nicotine and Colin- idiomatic, are characterized by a poor toierability especially in the above mentioned pathologies. The need was felt to have available drugs showing an improved therapeutic performance, i.e. endowed both of a lower toxicity and/or higher efficacy, so that they could be administered to patients in morbid conditions of oxidative stress and/or endothelial dysfunctions, without showing the drawbacks of the drugs of the prior art. It has now surprisingly and unexpectedly found that the aforementioned problems evidenced the administration of drugs; to patients affected by oxidative stress and/or endothelial dysfunctions, or to the elderly in general, are solved by a novel class of drugs as described hereinafter. An object of the invention are compounds or their salts having the following general formulas (I) and (II): having 5 or 6 atoms. or Y is YO, selected from the following: an alkylenoxy group R'O wherein R' is linear or branched when possible Ci'C2Qr preferably having from 1 to 6 carbon atoms, most preferably 2-4, or a cycloalkylene having from 5 to 7 carbon atoms, in the cycloalkylene ring one or more carbon atoms can be replaced by heteroatoms, the ring can have side chains of R' type, R' being as above defined; or wherein Dd,J and Rj are equal or different, Tic= (CO) when t = 0, Dd,J = X when t" = 0, X being as above def inked; TIE= (CO)tx or (X)tin, wherein tl and til have the 0 or 1 value; with the proviso that tl = 1 when til =0; tl = 0 when til = 1; X is as above defined; Y' is as Y above defined, but with three free valences instead of two, preferably: a -R'O- grout) wherein R' is as above defined, ! preferably an alkyl from 1 to 6 carbon atoms, most prey early 2- 4; or wherein n3 and n3' have the above mentioned meaning; wherein one hydrogen atom on one of the carbon actions is substituted by a free valence; wherein no is an integer from 1 to 6 preferably from 1 to 4; wherein one hydrogen atom on one of the carbon atoms is substituted by a free valence; treated groups with the carrier + the drug of formula A = R-T-^- wherein the free valence is saturated as above indicated; administering the drug at a dose equivalent to the maximum one tolerated by the rats that did not receive NEM, i.e. the highest dose administrable to the animal at which there is no manifest toxicity, i.e. such as to be symptomatologically observable; the drug complies with test 1, i.e. the drug can be used to prepare the compounds of general formula (I) and (II), when the group of rats treated with NEM + carrier + drug shows gastrointestinal damages; or in the group treated with NEM + carrier + drug are observed gastrointestinal damages greater than those of the group treated with the carrier, or of the group treated with the carrier + drug, or of the group treated with the carrier + NEM; wherein test 2 (CIP) is a test in vitro wherein human endothelial cells from the umbilical vein are harvested under stcindard conditions, then divided into two groups (each group replicated five times), of which one is treated with a mixture of the drug 10'^ M concentration in the culture medium, the other group with the carrier; then cumene hydro peroxide (CIP) having a 5 mM concentration in the culture medium is added to each of the two groups; the drug meets test 2, i.e. the drug Cain be used to prepare the compounds of general formula (I) and (II) , if a statistically significant inhibition of the apoptosis (cellular damage) induced by CIP is not obtained with p wherein test 3 (L-NAME) is a test in vivo carried out on four groups of rats (each group formed by 10 rats) for 4 weeks and receiving drinking water, the controls (two groups) and the treated (two groups), of which one group of the controls and of the treated respectively receives in the above 4 weeks drinking water added of N-a>-nitro-L-argentine methyl ester (L-NAME) at a concentration of 400 mg/liter, the controls in the 4 weeks being administered with the carrier and the treated in the 4 weeks with the carrier + the drug, administering the carrier or the drug + carrier once a day, the drug being administered at the maximum dose tolerated by the group of rats not pretreated with L-NAME, i.e.; the highest dose administrable to animals at which no manic est. toxicity appears, i.e. such as to be symptomatologically observable; after the said 4 weeks, the water supply is stopped for 24 hours and then scarify iced, determining the blood pressure 1 hour before sacrifice, and after sacrifice of the rats determining the plasma glutei pyruvic transaminase (GPT) after sacrifice, and examining the gastric tissue; the drug meets test 3, i.e. the drug can be used to prepare the compounds of general formula (I) and (11), when in the group of rats treated with L-NAME + carrier -)- drug, greater hepatic damages (defended as higher values of GPT) and/or gastric and/or cardiovascular damages (determined as higher values of blood-pressure) are found in comparison in comparison respectively with the group treated with the carrier alone, or with the group treated with the carrier + drug, or with the group treated with the carrier + L-NAME; wherein test 4, which must not be met by the precursors of B or B; with the free valences saturated as above defined, is the following: it is an analytical determination carried out by adding portions of methanol solutions of the precursor of B or B at a 10" M concentration, to a methanol solution of DPPH (2,2-diphenyl-l-picryl hydrazyl - free radical); after having maintained the solution at room temperature away from light for 30 minutes, it is read the absorbance at the wave length of 517 nm of the test solution and of a solution containing only DPPH in the same amount as in the test solution; and then the inhibition induced by the precursor towards the radical production by DPPH is calculated as a percentage by means of the following formula: (1 - As/Ac)X100 wherein Ag and A respectively the absorbance values of the solution containing the test compound + DPPH and that of the solution containing only DPPH. The criterium for acceptance of the compounds according to this test is the following: test 4 is met by precursor compounds if the inhibition percentage as above defined is higher than or equal to 50%; the precursor of B or B; must not meet test 4; wherein test 5 is the following: it is an analytical determination carried out by adding aliquots of 10"^ M methanol solutions of the precursor of B or B or of C = -T -Y- K, having the free valence S2.turated as above indicated, to a solution formed by admixing a 2 mM solution of desoxyribose in water with 100 mM of phosphate buffer and 1 mM of the salt Fe- (NH ) 2 (SO-) 2; after having thermostat teed the solution at 37°C for one hour, are added, in "he order, aliquots of aqueous solutions trichloroacetic acid 2.8% and of thiobarbituric acid 0-5 M, heating is effected at 100°C for 15 minutes and the absorbance of the solute ions I s then read at 532 nm; the inhibition induced by the precursor of B or By, or C = -T Y-H in the confront of radical production by Fe- is calculated as a percentage by means of the following formula: (1 - A3/A )X100 wherein Ag and A are respectively the absorbance values of the solution containing the tested compound and the iron salt and that of the solution containing only the iron salt, the compound meets test 5 when the inhibition percentage as above defined of the precursor of B or B^ or C = -Th.-y-H is higher than or equal to 50%; provided that in the compounds of formula (I) the following drugs under the following conditions are excluded: R—TTA - , as above defined, has not to belong to the following classes: drugs for use in incontinence antithrombotic drugs (ACE-inhibitors)/ prostaglandin’s; The drugs of the proviso to be excluded, as said, are the following: drugs for use in incontinence as described in the patent application WO 98/09348, antithrombotic drugs (ACE inhibitors) as described in the application WO 98/21193; prostaglandin derivatives as described in the patent application WO 98/58910. There are excluded also non steroid antiinflainmatory (NSAIDs) as described in WO 95/30641, WO 94/12463, WO 95/09831 respectively. Preferably the precursor compound of B or B^ (precursor of the X2 or X2g radical in the formulas (I) and (II) rasped - actively), is selected from the following classes of compounds: Aminoacids: asp artic acid (PI)r histamines (PII) , 5-hydroxy tryptophan (PHI), 4-thiazolidincarboxylic acid (PIV), 2-oxo-4-thia2olidincarboxylic acid (PV) mono and polyalcohols or thiols: 2-thiouracil (QI)/ 2-mercaptoethanol (QII), esperidine (QUI) , secalciferol (QIV), 1-a-OH vitamin D2 (QV), flocalcitriol (QVI), 22-oxacalcitriol (QVII) , the vitamin D3 derivative esterified with the vitamin A radical (QVIII), the compound of formula (QIX) , 24 , 28-methylene-la-hydroxyvitamin D2 (QX) the compound derived from la, 25-dihydroxyvitamin D2 (QXI) , 2'mercaptoimidazol (QXII) The drug precursor compounds either of B or B, or of C = -T -y-H are prepared according to the known methods in the prior art, and described for example in "The Merck Index, 12a Ed. (1996), herein incorporated by reference. When available, the corresponding isomers and optical isomers can be used. The derivative of vitair.in D3 with retinue acid (QVIII) is prepared as described in J? 53039261 (ref. C.A. IIS 117617); the compound of formula (QIX) according to EP 562,497; 24,28-methylene-la-hydroxyvitamin D2 (QX) according to EP 578,494; the derivative compound of denydroxyvitamin D2 (QXI) according to EP 549,318. The tests carried out to identify the drug corresponding to the R radical of the formulas (I) and (II) are in detail the following; Test 1 (NEM): evaluation of the gastrointestinal damage from oxidative stress induced by free radicals formed following administration of N-ethylmaleimide (NEM) (H.G. Nutley, F. Behead, . Huckstering "Effects of sulphydril reagents on per oxidation in microcosms" Archive. Biochem. Biophys. 118, 29-32 1967). The animals (rats) are distributed in the following groups (no. 10 animals for group): A) Control groups: 1° group: treatment: only carrier (aqueous suspension 1% w/v of carboxymethylcellulose; dose: 5 i.v/Kg when the drug is administered by so; or a physiologic solution when parenterally administered, i.e. by subcutaneous, intraperitoneal, intravenous or intramuscularly route) / 2° group: treatment: carrier as above defined + NEM, B) Groups treated with the drug: group I: treatment: carrier H- drug, grape II: treatment: carrier + drug + NEH. The administration routes are those known for the drug, and can be the oral or subcutaneous, intraperitoneal, intravenous or intramuscular route. The NEM dose is of 25 mg/kg in physiologic solution (sub cutaneous route) and the drug is administered one hour later, in suspension in the carrier, as a single dose which corresponds to the maximum one, or the highest still tolerated by the animals of the group of rats not pretreated with NEM, i.e. the highest administrable dose to said group at which there is no manifest toxicity in the animals, defined as a toxicity that is clearly recognizable for its symptoms. The animals are sacrificed after 24 hours and then one proceeds to the evaluation of the damage to the gastrointestinal mucosa. The drug meets test 1, i.e. it can be used to prepare the compounds of general formula (I) and (II), when the group of rats treated with KEM + carrier + drug shows gastrointestinal damages, or in said group the gastrointestinal damages noticed are greater than those shove by the group treated with the carrier alone, or the group treated with carrier + drug, or the group treated with carrier -j- NEM, even though the drug pharmacotherapeutic efficacy, assayed by using specific tests; is not significantly reduced. Test 2 (CIP); Protection perimeter of endothelial cell against the oxidative stress induced by coniine hydroperoxide (CIP). Human endothelial cells of the umbilical vein are prepared according to an usual standard procedure. Fresh umbilical veins are filled with a 0.1% by weight collagenase solution and incubated at 37'=C for 5 minutes. Afterwards the veins are perfused with medium M 199 (GIBCO; Grand Island; NY) pH 7.4 further added of other substances, as described in the examples» The cells are collected from the perforate by centrifugation and harvested in culture flasks T-75, pretreated with human fibronectin. The cells are then harvested in the same medium, further added with 10 nag/ml of bovine hypothalamic growth factor. When the cells of the primary cell culture (i.e. that directly obtained from ex-vivo) form a single layer of confluent cells (about 8,000,000 cells/flask), the culture is stopped and the layers washed and trypsinised. The cellular suspensions are transferred into the wells of a cell culture plate having 24 wells, half of which is then auditioned with the same culture medium containing the drug at a 10'^M concentration, and harvested in a thermostat at 37°C at a constant moisture. Only the cells coming from said first sub-cultures are used for the experiments with cumene hydroperoxide (CIP). The cells are identified as endothelial cells by morphological examination and by their specific immunological reaction towards factor VIII; said cultures did not show any contaminations from yachts or fibroblasts. Before starting the test, the cellular culture medium is removed and the cellular layers are carefully washed with a physiologic solution at a temperature of 37 . The wells of the culture plate are then incubated for one hour with CIP at a 5 Tim concentration in the culture medium. The evaluation of cellular damage (apoptosis) is carried out by determining the per cent variation of the DNA fragmentation with respect to the control group {treated with CIP alone), evaluating the fluorescence variation at the wave length of 405-450 nm. 5 replicates for each sample are carried out. The drug meets the test, i.e. it can be used for preparing the compounds of general formula (I) and (11)/ when a statistically significant inhibition of apoptosis (cellular damage) induced by CIP with respect to the group treated with CIP alone is not obtained at p Test 3 (L-NAME) : evaluation of the endothelial dysfunction induced by administration L-NAME (N -nitro-L-argentine-methyl ester) J. Clint. Investigation 90, 278-281,1S92. The endothelial dysfunction is evaluated by determining the damage to the gastrointestinal mucosa, the hepatic damage and blood hypertension induced by administration of L-NAME. The animals (rats) are divided in groups as herein below shown. The group receiving L-NAME is treated for 4 weeks with said compound dissolved at a concentration of 400 mg/liter in drinking water. The following groups are constituted (No. 10 initials for group): A) Control groups: 1° group: only carrier (aqueous suspension 1% w/v of carboxy-methyl cellulose, dose: 5 ml/Kg when the drug is administered by so, physiologic solution when administered parenterally), 2° group: carrier -»- L-NAME, B) Groups administered with the drug: 3° group: carrier + drug, 4° group: carrier + drug + L-NAME. The administration routes are those known for the drug, and can be the oral or subcutaneous, intraperiteneal, intravenous or intramuscular route. The drug is administered at that dose which results the highest still tolerated by the caimans of the group of rats not pretreated with L-NAME, i.e. the highest administrable dose at which there is no evident toxicity in the animals / i. e a toxicity recognizable for its symptoms. The drug is administered once a day for 4 weeks. At the end of the four weeks treatment access to water is prevented and after 24 hours the animals are sacrificed. One hour before the sacrifice blood-pressure is determined, and a blood pressure increase is taken as an evaluation of the damage to vascular endothelium. The damage to the gastric narcosis is evaluated as illustrated in test 1 (see example Fl). The hepatic damage is determined by evaluation of the glutei - pyruvic trans a-;incase (GPT increase) after sacrifice. The drug meets test 3, i.e. it can be used for preparing the compounds of general f oriole (I) and (II) , when in the group of rats treated with L-N.-ides + drug + carrier it is found an higher hepatic damage (GPT) and/or an higher gastric damage and/or an higher cardiovascular (blood-pressure) damage in comparison to that of the group treated with the carrier alone, or of the group treated with carrier + drug, or of the group treated with carrier -i- L-NAME; even if the drug pharmacy-therapeutic efficacy, assayed by specific tests, is not significantly reduced. Under the conditions indicated in the above described in vivo tests 1 and 3 the therapeutic index of the drug is reduced since the usual doses at which the drug can be effective are no longer tolerated. It has been found by the Applicant that the precursors of 3 or 3i do not meet test 4 reported hereinafter while they meet, as said, test 5. Test 4 is a colorimetric test which must not be satisfied by the precursor of B or B;^ (precursor of the X2 or X23 of the formulas (I) and (II) respectively). The ' inhibition of the production of radicals from DPPH (2,2-diphenyl-l-picr-yl-hyd-razyl) is described in M.S. Nester et Al. , Atherosclerosis. Thrombi. 15, 133S-1344, 1995. old uM solutions in methanol of the tested substances are prepared, and an aliquot of each of said solutions is added to a DPPH solution in methanol 0,1 M. After having stored the' solutions at room temperature away from light for 30 minutes, their absorbance’s are read at the wave length of 517 nm, together with that of the corresponding DPPH solution at the same concentration. The absorbance decrease with respect to that of the solution of DPPH at the same concentration of the test solutions is determined. The effectiveness of the tested compound in inhibiting formation of radicals by DPPH is expressed by the following formula: (1 - As/Ac)X100 wherein Ag and A are respectively the absorbance values of the solution containing the test compound together with DPPH and of the solution, containing only DPPH. Test 4 is satisfied when the inhibition is equal or greater than 50%. Test 5 is a colorimetric test wherein 0.1 ml aliquots of solutions the tested products are added to test tubes containing a solution formed by 0.2 ml of 2 raM desoxyribose, 0.4 ml of phosphate buffer of 1 mM Fe-'MNHJ J (504)2 in 2mM KCl. The test tubes are then maintained at 37*C for one hour. Then in each test tube 0. 5 ml of a 2.8% solution in water of trichloroacetic acid and C.5 ml of an aqueous 0.1 M solution of thiobarbituric acid are added, in the crder. A reference blank is formed ' adding to a test tube containing only the above described aqueous solution of reactants of methanol. The test tubes are closed and heated in an oil bath at 100°C for 15 minuets. A pink coloration is developed the intensity of which is proportional to the quantity of desoxyribose undergone to radical oxidative degradation. The solutions are cooled at room temperature and their absorbencies are read at 53 2 nm against the blank. The inhibition induced by the precursor of 3 or Boor C = -T-Y-H in the confront of radical production by Fe is determined by means of the following formula: (1 - A,/Ai)X100 wherein A and k are respectively the absorbance values of the solution containing the tested compound + the iron salt and that of the solution containing only the iron salt, the coir pound meets test 5 when the inhibition percentage of radical production as above defined from the precursor of 3 or 3^ or c = -T^-Y-K is higher than or equal to 50%. Unexpectedly the invention products of the formulas (I) and (II) have an improved therapeutic index, in oxidative stress conditions, compared with the precursor drugs. For illustrative purposes the above mentioned tests are referred to the following compounds (see the Examples): Test 1: precise drug: indomethacin Maximum administrable dose to rats: 7,5 mg/Kg p.o. By administering a higher dose a toxicity is manifested, characterized by naturopathy, tremor, sedation until death (within 24 hours). The group of rats treated with NEK + indomethacin at the above mentioned dose shows gastrointestinal damages. Since indomethacin in the groups treated with NEM causes gastrointestinal * damages, it meets test 1. Indomethacin can therefore be used as a drug for preparing the compounds (I) and (11) of the present invention. rest 2: precursor drugs: indomethacin, paracetamol and mesala-nine Indomethacin and paracetamol meet test 2 since the cellular damage (apoptosis) inhibition induced by CIP is not significantly different with respect to that of the controls. Therefore the a-bone drugs can be used as drugs for preparing the compounds (I) and (II) of the present invention. On the contrary me seal amine does not meet test 2, since it inhibits the apoptosis induced by CI?. Therefore mesa amine according to test 2 could not be used as a precursor to prepare the compounds (I) and (II) of the present invention. It has been however found that mesalair.ine submitted to test 1 causes gastrointestinal drainages. Thus also mesa amine can be used as a precursor for preparing the compounds (I) and (II) of the present invention. Test 3 precurosr drugs: paracetamol, simvastatin, omeprazole Paracetamol and simvastatin meet test 3 since they cause gastric and hepatic drainages greater than those induced both by L-NAME + carrier and by the drug + carrier. Therefore they can be used as precursors to prepare the compounds (I) and (II) of the present invention. On the contrary it has been found that omeprazole neither causes gastric nor hepatic damages, nor influences blood-pressure. According to test 3 omeprazole could not be used as a precursor for preparing the compounds (I) and (II) of the present invention. Test 4 (test for the precursor of B and B^^): precursor compound: N-acetylcysteine and 4-thiazolidincarboxylic acid N-acetylcysteine in said test inhibits of 100% the production of radicals induced by DPPH. Since said percentage is higher than the limit of 50%, said drug cannot be used in the present invention as precursor of B or B-, . 4-Thia20lidincarboxylic acid does not inhibit at any extent the production of radicals induced DPPK {Table V). Thus the drug does not meet test 4 as requested by the instant invention and it could be used as a precursor of B or B^ if it meets test 5, Test 5 (test for the precursor of B. B and C= -T-Y-H) : precursor compound: 4 - thiazolidincarboxylic acid Table III relating to this test shows that the 4- thiazolidincarbcxylic acid meets test 5 since the % inhibition is of 100%. Therefore the compound can be used as precursor of B or of B- . yin formula (III) is preferably selected from the following: The most preferred of Y is yi2 (pyridyl) substituted in positions 2 and 6. The bonds can also be in asymmetric position, for example Y12 can be substituted also in position 2 and 3; Yl (parasol) may be 3,5-disubstituted. The compounds according zoo the present invention of for-similar (I) and (II) can be transformed into the corresponding salts. For example one way to furor; salts is the following: when in the molecule one nitrogen atom sufficiently basic to be salaried, by reaction in organic solvent such as for example acetonitrile; tetrahydrofuran, is present; it is reacted with an equimolecular amount of the corresponding organic or inorganic acid. To form the salt, preferably in the formula of the invention compound Y or Y' of formula (III) is present. Examples of organic acids are: oxalic, tartaric, maleic, succinic; citric acids. Examples of inorganic acids are: nitric, hydrochloric, sulphur Ic, phosphoric acids. The derivatives according to the invention can be used in the therapeutic indications of the precursor drug, allowing to obtain the advantages exemplified hereinafter for some groups of these drugs: Anti-inflammatory drugs NSAIDs: the invention compounds result very well tolerated and effective, even when the organism is debilitated and is under conditions of oxidative stress. Said drugs can be used also in those pathologies wherein inflammation plays a significant pathogenesis role, such as for instance, but not limited to, in cancer, asthma, monadic infarction. Adrenergic blockers, of a- or -blocker type: the action spectrum the compo’ rids of formula (I) results wider than that the starting drugs: to a direct action on the smooth musculature the inhibition of the nervous beta-adrenergic signals governing the contraction of the hematic vessels is associated. The side effects (dyspnoea, bronchoconstriction) affecting the respiratory apparatus are lower. Antithrombotic drugs: the antiplatelet activity is potentiated and in the case of the aspirin derivatives the gastric tolerability is improved. Bronchodilators and drugs active on the cholinergic system: the side effects affecting the cardio-vascular apparatus (tachycardia, hypertension) result lowered. Expectorants and mucolytic drugs: the gastrointestinal tolerability results improved. Diphosphonates: the toxicity relating to the gastrointestinal tract is drastically lowered. Phosphodiesterase (PDE) inhibitors (bronchodilators): the therapeutic efficacy is improved, the dosage being actual; it is therefore possible, using the compounds of the invention to administer a lover dose of the drug and reduce the side effects. Anti leukotrienic drugs: better efficacy. ACE inhibitors: better therapeutic efficacy and lower side effects (dyspnoea, cough) affecting the respiratory apparatus. Antidiabetic drugs (insulin-sensitizing and hypoglycaeiTiizing) , antibiotic , antiviral, antitumoral, anticolitic drugs, drugs for the dementia therapy: better efficacy and/or tolerability. The drugs which can be used as precursors in the general formula of the compounds of the invention are all those meeting at least one of the above mentioned tests 1, 2, 3. Examples of precursor drugs which can be used are the following: For anti-inflammatory/analgesic drugs, the following can for example be mentioned: anti-inflammatory drugs: aceclofenac, acemetacin, acetyl-salicylic acid, 5-amino-acetylsalicylic acid, allophonic, almi-noprofen, amfenac, bendazac, bermoprofen, o'-baseball, bromfe-nac, bromosaligenin, bucloxic acid, butibufen, carpooler, cinmetacin, lianas, copra; diclofenac sodium, diflunisal, ditazol, enfenamic acid, etcdolac, EtO enervate, feline, fenbufen, enclose acid, fendosal, fenoprofen, fentiazac, fepradinol, flufenamic acid, fluidic, flunoxaprofen, floor -ibuprofen, glucametacin, glycol salicylate, ibuprofen, ibupro-xam, indomethacin, indoprofen, isofezolac, six-pack, ironical, ketoprofen, katabolic, lornoxicam, loxoprofen, meclofenamic acid, enfenamic acid, melcxicam, mesa amine, metiazinic acid, move azoles, napoleon, naïf l-oimd acid, oxaceprol, oxaprozin, oxyphenbutazone, parsalmide, perisoxal, phenyl ace-tylsalicylate, localizing, pyrazol, picric, purported, pranoprofen, protizinic acid., salacetamiide, salacetamiide - acetic acid, salicylsulphuric acid, salsa late, sulfide, stupor-f en; suxibuzone, tenoxicairi, taproot epic acid, tiarainide, tinoridine, tolfenainic acid, toileting; tropes in, penguin, improve en, zaltoprofen, zorrLSpirac , tomoxiprol; analgesic drugs: acetarr-inophen, acetaminosalol, amino- hlorthenoxazin, acetvlsalicylic 2-amino-4-picoline acid, ace- tylsalicylsalicylic acid, anileridine, benoxaprofen benzylmor- phone, 5-bromosalicylic acezate acid, bucketing, buprenorphine, butorphanol, capsaicin, cinchophen, ciramadol, cosmetician, colonizing, codeine, desomorphine, dezocine, dihydrocodeine, dihydromorphine, dimepheptanol, dipyrocetyl, eptazocine, ethoxazene, ethyl morphine, Eugene, floctafenine, fosfosal, gravening, hydrocodone, hydromorphone r hydroxypethidine, ibex- fennec, p-lactophenetide levorphanol, meptazinol, metabolize, metopon, morphine, nalbuphine, nicomorphine, norlevorphanol, normorphine, oxycodone, oxymorphone, pentazocine, phenazocine, phenocoll, phenoperidine, phenylbutazone, phenylsalicylate, phenylramidol, salicin, salicylamide, tiorphan, tramadol, dia- cerein, actarit. For respiratory and urogenital apparatus drugs (bronchodilators and drugs active on the cholinergic system, expectorant s/mucolytics, antiasthmatic/antiallergic antihi-staminic drugs), the following can be mentioned; broncodilaters and drugs active on the cholinergic system: acefylline, albuterol, baxnbutercl, bamifylline, bevonium methyl sulphate, bitolterol, carbutercl. clenbuterol, chlorprenaline, dioxethedrine, difylline, ephedrine/ epinephrine, eprosinol, etafredine, ethylnorepinephrine, etofylline, fenoterol, flutoprium bromide, hexoprenaline; ipratropium bromide, isoetharine; isoprotenerol, mabuterol, metaproterenol, oxybutynin, oxitropium bromide, pirbuterol, procaterol, protokylcl, proxyphylliae, reproterol, rimiterol, salmeterol, soterenol, terbutaline, 1-tecbromineacetic acid, tiotropium bromide, tretoouinol, tulobuterol, zaprinast, cyclodrine, NS-21, 2-hydroxy-2,2-diphenyl-N-(1,2,3,6-tetra hydro-pyridin-4-ylmethyl) acetamide; expectorant/mucolytic drugs: ambroxol, bromhexine, do-miodol/ erdosteine, guaiacol, guaifenesin, iodinated glycerol, letosteine, mesna, sobrerol, stepronin, terpin, tiopronin; antiasthmatic/antiallergic antihistaminic drugs: acrivastine, alloclamide, amlexanox, cetirizine, clobenzspam, chromoglycate, chromolyn, epinastine, fexofenadine, formoterol, histamine, hydroxyzine, levocabastine, lodoxamide, mabuterol, metron s, montelukast, nedocromil, repirinast, seratrodast, suplatast tosylate, terfenadine, tiaramide, urushiol, bromhexine. For cardiovascular drugs (ACE-.inhibitors, beta-blockers, antithrombotic and vasodilator drugs, antidiabetic and hypo"-glycemic drugs), the following can be mentioned: ACE-inhibitors: alacepril, benazepril, captopril, cero- napril, cilazapril, delapril, enalapril, enalaprilat, fo-sinopril/ imidapril, lisinopril, losartan, moveltipril, na-phthopidil; perindopril; quinapril, ramipril; spirapril, teiuo-capril, trandolapril, urapidil; beta-blockers: acebutolol; alprenolol; amosulalol, aroti-nolol, atenolol, betaxolol, bevantolol, bucumolol, bufetolol, bufuralol, b^unitrolol, bupranclol, butofilol, carazolol, car-teolol, carvedilol, celiprolcl, cetamolol; dilevalol, epanolol, esmolol, indenolol, labetalcl, mepindolol; metipranolol, metoprolol; moprolol, nadolol/ nadoxolcl/ nebivolol, nifenalol, nipridalol, oxprenolol, penbutolol; pindolol, practolol; pronethalol, propranolol, sotalol, sulfinalol, talinolol, ter-tatolol, tilisolol, timolol, toliprolol, xibenolol; antithrombotics and vasodilators: acetorphan, acetylsali-cylic acid, argatroban, bamethan, benfurodil hemisuccinatG; benziodarone, betahistine, brovincamine, bufeniode/-citicoline, clobenfurol, clopidogrel/ cyclandslate, dalteparin, dipyrida-mol, droprGnilamine, enoxaparin, fendiline, ifenprodil/ iloprost, indobufen, isbogrel, isoxsuprine, heparin, lamifiban, midrodine, nadroparin, nicotinoyl alcohol, nylidrin, ozagrel, perhexiline, phenylpropanolamine, prenylairdne, papaveroline, reviparin sodium salt; ridogrel, suloctidil, tinofedrine, tinzaparin, triflusal, xanthinol niacinate; antidiabetic drugs : acarbose, carbutair.ide, glibornuride glybuthiazcl(e), irdglitol, repaglinide, troglitazone, 1-butyl- 3-metanyl-urea; tolrestat, nicotinamide. For antitumoral drugs, the following can be mentioned: ancitabine, anthramycin; azacitidine, azaserine, 6-azauridine/ bicalutamide; carubicin, carsinophilin, chlorambucil, chlorozotocin, cytarabine, daunorubicin, defosfamide, deme-colcine; denopterin, 6-dia20-5-oxo-L-norleucins, docetaxel, doxifluridine, doxoriibicin, drcloxifene, edazrexate, eflorni-thine; enocitabine, epirubicin, epitiostanol, etanidazole, etoposide; fenretinide, fludarabine, fluorouracil, gemcitabi-ne, hexestrol; idarubicin, lonidaminS; mannoiuusuine/ melphalan, menogaril, 6-mercaptopurine, methotrexate, mitobronitol, mitolactol, mitomycins, mitoxantrone, mopidorriol, mycophenolic acid, ninopterin, nogalaxnycin; paclitaxel, pentostatin; pira-rubicin, piritrexim, plicamycin, podophyllic acid, porfimer sodium, porf iromycin, propagermaniuiri, puromycin, ranimustine, retinoic acid, roguinimex, streptonigrin; streptozocin, te -niposide, tenuazonic acid, thiamiprine, thioguanine, tomudex, topotecan, trimetrexate, tubercidin, ubenimex, vinblastine, vincristine, vindesine, vinorelbine, sorubicin. For antiulcer drugs the following can be mentioned: r-acetamidocaproic acid, arbaprostil, cetraxate, cimetidine, eca-bet, enprostil, esaprazole, irsogladine, misoprostol, omeprazole, ornoprostil, pantoprazole, plaunotol, rioprostil, rosaprostol, rotraxate, sofalcone, trimoprostil. Among anti-hyperlipidemic drugs (statines) the following can be xnantioned: atorvastatin, cilastatin, dermoscatin, fluvastatin, lovastatin, msvastatin, nystatin, pentostatin, pepstatin, privastatin sodium, simvastatin. Among antibiotic/antiviral drugs the following can be mentioned: antibiotics: amdinocillin, amoxicillin, ampicillinr apa~ Icillin, apicycline, aspcxicillin, azidamfenicol, azidocillin, azlocillin, aztreonair., benzoylpas, benzyl penicillinic acid, biapenem, bicozamycin, capreorr.ycin, carbenicillin, carindacillin, carumonam, cefaclor, cefadroxil, cefamandole, cefatrizine, cefazedone, cefazolin, cefbuperazone, cefclidin, cefdinir, cefditoren, cefepime, cefetamet, cefixime, cefmeno-xime , cefmetazole , cefminox, cef odizirrie , cefonicid , cef opera-zone / ceforanide, cefotaxime, cefotetan, cefotiam, cefoxitin, cefozopran, cefpimizole, cefpiramide, cefpirome, cefprozil, cefroxadine; cefsulodin, ceftazidime, cefteram, ceftezole, ceftibuten, cefticfur, ceftizoxime, ceftriaxone, cefuroxime, cefuzonam, cephacetrile sodium, cephalexin, cephaloglycin, cephaloridiner cephalosporin C, cephalothin, qephapirin sodium, cephradine, chloramphenicol, chlortetracycline, cinoxacin, clavulanic acid, clometocillin, cloxacillin, cyclacillin, cycloserine, demeclocycline, dicloxacillin, epicillin, fenbe-cillin, flomoxef, floxacillin, etacillin, imipenem, lenampi-cillin, loracarbef, lymecycline, mafenide, meclocycline, mero-penem, metampicillin, methacycline, methicillin sodium, mezlo* cillin, minocycline; moxalactarw mupirocin, tnyxin, negamycin, novobiocin, oxacillin, panipenem, penicillin G potassium salt, penicillin N, penicillin 0, penicillin V, phenethicillin potassium salt, pipacycline, piperacillin, pirlimycin, porfi-romycin, propicillin, guinacillin, ritipenem, rolitetracycline; sancycline, sedecamycin, spectinomycin, sulbactam, sulbe-nicillin, teirocillin, tetracycline, ticarcillin, tigemonam, tubercidin, azithromycin, clarithromycin, dirthromycin, enviomycin, eryx-hromycin, josamycin, midecamycin, miokamycin, oleandomycin, rifabutin, rifamide, rifamycin, rifaximan, rokitamycin, spiramycin, troleandromycin, viomycin, virginiamycin; amikacin, apramycin, arbekacin, dibskacin, dihydrostreptomycin, fortimicins, genzamicin, micronomicin, neomycin, netilmicin, paromomycin, ribostamycin, sisomaciny spectinomycin, streptomicin, tobramycin, trospectomycin; bacampicillin, cefcapene pivoxil, cefpodoxime proxetil, panipenem, pivampicillin, pivcefalexin, sultamicillin, talampicillin; carbomycin, clindamycin, lincomycin, mikamycin, rosaramicin, ciprofloxacin, clinafloxacin, difloxacin, enoxacin, enrof loxacin, f leroxacin, f lumeg^uine, grepaf loxacin, lomefloxacin, nadifloxacin, nalidixic acid, norfloxacin, ofloxacin, pazufloxacin, perloxacin, pipemidic acid, piromidic acid, rufloxacin, sparfloxacin, tosufloxacin, trovafloxacin. clomocycline , guamecycline , oxytetracycline, nif urpirinol, nifurprazine; p-aminosalicylic acid, p-aminosalicylic acid hydrazide; clofazimine, deoxydihydrostreptomycin; ethambutol; glyconiazide, isoniazid, opiniazide, phenyl aminosalicylate, rifampin, rifapentine, salinazid, 4-4'-sulfynyldianiline; Acediasulfone, dapsone, succisulfone, p-sulfanilylbenzylamine, thiasolsulfone, acetyl sulf amethoxypyrazine, mafenide, 4'- (methylsulfamoyl)sulfaXiilanilide, salazosulfadimidine, sulfabenzamide, sulfacetamide, sulfachlorpyridazine, sulfachrysoidine, sulfacytine, sulfadiazine, sulfadicramide, sulfadimethoxine, sulfadoxine, sulfaethidole, sulfaguanidine, sulfaguanole, sulfalene, sulfamerazine, sulfameter, sulfamethazine, sulfamethizole, sulfamethomidine, sulfamethoxazole, sulfamethoxypyridazine, sulfamethylthiasole, sulfametrole, sulfamidochrysoidine, sulfamoxole, sulfanilamide; 2-p-sulf anilylanilinoethanol, N- - sulf anilyl sulf anil amide , sulfanilylurea, N-sulfanilyl-3,4-xylamide, sulfaperine, sul-faphenazole, sulfaproxyline, sulfapyrazine, sulfapyridine;sulfasomizole, sulfasymazine, sulfathiazole, sulfathiourea, sulfisomidine, sulfisoxazole; 4 - sulfanilamide salicylic acid; negamycin, carumonan, cloxyguin, nitroxoline, arginine, metronidazole; antiviral drugs: acyclovir, amantadine, cidofovir, cytara-bine, didanosine, dideox>--adeno3ine, edoxudine, famciclovir, f loxuridine, ganciclovir, idoxuridine; indanavir , kethoxal, lamivudine, MADU, penciclovir, podophyllotcxin, ribavirin; rimantadine , saquinavir, sorivudine. stavudine, trifluridine, valacyclovir, vidarabine, xenasoic acid, zalcitabine, zidovudine. Among bone resorption inhibitors (diphosphonates) the following can be mentioned; alendronic acid, butedronic acid, etidronic acid, oxidronic acid, pamidronic acid, risedronic acid. Among antidemence drugs the following can be mentioned: amiridinei lazabemide, mofegiline^ salbeluzol, oxiracetam, ipidacrine, nebracetam, tacrine, velnacrine. The preferred substances are the following: among anti- inflammatory drugs: acetylsalicylic acid, 5 -aminoacetylsalicylic acid, carprofen, diclofenac sodium, diflu-nisal, iodole, flufenamic acid, flunixin, flurbiprofen, ibuprofen, indomethacin, indoprofen; ketoprofen, ketorolac/ lomoxicam, loxoprof en, meclof enamic acid, mef enamic acid, meloxicam, mesalamine, naproxen, niflumic acid, olsalazine, piroxicam, salsalate, sulindac, suprofen, tenoxicam, tiaprofenic acid, tolfenamic acid, tolmetin, somepirac, tomoxi-prol; among analgesic drugs: acetam.inophen, acetylsalicylsalicy-lic acid, benoxaprofen, buprenorphine, butorphanol, capsaicin, diacereine, dihydrocodeine, ethylmorphine, eugenol, phenylbutazone, meptazinol, morphine, nalbuphine, pentazocine, thiorphan, treadle, cataract. Among respiratory and urogenital apparatus drugs: (bronchodilators, drugs active on the cholinergic system, expectorants/mucolytics, antiasthmatics/antiallergic antihista- minic drugs) : bronchodilators and drugs active on the cholinergic system: albuterol, carbuterol, clenbuterol, difylline, etofylline, fenoterol, ipratropi;jm bromide, metaproterenol, oxybutynin, pirbuterol, salmeterol, terbutaline tiotropium bromide, zaprinast, cyclodrine, NS-21, 2-hydroxy-2,2-diphenyl-N-(1,2,3,6 -tetrahydro-pyridin-4-ylmethyl)acetamide; expectorant/mucolytic drugs: ambrcxol, bromexine, guaia-col, sobrerol; antiasthmatic/antiallergic antihistaminic drugs: cetirizine, chromoglycate, histamine, levocabastine, lodoxamide, montelukast, terfenadine, bromexine. Among cardiovascular drugs: ACE-inhibitors: captopril, enalapril, lisinopril, losar-tan, ramipril; beta blockers: alprenolol, atenolol, bupranolol; labetalol, metipranolol, metoprolol, pindolol, propranolol, timolol ; antithrombotic and vasoactive drugs: acetylsalicylic acid, acetorphan, argatroban, clopidogrel, dalteparin, dipyridamole, enoxaparin, heparin, iloprcst, midodrine, ozagrel, phenylpropanolamine, trifocal; antidiabetic drugs: toilette, nicotinamide. Among antitumoral drugs: anthramycin, daunorubicin, doxorubicin, epirubicin, fluorouracil, methotrexate, vinblastine. Among antiulcer drugs: cimetidine, omeprazole, pantoprazo- le. Among antihyperlipideirdc drugs: lovastatin, pravastatin soditim, simvastatin. Among antibiotic/antiviral drugs: antibiotic drugs: amoxicillin, ampicillin, aztreonam, biapenem, carbenecillin, cefaclor, cefadroxil, cef ainandole, cefatrizine, cefoxitin, clavulanic acid, dicloxacillin, imi-penem, meclocycline, methacycline, mcxalactam, panipenem, sulbactam, azithromycin, erythromycin, josamycin, miokamycin, ri-fabutine, rifamide, rifamycin, gentamicin, paromomycin, sisomicin, bacampicillin, carbomycin, clindamycin, ciprofloxacin, clinafloxacin, difloxacin, enrofloxacin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, pipemidic acid, apicycline, clomocycline, oxytetracycline, nifurpirinol, nifurprazine, isoniazid, rifampin, rifapentine, dapsone, thiazolsulfone, sulfamethoxazole, sulfamoxole, metronidazole, arginine; antiviral drugs: acyclovir, famciclo^-ir, ganciclovir, pen-ciclovir, ribavirin, vidarabine, zidovudine. Among bone resorption inhibitors: alendronic acid, etidro-nic acid, pamidronic acid. Among antidementia drugs: oxiracetam, tacrine, velnacrine. The above mentioned substances, A precursors, are prepared according to the methods known in the prior art. See for example in "The Merck Index, 12a Ed. (1996), herein incorporated by reference. When available, the corresponding isomers, comprising optical isomers, can be used. Tomoxiprol is obtained according to the method describeid in EP 12,866. The compounds of formula {I) or (II) are prepared with synthesis methods mentioned below. The choice of the reactions for each method depends on the reactive groups present in the precursor drug molecule, in the precursor compound of B or B^^, which can be, as above mentioned, bivalent or monovalent, and in the precursor compound of C. The reactions are carried out with methods well known in the prior art, which allow to obtain bonds among the precursor drug, the precursor drug of B or Bi and the precursor compound of C as above defined. When the reactive function of the precursor drug (for example -COOH, -OH) is engaged in a covalent bond, for example of ester, amide, ether type, said function can be restored with the methods well known in the prior art. Some synthesis schemes for obtaining the compounds of the invention are reported hereinafter: A) Synthesis of the compounds of formula (I). 1. Synthesis of the compound obtained by reaction between the precursor drug and the compound precursor of B. la. When the drug has general formula R-COOH and the functional group of the precursor compound of B which binds itself to the drug carboxylic function has the formula XZ, X being as above defined and Z = H, the reactions carried out depend on the nature of the second reactive group present in the precursor compound of B. la.l When the second reactive group present in the precursor compound of B is a carboxylic group, the synthesis general scheme expects the initial formation of the halide of the R-Coal acid (Hal = CI, Br) and the subsequent reaction with the HX group of the precursor compound of B: RCOOH Ronal + H-X-X2-COOH R-T;^-T3-X2'C00H (lA.l) X2/ T Tg being as above defined. When in the two reaction compounds other functional groups COOH and/or HX are present, they must be protected before the reaction according to the methods known in the art; for example as described in the volume by Th. W. Greene: "Protective groups in organic synthesis", Hayward University Press, IS50. The Ronal acylhalide is prepared according to the methods known in the prior art, for example by thionyl or orally chloride, P or P halides in inert solvents under the reaction conditions, such as for example toluene chloroform, DMF, etc. Specifically, if the HX group of the precursor compound of B is NH2' °^ '^^ ^^ ^^' ® precursor drug of formula R-COOH is first converted into the corresponding acyl halide RCOHal, as above mentioned, and then reacted with the HX group of the precursor compound of B in the presence of an organic base, such as triethylamine, pyridine, etc. using an inert solvent in the reaction conditions such as toluene, tetrahydrofuran urban, etc, at a temperature in the range 0°C-25°C. Alternatively to the previous synthesis, the precursor drug of formula R-COOH can be treated with an agent activating the carboxyl group selected from N,N' -carbonyldii-raidazol (CDI), N-hydroxybenzotriazol and dicyclohexylcar-bodiimide in solvent such as for example DMF, THF, chloroform etc. at a temperature in the range -5°C - 50®C and the obtained compound let react in situ with the reactive function of the precursor compound of B for obtaining the compound of formula (lA.1). la.2 When the precursor compound of 3 contains two fxmctional groups X2, cereal to or different from each other, X being as above defined and Z = H, the precursor drug having formula R-COOH is first treated with an agent activating the carboxyl group, as above described in all, and then with the precursor compound of B, after having protected one of the two reactive HX groups, for example by reaction with acetyl or ter-butyloxycarbonyl, restoring the initial function at the synthesis end. The scheme is the following: 2 . Nitroxyderivative synthesis. 2a. 1 When the compound obtained at the end of the previous step la. has formula (gal.), the acid can be converted into the corresponding sonic salt and then one can follow the known prior art methods for preparing the final composing, for example according to one of the following synthesis schemes: radical free from the oxygen atom, R3 is CI, Br; Iodine; OH. When R3 == OH the compound of formula (alb) is submitted to halogenation’s, for example with PBr3, PCI5 / SOCI2/ PPh3 + I2/ and then reacted with AgN03 in organic solvent such as acetonitrile, tetrahydrofuran. If R3 is CI, Br, Iodine, the compound of formula (lA.lb) is directly reacted with AgN03 as above mentioned. is obtained by treating an halogen-carboxylic acid of formula Hal-X _-COOH; X;;_ being as above defined, first with an agent activating the carboxyl group as described in a.c, and then with the compound of formula (IA.2) ; obtaining an halogen derivative, which is isolated and then dissolved in organic solvent, (ref. paragraph 2a.l)/ and treated with silver nitrate. The global reaction scheme is the following: lb. When the drug precursor has the reactive function HX, wherein X is as above defined, instead of a carboxylic group, the two functional groups present on the precursor compound of 3 can be the following: A carboxylic group, which reacts with the HX function of the drug precursor, and a KX group, the latter reactive group of the precursor compound of B being equal to or different from the functional group of the drug precursor. The formula of the precursor cornpo-ond of B is of the H-X- X2-C00H type, wherein X and X2 are as above defined. The H-X- function of the precursor compound of B is protected according to the known prior art methods and the carboxyl group is reacted^ as above mentioned, according to the following scheme: chloride. The resulting compound is dissolved in organic solvent, for example acetonitrile or tetrahydrofuran and reacted with silver nitrate. 2b. 2 To obtain the final nitroxyderivative starting from the compound of formula R-T-^-T£-X2-C00H (IB,2), obtained at the end of the synthesis described in lb. 2; the acid is transformed into the corresponding soda salt, it is reacted with a R4-X3_-R3 compound, previously defined in the reaction A. scheme of paragraph 2a. 1, obtaining according to the same process therein mentioned the final nitroxyderivative. Alternatively, when X is a linear C alkyl, the acid (IB. 2) is reacted with triphenylphosphine in the presence of an halogen ting agent such as Car or N-bromosuccinimide in tetrahedron urban and the resulting compound dissolved in organic solvent for example acetonitrile, tetrahydrofuran, is reacted with silver nitrate. 2b, 3 Alternatively to the synthesis process according to Ib.l and 2b, 1, it is possible to react in a first step the HX-function of the precursor compound of B HX-X2-COOH with the acyl chloride of an halogen acid of formula Hal-X; -CO-Co, wherein Hal is preferably 3r, and subsequently the carboxylic function of the so obtained compound, with the drug precursor R-HX. In the third and last step the -Hal group is substituted with -ONC2 according to the process B) Synthesis of compo-nods of formula (II). la. When the drug precursor is of formula R-COOH and the precursor compound of B-^ contains only one functional reactive group of formula XH; X being as above defined, R-COOH is initially converted into the corresponding acyl-halide, or treated with an agent activating the carboxyl group as described in la.l, and then reacted with the HX function of an halogen-acid compound, said function being equal to or different from that present on the precursor compound of B3_, said halogen-acid having the formula: wherein X ' is Y' as above defined without the oxygen atom through which the -NO2 group is linked, X and Hal are as above defined. The compound (Ixia’s) can be obtained with the known method of the prior art. For example when X = NH, it can be obtained from the corresponding hydroxy-ammoniac id, protecting the anionic group by the corresponding ter-bu-tyloxycarbonyl derivative and transforming the hydroxy 1 function into halogen group as described for the halogenation’s of the compound (lA.lb) in 2a-1. The free carboxylic function of the compound resulting from the reaction with the molecule of the drug precursor is reacted with the function present in the molecule of the precursor compound of B , as previously illustrated in all for the reaction between the R-COOH acid and the precursor compound of B, In the final step the halogen atom (Hal) present on the radical X' is substituted with an ONO2 group by adding AgN03 to an organic solution of the compound. The reaction scheme is the following, exemplified starting from the Rocco acid halide: lb. When the drug precursor and the precursor compound of B contain each a reactive group of general formula XH, the two groups in each of the two molecules being equal to or different from each other, wherein X is as above defined, the synthesis is carried out starting from an halo-gendiacid compound of formula X^^' being as above defined, said compound being prepared from the corresponding hydroxy-diacid as described for the halogenat ion of the compound (lA. lb) in 2a. 1. The halogendiacid compound is treated with an eguimolar amount of an agent activating the carboxyl group, under the conditions previously described in la.l., and then it is reacted with the reactive function of the drug precursor molecule. In the subsequent step the second carboxylic function is treated with an activating agent; as previously made for the first, and reacted with the precursor compound of B^ according to the following scheme: The halogen atom is then substituted with the ONO2 group as above mentioned. 3. Synthesis of the nitroso (s=l) derivatives of formula (I). 3a. 1 The compound of formula (lA.lb) wherein R3 = OH is reacted with sodas-um nitrite in a salver formed of a mixture of water with tetrahydrofuran in the presence of hydrochloric 3a.2 When the compound obtained at the end of step A in la. 2 has formula (IA.2) the correspoxiding nitroso derivative is obtained by treating an hydroxyacid of formula HO-X- _ being as above-defined, first with an agent activating the carboxyl forum, as described in la.l, then reacting it with 1A.2 and the resulting product with sodium nitrite as described in 3a.1. 3b. 1 To obtain the nitroso derivative starting from the compound of formula R-T3_-T3-X2-XH (IB.l) obtained at the end of the synthesis described in Ib.l^ the compound (13.1) is reacted with an hydroxyacid as described in 3a.2. 3b. 2 To obtain the nitroso derivative from the compound of formula R-T;^-T3-X2-CO0H (IB. 2) obtained at the end of the synthesis described in lb, 2, the acid is transformed into the sodic salt and reacted with a compound Hal-X-^-OH, as previously described, and the obtained alcohol is treated as described in 3a.1. 4) Synthesis of he nitroso derivatives of formula (II) 4a-1 When the drug is of formula R-COOH and the precursor compound of B- con-gains only one function reactive group of formula XH, X being as above defined, R-COOH is any- tidally converted into the corresponding acyl-halide or treated with an agent activating the carboxyl group as described in la.l, and then reacted with the HX function of an hydroxy-acid compound, said function being equal to or different from that present on the precursor compound of B-^f said hydroxy-acid having the formula: wherein X^' is Y' as above defined without the oxygen atom through which the -NO group is linked, X is as above defined. The free carboxylic function of the compound resulting from the reaction with the drug molecule is reacted with the function present in the molecule of the precursor compound of B^ / as previously illustrated in la.l for the reaction between the R-COOH acid and the precursor compound of B. In the final step the alcohol is transformed into the nitroso-derivative as described in 3a. 1. The reaction scheme is the following, exemplified starting from the RCOCl acid halide: 4b. When the drug and the precursor compo'ond of B contain each a reactive group of general formula XH, the two groups in each of the two molecules being equal to or different from each other, wherein X is as above defined, the synthesis is carried out starting from an hydroxy-diacid compound of formula Xi' being as above defined, said hydroxy diacid compound is treated with an eguimolar amount of an agent activating the carboxyl group, under the conditions previously described in la.l., and then it reacted with the reactive function of the drug molecule. In the subsequent step the second carboxylic function is treated with an activating agent, as previously made for the first one, and reacted with the precursor compound of Baccording to the following scheme: The obtained compound is reacted as described in 3a. 1. The compounds object of the present invention are formulated in the corresponding pharmaceutical compositions for parenterally, oral and topic use according to the well known knighthoods in the art, together with the usual excipients; see for example the volume "Remington's Pharmaceutical Sciences 15a Ed." The amount on molar basis of the active principle in these formulations is the same; or lower, in comparison with that used of the corresponding precursor drug. The daily administrable doses are those of the precursor drugs, or optionally lower. The daily doses can be found in the publications cf the field; such as for example in "Physician's Desk reference". The following examples have the purpose to illustrate the invention and are not to be considered as limitative of the same. EXAMPLE 1 Synthesis of the 3- [ 2-f luoro-cr-methyl- (1; 1' -biphenyl) -4-ace-tyl]thiazolidin-4-carboxylic acid 4-(nitrify)butyl ester (NO-Flurbiprofen), compound NCX 2002 starting from flurbiprofen (formula IX) and the precursor of B is (L)-4-thiazolidin carboxylic acid (formula PIV) a) Synthesis of 3-[2-flucro-a-methyl-(!;!'-biphenyl)-4-ace-tyl]thia2oliGin-4-carbGxylic acid To a solution of 2-f liioro-O'-inethyl tic acid (10 g, 41 moles) in toluene (100 nil) and N;N- dimethylformamide (10 ml) cooled at 0°C, oxalylchloride (3.52 ml; 82 mmoles) is added. After 2 hours at room temperature, the solution is evaporated at reduced pressure. The obtained residue is dissolved in acetone (50 ml) and the solution is added to a solution of 4-thiazolidincarboxylic acid (5.44 g, 41 mmoles) and triethylamine (14.9 ml, 106 mmoles) in acetone (50 ml) cooled at 0°C. After 2 hours the solution is acidified with HCl 4 N, concentrated under vacuum, the residue is treated with ethyl acetate and the organic phase is washed first with HCl 2 N/ then with water. The organic phase is anhydrified with sodium sulphate and evaporated at reduced pressure. 3y crystallization with ethyl acetate/n-hexane 9.4 g of the expected product in the form of a white solid having m.p. 142^C-147°C, is obtained. ^H-NMR {CDCI3): 7.74-7.62 (4H, m) , 7.35 (2K, t), 7.18-7.13 (2H, m), 5.06 (IH, m), 4,63 (IH, d). 4.42 (IH, d), 4.14 (IH, Q), 3.13 (2H, m), 1,53 (3H, d) . b) Synthesis of the 3- [ 2-f lurk-a-methyl- (1,1' -biphenyl) - 4-acetyl ]thiazolidin-4-carboxylic acid 4-(bromobutyl) ester To a solution of the acid obtained in the previous step a) (9.43 g, 26.24 anoles) in tetrahydrofuran (150 ml) triphenylphosphine (13.76 g, 52.49 mmoles) and carbon tetrabro-mide (174 g 52.45 mmoles) are added. The reaction mixture is let under stirring for 24 hours at room temperature. The solvent is removed by evaporation at reduced pressure. The obtained crude product is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate B/2. 2.25 g of the ester are obtained in an oil form. c) SvTithesis of the 3- [ 2-f fluoro-O'-methyl- (1,1' -biphenyl) -4-acetyl jthiasolidin-4-carboxylic acid 4-(nitrify)butyl ester To a solution of the ester obtained at the end of the previous step (2.6 g, 5,26 mmoles) in acetonitrile (20 ml) silver nitrate (1,07 g, 6.3 mmoles) is added. The reaction mixture is heated for 4 hours under reflux away from light. The formed salt is removed by filtration and the solution is evaporated at reduced pressure. The obtained residue is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate 7/3. 0.84 g of the 3-[2-fluoro-a-methyl-(1,1'biphenyl)- 4 - acetyl]thiasolidin-4-carboxylic acid 4-{nitroxy)butyl ester are obtained in an oil form. ^H-NMR (CDCI3): 7.56-7.09 (BH, m) , 5,77 (IH, dd), 4.67 (2H, d). 4.51 (2H, t). 4.24 (2H, t), 4.15 (IK, q), 3.30-3.17 (2H, m), 1.74-1.70 (4H, m), 1.52 (3K, d). EXAMPLE 2 Synthesis of the 3- (6-inethoxy-Q'-msthyl-2-naphthalenacetyl) thia20lidin-4-carboxylic acid 4 - (nitroxy) ester (NO-Nero- xenia) (NCX 2001) starting from naproxene (formula VI) and the precursor of B is (L)-4-thia2oiidin carboxylic acid (formula PIV) a) Synthesis of the 3-(6-methoxy-a-methyl-2-naphthalenacetyl) thiazolidin-4-carboxylic acid To a solution of 6-methoxy-a-methyl-2-naphthalenacetic acid (4.G2 g, 17.5 anoles) in toluene (30 it) and N,N-dimethyl-form amide (0.3 ml) cooled at O^C, oxalylchloride (2.92 ml, 34,06 mumbles) is added. After 2 hours at room temperature, the solution is evaporated at reduced pressure. The obtained residue is dissolved in acetone (50 ml) and the solution is added to a solution of 4-thiazolidincarboxylic acid (2.33 g, 17.5 mmoles) and triethylamine (6.34 ml, 45.5 mmoles) in acetone (50 ml) cooled at. After 2 hours the solution is acidified with HCl 4 N, concentrated under vacuum, the residue is treated with ethyl acetate and the organic phase is washed first with HCl 2 N, then with water. The organic phase is anhydrified with sodium sulphate and evaporated at reduced pressure. 4.43 g of the expected product are obtained in the form of a white solid having m.p. 165°C-168 %-NMR (CDCI3); 7.75-7.66 (3H; m) , 7.34 (IH; d) ; 7,14-7.11 (2H, m), 5,14 (IH, m), 4.80-4.61 (2H, m), 4.07 (IH, q), 3.91 (3H, s), 3.300.23 (2H, m) , 1.53 (3H, d). b) Synthesis of the 3-(6-methoxy-a-methyl-2-naphthalenacetyl) thia2olidin-4-carboxylic acid 4-(bromobuty1) ester To a solution of the acid obtained in the previous step a) (4 g, 11.6 mmoles) in tetrahedron furan (50 ml) triphenylphosphine (6.07 g, 23.1 mmoles) and carbon tetrabro-mide (7.66 g, 23.2 mmoles) are added. The reaction mixture is left under stirring for 24 hours at room temperature. The solvent is removed by evaporation at reduced pressure. The obtained crude product is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate 7/3. 2.25 g of the ester are obtained in an oil form. c) Synthesis of the 3-(-insthoxy-Q'-inethyl-2-naphthalenacetyl) thiasolidin-4-carboxylic acid 4 -(nitroxy)butyl ester To a solution of the ester obtained at the end of the previous step (2 g, 4,16 insoles) in acetonitrile (20 ml) silver nitrate (0,65 g, 5 mmoles) is added, The reaction mixture is heated for 5 hours under reflux away front light. The formed salt is removed by filtration and the solution is evaporated at reduced pressure. The obtained residue is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate 7/3. 0.99 g of the 3- (6-methoxy-a-methyl-2-naphthalenacetyl)thia2olidin-4-carboxylic acid 4- (nitroxy)butyl ester are obtained in an oil form, %-NMR {CDCI3): 7.66 (3H, m) , 7.38 (IH, m) , 7.15 {2H, m) , 5.06 (IH, dd), 4,66 (2H, d), 4.51 (2H, t), 4.25 (2H; t), 3.98 {IH, g), 3.92 (3H, s), 3.13 (2H, d), 1.84 (4H, m) , 1.53 (3H, d). EXAMPLE 3 Synthesis of the 3- {6-inethoxy-a-methyl-2-naphthalenacetyl) - (R) -2-oxothiazolidin-4-carboxylic acid 4-(nitroxy) butyl ester (NCX 2150) starting from naproxene (formula VI) and the precursor of B is (L)-2-cxo-4-thiazolidin carboxylic acid (formula ?V) a) synthesis of the 3-(6-methoxy-Q'-methyl-2-naphthalenacetyl)-(R)-2-oxothiazolidin-4-carboxylic acid To a solution of 6-methoxy-a-methyl-2-naphthalenacetic acid (7.0 g, 30.4 mmoles) in toluene (100 ml) and N, N - dime thy 1-formamide (10 ml) cooled at O^C, oxalylchloride (5.23 ml, 61 mmoles) is added. After 2 hours at room temperature the solution is evaporated at reduced pressure. To the solution of the obtained residue dissolved in tetrahydrofuran (50 ml) a mixture is added consisting of 2-oxothiazolidin-4-carboxylic acid (4.07 g, 27.5 mmoles), 4-dimethylairdnopyridine (0.64 g, 6,9 mmoles) , triethylamine (7.69 ml, 55.2 mmoles) in tetrahedron urban (50 ml) cooled at -loc. The mixture is left at room temperature for 24 hours. The reaction mixture is washed with HCl 5%, then with water. The organic phase is anhydrified with sodium sulphate and then evaporated at reduced pressure. The obtained residue is purified by chromatography or silica gel eluting with methylene chloride/methanol 95/5. 6.79 g of the expected product are obtained in the form of an amorphous solid. b) Si-thesis of the 3- ( e-methoxy-cr-methyl-2-naphthalenace- tyl)-(R)-2-cxothia2olidin-4'Carboxylic acid 4-(bromobutyl) Ester To a solution of 3 - ( 6 -methox"y-a'-methyl-2-naphthalenace-tyl) - (R)-2-oxothiasolidin-4-carboxylic acid (£.79 g, 18.9 mom-les) in tetrahydrofuran (100 ml) triphenylphosphine (9. SI g, 37.8 anoles) and carbon tetrabro-mide (12.53 g, 37.8 mmoles) are added. The reaction mixture is left under stirring for 16 hours at room temperature; then the solvent is removed by evaporation at reduced pressure. The obtained crude product is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate 7/3. 1.83 g of the ester are obtained in the form of an oil. c) Synthesis of the 3-( 6-methoxy-Q'-methyl-2-naphthalenacetyl)-(R)'2-oxothiazolidin-4-carboxylic acid 4-(nitro butyl) ester To a solution of the ester obtained at the end of the previous step (1.7 g, 3.44 mmoles) in acetonitrile (20 ml) silver nitrate (0.82 g, 4.B1 insoles) is added. The reaction mixture is heated for 6 hours under reflux away from light. The formed salt is removed b^' filtration and the solution is evaporated under pressure. The obtained residue is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate 7/3. 0.77 g of 3-(6-iuethoxy-a-methyl-2-naphthalenace- tyl)-(K)-2-oxothiazolidin-4-carboxylic acid 4-(nitroxy)butyl ester are obtained in an oil form. %-NMR (CDCI3): 7.74-7.67 {3H, m) , ':'.47 (IH, m) 7.14-7.10 {2H, m), 5.28 (IH, dd), 4.12-3.51 (5K, m), 3.90 (3H, s), 3.63 (IH, dd), 3.33 (IH, dd), 1.55 (3H. d), 1.30-1.23 (4H, m). EXAMPLE 4 Synthesis of [ 2- [ (2, 6-dichlorophenyl)£minor]-benseneacetyloxy] - (L)-histamine 4-(nitroxy)butyl ester lOx] (L)-histidine To a diclofenac solution (3 g, 10.13 rumbles) in tetrahydrofuran (50 ml) cooled at; 1,1'-carbonyldiimidazol (1.69 g, 10.13 mmoles) is added under stirring. After 10 minutes the solution is treated with (L) histidine (1.57 g, 10.13 mmoles) and left -"under stirring at room temperature for 4 hours. The reaction mixture is concentrated under vacuum, treated with methylene chloride and then washed in sequence with HCl 1% and then with water. The organic phase is anhydrified with sodium sulphate and evaporated under vacuum. The obtained residue is purified by chromatography on silica gel column, eluting with ethyl acetate. [2 -[(2,6 -dichlorophenyl)amino] benzeneacetyloxy] (L)-histidine is obtained. b) Synthesis of [2-[(2 6-dichlorophenyl)amino]benzeneacetyloxy] (L)-histidine 4-bromobutyl ester To a solution of [2-[(2,6-dichlorophenyl)amino]benzenea-cetyloxy] (L)-histidine (5 g, 11.54 mmoles) in tetrahydrofuran (100 ml) triphenylphosphine (9.08 g, 34.62 mmoles) and carbon tetra bromide (11.48 g, 34.62 mmoles) are added under stirring. The reaction mixture is left at room temperature for 24 hours, then the solvent is removed by evaporation at reduced pressure. The obtained crude product is purified by chromatography on silica gel eluting with n-hexane/ethyl acerate 1/1. (S)-[2-[ (2, 6 -dichlorophenyl) amino jbenzeneacetylcx-y] (L) -histidine 4 - bromobutyl ester is obtained. c) Syiithesis of [ 2- [ ( 2 , 6-dichlorophenyl)air. no]ben2eneacety- lox] (L)-histidine 4-nitroxybutyl ester To a solution of [ 2-[ ( 2 / 6-dichlorophenyl )airing]benzenea-cetyloxy] (L)-histidine 4-bromobutyl ester (3 g, 5.28 mmoles) in acetonitrile (30 ml) silver nitrate (1.79 g, 10.55 nunol) is added. The reaction mixture is heated under reflux for 6 hours sheltered from the light/ the formed salt is removed by filtration and the solution is evaporated under reduced pressure. The obtained residue is purged by chromatography on silica gel column eluting with n-hexane/ethyl acetate 1/1. [2-[(2,6-dichlorophenyl)amino]benseneacetyloxy] (L)-histidine 4-nitroxybutylester is obtained. Yield 35%. EXAMPLE 5 Synthesis of 5-[[4-oxo-(4-nitroxybutyloxy)butanoyl]amino]-1,2/3,4-tetrahydroacridine wherein the precursor drug of the invention coxripound is terrine of formula (XXXV) and the precursor compound of the bridging group B is succinic acid of formula (RI): a) Synthesis of succinic acid 4-chlorobutyl monoester To a solution of succinic anhydride (2 g, 19.58 xnmoles) in chloroform (30 ml), cooled at, N,N'- (4.2 g, 20. 35 xnmoles ■ sisal 4-ciinethylajninopyridine (100 mg, 0.8 mmoles) are added under stirring. After 30 minutes 4-chlorobutanol (2.1 g, 19,35 mmoles) is added. The reaction mixture is left at room temperature for 7 hours under stirring, then it is acidified with HCl 5% and it is extracted with ethyl acetate. The organic phase is washed with brine, anhydrified with sodium sulphate and evaporated at reduced pressure. The crude product is purified by chroinatography on silica gel column eluting with methylene chloride/methanol 8/2. Succinic acid 4-chlorobutyl monoester is obtained. b) Synthesis of 5-[[4-Oxo-(4-chlorobutyloxy)butanoyl]amino]- 1/2,3,4-tetrahydroacridine To a solution of succinic acid 4-chlorobutyl monoester (2.9 g, 10.02 mmoles) in N,N-dimethylformamide (30 ml), cooled at 0°C, N,N'-dicyclohexylcarbodiimide (2.2 g, 10.66 mmoles) and 4-dimethylaminopyridins (100 mg, 0.8 mmoles) are added under stirring. After 5 minutes terrine (2 g, 10,08 mmoles) is added. The reaction mixture is left a- room temperature for 24 hours, then acidified with HCl 5% and extracted with ethyl acetate. The organic phase is washed with brine, anhydrified with sodium sulphate and evaporated at reduced pressure. The crude product is purified by chromatography on silica gel eluting with methylene chloride/methanol £/2. 5-[ [4-oxo-(4-chlorobutyloxy)-butanoyl]amino]-1,2,3,4 -tetrahydroacridine is obtained. c) synthesis of 5-[[4-Oxo-{4-nizroxybutyloxy)butanoyljamino]-1,2,3,4-tetrahydroacridine To a solution of 5-[4-oxo-(4-chlorobutyloxy)butanol]-amino]-1;2,3;4-tetrahydroacridine (3 g, 7,71 mmoles) in acetonitrile (50 ml) silver narrate (1.79 g, 10.56 mmoles) is added under stirring. The reaction mixture is heated under reflux for 36 hours away from light::/ the formed salt is removed by filtration and the solution is evaporated at reduced pressure. The obtained residue is purified by chromatography on silica gel column eluting with ethyl acetate. 5-[[4-oxo-(4-nitroxybutyloxy)butanoyl]amino]-1,2,3,4-tetrahydroacridine is obtained. Yield 27%. EXAMPLE 6 Synthesis of [ 4-amino- [ 4-oxo' (4 -nitroxybutyloxy)butanoyl ] -1-hyroxybutyliden] biphosphonic acid wherein the precursor drug of the invention compound is alendronic acid of finagle (XXX^/I) and the precursor compound of the bridging group 3 is succinic acid of formula (RI); The compound is synthesized following the synthesis procedure reported in Example 5. Yield 19%. EXAMPLE 7 Synthesis of [ 4-oxo- { 4-nitroxybutyloxy)butanoyl 4- ( 2-ainino-3 , 5-dibromophenyl) -methylaiaino ] cyclohexanol ester wherein the precursor drug of the invention compound is am-broxol of formula (XII) and the precursor compound of the bridging group B is succinic acid of formula (RI): a) Synthesis of 4 - [ ( 2-Tert-bucoxycarbonylainino-3 , 5-dibromophe- nil)methylamine] trans cyclohexanol To a mixture of 4- [ ( 2-amino-3 , 5-dibromophenyl )methylairiino-]cyclohexanol (5 g, 13.22 mmoles) in dioxane (35 ml) and water (50 ml), triethylajTiine (3.31 ml, 23.7 mmoles) and di-tert-butyl dicarbonate (3.46 g, 15.66 mmoles) are added under stirring. After 24 hours the solution is concentrated under vacuum, treated with HCl 1% until having neutral pH in the solution, and it is extracted with ethyl acetate. The organic phase is anhydrified with sodium sulphate and evaporated under vacuum. 4 - [ ( 2 - tert - butoxycarbonylamino -3,5 - dibromophenyl) methyl aim -no]cyclohexanol is obtained which is used without further purification. b) Synthesis of [4-Oxo-(4 -chlorobutyloxy)butanoyl]-4 -(2-tert- butoxycarbonylamino- 3 , 5-dibromophenyl) methylamino] cycle- hexapod ester To a solution of succinic acid 4-chlorobutyl monoester (4 g; 19.18 mmol) in tetrahydrofuran (40 ml) , 1,1'-carbonyl-diimidazol (3.4 g, 20.96 mmoles) is added under stirring. After 10 minutes the solution is treated with 4-[ (2-tert-butoxycarbo-nylamino-3, 5-dibromophenyl) methyl amino]cyclohexanol (9.8 g, 20.5 mmoles) and it is left at room temperature for 4 hours. The reaction mixture is concentrated under vacuum, treated with methylene chloride, washed with HCl 1% and then with water. The organic phase is anhydrified with sodium sulphate and evaporated under vacuum. The obtained residue is purified by chromatography on silica gel column, eluting with n-hexane/ethyl acetate 1/1. [4-oxo- ( 4-chlorobutyloxy)butanoyl-4-( 2 -tert-butoxycarbonylamino-3.5-dibromophenyi) methylamino] cyclohexanol ester is obtained. c) Synthesis of [4-Oxo-(4-nitrox%^butyloxy)butanoyl-4 -(2-tert- butoxycarbonylamino-3,5-dibromophenyi) methylamino] cyclohexanol ester To a solution of [4-oxo-{4-chlorobutyloxy)butanoyl-4-(2-tert-butoxycarbonylamino- 3 , 5-dibromophenyi) methylamino] cyclohexanol ester (4 g, 5.9 8 mmoles) in acetonitrile (70 ml) silver nitrate (1.5 g, 8.83 mmoles) is added under stirring. The reaction mixture is heated under reflux for 24 hours away from light, the formed salt is removed by filtration and the solution is evaporated at reduced pressure. The obtained residue is purified by chromatography on silica gel eluting with n-hexane/ethyl acetate 7/3. [4-oxo-(4-nitroxy-butyloxy)butanoyl-4-(2-tert-butoxycarbonylamino-3,5-dibromophenyl) methylamino] cyclohexanol ester is obtained. d) synthesis of [4-[4-Oxo-(4-nitroxybutyloxy)butanoyl](2-amino- 3,5- dayroom phenyl) methylamino] cyclohexanol ester To a solution of [4-oxo-{4-nitroxybutyloxy)butanoyl-4-(2-tert-butoxycarbonylamino-3,5-dibromophenyi) methylamino] cyclohexanol ester (3.2 g, 4.6 mmoles) in ethyl acetate (50 ml) ; cooled at ethyl acetate/HCl 5N (6.5 ml) is added under stirring. The -solution is left at D°C for 4 hours, the precipitate is filtered. The obtained carded product is treated with ethyl acetate and with 5% sodium bicarbonate, then with water. The organic phase is anhydrified wilh sodium sulphate and evaporated at reduced pressure, [4-oxo-(4-nitro- xybutyloxy) butanoyl - {2- airJ_nc o , 5 - dibrcro phenyl) methylamino ] cyclohexanol ester is obtained. Yield 17*. PHARMACOLOGICAL TESTS EXAMPLE Acute Toxicity Acute toxicity has been evaluated by adminisL-ering to a group of 10 rats weighing 20 g a single dose of each of the tested compounds, by canola, by so in an ac--eons suspension of carboxymethylcellulose 2% w/v. The animals are kept under observation for 14 days. In no animal of the group toxic symptoms appeared even after administration of a 100 mg/Kg dose. EXAMPLE Fl Test 1 - experimental model in vivo with N-ethylmaleimide (NEM): study of the gastric tolerability of some drugs screened as precursors of the compounds of the invents-ion. The animals (rats, weight about 200 g) are distributed in the following groups (No. 10 animals for group): A) Control groups: 1 group: treatment: only carrier (caribous suspension 1% w/v of carboxyTT.ethylcellulose, dose: 5 ml/Kg when the drug is administered by so, physiologic solution when by parenterally route), 2° group: treatment: carrier N'EM, B) Groups administered with each drug: group I: treatment: carrier The drugs assayed in this experiment are the following (Table I): indomethacin, ambrcxcl, mesa amine, sodic alendronate ; terrine, omeprazole, misoprostol. Indomethacin, amoroso and alendronate are administered by OS, mesalamine by intracolonic (rectal) route and tacrine, ome-prazol, misoprostol by subcutaneous route. The maximum tolerated dose; determined by administering each substance by the above said routes to the animals not treated with NEM, is reported in Table I. With higher doses than those reported in the Table; neuropathy, diarrhea, depression, tremor and sedation have appeared in the animals. In this experimental model the animals are at first treated with NEM by subcutaneous injection at a dose of 25 mg/kg in physiologic solution. The drug is administered one hour later, in suspension in the carrier. Animals are sacrificed after 24 hours and evaluation of the damage to the gastrointestinal mucosa is made by counting the number of rats, inside each group, with lesions to the stomach at a visual inspection. The total number of said rats is then divided by the total number of rats of the group and multiplied by 100. The thus obtained percentages are reported in Table I. The Table shows that in the groups of rats treated with said drugs without NEM, no gastric lesions were detectable. All the rats of group II (treated with NEM) showed gastric lesions after adrrdnistration vita the following drugs: indo-methacin, amoroso; mesalairdne, sodic alendronate, tacrine. Said drugs therefore can be used in the synthesis of the products of the invention. Omeprazole and misoprostol cannot instead be used, on the basis of the results provided in test 1, for preparing the products of the invention. EXAMPLE F2 Test 2 (in vitro): inhibition of apoptosis (DNA fragmentation) induced in the endothelial cells by CIP in the presence of some drugs screened as precursors of the compounds of the invention. The following precursor drugs (Table II): indomethacin, paracetamol; clopidogrel, salbutamol, amoroso, sodic alendronate , diphylline, satirizing; enalapril, nicotinamide, am-pickling, aciclovir, mesalairdne, tacrine, simvastine, OMe -pyrazol have been tested. Human endothelial cells of the umbilical vein are prepared according to a standard method, fresh umbilical veins are filled with a collagenase solution 0.1% by weight and incubated at 37'='C for 5 minuses. Subsequently the veins are perfused with the medium M 199 (GIBCO, Grand Island, MY) pH 7.4 vita 0.1% (weight/volume) of collagenase, added with 10% of bovine fetus serum (10 mcg/ml), sodium heparin (50 rr.cg/ml) , thiinidine (2.4 mcg/ml) , glutamine (230 mcg/ml) , penicillin (100 Ul/ml), streptomycin (100 mcg/ml) and streptomycin 5 (0.125 mcg/ml). The cells are collected from -he perforate by centrifugation at 800 rpm and harvested in culture flasks T-75, pretreated with human fibronectin. Cells are rhea harvested in the same medium, added with bovine hypothalamic growth factor (100 ni/ml). When the cells of the primary cell culture (the cells directly removed from ex-vivo umbilical vein) form a single layer of confluent cells (about 8,000,000 cells/flask); harvesting is stopped and the layers are washed and trypsinized. The cellular suspensions are transferred into wells of a culture plate having 24 wells, half of said wells being added with the same culture medium containing the drug at a 10*% concentration, and harvested in a thermostat at 37 at a constant moisture (90%), CO2 = 5%. When the drug is not soluble in the culture medium, it is formerly dissolved in a small amount of di-methylsulphoxide. The maximum amount of dimethylsulphoxide which can be added to the culture medium is 0.5%. Only the cells coming from these first subcultures are used for the tests with cumene hydroperoxide (CI?). The cells are identified as endothelial cells ■ by morphological examination and by the specific immunological reaction towards factor VIII; these cultures did never show contaminations from yachts or fibroblasts. Before starting the test, the cellular culture medium is removed and the cellular layers are carefully washed with a standard physiologic solution buffered with phosphate 0.1 M pH 7.0. at the temperature of 37 . The content of each well is then incubated for one hour with a CI? suspension in the culture medium at a 5 mM concentration. Evaluation of the cellular damage (apoptosis) is carried out by determining the per cent variation of the DNA fragmentation in the cultures containing hue drug + CIP with respect to the controls treated with CIP only. Said % variation of DNA fragmentation is determined by evaluating the fluorescence variation by a BX60 Olympus microscope (Olympus Co, , Roma) set at the wave length of 405-450 nm, of the test samples with respect to the optical density of the controls. The fluorescence of each sample was determined on 5 replicates, Statistic evaluation has been made with t Student test (p Results are given in Table II skid show that indomethacin, paracetamol,. clopidogrel, salbutamol, sodic alendronate, diphylline, satirizing, enalapril, nicotinamide, ampicilline, aciclovir, tacrine, omeprazole do not significantly inhibit apoptosis; these drugs can therefore be used for preparing the products of the invention. On the contrary ainbrcxol, laesalanine and simvastatine inhibit apoptosis. Therefore on the basis of the results of test 2 these compounds could not be used for preparing the products of the invention, EXAMPLE F3 Test 3 - experimental in vivo model with K"-nitro-L-argentine-methyl ester (L-NAME): gastric tolerability (gastrointestinal damage incidence), hepatic (GPT dosage, glutei - pyruvic transaminase) and cardiovascular {blood pressure) tolerability of some drugs screened as precursors of the compounds of the invention. The experimental model adopted is according to J. Clint. Investigation 90, 278-281,1532. The endothelial"dysf-unction is evaluated shy determining the damage induced by L-NAME administration to the gastrointestinal mucosa, the hepatic dirge (GPT increase) , and the vascular endothelium or cardiovascular damage as blood hypertension. The animals (rats, average weight 200 g) are divided in groups as herein below described. The group receiving L-NAME is treated for 4 weeks with said compound dissolved at the concentration of 400 mg/liter in drinking grater. The following groups (No. 10 animals for group) are constituted: A) Control groups: 1° group: treatment: only carrier (aqueous suspension 1% w/v of carboxymethylcelluLose; dose: 5 ml/Kg when the drug is administered tee so, physiologic solution when by parenterally roué), 2 group: treatment: carrier - L-NAME, B) Groups treated with the drug: 3° group: treatment: carrier -^ drug, 4° group: treatment: carrier drug + L-NA2 The drugs used in the test are paracetamol, doxorubicin, simvastatine, omeprazole and misoprostol. Each drug is administered once a day for 4 weeks. The maximum tolerated dose of the drug being administered to the animals is determined evaluating, in a separate dose scaling up experiment on untreated animals, the appearance in the animals of symptoms such as entreaty, diarrhea, depression, tremor, sedation, At the end of the four weeks access to water is prevented and after 24 hours the animals are sacrificed. One hour before the sacrifice blood pressure is determined and a blood pressure increase is taken as an indication of a damage being occurred to vascular endothelium. The damage to the gas :ric -mucosa is evaluated as previously mentioned in test '.. (ex. Fl). The hepatic damage is determined by evaluation after the sacrifice of the glutamic-pyruvic transaminase (GPT increase). The drug meets test 3 and it can therefore be used for preparing the compounds of the invention, when in the group of rats treated with L-NAME + drug + carrier, an higher hepatic damage (higher GPT values) and/or higher gastric damage and/or higher cardiovascular damage (higher blood.pessure) are found in comparison with the group treated with the carrier only, or the group treated with carrier + drug, or the group treated with carrier + L-NAME. The test results are reported in Table IV, The % gastric lesions have been determined as in Test 1. The % GPT and % blood pressure values are referred to the corresponding value found in the animals of the 1st group of the control groups. The average value of the blood pressure in this group was of 105 ± 8 mmHg. The results obtained show that paracetamol, doxorubicin and sirrrvastatine cause hepatic damage and gastroenteropathy (GPT values and the gastric lesions are % higher compared both with the corresponding groups treated with the drug, in the absence of L-NAME, and with the controls treated with L-NAME) . These drugs can therefore be used for preparing the products of the invention. Omeprazole and misoprostol should not instead be used, on the basis of this test, for preparing the products of the invention. EXAMPLE F4 Test 4: inhibition of the radical production frown DPPH of some substances used as precursors of B or Bl (ref. Formulas I aid II of the invention) The method is based on a colorimetric test in which DPPH (2; 2-diphenyl-l-picryl-hydrazyl) is used as the compound-forming radicals (M.S. Nester et Al. , Atherosclerosis. Thrombus. 15, 1338-1344; 1995). Solutions in methanol of the tested substances at a final concentration 100 uM are initially prepared. 0,1 ml of each of these solutions are added to aliquots of 1 ml of a methanol solution 0.1 M of DPPH and then the final volume is brought to 1.5 ml. After having stored the solutions at room temperature away from light for 30 minutes, the absorbance at the wave length of 517 nm is read. It is determined the absorbance decrease with respect to the absorbance of a solution containing the same concentration of DPPH. The efficacy of the test compound to inhibit the production of radicals, or antiradical activity, is expressed by the following formula: {1 - As/A(.)X100 wherein Ag and A^ are, respectively, the absorbance values of the solution containing the test compound together + DPPH and of the solution containing only DPPH. The compound to be used according to the present invention does not meet test 4 if it inhibits radical production as ago- vet defined by a percentage of 50% or higher. In Table V the results obtained with the following substances are reported: N-acetylcisteine, cysteine, ferules acid, (L)-Caroline/ gent sic acid, 4-thiazolidin carboxylic acid and 2-OXO-4-thiazolidincarboxylic acid. Table V shows that: N-acetylciSteine, cysteine, ferule acid, (L)-Caroline, gneissic acid .meet test 4 since they inhibit the production of radicals induced by DPPH in an extent higher than 50%, therefore they cannot be used as precursors of B or B- of the compounds of the invention. 4-Thiazolidin carboxylic acid and 2-oxo-4-thiazolidincarboxylic acid do not meet test 4 since they do not inhibit radical production from DPPH in an extent cereal or higher than 50%, and therefore they can be used as precursors of compounds B or B according to the present invention, provided they meet following test 5. EXAMPLE F5 Test 5t inhibition of the radical production from Fe from compounds used as precursors of B, B or C = -T-Y-H 0.1 ml aliquots of 10'- M ethanolic solutions of 4-thiazolidin carboxylic acid and 2-oxo-4-thia2olidin carboxylic acid are added to test tubes containing an aqueous solution formed by mixing 0»2 ml of 2 mM deoryribose, 0.4 rally of buffer phosphate pH 7.4 100 mM and 0.1 ml of 1 mM Fe^^ (KH4 >2(S04)2 in 2mM HCl. The test tubes are rhea kept at a temperature of 37 for one hour. Then in each test tube are added in the order 0.5 ml of. a 2.8% solution in trichloroacetic acid in water and 0.5 ml of an aqueous solution 0.1 M thio barbituric acid. A reference blank is constituted by substituting the above 0.1 ml aliquots of the test compound methanolic solutions with 0.1 ml of methanol. The test tubes are closed and heated in an oil bath at 100°C for 15 minutes, A pink coloration develops the intensity of which is proportional to the quantity of deoxyribose undergone to radical oxidative degradation. The solutions are cooled at room temperature and their absorbance at 532 nm are read against the blank. The inhibition induced the precursor of B or B: or C = -T-Y-H (wherein the free valence is saturated as above defined) in the confront of radical production from Fe'- is determined as a percentage by means of the following formula: (1 - As/Ac)Clod wherein Ag and A are respectively the absorbance values of the solution containing the tested compound + the iron salt and that of the solution containing only the iron salt. The results are reported in Table III, from which it is drawn that both acids meet test 5, since they inhibit radical production from Fe in a percentage higher than 50%. Therefore both 4-thiasolidin carboxylic acid and 2-cxo-4-thiazolidin carboxylic acid can be used as precursors of 3, B;;_ or of C = -T-Y-H, for obtaining the compounds of chem. present invention, EXAMPLE F6 Gastric tolerability test of the compounds according to the invention in the confront of hue corresponding precursor drugs in conditions of endothelial dysfunctions induced by L-NAME (N'nitro-L-argentine-methyl ester) . Example F3 was repeated and it was evaluated the gastric tolerability both of the following precursor drugs and of the corresponding derivatives according to he present invention: Diclofenac and the corresponding derivative according to Ex. 4. Amoroso and the corresponding derivative according to Ex. 7, Alendronate and the corresponding derivative according to Ex. 6. Tacrine and corresponding derivative according so Ex. 5. The results are reported in Table VI and show that, by administering at the same dose the compounds of the invention and the corresponding precursor drug, naturopathy incidence results remarkably reduced or disappeared in the groups treated with the compounds of the invention. EXAMPLE 8 Synthesis of 3-[2-(acetyl)benzoyljthiasolidin-4-carboxylic acid-4-(nitroxy)b-butyl ester meant r (formula XCI). starting from acetylsalicylic acid (XCII) and thiazolidin-4-carboxylic acid (formula PIV) EXAMPLE 10 Synthesis of 3-[[2-[4-[(4-chlorophenyl)phenylinethyl]-1-pyperazinyl]ethoxy]acetyl]-thiazolidin-4 -carboxylic acid-4 -(nitroxy)butyl ester of formula {XCV] EX?^MPLE 11 Synthesis of N[(S)l-[N[l-(ethoxycarbonyl)-3-phenylpropyl]L- Albany]-L-praline] histamine 4(nitric)butyl ester of formula (XCVIII) EXAMPLE 13 Synthesis of 3- [a- ( 2-chlorophenyl) -6 , 7-dihydro-t.liienol[ 3 . 2-c]pyridine - 5(4H)acetyl]thiazolidin-4 -carboxylic acid 4 -(nitroxy)butyl ester of formula (XCXII) Compound (XCXII) is obtained according to the procedure followed in Example 1. Yield : 15%. Elemental analysis' calculated % C 51.15 H 4.85 N 7.78 S 11.87 CI 6.55 found% C 55.48 H 5.60 N 7.61 S 11.85 CI 6.59 EXA3?g>LE 14 Synthesis of own- [1- [5- ( 2, 5-dihydro-5-cxo~3-furanyl) -3-xnethyl-2- benzofuranyl]ethyloxy-4-oxo-butanoyl] cysteine 4(nitroxy)butyl EXAMPLE 16 Synthesis of 5-inethoxy-2- [ [ [ 4-oxo-4- (nitroxy jbutyryloxy] -3,5-dixnethyl- 2-pyridinyl Dimethyl ] sulphinyl ] -IH-bens imidazol of formula (XCXVIII) starting from 4-hydroxyomeprazols of formula (XXII) and succinic acid of formula (RI) Compound (XCXVIII) was obtained following the procedure described in Example 7. Yield 15% Elemental analysis calculated % C 52.64 H 4.97 N 10.23 S 5.86 found% C 52.68 H 5.01 N 10.15 S 5.81 EXAMPLE 17 Synthesis of] ]-2,2-dimethylbutanoic acidl,2,3,7,8,8-hexahydro-3,7-dimethyl- 8 -[2 -[tetrahydro-4-14-oxo- (4-nitroxybutyloxy)butiryloxy ] - 6-oxo-2H-piran-2-yl ] ethyl ] -1-naphthalenyl ester of formula (XCXIX) starting from simvastatine of formula {XXI) clan succinic acid of formula (RI) (XXI) (RI) Compound (XCXIX) was synthesized following the procedure of Example 7. Yield 12%. Elemental analysis calculated % C 62.35 H 7,77 N 2.20 fluid% C 62.50 H 7.81 N 2.17 EXAMPLE 18 Synthesis of 3 - [ 4 - D-a- ainincbenzylpenicillaminoyl ] thiazolidin carboxylic acid 4 -(nitroxy)butyl ester of formula (XCXX) starting from ampicillin of formula (XVI) and 2-oxo- 4 -tbiazolidin carboxylic acid of formula (PV) Compo-and (XCXX) was obtained following the procedure of Example 3. Yield 19%. Elemental analysis calculated % C 48.39 H 4.91 N 11,76 S 10.77 found% C 48.43 H 4.99 N 11.71 S 10.74 EXAMPLE 19 Synthesis of 9-[ [2-[4-oxo-(4-nitroxybutylcxy)butiryloxy] ethoxy] -methyl ]guanine of formula (XCXXI) Synthesis of ( 8S-cis) -10[ (5-aminO; 2,3, 6-tri-deoxy-a-L-lyxo-exo pyrimidyl) oxy ] - 7 , 8 , 9 ,10 -1etrahydro ,5,8,11- trihydroxy - 8 - [ [ [ 4 -ox- {4-niuroxybutyloxy)butyric-oxy- ]methyi-oxo] -l-methoxy-S , 12-naphtacenedione of formula (XCXXII) EXAMPLE F7 ExaTL©ls Fl was repeated with four groups of rats (each group of ten anural) , ail of them receiving NEM, and orally administered as it follows : a. control group : the vehicle .formed of an aqueous suspension 1% v;/v of carboxymethylcellulose, b. one group (group b - corporative ) administered at the same time with 5 mg/Kg (0.02 mmoles/Kg) of flurbiprofen + 2.7 mg/Kg (0.02 mmoles/Kg) of 4-thia2olidin carboxylic acid in the same above vehicle, c. one group (group c - comparative) administered at the same time with 7.4 ma/Kl (0.02 mmoles/Kg) of 4-(nitroxy)butyl ester of f turboprop en synthesised according to the method described in vole 94/12463, +2.7 mg/Kg (0.02 mmoles/Kg) of 4-thia2olidin carboxylic in the same above vehicle, d. one group (group d) administered with 9.B mg/Kg (0.02 mmoles/Kg) of 3- [2-f fluoro-a-methyl- (1,1' -biphenyl) -4-ace- tyl]thiazclidin'4-carboxylic acid 4-(nitroxy)butyl ester synthetics as from Ex. l ( indicated as NO-Flurbiprofen in Table VII), in the above same vehicle. The results are reported in Table VII and show that the mixtures administered respectively to groups b and c (corporative), differently from the cot pound of the invention administered to group d, were almost ineffective (group b) or much less effective (group c) in reducing gastric lesions. WE CLAIM: 1. Compounds or their salts having the following general formula (I): Wherein: s - 2; boo = 1; A = R-Ti-, wherein R is the radical of the drug, as defined hereunder, having the formula R-Ti-Z or R-Ti-OZ in which Z is H or C1-C5 alkyl, selected from the following classes: anti-inflammatory drugs: acetylsalicylic acid, 5- amino acetylsalicylic acid, carrageen, diclofenac sodium, diflunisal, iodole, flufenamic acid, flummoxing, flurbiprofen, ibuprofen, indomethacin, indoprofen, ketoprofen, ketorolac, lornoxicam, loxoprofen, meclofenamic acid, mefenamic acid, meloxicam, mesalamine, nap oxen, inflame acid, olsalazine, piroxicam, salsa late, sulfide, supreme, enoxacin, saprogenic acid, tolfenamic acid, tormenting, zomepirac; analgesic drugs: acetaminophen, acetylsalicylsalicylic acid, benoxaprofen, treadle; bronchodilators drugs: salbutamol, carbuterol, clenbuterol, fenoterol, metaproterenol, pirbuterol, salmeterol, terbutaline; expectorant: ambroxol, bromating, guanacos; antihistaminic drugs: cetirizine, levocabastine, terfenadine; ACE-inhibitors: alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, imidapril, lisinopril, losartan, moveltipril, naphthopidil, perindopril, quinapril, ramipril, spirapril, temocapril, trandolapril, urapidil; beta blockers: acebutolol, alprenolol, amosulalol, arotinolol, atenolol, betaxolol, bevantolol, bucumolol, bufetolol, bufuralol, bunitrolol, bupranolol, butofilol, carazolol, carteolol, carvedilol, celiprolol, cetamolol, dilevalol, epanolol, esmolol, indenolol, labetalol, mepindolol, metipranolol, metoprolol, moprolol, nadolol, nadoxolol, nebivolol, nifenalol, nipridalol, oxprenolol, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, sulfinalol, talinolol, tertatolol, tilisolol, timolol, toliprolol, xibenolol; antithrombotic and vasoactive drugs: argatroban, benfurodil hemisuccinate, clopidogrel, dalteparin, dipyridamole, enoxaparin, iloprost, ozagrel, triflusal; antidiabetic drugs: nicotinamide; antitumoral drugs: anthramycin, daunorubicin, doxorubicin, epirubicin; antiulcer drugs: cimetidine, omeprazole, pantoprazole; antihyperlipidemic drugs: atorvastatin, fluvastatin, lovastatin, pravastatin sodium salt, simvastatin; antibiotics drugs: amoxicillin, ampicillin/ aztreonam, biapenem, carbenecillin, cefaclor, cefadroxil, cefamandole, cefatrizine, cefoxitin, dicloxacillin, imipenem, moxalactam, panipenein, bacampicillin; antiviral drugs: acyclovir, famciclovir, ganciclovir, penciclovir, vidarabine, zidovudine; bone resorption inhibitors: alendronic acid, neridronic acid, pamidronic acid; antidementia drugs: tacrine; Ti = (CO), 0, S, N or NRic wherein Ric is H or C1-C5 alkyl; B = -TB-X2-TBI- wherein TB and TOBY are equal or different and can be selected from (CO) , O, S, N or Uric wherein Rica is as above defined; X2 is a bivalent bridging group such as the corresponding precursor of B, having the formula Z'-TB-X2-TBI-Z' in which Z', Z' are independently H or OH, is selected from the following compounds: - Amino acids: asp artic acid (PI), histamine (PII), 5-hydroxytryptophan (P'ill) , 4-thiazolidincarboxylic acid (PIV), 2'0x0-4-thiazolidincarboxylic acid (PV): wherein: nix is an integer between 0 and 3; null is an integer between 1 and 3; RITA' equal to or different from each other are H or a linear or branched C1-C4 alkyl; Y^ is a saturated, unsaturated or aromatic heterocyclic ring containing at least one nitrogen atom, said ring having 5 or 6 atoms; or Y is Yo, selected from the following: an alkylene group R'O wherein R' is linear or when possible branched C1-C2o alkyl, or a cycloalkyl having from 5 to 7 carbon atoms, in the cycloalkylenic ring one or more carbon atoms can be replaced by heteroatoms, the ring can have side chains of R' type, R' being as above defined; or 4. The compounds as claimed in claim 3, wherein Y is Y12 (pyridyl), substituted in position 2 and 6. 5. The compounds or salts, or their compositions as claimed in claims 1 to 4 for use as drugs. 6. A pharmaceutical formulation containing the compounds or their salts as claimed in claims 1 to 4 and a pharmaceutically acceptable carrier.

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