Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
  • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
  • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D277/38—Nitrogen atoms
  • C07D277/44—Acylated amino or imino radicals
  • C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
  • A61K31/425—Thiazoles
  • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/04—Anorexiants; Antiobesity agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/04—Antibacterial agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/12—Antivirals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
  • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
  • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
  • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

• the invention relates to 2-carbamide-4-phenylthiazole derivatives, to their preparation and to their therapeutic application.
• Y represents a hydrogen atom or a halogen
• R 3 represents:
• R 7 is selected from the group consisting of: • - (C 1 -C 8 ) alkyl-COO- (C 1 -C 8 ) alkyl, -CO- (C 1 -C 8 ) alkyl wherein the alkyl is substituted by at least one halogen atom,
• -SO 2 -phenyl wherein the phenyl is substituted by at least one -O- (C 1 -C 8 ) alkyl, -SO 2 -heteroaryl group where the heteroaryl is a pyrazole, an isoxazole or an imidazole and wherein the heteroaryl is independently substituted with at least one group selected from halogen or - (C r C 8 ) alkyl,
• R 7 is as previously defined
• R 8 is selected from the group consisting of:
• heteroaryl O -SO 2 -heteroaryl wherein the heteroaryl is a pyrazole, an isoxazole or an imidazole and wherein the heteroaryl is optionally independently substituted with at least one group selected from halogen or - (C 1 -C 8 ) alkyl, • -SO 2 -N ((C r C 8 ) alkyl) 2 ,
• R 8 , R 9 , Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh are as defined above,
• R 8 , R 9 , Ra, Rb, Rc, Rd Re, Rf, Rg and Rh are as defined above, in the form of base or acid addition salt, and in the state hydrates or solvates.
• a preferred halogen is a fluorine.
• the compounds of formula (I) may comprise one or more asymmetric carbon atoms. They can therefore exist as enantiomers or diastereoisomers. These enantiomers, diastereoisomers, as well as their mixtures, including the racemic mixtures, form part of the invention.
• the compounds of formula (I) may exist in the form of bases or addition salts with acids. Such addition salts are part of the invention. These salts are advantageously prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful, for example, for the purification or the isolation of the compounds of formula (I) are also part of the invention.
• the compounds of formula (I) may also exist in the form of hydrates or solvates, namely in the form of associations or combinations with one or more water molecules or with a solvent. Such hydrates and solvates are also part of the invention.
• t and z may take the values from 1 to 10, a carbon chain which can have from t to z carbon atoms, for example Ci -3 a carbon chain which can have from 1 to 3 carbon atoms; a halogen atom is, for example, a fluorine, a chlorine, a bromine or an iodine; an alkyl group: a linear or branched saturated aliphatic group, optionally substituted by a halogen atom.
• a cycloalkyl group a cyclic alkyl group.
• a perfluoroalkyl group an alkyl radical, as defined above, for which all the carbon atoms are substituted by fluorine atoms.
• R 1 , R 2 , R 3 and Y are as previously defined.
• Preferred compounds of the invention of the formula (La) are those in which R 1 is in the 2-position and R 2 is in the 5-position of the phenyl.
• Compounds of the invention of formula (La) are those in which R 1 is in the 2-position and R 2 is in the 5-position of the phenyl.
• R 1 represents a group -O- (C -), C 8 ) alkyl and / or;
• R 2 represents a (C 1 -C 8 ) alkyl, (C 3 -C 10 ) cycloalkyl, perfluoro (Cr C 4 ) alkyl or -O- (C 1 -C 8 ) alkyl group.
• R 1 represents a group -O- (C 1 -C 8 ) alkyl and / or;
• R 2 represents a group (C 3 -C 10 ) cycloalkyl or -O- (C 1 -C 8 ) alkyl.
• R 3 represents a group of formula - (CH 2 ) a -A where a represents 1, 2 , 3 or 4, and A is selected from the group consisting of:
• R 7 , R 1, R 2 , Y and p are as defined above.
• R 3 represents a group of formula -CO (CH 2 ) trA where b represents 0, 1, 2, 3 or 4, and A is selected from the group consisting of:
• R 7 , R 1, R 2 , Y and -p are as previously defined.
• R 1 , R 2 , Y- and p are as defined above.
• R 7 , R 1 , R 2 , Y and p are as defined above.
• R 7 is selected from the group consisting of • - (C 1 -C 8 ) alkyl-COO- (C 1 -C 8 ) alkyl
• -SO 2 -phenyl wherein the phenyl is substituted by at least one -O- (C 1 -C 8 ) alkyl, -SO 2 -heteroaryl group wherein the heteroaryl is a pyrazole or isoxazole or imidazole and wherein heteroaryl is independently substituted by at least one group selected from halogen or - (C 1 -C 8 ) alkyl,
• M + is an alkali metal cation selected from Li + , Na + and K + , and when there are two alkyl or cycloalkyl substituents bonded to the nitrogen atom, they can be independently identical or different.
• R 7 represents -SO 2 - (C 3 -C 10 ) cycloalkyl.
• R 3 represents a group of formula - (CH 2 ) a -C where a represents 1 , 2, 3 or 4, and C is selected from the group consisting of:
• R 8 , R 9 , Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, R 1 , R 2 , Y and p are as defined above.
• R 3 represents a group of formula -CO (CH 2 ) b -C in which b represents 0, 1, 2, 3 or 4, and C is selected from the group consisting of:
• R 8 , R 9 , Ra, Rb, Rc, Rd, Re, Rf 1 Rg, Rh, R 1 , R 2 , Y and p are as defined above.
• R 8 , Ra, Rb, Rc, Rd, R 1 , R 2 , Y and p are as defined above.
• R 8 , R 9 , Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, R 1 , R 2 , Y and p are as defined above.
• the sixth group include a subgroup of compounds for which R 8 is a hydrogen atom or a (C r -C 8) alkyl alkyl.
• Certain intermediates useful for the preparation of the compounds of formula (I) may also serve as the final product of formula (I), as will appear in the examples given below.
• certain compounds of formula (I) of the invention may serve as useful intermediates for the preparation of compounds of formula (I) according to the invention.
• the protective group Gp is understood to mean a group that makes it possible, on the one hand, to protect a reactive function such as a hydroxyl or an amine during a synthesis and, on the other hand, to regenerate the intact reactive function. at the end of synthesis.
• Examples of protecting groups and methods of protection and deprotection are given in "Protective Groups in Organic Synthesis", Green et al., 2nd Edition (John Wiley & Sons, Inc., New York).
• the term "leaving group X" in the following is understood to mean a group that can be easily cleaved from a molecule by breaking a heterolytic link, starting from an electronic pair. This group can thus be easily replaced by another group during a substitution reaction, for example.
• Such leaving groups are, for example, halogens or an activated hydroxyl group such as mesyl (methanesulfonyl), tosyl (toluenesulfonyl), triflate, acetate, etc.
• Examples of leaving groups as well as references for their preparation are given in Advances in Organic Chemistry, J. March, 3 rd Edition, Wiley Interscience, p. 310-316.
• the precursor of R 1 , R 2 or R 3 , a substituent RY R ' 2 or R' 3 can be converted into R 1 , R 2 and R 3 by one or more chemical reactions.
• group Z is meant in the following, a leaving group or a functional carboxylic acid derivative, such as an acid chloride, a mixed or symmetrical anhydride, or the acid suitably activated for example with benzotriazol-1-yloxytris (dimethylamino) phosphonium hexafluoro phosphate (BOP), O-benzotriazol-1-yl-NNN'.N'-tetramethyluronium hexafluorophosphate (HBTU) or O-benzotriazol-1-yl-NNN'.N'-tetramethyluronium tetrafluoroborate (TBTU).
• benzotriazol-1-yloxytris dimethylamino) phosphonium hexafluoro phosphate
• HBTU O-benzotriazol-1-yl-NNN'.N'-tetramethyluronium tetrafluoroborate
• TBTU O-benzotriazol-1-y
• R 1, R ' 2 and / or R' 3 represent a group containing an amine or hydroxyl function
• these functions may be protected intermediately: an amino function may be protected by an alkanoyl group, benzyl, te / t-butoxycarbonyl (Boc), benzyloxycarbonyl, or 9-fluorenylmethoxycarbonyl (Fmoc), for example; a hydroxyl function can be protected in the form of ether or ester, for example.
• the compounds of the invention may be prepared according to various methods described in this patent application. According to another aspect, the present invention relates to processes for preparing the products of formula (I) and their intermediate products.
• the compounds of formula (I) of the invention may be prepared according to general scheme 1 below.
• the compounds of the invention are obtained by coupling of the aminothiazole derivative of formula (II) in which R 1 , R 2 , Y are as defined above, with an amino derivative of formula (III) wherein R ' 3 represents a precursor group of R 3 or a group R 3 as defined in the foregoing and p is as defined in the foregoing.
• aminothiazole derivatives of formula (II) can be obtained according to the methods described in the patent application WO2004 / 096798.
• the aminothiazole derivative of formula (II) is brought into the presence of a coupling agent for a period of 2 to 16 hours, then with the amino derivative of formula (III) for a period of 0.5 to 4 hours.
• the coupling agent may be chosen from those known to those skilled in the art, for example phosgene, di- (N-succinimidyl) carbonate, 1,1'-carbonyl-diimidazole, according to the methods described in "Encyclopedia of Reagents for Organic Synthesis, LA Paquette, Volume 2, p 1006; volume 4, p 2304; volume 6, p 4107.
• the reaction can be carried out in various solvents, for example dichloromethane, dimethylformamide, toluene, in the presence of a base such as triethylamine, K 2 CO 3 , at a temperature varying from 0 ° C. at 100 ° C.
• a base such as triethylamine, K 2 CO 3
• amino derivatives of formula (III) are known or can be prepared according to the methods described in particular in document WO 87/01706 or according to the methods described in the following.
• the groups A 'and C respectively represent a precursor group of group A or C, or a group A or C as defined above.
• the compounds of formula (III) in which R ' 3 represents a precursor group of R 3 or a group R 3 as defined above and in which p is as defined in the foregoing, are obtained from compounds of formula (IV) by deprotection of the nitrogen of piperazine or protected homo-piperazine according to methods known to those skilled in the art or described in the literature (WO03 / 104230 and WO03 / 057145). For example, we can proceed as follows:
• the compounds of formula (IV) are commercially available or can be synthesized from commercial compounds, according to methods known to those skilled in the art.
• the compounds of formula (IV), in which R 3 represents a precursor group of the group R 3 with R 3 representing a group -CO (CH 2 ) t rA or -CO (CH 2 ) b -C (compounds of formula (IV .2) or (IV.5)), can also be obtained according to the following diagram 2:
• TBTU or CDI in a solvent such as, for example, THF, acetonitrile or DMF at temperatures ranging from 0 ° C. to 150 ° C.
• a reducing agent such as NaHB (OAc) 3 , NaBH 3 CN
• solvent such as 1,2-dichloroethane, dichloromethane, methanol
• the reaction is carried out without solvent or in a solvent such as tetrahydrofuran, dimethylformamide, toluene, or acetonitrile in the absence of base or in the presence of a base such as triethylamine or K 2 CO 3 , at temperatures ranging from room temperature to 200 ° C for a period of 1 to 24 hours.
• the B 'and D' ketones used are commercial or can be synthesized according to the methods described in Organic Process Research & Development, 2004, 8, 939; Synthesis, 1989, 10, 767
• the compounds of formula (I) may also be prepared according to scheme 6 below.
• the starting compounds and reagents when their method of preparation is not described, are commercially available or described in the literature, or they can be prepared according to methods described therein or which are known to those skilled in the art.
• DCM dichloromethane
• DlPEA diisopropylethylamine
• BOP benzotriazol-1-yl-oxy-tris (dimethylamino) -phosphonium hexafluorophosphate
• TBTU 2- (1H-Benzotriazol-1-yl) -1,1,3,3-tetramethyluroniumtetrafluoroborate
• BSA bis (trimethylsilyl) acetamide
• AcOEt ethyl acetate
• PF Melting Point (in degrees Celsius) as measured on a B ⁇ chi B545 apparatus with a temperature gradient of 1 ° C per minute.
• - MH + molecular mass of the form of the molecule ionized by a proton.
• the compounds are analyzed by coupling HPLC - UV - MS (liquid chromatography - UV detection - mass spectrometry).
• the device marketed by Agilent, consists of an HP1100 chromatograph equipped with an Agilent diode array detector and MSD Quad quadrupole mass spectrometer.
• NMR nuclear magnetic resonance performed with a Bruker Avance 200 spectrometer (200 MHz).
• the solvent used is deuterated DMSO and the chemical shifts are expressed relative to the TMS.
• - OC D rotary power.
• a solution of 4.0 g of the compound obtained in step 1.2 in 30 ml of methanol is hydrogenated in a closed reactor, under irradiation with microwaves, at 80 ° C. for 10 min in the presence of 1.7 g of Pd / C at 10% wet and 2.02 g of ammonium formate.
• the medium is filtered and then evaporated to give 2.89 g of a colorless oil.
• the medium is filtered, the solid is rinsed with ether and then taken up in DCM and treated with 1M sodium hydroxide.
• the organic phase is washed with water and then with saturated NaCl solution. After drying over MgSO 4 , the solution is concentrated to give 3.16 g of the desired compound.
• Example 5 3 - ((R) -3- [4- (4-Cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl-piperazin-1-ylmethyl] -piperidin-1-yl) -propionic acid (Compound No. 5)
• 0.31 ml of 5M sodium hydroxide is added at 0 ° C.
• the medium is stirred for 24 hours at RT.
• the medium is concentrated and then taken up in the water.
• a solution of 6N HCl is added dropwise until a precipitate appears.
• the solid is extracted in DCM and after drying over MgSO 4 , the organic phase is concentrated to give 0.15 g of the expected product.
• Example 6 4- (Tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl-amide (Compound No. 11 This compound can be obtained according to the process described in Preparation 1.4 between 4- (5-cyclohexyl-2-methoxyphenyl) thiazol-2-amine and 1- (tetrahydro-2H-pyran-4-yl) piperazine described in J. Med. Chem .; IN; 47; 11; 2004; 2833 - 2838.
• the medium is diluted in DCM.
• the organic phase is washed twice with saturated NaHCO 3 solution and then with saturated NaCl solution. After drying over MgSO 4 , the organic phase is concentrated to give 0.16 g of crude.
• the solid is purified by flash chromatography on silica gel to give 0.12 g of the expected compound in the form of a white solid.
• Chemokines are low molecular weight proteins that belong to the family of proinflammatory cytokines and are involved in the chemotaxis of leukocytes and endothelial cells. Chemokines control many biological processes and are associated with inflammatory disorders that occur during stress, injury or infection; modulation of the effects of chemokines makes it possible to prevent or treat pathologies such as asthma, arthritis, allergies, autoimmune diseases, atherosclerosis or angiogenesis (CD, Paavola et al., J. Biol Chem., 1998, 273, (50), 33157-33165).
• pathologies such as asthma, arthritis, allergies, autoimmune diseases, atherosclerosis or angiogenesis
• hMCP-1 of the human human monocyte chemotactic protein
• the inhibitory activity of the compounds according to the invention was measured on cells expressing the human CCR2b receptor.
• the concentration of natural agonist hMCP-1 which inhibits 50% (Cl 50 ) of CCR2b receptor activity is 0.57 nM.
• the compounds according to the invention have an IC50 generally of between 0.1 ⁇ M and 0.1 nM, and preferably between 100 nM and 0.1 nM.
• reaction buffer PBS buffer, 50 nM Hepes, 1 mM CaCl 2 , 5 mM MgCl 2 0.5% BSA without fatty acid, adjusted to pH 7.4.
• Reaction buffer PBS buffer, 50 nM Hepes, 1 mM CaCl 2 , 5 mM MgCl 2 0.5% BSA without fatty acid, adjusted to pH 7.4.
• compound no. 9 showed a Cl 50 of 4 nM
• compound no. 10 showed a Cl 50 of 53 nM, compound no.
• the compounds according to the invention can therefore be used for the preparation of medicaments, in particular chemokine effect-antagonizing drugs.
• the present invention relates to medicaments which comprise a compound of formula (1), or an addition salt thereof to a pharmaceutically acceptable acid, or a hydrate or a solvate.
• - diseases and acute and chronic immuno-inflammatory syndromes such as atherosclerosis, restenosis, chronic lung diseases, in particular COPD ( chronic obstructive pulmonary disease); respiratory distress syndrome; Bronchial hyperactivity; colitis; silicosis; fibrous pathologies, pulmonary fibrosis, cystic fibrosis; viral or bacterial infections, AIDS, meningitis, malaria, leprosy, tuberculosis, herpes, cytomegalovirus infections; septic shock, sepsis, endotoxic shock; rejection of transplants; bone pathologies such as osteoporosis, osteoarthritis; conjunctivitis; atypical dermatitis or contact dermatitis; eczema; glomerulonephritis; pancreatitis; ulcerative colitis, autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, lateral amyotrophic
• the present invention relates to pharmaceutical compositions comprising, as active principle, a compound according to the invention.
• These pharmaceutical compositions contain an effective dose of at least one compound according to the invention, or a pharmaceutically acceptable salt, a hydrate or solvate of said compound, as well as at least one pharmaceutically acceptable excipient.
• excipients are chosen according to the pharmaceutical form and the desired mode of administration, from the usual excipients which are known to those skilled in the art.
• the active ingredient of formula (I) above, or its salt, solvate or hydrate may be administered in unit dosage form, in admixture with conventional pharmaceutical excipients, to animals and humans for the prophylaxis or treatment of the above disorders or diseases.
• Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, oral, intratracheal, intraocular, intranasal forms of administration. by inhalation, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants.
• the compounds according to the invention can be used in creams, gels, ointments or lotions.
• a unitary form of administration of a compound according to the invention in tablet form may comprise the following components: Compound according to the invention 50.0 mg
• the dose of active ingredient administered per day can reach 0.1 to 1000 mg / kg, in one or more doses.
• the dosage appropriate to each patient is determined by the physician according to the mode of administration, the weight and the response of said patient.
• the present invention also relates to a method of treatment of the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention, or one of its pharmaceutically acceptable salts or hydrates or solvates.

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