MXPA06007934A

MXPA06007934A - Thiazole derivatives and use thereof

Info

Publication number: MXPA06007934A
Application number: MXPA/A/2006/007934A
Authority: MX
Inventors: Wolfgang Sauer; Matthias Schwarz; Anna Quattropani; Thomas Rueckle; Jerome Dorbais; Christophe Cleva; Gwenaelle Desforges
Original assignee: Applied Research Systems Ars Holding Nv; Christophe Cleva; Gwenaelle Desforges; Jerome Dorbais; Anna Quattropani; Thomas Rueckle; Wolfgang Sauer; Matthias Schwarz
Priority date: 2004-01-12
Filing date: 2006-07-11
Publication date: 2006-12-13

Abstract

The present invention is related to thiazole derivatives of Formula (I) in particular for the treatment and/or prophylaxis of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplantation, graft rejection or lung injuries.

Description

DERIVATIVES OF TIAZOL AND USE OF THEM FIELD OF THE INVENTION The present invention relates to the use of thiazole derivatives of Formula (I) for the treatment and / or prophylaxis of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, allergy, asthma, pancreatitis, failure of multiple organs, kidney diseases, platelet aggregation, cancer, sperm motility, rejection of grafts or lung injuries. Specifically, the present invention relates to thiazole derivatives for modulation, especially the inhibition of the activity or function of the phosphoinositide-3-kinases, PI3K.

BACKGROUND OF THE INVENTION Phosphoinositide 3-kinases (PI3K) have a critical signaling role in cell proliferation, cell survival, vascularization, membrane movement, glucose transport, neurite excrescence, membrane folding, superoxide production, actin rearrangement and chemotaxis (Cantley, 2000, Science, 296, 1655-1657 and Vanhaesebroeck et al., 2001, Annu., Rev. Biochem., 70, 535-602).

The term PI3K is given to a family of lipid kinases that in mammals, consist of eight identified PI3K that are divided into three subfamilies according to their structure and substrate specificity. The Class I group of PI3K consists of two subgroups, Class IA and Class IB. Class IA consists of an 85 kDa regulatory unit (responsible for protein-protein interactions via the interaction of the Src 2 homology 2 (SH2) domain with the phosphotyrosine residues of other proteins) and a catalytic subunit of 110 kDa . Three catalytic forms (p100a, P110β and p110d) and five regulatory isoforms (p85a, p85β, p55 ?, p55a and p50a) exist for this class. Class IB is stimulated by the ß subunits? of the G protein of heterodimeric G proteins. The only characterized member of the Class IB is PI3K? (catalytic subunit p110? complexed with a regulatory protein of 101 kDa, p101). Class II PI3Ks comprise isoforms α, β, and α, which are approximately 170 kDa and are characterized by the presence of a C 2 C terminal domain. Class III PI3Ks include the 3-kinases specific for phosphatidylinositol. The p110a and ß isoforms conserved in an evolutionary way are expressed in a ubiquitous way, while d and? are expressed more specifically in the system of hematopoietic cells, the cells of the smooth muscle, myocytes and endothelial cells (Vanhaesebroeck et al., 1997, Trends Biochem Sci., 22 (7), 267-72). Its expression can also be regulated in an inducible manner, depending on the type of cell tissue and the stimuli, as well as the context of the disease. PI3K are enzymes involved in phospholipid signaling and are activated in response to a variety of extracellular signals such as growth factors, mitogens, integrin hormones (cell-cell interactions), cytokines, viruses and neurotransmitters and also by intracellular cross-regulation by other signaling molecules (crosstalk, where the original signal can activate some parallel trajectories that in a second step, transmit the signals to PI3K by intracellular signaling events), such as small GTPases, kinases or phosphatases, for example. Phosphatidylinositol (Ptdlns) is the basic building block for intracellular inositol lipids in eukaryotic cells, consisting of D-myo-inositol-1-phosphate (Insl P) linked via its phosphate group to diacylglycerol. The higher inositol group of Ptdlns has five free hydroxy groups and three of these are found to be phosphorylated in the cells in different combinations. Ptdlns and their phosphorylated derivatives are collectively referred to as inositol phospholipids or phosphoinositides (Pls). Eight species of Pl have been documented in eukaryotic cells (Vanhaesebroeck et al., 2001, above). The PIs all reside in the membranes and are substrates for the kinases, phosphatases and lipases.

In vitro, PI3K phosphorylates the 3-hydroxyl group of the inositol ring on three different substrates: phosphatidylinositol (Ptdlns), phosphatidylinositol-4-phosphate (PI (4) P) and phosphatidylinositol-4,5-bisphosphonate (PI ( 4,5) P2), respectively, generating three lipid products, namely phosphatidylinositol-3-monophosphate (PI (3) P), phosphatidylinositol-3,4-bisphosphonate (PI (3,4) P2) and phosphatidylinositol-3, 4,5-trisphosphate (PI (3,4,5) P3 (see Reaction Scheme A below).

PI. { 3) P (3-phosphatidylsitotrophophosphate) Reaction Scheme A The preferred substrate for Class I PI3K is PI (4,5) P2. Class II PIK has a strong preference for Ptdlns as a substrate over PI (4) P and PI (4,5) P2. Class III PI3K can only use Ptdlns as a substrate in vivo and are probably responsible for the generation of most PI (3) P in cells (Vanhaesebroeck et al, 2001, above). The pathway of intracellular signaling of phosphoinositides begins with the binding of a signaling molecule (extracellular ligands, stimuli, receptor dimerization, transactivation by the heterologous receptor (eg, receptor tyrosine kinase)) to a transmembrane receptor bound to the protein G, integrated into the plasma membrane that results in the activation of PI3K. Once activated, the PI3K converts the phospholipid of the membrane Pl (4,5) P2 to PI (3,4,5) P3 which in turn can also be converted into another 3 'phosphorylated form of the phosphoinositides by the phosphoinositide phosphatases 5 'specific, thus, the enzymatic activity of PI3K results directly or indirectly in the generation of two subtypes of 3'-phosphoinositide that functions as second messengers in the transduction of the intracellular signal (Leslie et al., 2001, Chem. Rev. 101 (8) 2365-80; Katso et al., 2001, Annu., Rev. Cell Dev. Biol. 1, 615-75 and Toker et al, 2002, Cell Mol. Life Sci. 59 (5) 761-79). The role as second messengers of the phosphorylated products of Ptdlns is involved in a variety of transduction signal pathways, including those essential for proliferation cellular, cell differentiation, cell growth, cell size, cell survival, apoptosis, adhesion, cell motility, cell migration, chemotaxis, invasion, cytoskeletal rearrangement, changes in the form of the cell, the movement of the gallbladder and the metabolic pathway (Steln, 2000, Mol. Med. Today 6 (9) 347-57). Chemotaxis, the directed movement of cells towards a concentration gradient of chemical attractants, also called chemokines, is involved in many important diseases such as inflammation / autoimmunity, neurodegeneration, angiogenesis, invasion / metastasis and wound healing (Wyman et al. ., 2000, Immunol Today 21 (6) 260-4, Hirsch et al., 2000, Science 287 (5455) 1049-53, Hirsch et al., 2001, FASEB J. 15 (11) 2019-21 and Gerard et al. al., 2001, Nat Immunol, 2 (2) 108-15). The activation of PI3-kinase, therefore, is believed to be involved in a range of cellular responses including cell growth, differentiation and apoptosis (Parker et al., 1995, Current Biology, 5, 577-99; Yao et al., 1995, Science, 267, 2003-05). Recent biochemical studies have revealed that Class I PI3K (eg, PI3K isoform of Class IB) are double specific kinase enzymes, ie, they show both lipid kinases (phosphoinositide phosphorylation) activity and protein kinase activity , since they are able to induce phosphorylation of other proteins as substrates, including autophosphorylation as an intramolecular regulatory mechanism.

PI3K appears to be involved in several aspects of leukocyte activation. It has been shown that an activity of PI3-kinase associated with p85 is physically associated with the cytoplasmic domain of CD28, which is an important costimulatory molecule for the activation of T lymphocytes in response to antigen (Pages et al., 1994, Nature, 369, 327-29). These effects are linked to increases in the transcription of several genes, including interleukin-2 (IL2), an important growth factor of T lymphocytes (Fraser et al., 1991, Science, 251, 313-16). The mutation of CD28 so that it can interact with PI3-kinase leads to failure to initiate IL2 production, suggesting a critical role for PI3-kinase in the activation of T lymphocytes. The cellular processes in which PI3K plays an essential role include the suppression of apoptosis, reorganization of the actin skeleton, cardiac myocyte growth, stimulation of glycogen synthase by insulin, neutrophil priming mediated by TNFa and generation of superoxide, and migration of leukocyte and adhesion to cells endothelial PI3K? has been identified as a mediator of the beta-gamma G-dependent regulation of JNK activity, where beta-gamma G are subunits of the heterotrimeric g proteins (Lopez-Llasaca et al., 1998, J Biol. Chem. 273 (5) 2505-8). Recently, it has been described that PI3K? it retransmits inflammatory signals through several receptors coupled to G (i) (Laffargue et al., 2002, Immunity 16 (3) 441-51) and is central to the function of the cells of mast cells, stimuli in the context of leukocytes, immunology includes cytokines, chemokines, adenosines, antibodies, integrins, aggregation factors, growth factors, viruses or hormones, for example (Lawlor et al., 2001, J. Cell Sci., 114 (Pt 16) 2903-1 and Stefens et al., 2002, Curr, Opinion Cell Biol. 14 (2), 203-13). Specific inhibitors against the individual members of a family of enzymes provide valuable tools to denigrate the functions of each enzyme. Two compounds, LY294002 and wortmanin (see hereafter), have been widely used as inhibitors of PI3-kinase. These compounds are non-specific PI3K inhibitors, since they do not distinguish between the four PI3-kinase members of Class I.

The IC5o values of the wortmanin against each of the several PI3-kinases of Class I are in the range of 1-10 nM, and the Cl50 values for the LY294002 against each of these PI3-kinases are approximately 15 -20 μM (Fruman et al., 1998, Ann. Rev. Biochem., 67, 481-507), also 5-10 mM in protein kinase CK2 and some inhibitory activity in phospholipases. Wortmanin is a fungal metabolite that irreversibly inhibits the activity of PI3K by covalently joining the catalytic domain of this enzyme. The inhibition of PI3K activity by wortmanin eliminates the subsequent cellular response to the extracellular factor (Thelen et al., 1994, Proc Nati Acad Sci USA, 91, 4960-64). Experiments with wortmanin show that the activity of PI3K in hematopoietic lineage cells, particularly neutrophils, monocytes and other types of leukocytes, are involved in many of the non-immune memory responses associated with acute inflammation or chronicle. Based on the studies using the wortmanin, there is evidence that the function of the PI3-kinase is also required for some aspects of leukocyte signaling through the G-protein coupled receptors (Thelen et al., 1994). In addition, it has been shown that wortmanin and LY294002 block neutrophil migration and superoxide release. However, since these compounds do not distinguish between the various isoforms of PI3K, it remains unclear which particular isoform or isoforms of PI3K are involved in this phenomenon. Some results have indicated that inhibitors of PI3K, for example, LY294002, can increase antitumor activity in vivo of certain cytotoxic agents (e.g., paclitaxel) (Grant, 2003, Current Drugs, 6 (10), 946-948). Recently, 5-phenylthiazole derivatives have recently been developed as inhibitors of PI3K (WO 03/072557). The high relevance of the trajectory of PI3K in some widely dispersed diseases accentuates the need to develop inhibitors, including selective inhibitors of PIK.

BRIEF DESCRIPTION OF THE INVENTION It is an object of the invention to provide substances that are suitable for the treatment and / or prevention of disorders related to the phosphoinositide-3-kinases, PI3K. It is also an object of the present invention to provide substances that are suitable for the treatment and / or prevention of autoimmune and / or inflammatory disorders. It is also an object of the present invention to provide substances that are suitable for the treatment and / or prevention of cardiovascular diseases. It is also an object of the present invention to provide substances that are suitable for the treatment and / or prevention of neurodegenerative disorders.

It is also an object of the present invention to provide substances that are suitable for the treatment and / or prevention of a disorder selected from bacterial and viral infections, kidney diseases, platelet aggregation, cancer, transplants, graft rejection, lung lesions., respiratory diseases and ischemic conditions. Notably, it is an object of the present invention to provide chemical compounds that are capable of modulating, especially inhibiting the activity or function of the phosphoinositide-3-kinases, PI3K in disease states in mammals, especially humans. It is a further object of the present invention to provide a new category of pharmaceutical formulations for the treatment of and / or mediated diseases, selected from autoimmune, inflammatory disorders, cardiovascular diseases, neurodegenerative disorders, bacterial and viral infections, kidney diseases, platelet aggregation, cancer. , transplants, rejection of grafts, lung injuries, respiratory diseases and ischemic conditions. It is finally an object of the present invention to provide a method for the treatment and / or prevention of disorders selected from autoimmune, inflammatory, cardiovascular diseases, neurodegenerative disorders, bacterial and viral infections, kidney diseases, platelet aggregation, cancer, transplants, rejection of grafts or lesions of the lung, respiratory diseases and ischemic conditions.

In a first aspect, the invention provides thiazole derivatives of Formula (I): (i) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and X are defined in the detailed description below, to be used as a medicament. In a second aspect, the invention provides a pharmaceutical composition comprising a compound of Formula (I), together with a pharmaceutically acceptable excipient or carrier. In a third aspect, the invention provides the use of a compound of Formula (I) for the preparation of a pharmaceutical composition useful for a variety of therapies, including alleviating, preventing and / or treating a disorder selected from autoimmune, inflammatory disorders, diseases cardiovascular diseases, neurodegenerative disorders, bacterial and viral infections, renal diseases, platelet aggregation, cancer, transplants, rejection of grafts or lung lesions, respiratory diseases and ischemic conditions and other diseases and disorders associated with phosphoinositide-3-kinases, PI3K.

In a third aspect, the invention provides a method for treating a patient suffering from a disorder selected from autoimmune, inflammatory, cardiovascular diseases, neurodegenerative disorders, bacterial and viral infections, kidney diseases, platelet aggregation, cancer, transplants, graft rejection. or lung injuries, respiratory diseases and ischemic conditions and other diseases and disorders associated with phosphoinositide-3-kinases, PI3K. The method comprises administering a compound according to the Formula (I) In a fourth aspect, the invention provides the use of a thiazole according to the invention for the preparation of a pharmaceutical formulation for the treatment of a disorder selected from autoimmune, inflammatory disorders, cardiovascular diseases, neurodegenerative disorders, bacterial and viral infections, diseases renal, platelet aggregation, cancer, transplants, rejection of grafts or lung lesions, respiratory diseases and ischemic conditions and other diseases and disorders associated with phosphoinositide-3-kinases, PI3K. In a fifth aspect, the invention provides thiazole derivatives of Formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and X are defined in the detailed description.

DETAILED DESCRIPTION OF THE INVENTION The following paragraphs provide the definitions of various chemical moieties constituting the compounds according to the invention, and are intended to be applied uniformly throughout the specification and the claims unless stated otherwise than the definition given provides a definition. more espacious. "CrC6 alkyl" refers to monovalent alkyl groups having from 1 to 6 carbon atoms. Ester term is exemplified by groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, terbutyl, n-hexyl and the like. "Aryl" refers to an unsaturated carbocyclic aromatic group of 6 to 14 carbon atoms, having a single ring (e.g., phenyl) or multiple fused rings (e.g., naphthyl). Aryl includes phenyl, naphthyl, phenanthrenyl and the like. "C 6 alkyl alkylaryl" refers to C 1 -C 6 alkyl group having an aryl substituent, including benzyl, phenethyl and the like. "Heteroaryl" refers to a monocyclic heteroaromatic group, or a bicyclic or tricyclic heteroaromatic group of fused rings. Particular examples of heteroaromatic groups include pyridyl, pyrrolyl, pyrimidinyl, furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2. , 3-oxadiazolyl, 1,4-oxadiazolyl, 1, 2,5-oxadiazolyl, 1,4-oxadiazolyl, 1,4-triazinyl, 1,2,3-triazinyl, benzofuryl, [2,3-dihydro] benzofuryl, isobenzofuryl, benzothienyl, benzotriazolylisobenzothienyl, indolyl, isoindolyl, 3H-indolyl, benzimidazolyl, imidazo [1,2-a] pyridyl, benzothiazolyl, benzoxazolyl, quinolicinyl, quinazolinyl, phthalazinyl, quinoxalinyl, cinolinyl, naphthyridinyl, pyrid [3,4-b] pyrid It, pyrido [3,2-b] pyridyl, pyrido [4,3-b] pyridyl, quinolin, isoquinolyl, tetrazolyl, 5,6,7,8-tetrahydroquinolyl, 5,6,7,8-tetrahydroisoquinolyl optionally substituted, purinyl, pteridinyl, carbazolyl, xanthenyl or benzoquinolyl. "C-pCe alkylheteroaryl" refers to C6 alkyl groups having a heteroaryl substituent, including 2-furylmethyl, 2-thienylmethyl, 2- (1H-indol-3-yl) ethyl and the like. "C2-C6 alkenyl" refers to alkenyl groups having, preferably, 2 to 6 carbon atoms and having at least 1 or 2 sites of alkenyl unsaturation. Preferred alkenyl groups include ethenyl (-CH = CH2), n-2-propenyl (allyl, -CH2CH = CH2) and the like. "C2-C6 alkenylaryl" refers to C2-C6 alkenyl groups having an aryl substituent, including 2-phenyl vinyl and the like. "C2-C6 alkenylheteroaryl" refers to C2-C6 alkenyl groups having a heteroaryl substituent, including 2- (3-pyridinyl) vinyl and the like. "C2-C6 alkynyl" refers to alkynyl groups, preferably having 2 to 6 carbon atoms and having at least 1 -2 sites of alkynyl unsaturation, preferred alkynyl groups include ethynyl (-C = CH), propargyl (-CH2C = CH), and the like. "C2-C6 alkynylaryl" refers to C2-C6 alkynyl groups having an aryl substituent, including phenylethynyl and the like. "C2-C6 alkynyl heteroaryl" refers to alkynyl groups of C2-C6 having a heteroaryl substituent, including 2-thienylethynyl and the like. "C3-C8 cycloalkyl" refers to a saturated carbocyclic group of 3 to 8 carbon atoms, having a single ring (e.g., cyclohexyl) or multiple fused rings (e.g., norbornyl). C3-C8 cycloalkyl includes cyclopentyl, cyclohexyl, norbornyl and the like. "Heterocycloalkyl" refers to a C3-C8 cycloalkyl group according to the above definition, in which up to 3 carbon atoms are replaced with heteroatoms selected from the group consisting of O, S, NR, R being defined as hydrogen or methyl. Heterocycloalkyl includes pyrrolidine, piperidine, piperazine, 1-methylpiperazine, morpholine, tetrahydrofuran and the like. "C 6 alkyl alkylcycloalkyl" refers to C 1 -C 6 alkyl groups having a cycloalkyl substituent, including cyclohexylmethyl, cyclopentylpropyl and the like. "CrC6 alkylheterocycloalkyl" refers to C- | -C6 alkyl groups having a heterocycloalkyl substituent, including 2- (1- pyrrolidinyl) ethyl, morpholinylmethyl, morpholinylethyl, morpholinylpropyl, piperidinylethyl, tetrahydrofuranylmethyl and the like. "Carboxy" refers to the group -C (0) OH. "CrC6 alkylcarboxy" refers to C6 alkyl groups having a carboxy substituent, including 2-carboxyethyl and the like. "Arylcarboxi" refers to aryl groups having a carboxy substituent, including carboxylic acid, hydroxamic acid, amide, 1- (4-benzyl-piperazin) -carbonyl, N- (aminoketic acid methyl ester) carbonyl, N- (acid aminoacetic) carbonyl, N- (3-aminopropionic acid methyl ester) carbonyl, N- (3-aminopropionic acid) carbonyl and the like. "Acyl" refers to the group -C (0) R, wherein R includes "CTCß alkyl", "aryl", "heteroaryl", "C3-C8 cycloalkyl", "Heterocycloalkyl", "CrC6 alkylaryl" or "C-C6 alkylheteroaryl". "C -C6 alkylaryl" refers to alkyl groups of CrC6 having an acyl substituent, including 2-acetylethyl and the like. "Alkylacyl of C -? - C6" refers to C -? - C6 alkyl groups having an acyl substituent, including acetyl, benzoyl and the like. "Arylacil" refers to aryl groups having an acyl substituent, including 2-acetylphenyl and the like. "Heteroarylacil" refers to heteroaryl groups having an acyl substituent, including 2-acetylpyridyl and the like.

"(Hetero) C3-C8 cycloalkylacyl" refers to cycloalkyl or heterocycloalkyl groups of 3 to 8 members having an acyl substituent, including 4-acetyl piperidine, 4-benzoyl piperidine and the like. "Acyloxy" refers to the group -OC (0) R, wherein R includes H, "Ci-Cβ alkyl", "C2-C6 alkenyl", "C2-C6 alkynyl", "C3-C8 cycloalkyl" "," heterocycloalkyl, "" heterocycloalkyl "," aryl "," heteroaryl "," alkylaryl of CI-CT "or" C 1 -C 6 alkylheteroaryl "," C2-C6 alkenylaryl "," C2-C6 alkenylheteroaryl "," alkylaryl C2-C6"," C2-C6 alkynyl-heteroaryl "," C-C6-alkylcycloalkyl "," C6-C6-alkylheterocycloalkyl "and the like. "Alkylalkoxy of C C6" refers to alkyl groups of CrC6 having an acyloxy substituent, including ethyl ester of aminopropionic acid and the like. "Alkoxy" refers to the group -O-R, wherein R includes "C-i-Ce alkyl" or "aryl" or "heteroaryl" or "C-C6 alkylaryl" or "C- | -C6 alkylheteroaryl". Preferred alkoxy groups include, by way of example, methoxy, ethoxy, phenoxy and the like. "Alkylalkoxy of C C6" refers to C -? - C6 alkyl groups having an alkoxy substituent, including methoxy, methoxyethyl and the like. "Alkoxycarbonyl" refers to the group -C (0) OR, wherein R includes H, "C6-alkyl" or "aryl" or "heteroaryl" or "C-C6 alkylaryl" or "CrC6 alkylheteroaryl" and the similar.

"CrC6 alkylalkoxycarbonyl" refers to C-1-C5 alkyl groups having an alkoxycarbonyl substituent, including 2- (benzyloxycarbonyl) ethyl and the like. "Aminocarbonyl" refers to the group -C (0) NRR ', wherein each R, R' independently includes hydrogen or alkyl or aryl or heteroaryl of C? -C6 or "alkylaryl of CrC6" or "alkylheteroaryl of CrC6"? and the similar. "C Cβ alkylaminocarbonyl" refers to C6 alkyl groups having an aminocarbonyl substituent, including 2- (dimethylaminocarbonyl) ethyl and the like. "Arylaminocarbonyl" refers to aryl groups having an aminocarbonyl substituent, including aminoacetyl and the like. "Acylamino" refers to the group NRC (0) R ', wherein each R, R' are, independently hydrogen, "CrC6 alkyl", "C2-C6 alkenyl", "C3-C8 cycloalkyl", "heterocycloalkyl", "aryl", "heteroaryl", "C6 alkylaryl" or "C6 alkylheteroaryl", "C2-C6 alkenylaryl", "C2-C6 alkenylheteroaryl", "C2-C6 alkynylaryl", "C2-C6 alkynylheteroaryl", "CrC6 alkylcycloalkyl", "C -Cß alkylheterocycloalkyl" and the like. "Alkylamino of C Cß" refers to C? -C6 alkyl groups having an acylamino substituent, including 2- (propionylamino) ethyl and the like. "Ureido" refers to the group -NRC (0) NR'R ", wherein each R, R ', R" is, independently hydrogen, "C -? - C6 alkyl", "alkenyl" C2-C6"," C2-C6 alkynyl "," C3-C8 cycloalkyl "," heterocycloalkyl "," aryl "," heteroaryl "," C6 alkylaryl "or" CrC6 alkylheteroaryl "," C2 alkenylaryl " -C6"," C2-C6 alkenylheteroaryl "," C2-C6 alkynylaryl "," C2-C6 alkynylheteroaryl "," C6 alkylcycloalkyl "," CrC6 alkylheterocycloalkyl ", and wherein R 'and R", together with the nitrogen atom to which they are attached, they can optionally form a 3-8 membered heterocycloalkyl ring. "Alkyl ureido of C -? - C6" refers to C -? - C6 alkyl groups having a ureido substituent, including 2- (N'-methylureido) ethyl and the like. "Carbamate" refers to the group -NRC (0) OR ', where each R, R 'is independently hydrogen, "C -? - C6 alkyl", "C2 - C6 alkenyl", "C2 - C6 alkynyl", "C3 - C8 cycloalkyl", "heterocycloalkyl", "aryl" , "heteroaryl", "C6 alkyl alkylaryl" or "C -? - C6 alkylheteroaryl", "C2-C6 alkenylaryl", "C2-C6 alkenylheteroaryl", "C2-C6 alkynylaryl", "C2 alkynylheteroaryl" -C6"," C 1 -C 6 alkylcycloalkyl "," C 6 C alkylheterocycloalkyl ". "Amino" refers to the group -NRR ', wherein each R, R' is independently hydrogen or "Ci-Ce alkyl" or "aryl" or "heteroaryl" or "alkylaryl of C -? - C6" or "Ci-Cβ alkylheteroaryl" or "cycloalkyl", or "heterocycloalkyl", and wherein R and R ', together with the nitrogen atom to which they are attached, can optionally form a 3-8 membered heterocycloalkyl ring.

"Alkylamino of C C6" refers to C5 alkyl groups having an amino substituent, including 2- (1-pyrrolidinyl) ethyl and the like. "Ammonium" refers to a positively charged group -N + RR'R ", wherein each R, R ', R" is independently, "C -? - C6 alkyl" or "C -? - alkylaryl" C6"or" C-C6 alkylheteroaryl "or" cycloalkyl ", or" heterocycloalkyl ", and wherein R and R ', together with the nitrogen atom to which they are attached, can optionally form a 3-8 membered heterocycloalkyl ring . "C 1 -C 6 alkylammonium" refers to C 1 -C 6 alkyl groups, which have an ammonium substituent, including 2- (1-pyrrolidinyl) ethyl and the like. "Halogen" refers to fluorine, chlorine, bromine and iodine atoms. "Sulfonyloxy" refers to a group -OS02-R, wherein R is selected from H, "CrC6 alkyl", "C6 alkyl" substituted with halogens, for example, a group -OSO2-CF3, "alkenyl C2-C6"," C2-C6 alkynyl "," C3-C8 cycloalkyl "," heterocycloalkyl "," aryl "," heteroaryl "," C-C6 alkylaryl "or" C6 alkylheteroaryl ", "C2-C6 alkenylaryl", "C2-C6 alkenylheteroaryl", "C2-C6 alkynylaryl", "C2-C6 alkynylheteroaryl", "C6-6 alkylcycloalkyl", "CrC6 alkylheterocycloalkyl". "C C6 alkylsulfonyloxy" refers to C1-C5 alkyl groups having a sulfonyloxy substituent, including 2- (methylsulfonyloxy) ethyl and the like. "Sulfonyl" refers to a group "-SO2-R", wherein R is selected from H, "aryl", "heteroaryl", "C6-C6 alkyl", "C6-alkyl-C6" substituted with halogens, for example, a group -S02-CF3, "C2-C6 alkenyl", "C2-C6 alkynyl", "C3-C8 cycloalkyl", "heterocycloalkyl", "aryl", "heteroaryl", "C6-C6 alkylaryl" or "C6-C6-alkylheteroaryl", "C2-C6-alkenylaryl", "C2-C6-alkenylheteroaryl", "C2-C6 alkynylaryl", "C2-C6 alkynylheteroaryl", "alkylcycloalkyl" of CrC6"," CrC6 alkylheterocycloalkyl ". "C 6 -alkylsulfonyl" refers to C 5 C alkyl groups having a sulfonyl substituent, including 2- (methylsulfonyl) ethyl and the like. "Sulfinyl" refers to a group "-S (0) -R", wherein R is selected from H, "C alquilo-C6 alkyl" "C6 alkyl" substituted with halogens, eg, a group -SO-CF3, "C2-C6 alkenyl", "C2-C6 alkynyl", "C3-C8 cycloalkyl", "heterocycloalkyl", "aryl", "heteroaryl", "C6 alkylaryl" or "alkylheteroaryl" of CrC6"," C2-C6 alkenylaryl "," C2-C6 alkenylheteroaryl "," C2-C6 alkynylaryl "," C2-C6 alkynylheteroaryl "," C6 alkylcycloalkyl "," C6-C6 alkylheterocycloalkyl " "" Ci-Cß alkylsulfinyl "refers to C5 alkyl groups having a sulfinyl substituent, including 2- (methylsulfinyl) ethyl and the like." Sulfanyl "refers to -SR groups, wherein R includes H, "C6 alkyl", "C6 alkyl" substituted with halogens, for example, an -SO-CF3 group, "C2-C6 alkenyl", "C2-C6 alkynyl", "C3-C8 cycloalkyl" , "heterocycloalkyl", "aryl", "heteroaryl", "alkylaryl of CrC6" or "alkylheteroaryl of C? -C6", "C2-C6 alkenylaryl", "C2-C6 alkenylheteroaryl", "C2-C6 alkynylaryl", "C2-C6 alkynylheteroaryl", "alkylcycloalkyl" of C? -C6"," CrC6 alkylheterocycloalkyl. "Preferred sulfanyl groups include methylsulfanyl, ethylsulfanyl, and the like." CrC6 alkylsulfanyl "refers to C5 alkyl groups having a sulfanyl substituent, including 2- (ethylsulfanyl) ethyl and the like. "Sulfonylamino" refers to a group -NRS02-R ', wherein each R, R 'independently includes hydrogen, "C -? - C6 alkyl", "C2-C6 alkenyl", "C2-C6 alkynyl", "C3-C8 cycloalkyl", "heterocycloalkyl", " "aryl", "heteroaryl", "C6 alkylaryl" or "Ci-Cß alkylheteroaryl", "C2-C6 alkenylaryl", "C2-C6 alkenylheteroaryl", "C2-C6 alkynylaryl", "C2 alkynylheteroaryl" -C6"," CrC6 alkylcycloalkyl "," C6 alkylheterocycloalkyl ". "C 1 -C 5 Alkylsulfonylamino" refers to C 1 -C 5 alkyl groups having a sulfonylamino substituent, including 2- (ethylsulfonylamino) ethyl and the like. "Aminosulfonyl" refers to a group -SO2-NRR ', wherein R, R 'include, independently hydrogen, "C -? - C6 alkyl", "C2-C6 alkenyl", "C2-C6 alkynyl", "C3-C8 cycloalkyl", "heterocycloalkyl", "aryl" , "heteroaryl", "C6 alkyl alkylaryl" or "C6-C6 alkylheteroaryl", "C2-C6 alkenylaryl", "C2-C6 alkenylheteroaryl", "C2-C6 alkynylaryl", "C2-C6 alkenylheteroaryl" , "C6 alkylcycloalkyl", "CrC6 alkylheterocycloalkyl".

"C 6 -Calkylaminosulfonyl" refers to C 1 -C 6 alkyl groups having an aminosulfonyl substituent, including 2- (cyclohexylaminosulfonyl) ethyl and the like. "Substituted or unsubstituted": unless otherwise restricted by the definition of the individual substituent, the groups set forth above, such as the groups "alkenyl", "alkynyl", "aryl", "heteroaryl", "cycloalkyl" , "heterocycloalkyl", etc., may be optionally substituted with 1 to 5 substituents selected from the group consisting of "C? -C6 alkyl", "C2-C6 alkenyl", "C2-C6 alkynyl", "cycloalkyl" "," heterocycloalkyl "," CrC6 alkylaryl "," C-pCe alkylheteroaryl "," CrC6 alkylcycloalkyl "," CrC6 alkylheterocycloalkyl "," amino "," ammonium "," acyl "," acyloxy "," acylamino " "," aminocarbonyl "," alkoxycarbonyl "," ureido "," aryl "," carbamate ", "heteroaryl", "sulfinyl", "sulfonyl", "alkoxy", "sulfanyl", "halogen", "carboxy", trihalomethyl, cyano, hydroxy, mercapto, nitro and the like. "Substituted" refers to groups substituted with 1 to 5 substituents selected from the group consisting of "CrC6 alkyl", "C2-C6 alkenyl", "C2-C6 alkynyl", "cycloalkyl", "heterocycloalkyl", " alkylaryl of CrC6"," C? -C6-heteroaryl "," C12 alkylcycloalkyl "," CrC6 alkylheterocycloalkyl "," amino "," aminosulfonyl "," ammonium "," acylamino "," aminocarbonyl ", "aryl", "heteroaryl", "sulfinyl", "sulfonyl", "alkoxy", "alkoxycarbonyl", "carbamate", "sulfanyl", "halogen", trihalomethyl, cyano, hydroxy, mercapto, nitro, and the like.

"Pharmaceutically acceptable salts or cationic complexes" is intended to define salts such as alkali metal salts (eg, sodium and potassium), alkaline earth metal salts (eg, calcium or magnesium), aluminum salts, salts of ammonium and salts with organic amines such as with methylamine, dimethylamine, trimethylamine, ethylamine, triethylamine, morpholine, N-Me-D-glucamine, N, N'-bis (phenylmethyl) -1, 2-ethanediamine, ethanolamine, dietanolamine, ethylenediamine, N-methylmorpholine, piperidine, benzathine (N, N'-dibenzylethylenediamine), choline, ethylenediamine, meglumine (N-methylglucamine), benetamine (N-benzylphenethylamine), diethylamine, piperazine, tromethamine (2-amino-2-hydroxymethyl- 1,3-propanediol), procaine, as well as amines of the formula -NR, R ', R ", wherein R, R', R" are independently hydrogen, alkyl or benzyl. Especially preferred salts are the sodium and potassium salts. "Pharmaceutically acceptable salts or complexes" refers to salts or complexes of the compounds of Formula (I) identified below, which retain the desired biological activity. Examples of such salts include, but are not limited to, the acid addition salts formed with inorganic acids (eg, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like), and salts formed with organic acids. such as acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalene sulfonic acid, naphthalene disulfonic acid and acid polygalacturonic The compounds can also be administered as pharmaceutically acceptable quaternary salts known to a person skilled in the art, which specifically include the quaternary ammonium salt of the formula -NR, R ', R "+ Z", wherein R, R? "are, independently, hydrogen, alkyl or benzyl, CrC6 alkyl, C-C6 alkenyl, C2-C6 alkynyl, C6 alkylaryl, CrC6 alkylheteroaryl, cycloalkyl, heterocycloalkyl, and Z is a counterion, including chloride, bromide, iodide, -O-alkyl, toluenesulfonate, methyl sulfonate, sulfonate, phosphate or carboxylate (such as benzoate, succinate, acetate, glycolate, maleate, malate, fumarate, citrate, tartrate, ascorbate, cinnamoate, mandeloate and diphenylacetate). "Pharmaceutically active derivative" refers to any compound which, after administration to the container, is capable of directly or indirectly providing the activity described herein. of the present invention are modulators of the Phosphateinositides 3-kinases (PI3K). When the enzyme phosphatoinositide 3-kinase (PI3K) is inhibited by the compounds of the present invention, PI3K is not able to exert its enzymatic, biological and / or pharmacological effects. The compounds of the present invention are therefore useful in the treatment and prevention of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplants, rejection of grafts or lung injuries. The General Formula (I) according to the present invention also comprises its tautomers, its geometric isomers, its optimally active forms such as enantiomers, diastereomers and their racemic forms, as well as the pharmaceutically acceptable salts thereof. Preferred pharmaceutically acceptable salts of Formula (1) are the acid addition salts formed with pharmaceutically acceptable acids such as hydrochloride, hydrobromide, sulfate or bisulfate, phosphate or acid phosphate salts, acetate, benzoate, succinate, fumarate, maleate, lactate, citrate, tartrate, gluconate, methanesulfonate, benzenesulfonate and para-toluenesulfonate. The compounds according to Formula (I), are suitable for modulation, remarkable for the inhibition of the activity of phosphoinositides 3-kinases (PI3K). Therefore, it is believed that the compounds of the present invention are also particularly useful for the treatment and / or prevention of disorders that are mediated by PI3K, particularly PI3K ?. The treatment involves the remarkable modulation of the inhibition or deregulation of the phosphoinositides 3-kinases. The compounds according to Formula (I) are suitable for use as a medicament. In one embodiment, the invention provides thiazole derivatives of Formula (I), wherein R1 is selected from -NR5R6 and -S02R7, preferably -NR5R6; R2, R3 and R5 are, independently of H, optionally substituted C-? - C6 alkyl, including methyl, optionally substituted C2-C6 alkenyl and optionally substituted C2-C6 alkynyl; R4 is selected from H; optionally substituted C-pCβ alkyl, including methyl and ethyl; C2-C6 alkenyl optionally substituted; optionally substituted C2-C6 alkynyl; and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted C6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C2-C6 alkynyl; optionally substituted CrC6 alkylalkoxycarbonyl, including ethyl propanoate; optionally substituted C-? -C6 alkylaryloxy, including the amino-propionic acid ethyl ester; R 6 is selected from optionally substituted C 1 -C 6 alkyl, including t-butyl, 2-cyanoethyl, 2-cyanomethyl, 3-hydroxypropyl, 2-hydroxyethyl, 4-hydroxybutyl, 2-methylpropyl, 2,2-dimethylpropyl and 1 -methylpropyl; optionally substituted C2-C6 alkenyl, including allyl and 2-methyl-allyl; optionally substituted C2-C6 alkynyl; optionally substituted C 1 -C alkylalkoxy, including methoxyethyl, for example, 2-methoxyethyl and 3,3-diethoxy-propyl, 2,2-diethoxy-ethyl; optionally substituted C-pCβ alkylacyl, including methylenephenyl ketone; optionally substituted CrC6 alkylcarboxy, including propanoic acid, butanoic acid; C6 C-alkylamino substituted optionally, including ethyl-2-acetamide; optionally substituted C -? - C6 alkylamino, including 2-dimethylaminoethyl, 3-dimethylaminopropyl; optionally substituted C 6 C alkylaminocarbonyl, including 3-propionamide; optionally substituted C-pCβ alkylalkoxycarbonyl, including 4-butyric acid methyl ester; optionally substituted aryl, including optionally substituted phenyl such as phenyl, methoxyphenyl (e.g., 2,5-dimethoxyphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl), acetylaminophenyl (e.g., 4-acetylaminophenyl, 2-acetylaminophenyl), aminophenyl, dimethylaminophenyl (e.g., 4-dimethylaminophenyl), nitrophenyl (e.g., 3-nitrophenyl, 4-nitrophenyl, 2-nitrophenyl), ethylphenyl (e.g., 2-ethylphenyl), methylphenyl (e.g., 2-methylphenyl) bromophenyl (e.g., 4-bromophenyl), chlorophenyl (e.g., 4-chlorophenyl, 2-chlorophenyl, 3-chlorophenyl), hydroxyphenyl (e.g., 3-hydroxyphenyl, 4-hydroxyphenyl, 2-hydroxyphenyl), cyanophenyl (e.g. 4-cyanophenyl, 3-cyanophenyl), 3- (1-hydroxyethyl) phenyl, phenyl hydroxamic acid, 3- (N-hydroxycarbamimidoyl) -phenyl-4-yl, acetylfenyl (e.g., 3-acetylphenyl, 2-acetylphenyl), benzylpiperazinecarbonylphenyl (e.g., 4-benzylpiperazin-1-yl-carbonylphenyl), optionally substituted phenyl with heteroaryl such as oxazolylphenyl (for example, 3- (1, 3-oxazol-5-yl) phenyl), tetrazolylphenyl (for example, 3- (1 H-tetrazol-5-yl) phenyl, 4- (1 H -tetrazol-5-yl) phenyl), oxadiazolylphenyl (for example, 3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl, 3- (5-hydroxy-1, 2,4-oxadiazole -3-yl) phenyl), thiadiazolylphenyl (for example, 3- (5-amino- 1, 3,4-thiadiazol-2-yl) phenyl), 3- (2,4-dioxo-1,3-thiazolidin-5-ylidene) methylene, 3-hydroxyethylphenyl, 3-hydroxymethylphenyl, 2-hydroxyethylphenyl; optionally substituted arylaminosulfonyl, such as dimethylpyrimidinaminosulfonylphenyl (for example, 4-. {[[(4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl), methyl isoxazolaminosulfonylphenyl (e.g. 4 - [(5-methylisoxazole- 3-yl) amino] sulfonyl, phenyl), dimethoxypyrimidineaminesulfonylphenyl (for example, 4-. {[[(2,6-dimethoxypyrimidin-4-yl) amino] sulfonyl} phenyl), pyridinylaminosulfonylphenyl (e.g. - [(pyridin-2-ylamino) sulfonyl] phenol), aminosulfonylphenyl (for example, 4- (aminosulfonyl) phenyl, 3- (aminosulfonyl) phenyl, 4 - [(methylamino) sulfonyl] phenyl, 4- [(dimethylamino) ) sulfonyl] phenyl, 3 - [(butylamino) sulfonyl] phenyl, 4- (morpholin-4-ylsulfonyl) phenyl); optionally substituted arylsulfonyl, such as 3 - [(2-hydroxyethane) sulfonyl] phenyl, 3- (methanesulfonyl) phenyl, 2- (methanesulfonyl) phenyl; 4 - [(dimethylamino) sulfonyl] phenyl; optionally substituted fused phenyl, such as benzofuran-5-yl, 2,3-dihydro-benzofuran-5-yl, 1,1-dioxo-benzo [b] thiophen-6-yl; optionally substituted arylaminocarbonyl, for example, phenyl 3-hydroxamic acid, 3- (aminocarbonyl) phenyl, 4- [N- (3-amino-propionic acid methyl ester) carbonyl] phenyl, 4- [N- (methyl ester of the acid aminoacetic) carbonyl] phenyl, 4- [N- (3-amino-propionic acid) carbonyl] phenyl, 4- [N- (aminoacetic acid) carbonyl] phenyl; optionally substituted C -? - C6 arylalkylcarboxy, including 4- (acetic acid) phenyl, 3- (3-propionic acid) phenyl; C 1 -C 6 arylalkylacyl optionally substituted, for example, 4- (methyl ester of acetic acid) phenyl, 4- (methyl ester of 3-propionic acid) phenyl, 3- (methyl ester of acetic acid) phenyl, 3- (methyl ester) of 3-propionic acid) phenyl; optionally substituted heteroaryl, including optionally substituted pyridine, such as pyridine (e.g., 2-pyridine, 3-pyridine, 4-pyridine), methoxypyridine (e.g., 6-methoxypyridin-3-yl), chloropyridine (e.g. chloropyridin-3-yl, 2-chloropyridin-3-yl, 2-chloropyridin-4-yl), fluoropyridine (e.g., 2-fluoropyridin-3-yl, 6-fluoropyridin-3-yl), cyanopyridine (e.g. 6-cyanopyridin-3-yl), acetamidopyridine (e.g., 6-acetamidopyridin-3-yl), fused pyridine optionally substituted such as quinolin-3-yl, quinolin-5-yl, quinolin-6-yl; C3-C8 cycloalkyl optionally substituted, including optionally substituted cyclohexyl (e.g., 2- (hydroxymethyl) cyclohexyl, cyclohexyl), cyclopentyl, cyclopropyl, cyclobutyl, indan-2-yl; optionally substituted heterocycloalkyl; C 1 -C 6 alkylaryl optionally substituted, including benzyl, 2-phenylethyl, 2- (4-hydroxyphenyl) ethyl and 2-hydroxy-2-phenylethyl; optionally substituted C 1 -C 6 alkylheteroaryl, including pyridin-3-yl-methyl, pyridin-4-yl-methyl, 2- (1 H-tetrazol-5-yl) ethyl, 2- (2-hydroxy-1, 3,4 -oxadiazol-5-yl) ethyl, 3- (2-hydroxy-1, 3,4-oxadiazol-5-yl) propyl and 3- (1 H-imidazol-1-yl) propyl; optionally substituted C3-C8 CrC6-cycloalkyl alkyl, including cyclopropylmethyl; optionally substituted CrC6 alkylheterocycloalkyl, including tetrahydrofuranmethyl (e.g., tetrahydrofuran-2-ylmethyl), 3- (morpholin-4-yl) propyl, 2- (morpholin-4-yl) ethyl, 2- (pyrrolidin-1-) il) ethyl, 2- (piperidin-1-yl) ethyl, 3- (pyrrolidin-1-yl) propyl, 2- (1-methyl-pyrrolidin-2-yl) ethyl, (1-ethyl-pyrrolidin-2-yl) il) methyl, 3- (1-pyrrolidin-2-on) propyl; or alternatively, R5 and R6, together with the carbon atoms to which they are attached, form a saturated ring or an optionally substituted 5-8 membered aromatic ring, optionally containing one or more heteroatoms selected from O, N and S, including optionally substituted piperidine, such as piperidine, hydroxyethylpiperidine (e.g., 2-hydroxyethylpiperidin-1-yl), piperidine carboxylate (e.g., piperidin-1-yl 3-methyl carboxylate), optionally substituted pyrrolidine, including pyrrolidine, hydroxypyrrolidine (e.g., 3-hydroxypyrrolidin-1-yl), piperazine (e.g., 4-methylpiperazin-1-yl) and morpholine (e.g., morpholin-4-yl); R7 is selected from C6 alkyl optionally substituted; C2-C6 alkenyl optionally substituted; optionally substituted C2-C6 alkynyl; and NR10R11, wherein R10 and R1 are independently selected from H, optionally substituted C6-alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted C2-C6 alkynyl; or alternatively, R10 and R11, together with the carbon atoms to which they are attached, form a saturated, partially unsaturated or aromatic ring optionally substituted with 5-8 members, optionally containing one or more heteroatoms selected from O, N and S; X is selected from O and S; as well as the isomers and mixtures of these to be used as a medicine. In a specific embodiment, the invention provides thiazole derivatives of Formula (I), wherein R 1 is -NR 5 R 6. In another specific embodiment, the invention provides thiazole derivatives of Formula (I), wherein R2 is H. In another specific embodiment, the invention provides thiazole derivatives of Formula (I), wherein R3 is methyl. In another specific embodiment, the invention provides thiazole derivatives, wherein R4 is selected from optionally substituted C6 alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted C2-C6 alkynyl. In another specific embodiment, the invention provides thiazole derivatives, R 4 is -NR 8 R 9, wherein R 8 and R 9 are independently selected from H, optionally substituted C 1 -C 6 alkyl, alkenyl C2-C6 optionally substituted; optionally substituted C2-C6 alkynyl and optionally substituted CrC6 alkylalkoxycarbonyl. In another specific embodiment, the invention provides thiazole derivatives, wherein R 5 is H and R 6 is selected from optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, alkynyl C2-C6 optionally substituted, optionally substituted C, C6 alkylalkoxy, optionally substituted C-pCβ alkylacyl, optionally substituted C-? -C6 alkylcarboxy, optionally substituted C-? - C6 alkylamino, optionally substituted C- | C6 alkylamino; , optionally substituted C 6 -alkylcarbonyl, optionally substituted C 1 -C 6 alkylalkoxycarbonyl, optionally substituted C 3 -C 6 -alkylcycloalkyl, and optionally substituted C 1 -C 6 alkylheterocycloaicyl. In another specific embodiment, the invention provides thiazole derivatives, wherein R5 is H and R6 is optionally selected from C-pCβ alkylaryl and optionally substituted C-Cß alkylheteroaryl. In another specific embodiment, the invention provides thiazole derivatives, wherein R 5 is H and R 6 is selected from optionally substituted C 1 -C 7 arylalkyl and optionally substituted C 6 C heteroarylalkyl. In another specific embodiment, the invention provides thiazole derivatives, wherein R 5 is H and R 6 is selected from optionally substituted aryl and optionally substituted heteroaryl. In another specific embodiment, the invention provides thiazole derivatives, wherein R 5 is H and R 6 is selected from optionally substituted phenyl. In another specific embodiment, the invention provides thiazole derivatives, wherein R 5 is H and R 6 is selected from optionally substituted pyridine.

In another specific embodiment, the invention provides thiazole derivatives, wherein R5 is H and R6 is selected from optionally substituted heterocycloalkyl and optionally substituted C3-C8 cycloalkyl. In another specific embodiment, the invention provides thiazole derivatives, wherein R5 and R6, together with the carbon atoms to which they are attached, form an optionally substituted 5-8 membered saturated or aromatic ring optionally containing one or more heteroatoms selected from O, N and S. In another specific embodiment, the invention provides thiazole derivatives, wherein R5 and R6, together with the carbon atoms to which they are attached, form a 5-8 membered saturated ring optionally substituted, optionally containing an oxygen atom additionally. In another specific embodiment, the invention provides bis-thiazole derivatives, ie, thiazole derivatives of Formula (I), wherein X is S. In a preferred embodiment, the invention provides thiazole derivatives of Formula (I), in which where R1 is -NR5R6; R is H; R3 is methyl; R 4 is selected from optionally substituted C Cβ alkyl, optionally substituted C 2 -C 6 alkenyl; optionally substituted C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted C6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C2-C6 alkynyl and optionally substituted C 1 -C alkylalkoxycarbonyl; R5 is H and R6 is selects optionally substituted C-pCβ alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C6 alkyl alkyloxy optionally substituted C-pCβ alkylacyl, optionally substituted C6 alkylcarboxy, alkylacylamino Optionally substituted CrC6, optionally substituted CrC6 alkylamino, optionally substituted CrC6 alkylaminocarbonyl, optionally substituted CrC6 alkylalkoxycarbonyl, optionally substituted C3-C8 alkyl C6alkyl alkyl, and optionally substituted CrC6 alkylheterocycloalkyl and X is S. Another preferred embodiment, the invention provides the thiazole derivatives of Formula (I), wherein R 1 is -NR 5 R 6; R2 is H; R3 is methyl; R4 is selected from optionally substituted CrC6 alkyl, optionally substituted C2-C6 alkenyl; C2-C6 alkynyl optionally substituted and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted CrC6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C-C6 alkynyl and optionally substituted C6-C6 alkylalkoxycarbonyl; R5 is H and R6 is selected from optionally substituted C-α-C6 alkylaryl and optionally substituted C --C6 alkylheteroaryl and X is S. In another preferred embodiment, the invention provides thiazole derivatives of Formula (I), where R1 is -NR5R6; R2 is H; R3 is methyl; R4 is selected from optionally substituted CrC6 alkyl, optionally substituted C2-C6 alkenyl; C2-C6 alkynyl optionally substituted and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted C6-alkyl, optionally substituted C2-C6-alkenyl; optionally substituted C2-C6 alkynyl and optionally substituted C-? -C6 alkylalkoxycarbonyl; R5 is H and R6 is selected from (sic). In another specific embodiment, the invention provides thiazole derivatives wherein R5 is H and R6 is selected from optionally substituted aryl, including optionally substituted phenyl and optionally substituted heteroaryl, including optionally substituted pyridine and X is S. In another preferred embodiment, the invention provides thiazole derivatives of Formula (I), wherein R1 is -NR5R6; W is H; R3 is methyl; R4 is selected from optionally substituted CrC6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted C6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C2-C6 alkynyl and optionally substituted C6-C6 alkylalkoxycarbonyl; R5 is H and R6 is selected from optionally substituted heterocycloalkyl and optionally substituted C3-C8 cycloalkyl and X is S. In another preferred embodiment, the invention provides thiazole derivatives of Formula (I), wherein R1 is -NR5R6; R2 is H; R3 is methyl; R4 is selected from optionally substituted C-pCβ alkyl, optionally substituted C2-C6 alkenyl; C2-C6 alkynyl optionally substituted and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted C-C-alkyl, optionally substituted C2-C6-alkenyl; optionally substituted C2-C6 alkynyl and optionally substituted CrC6 alkylalkoxycarbonyl; R5 and R6, together with the carbon atoms to which they are attached, form an optionally substituted 5-8 membered saturated or aromatic ring, optionally containing one or more heteroatoms selected from O, N and S, and X is S. In another embodiment, the invention provides the use of a thiazole derivative of Formula (I), wherein R1 is selected from -NR5R6 and -S02R7, preferably -NR5R6; R2, R3 and R5 are independently selected from H, optionally substituted C-C3 alkyl, including methyl, optionally substituted C2-C6 alkenyl and optionally substituted C2-C6 alkynyl; and -NR8R9, wherein R8 and R9 are independently selected from H, optionally substituted C- | -C6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C2-C6 alkynyl; optionally substituted C 1 -C 6 alkylalkoxycarbonyl, including ethyl propanoate; optionally substituted C-pCβ alkyloxyloxy, including amino-propionic acid ethyl ester; R6 is selected from H, optionally substituted CrC6 alkyl, including t-butyl, 2-cyanoethyl, cyanomethyl, 3-hydroxypropyl, 2-hydroxyethyl, 4-hydroxybutyl, 2-isobutyl, 2,2-dimethylpropyl and 1-methylpropyl; optionally substituted C2-C6 alkenyl, including allyl and 2-methylprop-2-en-1-ylo; optionally substituted C2-C6 alkynyl; optionally substituted CrC6 alkylalkoxy, including methoxyethyl, for example, 2-methoxyethyl, 2,2-diethoxyethyl and 3,3-diethoxypropyl; C 1 -C 7 alkylacyl optionally substituted, including methylene phenyl ketone; optionally substituted CrC6 alkylcarboxy, including propanoic acid, butanoic acid; optionally substituted CrC6 alkylacylamino, including ethyl-2-acetamide; optionally substituted C 6 alkylamino, including 2-dimethylaminoethyl, 3-dimethylaminopropyl; C 1 -C 7 alkylaminocarbonyl optionally substituted, including 3-propionamide; optionally substituted C 1 -C 6 alkylalkoxycarbonyl, including the 4-butyric acid methyl ester; optionally substituted aryl, optionally including phenyl such as phenyl, methoxyphenyl (e.g., 2,5-dimethoxyphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl), acetylaminophenyl (e.g., 4-acetylaminophenyl, 2-acetylaminophenyl), aminophenyl, dimethylaminophenyl (e.g., 4-dimethylaminophenyl), nitrophenyl (e.g., 3-nitrophenyl, 4-nitrophenyl, 2-nitrophenyl), ethylphenyl (e.g., 2-ethylphenyl), methylphenyl (eg example, 2-methylfenyl), bromophenyl (e.g., 4-bromophenyl), chlorophenyl (e.g., 4-chlorophenyl, 2-chlorophenyl, 3-chlorophenyl), hydroxyphenyl (e.g., 3-hydroxyphenyl, 4-hydroxyphenyl, 2- hydroxyphenyl), cyanophenyl (e.g., 4-cyanophenyl, 3-cyanophenyl), 3- (1-hydroxyethyl) phenyl, phenyl hydroxamic acid, 3- (N-hydroxycarbamimidoyl) -phenyl-4-yl, acetylphenyl (e.g. 3-acetylphenyl, 2-acetylphenyl), benzylpiperazinecarbonylphenyl (for example, 4-benzylpiperazin-1-yl-carbonylphenyl), phenyl optionally substituted with heteroaryl such as oxazolylphenyl (for example, 3- (1,3-oxazol-5-yl) phenyl), tetrazolylphenyl (e.g., 3- (1 H-tetrazol-5-yl) phenyl, 4- (1 H-tetrazol-5-yl) phenyl), oxadiazolylphenyl (e.g. 3- (5-hydroxy-1) , 3,4-oxadiazol-2-yl) phenyl, 3- (5-hydroxy-1, 2,4-oxadiazol-3-yl) phenyl), thiadiazolylphenyl (for example, 3- (5-amino-1, 3,4-thiadiazol-2-yl) phenyl), 3- (2,4-dioxo-1,3-thiazolidin-5-ylidene) methylphenyl, 3-hydroxyethylphenyl, 3-hydroxymethyl enyl, 2-hydroxyethylphenyl, optionally substituted arylaminosulfonyl, such as dimethylpyrimidinaminosulfonylphenyl (for example, 4-. { [(4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl), methyl isoxazolaminosulfonylphenyl (for example, 4-. {[[(5-methyl-isoxazol-3-yl) amino] sulfonyl} phenyl), dimethoxypyrimidinaminosulfonylphenyl (for example, 4- { [(2, 6-dimethoxypyrimidin-4-yl) amino] sulfonyl, phenyl), pyridinylaminosulfonylphenyl (e.g. 4 - [(pyridin-2-ylamino) sulfonyl] phenyl), aminosulfonylphenyl (e.g. 4- (aminosulfonyl) phenyl, - (aminosulfonyl) phenyl, 4 - [(methylamino) sulfonyljphenyl, 4- [(dimethylamino) sulfonyl] phenyl, 3 - [(butylamino) sulfonyl] phenyl, 4- (morpholin-4-ylsulfonyl) phenyl), substituted arylsulfonyl optionally such as 3 - [(2-hydroxyethane) sulfonyl] phenyl, 3- (methanesulfonyl) phenyl, 2- (methanesulfonyl) phenyl; phenyl fused optionally substituted such as benzofuran-5-yl, 2,3-dihydro-benzofuran-5-yl, 1,1-dioxo-benzo [b] thiophen-6-yl; optionally substituted arylaminocarbonyl, for example, phenyl 3-hydroxamic acid, 3- (aminocarbonyl) phenyl, 4- [N- (3-amino-propionic acid methyl ester) carbonyl] phenyl, 4- [N- (methyl ester of the acid aminoacetic) carbonyl] phenyl, 4- [N- (3-amino-propionic acid) carbonyl] phenyl, 4- [N- (amino-acetic acid) carbonyl] phenyl; optionally substituted C 1 -C arylalkylcarboxy, including 4- (acetic acid) phenyl, 3- (3-propionic acid) phenyl; CrC6 arylalkylacyl optionally substituted, for example, 4- (methyl ester of acetic acid) phenyl, 4- (methyl ester of 3-propionic acid) phenyl, 3- (methyl ester of acetic acid) phenyl, 3- (methyl ester of the 3-propionic acid) phenyl; optionally substituted heteroaryl, including optionally substituted pyridine such as pyridine (e.g., 2-pyridine, 3-pyridine, 4-pyridine), methoxypyridine (e.g., 6-methoxypyridin-3-yl), chloropyridine (e.g., 6-chloropyridine) -3-yl, 2-chloropyridin-3-yl, 2-chloropyridin-4-yl), fluoropyridine (e.g., 2-fluoropyridin-3-yl, 6-fluoropyridin-3-yl), cyanopyridine (e.g. -cianopyridin-3-yl), acetamidopyridine (e.g., 6-acetamidopyridin-3-yl), fused pyridine optionally substituted such as quinolin-3-yl, quinolin-5-yl, quinolin-6-yl; C3-C8 cycloalkyl optionally substituted, including optionally substituted cyclohexyl (e.g., 2- (hydroxymethyl) cyclohexyl, cyclohexyl), cyclopentyl, cyclopropyl, cyclobutyl, indan-2-yl; optionally substituted heterocycloalkyl; optionally substituted C-? -C6 alkylaryl, including benzyl, 2-phenylethyl, 2- (4-hydroxyphenyl) ethyl and 2-hydroxy-2-phenylethyl; optionally substituted C 1 -C 6 alkylheteroaryl, including pyridin-3-ylmethyl, pyridin-4-ylmethyl, 2- (1 H-tetrazol-5-yl) ethyl, 2- (2-hydroxy-1, 3,4-oxadiazol-5-yl) ethyl, 3- (2-hydroxy-1, 3,4-oxadiazol-5-yl) propyl and 3- (1 H-imidazol-1-yl) propyl; optionally substituted C3-C6-C6-cycloalkyl alkyl, including cyclopropylmethyl; optionally substituted CrC6 alkylheterocycloalkyl, including tetrahydrofuranmethyl (e.g., tetrahydrofuran-2-ylmethyl), 3- (morpholin-4-yl) propyl, 2- (morpholin-4-yl) ethyl, 2- (pyrrolidin-1-) il) ethyl, 2- (piperidin-1-yl) ethyl, 3- (pyrrolidin-1-yl) propyl, 2- (1-methyl-pyrrolidin-2-yl) ethyl, (1-ethyl-pyrrolidin-2-) L) methyl, 3- (1-pyrrolidin-2-on) propyl; or alternatively R5 and R6, together with the carbon atoms to which they are attached, form a saturated ring or an optionally substituted aromatic ring of 5-8 members containing one or more heteroatoms selected from O, N and S, including optionally substituted piperidine, such as piperidine, hydroxyethylpiperidine (e.g., 2-hydroxyethylpiperidin-1-yl), piperidinecarboxylate (e.g., piperidin-1-yl 3-methyl carboxylate), optionally substituted pyrrolidine, including pyrrolidine, hydroxypyrrolidine (e.g., 3-hydroxypyrrolidin-1-yl), piperazine (e.g., 4-methylpiperazin-1-yl) and morpholine (e.g., morpholin-4-yl); R7 is selected from C6 alkyl optionally substituted; C2-C6 alkenyl optionally substituted; optionally substituted C2-C6 alkynyl; and NR10R11, wherein R10 and R11 are independently selected from H, optionally substituted C6 alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted C2-C6 alkynyl; or alternatively R10 and R11, together with the carbon atoms to which they are attached, form a saturated, partially unsaturated or aromatic ring optionally substituted with 5-8 members, optionally containing one or more heteroatoms selected from O, N and S; X is selected from O and S; as well as the isomers and mixtures thereof for the preparation of a medicament for the prophylaxis and / or treatment of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplants. , rejection of grafts or lesions of the lung. In another embodiment, the invention provides thiazole derivatives of Formula (I), wherein R1 is selected from -NR5R6 and -S02R7, preferably -NR5R6; R2, R3 and R5 are independently selected from H, optionally substituted C6-C6 alkyl, including methyl, optionally substituted C2-C6 alkenyl and optionally substituted C2-C6 alkynyl; R4 is selected from H; optionally substituted CrC6 alkyl, including methyl and ethyl; C2-C6 alkenyl optionally substituted; optionally substituted C2-C6 alkynyl; and -NR8R9 wherein R8 and R9 are independently selected from H, optionally substituted C-? -C6 alkyl, optionally substituted C2-C6 alkenyl; optionally substituted C2-C6 alkynyl; optionally substituted C 1 -C 6 alkylalkoxycarbonyl, including ethyl propanoate; C 1 -C 6 alkyloxyloxy optionally substituted, including amino-propionic acid ethyl ester; R6 is selected from optionally substituted C6-alkyl, including t-butyl, 2-cyanoethyl, 2-cyanomethyl, 3-hydroxypropyl, 2-hydroxyethyl, 4-hydroxybutyl, 2-methylpropyl, 2,2-dimethylpropyl and 1-methylpropyl; optionally substituted C2-C6 alkynyl; Ci-Cd alkylalkoxy optionally substituted, including methoxyethyl, for example, 2-methoxyethyl and 3,3-diethoxy-propyl, 2,2-diethoxy-ethyl; optionally substituted C-pCβ alkylacyl, including methylenephenyl ketone; optionally substituted C6-C-alkylcarboxy, including propanoic acid, butanoic acid; optionally substituted d-Cß alkylacylamino, including ethyl-2-acetamide; optionally substituted C 6 alkylamino, including 2-dimethylaminoethyl, 3-dimethylaminopropyl; optionally substituted C 6 C alkylaminocarbonyl, including 3-propionamide; optionally substituted C 1 -C 6 alkylalkoxycarbonyl, including the 4-butyric acid methyl ester; fused phenyl optionally substituted, such as benzofuran-5-yl, 2,3-dihydro-benzofuran-5-yl, 1,1-dioxo-benzo [b] thiophen-6-yl; optionally substituted arylaminocarbonyl, for example, phenyl 3-hydroxamic acid, 3- (aminocarbonyl) phenyl, 4- [N- (3-amino-propionic acid methyl ester) carbonyl] phenyl, 4- [N- (methyl ester of the acid aminoacetic) carbonyl] phenyl, 4- [N- (3-amino-piO-pionic acid) carbonyl] phenyl, 4- [N- (amino-acetic acid) carbonyl] phenyl; optionally substituted CrC6 arylalkylcarboxy, including 4- (acetic acid) phenyl, 3- (3-propionic acid) phenyl; Ci-Cß arylalkylalkyl optionally substituted, for example, 4- (methyl ester of acetic acid) phenyl, 4- (methyl ester of 3-propionic acid) phenyl, 3- (methyl ester of acetic acid) phenyl, 3- (ester 3-propionic acid methyl) phenyl; optionally substituted pyridine, such as pyridine (e.g., 2-pyridine, 3-pyridine, 4-pyridine), methoxypyridine (e.g., 6-methoxypyrdin-3-) ilo), chloropyridine (for example, 6-chloropyridin-3-yl, 2-chloropyridin-3-yl, 2-chloropyridin-4-yl), fluoropyridine (e.g., 2-fluoropyridin-3-yl, 6-fluoropyridin -3-yl), cyanopyridine (e.g., 6-cyanopyridin-3-yl), acetamidopyridine (e.g., 6-acetamidopyridin-3-yl), fused pyridine optionally substituted, such as quinolin-3-yl, quinolin-5 -yl, quinolin-6-yl; C3-C8 cycloalkyl optionally substituted, including optionally substituted cyclohexyl (e.g., 2- (hydroxymethyl) cyclohexyl, cyclohexyl), cyclopentyl, cyclopropyl, cyclobutyl, indan-2-yl; alkylaryl Optionally substituted CrC6, including benzyl, 2-phenylethyl, 2- (4-hydroxyphenyl) ethyl and 2-hydroxy-2-phenylethyl; optionally substituted C 3 -C 6 alkyl C 3 -C 8 cycloalkyl, including cyclopropylmethyl; optionally substituted C 1 -C 6 alkylheterocycloalkyl, including tetrahydrofuranmethyl (e.g., tetrahydrofuran-2-ylmethyl), 3- (morpholin-4-yl) propyl, 2- (morpholin-4-yl) ethyl, 2- (pyrrolidin-1) -yl) ethyl, 2- (piperidin-1-yl) ethyl, 3- (pyrrolidin-1-yl) propyl, 2- (1-methyl-pyrrolidin-2-yl) ethyl, (1-ethyl-pyrrolidin-2) -yl) methyl, 3- (1-pyrrolidin-2-on) propyl; or alternatively, R5 and R6, together with the carbon atoms to which they are attached, form a saturated ring or an optionally substituted 5-8 membered aromatic ring, optionally containing one or more heteroatoms selected from O, N and S, including optionally substituted piperidine, such as piperidine, hydroxyethylpiperidine (e.g., 2-hydroxyethylpiperidin-1-yl), piperidinecarboxylate (e.g., 3-methyl carboxylate) of piperidin-1-yl), optionally substituted pyrrolidine, including pyrrolidine, hydroxypyrrolidine (e.g., 3-hydroxypyrrolidin-1-yl), piperazine (e.g., 4-methylpiperazin-1-yl) and morpholine (e.g. morpholin-4-yl); R7 is selected from optionally substituted C-? - C6 alkyl; C2-C6 alkenyl optionally substituted; optionally substituted C2-C6 alkynyl; and NR10R11, wherein R10 and R11 are independently selected from H, optionally substituted C6 alkyl, alkenyl C2-C6 optionally substituted and optionally substituted C2-C6 alkynyl; or alternatively R10 and R11, together with the carbon atoms to which they are attached, form a saturated, partially unsaturated or aromatic ring optionally substituted with 5-8 members, optionally containing one or more heteroatoms selected from O, N and S; X is selected from O and S; The compounds of the present invention include, in particular, those of the group consisting of: Example No. Name 1 acid 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} benzoic; 2 - [2 '- (acetylamino) -4'-methyl-4,5'-b'-1,3-thiazol-2-yl] amino acid} benzoic; 3 N- [2- (benzylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 4 N-. { 4'-methyl-2 - [(2-phenylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 5 N- (4'-methyl-2-piperidin-1-yl-4,5'-b- 1, 3-thiazol-2'-yl) acetamide; 6 N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 7 N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazole-2'-Ijacetamide; 8 N- [4'-methyl-2- (pyridin-2-ylamino) -4,5'-bi-1,3-thiazole-2'-yl-acetamide; 9 N-. { 2 - [(4-methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 10 N-. { 2 - [(4-hydroxyphenyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; 11 N-. { 4'-methyl-2 - [(4-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2 * -yl} acetamide; 12 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - benzamide; 13 N- [2- ( { 4 - [(4-benzylpiperazin-1-yl) carbonyl] phenyl} amino) -4'-methyl-4,5'-bi-1,3-thiazole-2 '-yl] acetamide; 14 N- (2-amino-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2-anilino-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 16 N- (4'-methyl-2-morpholin-4-yl-4,5'-b- 1, 3-thiazol-2'-yl) acetamide; 17 N- [4'-methyl-2- (4-methylpiperazin-1-yl) -4,5'-bi-1,3-thiazol-2'-yl-acetamide; 18 1 - [2 '- (Acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] piperidn-3-carboxylic acid methyl ester; 19 N-. { 2- [4- (2-hydroxyethyl) piperidin-1-yl] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 20 N- (4'-methyl-2-pyrrolidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 21 N- [2- (3-hydroxypyrrolidin-1-yl) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 22 N- [2- (tert-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 23 N-. { 2 - [(6-methoxypyrdin-3-yl) amino] -4'-methyl-4,5'-b, -1,3-t-azo-2'-yl} acetamide; 24 N- ^ - Ke-chloropyridin-S-i aminoj ^ '- meti S'-bi-I .S-thiazole ^' - il} acetamide; 25 N-. { 2 - [(4-cyanophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 26 N-. { 2 - [(4-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 27 N-. { 2 - [(2-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-acetamide; 28 N-. { 2 - [(2-methoxyphenyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; 29 N-. { 2 - [(3-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 30 N-. { 2 - [(3-hydroxyphenyl) amino] -4'-methyt-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 31 N-. { 4'-methyl-2 - [(2-morpholin-4-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 32 N-. { 4'-methyl-2 - [(2-piperidin-1-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 33 N-. { 2 - [(2-methoxyethyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; 34 N- [2- (cyclohexylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 4'-methyl-2 - [(3-morpholin-4-ylpropyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 36 N-. { 4'-methyl-2 - [(tetrahydrofuran-2-ylmethyl) amino] -4,5'-bi-1,3-thiazole-2'-yl} acetamide; 37 N-. { 2 - [(2-hydroxy-2-phenylethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 38 N- [2- (1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 39 N-. { 2 - [(3-cyanophenyl) amino] -4'-methyl-4,5'-b- 1, 3-thiazol-2'-yl-acetamide; 40 [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] formamide; 41 N- ( { [2- (Allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino}. Carbonyl) -ethanolaninate; 42 N-. { 4-Methyl-5- [2- (pyridin-3-ylamino) -1,3-thiazol-4-yl] -1,3-oxazol-2-yl} acetamide; 43 N-. { 2 - [(2-fluoropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; 44 N-. { 2 - [(2-cyanoethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 45 N-. { 2 - [(3,3-diethoxypropyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; 46 N-. { 2 - [(2,2-diethoxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 47 N-. { 4'-methyl-2 - [(2-oxo-2-phenyletyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 48 N-. { 2 - [(2-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 49 N- (4'-methyl-2- { [3- (1, 3-oxazol-5-yl) phenyl] amino.} -4,5'-b- 1, 3-thiazole-2 '-il) acetamide; 50 N- (4'-methyl-2 { [3- (1 H-tetrazol-5-yl) phenyl] amino.} -4,5'-bi-1,3-thiazole- 2'- L) acetamide; 51 N- (4'-methyl-2- { [4- (1 H-tetrazol-5-yl) phenyl] amino} -4,5'-bi-1,3-thiazole-2'- il) acetamide; 52 N-. { 4'-Methyl-2- [2- (1 H-tetrazol-5-yl) -ethylamino] - [4,5 '] bit-azolyl-2'-yl} - acetamide; 53 N- (2- { [3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl] amino.} -4'-methyl-4,5'-bi-1 , 3-thiazol-2'-yl) acetamide; 54 N- (2- { [3- (5-amino-1, 3,4-thiadiazol-2-yl) phenyl] amino.}. 4'-methylene-4,5'-bi- 1,3-thiazol-2'-yl) acetamide; N- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alanine; 56 5- (2- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Ethyl) -1,3, 4-oxadiazole-2-olate; 57 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} butanoic acid; 58 N- (2- { [3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) propyl] amino.} -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 59 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -N-hydroxybenzamide; 60 acid 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - N-hydroxybenzenecarboximide; N- (2-. {[3- (5-hydroxy-1, 2,4-oxadiazol-3-yl) phenyl] amino} -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 62 N- [2- ( { 3 - [(Z) - (2,4-dioxo-1, 3-thiazolidin-5-ylidene) methyl] phenyl} - amino) -4'- methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 63 N- [4'-methyl-2- ( { 4 - [(pyridin-2-ylamino) sulfonyl] phenyl} amino) -4,5'-bi- 1, 3-thiazole-2'- il] acetamide; 64 N- (2- {[2- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[[3- (hydroxymethyl) phenyl] amino} -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl) acetamide; N- (2- {[4- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole-2'- 1) acetamide; 67 N- [2- ( { 3 - [(2-hydroxyethyl) sulfonyl] phenyl}. Amino) -4'-methyl-4,5'-b, -1,3-thiazole-2'-il ] acetamide; 68 N- [2- ( {4 - [(dimethylamino) sulfonyl] phenyl} amino) -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl] acetamide; 69 N- (2- { [3- (Aminosulfonyl) phenyl] amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 70 N-. { 2 - [(2-chloropyridin-4-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 71 N- [4'-methyl-2- (. {4 - [(methylamino) sulfonyl] phenyl} amino) -4,5'-bi-1, 3-thiazol-2'-yl] acetamide; N- (5- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino] pyridin-2-yl) acetamide; 73 N- [2- (2,3-dihydro-1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl] acetamide; N- (4'-methyl-2- { [2- (1-methylpyrrolidin-2-yl) ethyl] amino.} -4,5'-bi-1, 3-thiazole-2 ' -yl) acetamide; 75 N-. { 4'-methyl-2 - [(2-pyrrolidin-1-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 76 N- (4'-methyl-2 { [3- (2-oxopyrrolidin-1-yl) propyl] amino} -4,5'-b, -1,3-thiazole-2 '-il) acetamide; 77 N- (2-. {[[2- (acetylamino) ethyl] amino} -4'-methyl-4,5'-bi-1,3-t-azoI-2 ' - il) acetamide; N- (2-. {[[2- (dimethylamino) ethyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole-2'-l) acetamide; 79 N-. { 2 - [(2-hydroxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 80 N- (2- { [2- (4-hydroxyphenyl) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2-. {[[3- (dimethylamino) propyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 82 N-. { 2 - [(3-hydroxypropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; N- (2- {[[3- (1 H-imidazol-1-yl) propyl] amino} -4'-methyI-4,5'-bi-1, 3-thiazole-2'- il) acetamide; 4 N3- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alaninamide; 85 N-. { 4'-methyl-2 - [(2-methylprop-2-en-1-yl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 86 N-. { 2 - [(2-hydroxy-phenyl) -amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-acetamide; 87 N-. { 2 - [(6-fluoropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 88 N-. { 2 - [(4-cyanophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 89 N-. { 2 - [(6-cyanopyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 90 N-. { 2 - [(3-methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 91 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - benzamide; 92 N-. { 4'-methyl-2 - [(2-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; 93 N-. { 4'-methyl-2 - [(3-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; 94 N- '-methyl ^ quinolin-S-ylaminoH.d'-bi-l, 3-thiazol-2'-yl-acetamide; 95 N- [4'-methyl-2- (quinolin-5-ylamino) -4,5'-bi-1,3-thiazole-2'-yl-acetamide; 96 N- [4'-methyl-2- (quinolin-6-ylamino) -4,5'-bi-1,3-thiazole-2'-yl-acetamide; 97 N- [2- (Cyclopentylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-acetamide; 98 N- [2- (Cyclopropylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-acetamide; 99 N-. { 4'-methyl-2 - [(pyridin-3-ylmethyl) amino] -4,5'-b- 1, 3-thiazol-2'-yl} acetamide; 100 N-. { 2 - [(4-hydroxybutyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 101 N- (4'-methyl-2-. {[[3- (methylsulfonyl) phenyl] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; 102 N-. { 4'-methyl-2 - [(3-pyrrolidin-1-ylpropyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 103 N-. { 2 - [(1,1-Dioxido-1-benzothien-6-yl) amino] -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl} acetamide; 104 N- (2-. {[[(1-ethylpyrrolidin-2-yl) methyl] amino.} -4- -methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 105 N-. { 2 - [(Cyanomethyl) amino] -4'-methyl-4,15'-bi-1,3-thiazole-2'-Ijacetamide; 106 N- [2- (isobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 107 N-. { 2 - [(2,2-dimethylpropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 108 N- (2- { [(Cis) -2- (hydroxymethyl) cyclohexyl] amino.} -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 109 N- (2-. {[[(Trans) -2- (hydroxymethyl) cyclohexyl] amino} -4'-methyl-4,5'-bi- 1, 3-thiazole-2'-il acetamide; 110 N- [2- (sec-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 111 N-. { 4'-methyl-2 - [(pyridin-4-ylmethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; 1 N- (4'-methyl-2 { [4- (morpholin-4-ylsulfonyl) phenyl] amino} -4,5'-bi-1, 3-thiazole-2'-yl) acetamide; 113 N- [2- ( { 3 - [(butylamino) sulfonyl] phenyl} amino) -4 * -methyl-4,5'-bi-1, 3-thiazol-2'-yl] acetamide; 114 N-. { 2 - [(cyclopropylmethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 115 N- [2- (cyclobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 1 16 N- [2- (2,3-dihydro-1 H -inden-2-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 1 17 N- (4'-methyl-2 { [2- (methylsulfonyl) phenyl] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; 18 N- (4'-methyl-2- { [2- (1 H-1, 2,4-triazol-1-yl) ethyl] amino.} -4,5'-b-1 , 3-thiazol-2'-yl) acetamide; 1 19 N- (2- { [3- (1-Hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl) acetamide; 120 (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) -methyl acetate; 121 N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} - benzoyl) -beta-alaninate of methyl; 122 N- (4- {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - benzoyl) glycinate methyl; Methyl 3- (3- {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - phenyl) propanoate; 124 3- (4 { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) propanoic acid; 125 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - methyl butanoate; 126 (3- { [2 '- (acetylamino) -4'-methyl-4,5'-bi- 1, 3-thiazol-2-yl] amino} - phenyl) -acetate methyl; 127 N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] urea; 128 N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] urea; 129 N- (4'-methyl-2-piperidin-1-yl-4,5'-b, -1,3-thiazole-2'-yl) urea; 130 N- (2-anilino-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) urea; 131 N-. { 2 - [(4-hydroxyphenyl) amino] -4'-methyI-4,5'-bi-1,3-thiazol-2'-yl} urea; 132 N- [2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; 133 (4- {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - phenyl) acetic acid; 134 N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} - benzoyl) beta-alanine; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} - benzoyl) glycine; 136 3- (3 { [2 '- (acetylamino) -4'-meu? -4,5'-b¡-1,3-thiazol-2-yl] amino} phenyl) propanoic; N-. { 2 - [(4-Ethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(4-methylphenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) amin] sulfonyl} phenyl) amino] -4'-methyl-4,5'-bi-1 , 3-thiazole-2'-il} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl} phenyl) amino] -4,5'-b, -1,3-thiazole-2 '-il} acetamide; N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] propanamide; N-. { 2 - [(4- {[[2,6-dimethoxypyrimidin-4-yl) amino] sulfonyl} phenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole 2'-il} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl, phenyl) amino] -4,5'-bi-1,3-thiazole-2 ' -il} propanamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole- 2'-l} propanamide; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) -acetamide; N-. { 2- (4-aminophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-Ethylphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-methylphenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 2 - [(4-Bromophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[4- (aminosulfonyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl) acetamide; N-. { 2 - [(2,5-dimethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-Acetylphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[4- (dimethylamino) phenylamino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide. In a particular embodiment, the invention provides the compounds according to Formula (I), selected from the following group: 5 N- (4'-methyl-2-piperidin-1-yl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 7 N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; 8 N- [4'-methyl-2- (pyridin-2-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; 16 N- (4'-methyl-2-morpholin-4-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [4'-methyl-2- (4-methyerazin-1-yl) -4,5'-b, -1,3-thiazol-2'-yl-acetamide; 18 methyl 1 - [2- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] piperidin-3-carboxylate; 19 N-. { 2- [4- (2-hydroxyethyl) p -peridin-1-yl] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; 20 N- (4'-methyl-2-pyrrolidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 21 N- [2- (3-hydroxypyrrolidin-1 -yl) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 22 N- [2- (tert-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 23 N-. { 2 - [(6-methoxypyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 24 N-. { 2 - [(6-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 31 N-. { 4-methyl-2 - [(2-morpholin-4-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 32 N-. { 4'-methyl-2 - [(2-piperidin-1-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 33 N-. { 2 - [(2-methoxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 34 N-p-Iichexyl-aminoH'-methyM.d'-bi-I .S-thiazole-yl-acetamide; N-. { 4'-methyl-2 - [(3-morpholin-4-ylpropyl) arnino] -4,5'-bi-1,3-thiazole-2'-yl} acetamide; 36 N-. { 4, -metl-2 - [(tetrahydrofuran-2-ylmethyl) amino] -4,5'-bi-1,3-thiazole-2, -1} acetamide; 38 N- [2- (1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-acetamide; 40 [4'-meth] l-2- (pyridin-3-ylamino) -4,5'-bi-1 ^ -thiazole ^ '- il-formamide; 42 N-. { 4-Methyl-5- [2- (pyridin-3-ylamino) -1,3-thiazol-4-yl] -1,3-oxazol-2-yl} acetamide; 43 N-. { 2 - [(2-fluoropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 44 N-. { 2 - [(2-Cyanoethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 45 N-. { 2 - [(3,3-diethoxypropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 46 N-. { 2 - [(2,2-diethoxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 47 N-. { 4'-methyl-2 - [(2-oxo-2-phenylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 48 N-. { 2 - [(2-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 55 N- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alanine; 57 4- acid. { [2 '- (acetylamino) -4, -methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - butanoic; 70 N-. { 2 - [(2-chloropyridin-4-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (5- {2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.}. Pyridin- 2- il) acetamide; 73 N- [2- (2,3-dihydro-1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl] acetamide; N- (4'-methyl-2- { [2- (1-methy1-pyrrolidin-2-yl) ethyl] amino} -4,5'-bi-1,3-thiazole-2 ' -yl) acetamide; 75 N-. { 4'-methyl-2 - [(2-pyrrolidin-1-ylethyl) amino] -4,5'-b- 1, 3-thiazol-2'-yl-acetamide; 76 N- (4'-methyl-2 { [3- (2-oxopyrrolidin-1-yl) propyl] amino.} -4,5'-bi-1, 3-thiazole-2'-yl acetamide; 77 N- (2-. {[[2- (acetylamino) ethyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- { [2- (dimethylamino) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 79 N-. { 2 - [(2-hydroxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2-. {[[3- (dimethylamino) propyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 82 N ^ -KS-hydroxypropyl aminoH'-methyl ^ .d'-bi-I .S-thiazole ^ '- il} acetamide; 84 N-3- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alaninamide; 89 N-. { 2 - [(6-cyano-pyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-1} acetamide; 94 N- [4'-methyl-2- (quinolin-3-ylamino) -4,5'-b- 1, 3-thiazol-2'-yl] acetamide; 95 N- [4'-meth yl-2- (quinolin-5-ylamino) -4,5'-bi-1,3-thiazole-2'-1] acetamide; 96 N- [4'-methyl-2- (quinolin-6-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; 97 N- [2- (Cyclopentylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 98 N- [2- (cyclopropylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 100 N-. { 2 - [(4-hydroxybutyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; 102 N-. { 4'-methyl-2 - [(3-pyrrolidin-1-ylpropyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; 103 N-. { 2 - [(1,1-Dioxido-1-benzothien-6-yl) amino] -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl} acetamide; N- (2- {[[(1-ethylpyrrolidin-2-yl) methyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 105 N-. { 2 - [(Cyanomethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 106 N- [2- (isobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 107 N-. { 2 - [(2,2-dimethylpropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 108 N- (2- { [(Cis) -2- (hydroxymethyl) cyclohexyl] amino.} -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 109 N- (2-. {[[(Trans) -2- (hydroxymethyl) cyclohexyl] amino.} -4'-methyl-4,5'-b-1, 3-thiazole-2'-yl) acetamide; 110 N- [2- (sec-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 114 N-. { 2 - [(cyclopropylmethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 115 N- [2- (cyclobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; 116 N- [2- (2,3-dihydro-1 H -inden-2-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; 125 4- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} methyl butanoate; 128 N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] urea; 129 N- (4'-methyl-2-piperidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) urea; In another embodiment, the invention provides the compounds according to Formula (I), selected from the following group: 3 N- [2- (benzylamino) -4'-methyl-4,5'-bi-1,3-thiazole -2'-il] acetamide; 4 N-. { 4'-methyl-2 - [(2-phenylethyl) amino] -4,5, -bi-1,3-t-azole-2'-yl} acetamide; 12 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} - benzamide; 13 N- [2- ( { 4 - [(4-benzylpiperazin-1-yl) carbonyl] phenyl} amino) -4'-methyl-4,5'-bi-1,3-thiazole-2 '-yl] acetamide; 5 N ^ - ^ - cyanopheniaminoH'-methyl ^ .d'-bi-l, 3-thiazol-2'-yl} acetamide; 7 N-. { 2 - [(2-chlorophenol) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 29 N-. { 2 - [(3-chlorophenyl) amino] -4'-methyl-4, d-bi-1,3-tiazole-2'-yl} acetamide; 37 N-. { 2 - [(2-hydroxy-2-phenylethyl) amino] -4'-methyl-4, d-bi-1,3-tiazole-2'-yl} acetamide; d 39 N-. { 2 - [(3-cyanophenyl) amino] -4'-methyl-4, d-bi-1,3-thiazol-2'-yl} acetamide; 41 N-α-aminolaminoH'-metiM.d'-bi-I .S-thiazole ^ '- ylmaminocarbonyl) - ethyl beta-alaninate; 49 N- (4'-meth yl-2- { [3- (1, 3-oxazol-d-yl) phenyl] amino.} -4, d-bi-1,3-thiazole- 2'-0 il) acetamide; 50 N- (4'-methyl-2- { [3- (1 H-tetrazol-d-yl) phenyl] amino} -4, d-bi-1,3-thiazole-2'- il) acetamide; 51 N- (4'-methyl-2 { [4- (1 H-tetrazol-5-yl) phenyl] amino.} -4,5'-b- 1, 3-thiazoI-2 ' - il) acetamide; d 52 N-. { 4'-Methyl-2- [2- (1 H-tetrazol-d-yl) -eti-amino] - [4, d '] -bitiazolyl-2'-yl} acetamide; 53 N- (2- { [3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl] amino}. 4'-methyl-4, dibi- 1,3-thiazol-2'-yl) acetamide; 54 N- (2- { [3- (d-amino-1, 3,4-thiadiazol-2-yl) phenyl] amino.}. 4'-methyl-4, d-amino- 1,3-thiazol-2'-yl) acetamide; 56 d- (2- { [2 '- (acetylamino) -4'-methyl-4, d-bi-1,3-thiazol-2-yl] amino.} Ethyl) -1,3, 4-oxadiazole-2-olate; d8 N- (2- {[3- (d-hydroxy-1, 3,4-oxadiazol-2-yl) propyl] amino} -4'-methyl-4, d-bi-1, 3-thiazol-2'-yl) acetamide; 59 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -N-hydroxybenzamide; 60 acid 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -N-hydroxybenzenecarboximide; 61 N- (2- { [3- (d-hydroxy-1, 2,4-oxadiazol-3-yl) phenyl] amino.} -4'-methyl-4, d'-bi-1 , 3-thiazol-2'-yl) acetamide; 62 N- [2- ( { 3 - [(Z) - (2,4-dioxo-1,3-thiazolid-5-ylden) methyl] phenyl} amino) -4 '- methyl! -4,5'-bi-1, 3-thiazol-2'-yl] acetamide; 63 N- [4'-methyl-2- ( { 4 - [(pyridin-2-ylamino) sulfonyl] phenyl} amino) -4,5'-bi- 1, 3-thiazole-2'- il] acetamide; N- (2- { [2- (2-hydroxyethyl) phenyl] amino} -4-methyl-4, d-b, -1,3-thiazol-2'-yl) acetamide; d N- (2-. {[[3- (hydroxymethyl) pheny] amino] -4'-methylene-4, d-b, -1,3-thiazole-2'-yl) acetamide; 6 N- (2- {[4- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4, d-bi-1,3-thiazol-2'-yl) acetamide; 7 N- [2- ( { 3 - [(2-hydroxyethyl) sulfonyl] phenyl}. Amino) -4'-methyl-4, d-bi-1, 3-thiazole-2'-yl] acetamide; 8 N- [2- ( { 4 - [(dimethylamino) sulfonyl] phenyl} amino) -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl] acetamide; 71 N- [4'-methyl-2- (. {4 - [(methylamino) sulfonyl] phenyl} amino) -4, d-b-1, 3-thiazol-2'-yl] acetamide; 80 N- (2- { [2- (4-hydroxyphenyl) ethyl] amino.} -4'-methyl-4, d * -bi-1,3-t-azole-2'-il acetamide; d 83 N- (2- { [3- (1 H-imidazol-1-yl) propylamino} -4'-methyl-4, d-bi-1,3-thiazole-2'-yl acetamide; 85 N-. { 4'-methyl-2 - [(2-methylprop-2-en-1-yl) amino] -4, d'-bi-1,3-thiazol-2'-yl} acetamide; 86 N-. { 2 - [(2-hydroxyphenyl) amino] -4'-methyl-4, d-bi-1,3-t-azo-2'-yl} acetamide; 88 N-. { 2 - [(4-cyanophenyl) amino] -4'-methyl-4, d-bi-1,3-thiazol-2'-yl} acetamide; 90 N-. { 2 - [(3-methoxyphenyl) amino] -4'-methyl-4, d-bi-1,3-thiazol-2'-yl} - acetamide; d 91 3-. { [2 '- (acetylamino) -4'-methyl-4, d'-bi-1,3-thiazol-2-yl] amino} - benzamide; 92 N-. { 4'-methyl-2 - [(2-nitrophenol) amino] -4, d'-bi-1,3-thiazol-2'-yl} acetamide; 99 N-. { 4'-methyl-2 - [(pyridin-3-ylmethyl) amino] -4, d'-bi-1,3-thiazol-2'-yl} acetamide; 101 N- (4'-methyl-2-. {[[3- (methylsulfonyl) phenyl] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; 111 N-. { 4'-methyl-2 - [(pyridin-4-ylmethyl) amyr? O] -4,5'-bi-1,3-thiazole-2'-IJacetamide; 112 N- (4'-methyl-2- { [4- (morpholin-4-ylsulfonyl) pheny] amino] -4,5'-bi-1, 3-thiazole-2'-; l) acetamide; 113 N- [2- ( { 3 - [(butylamino) sulfonyl] phenyl} amino) -4'-methyl-4, d-bib-1, 3-thiazol-2'-yl] acetamide; 117 N- (4'-methyl-2- { [2- (methylsulfonyl) phenyI] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; 118 N- (4'-methyl-2- { [2- (1 H-1, 2,4-triazol-1-yl) ethyl] amino.} -4,5'-bi-1, 3 -thiazole- 2'-1) acetamide; 119 N- (2- {[3- (1-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; 120 (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) -ethyl acetate; 121 N- (4- { [2 '- (methyl acetylaminoH'-methyl-4, d'-bi-1, 3-thiazol-2-yl] amino.} - benzoyl) -beta-alaninate; 122 N- (4- { [2 '- (acetylamino) -4'-methyl-4, methyl-d-1, 3-thiazol-2-yl] amino.} - benzoyl) glycinate; 123 3- (3- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.}. Phenol) -propanoate methyl; 124 3- (4 { [2 '- (acetylamino) -4'-methyl-4,5'-b- 1, 3-thiazol-2-yl] amino.} - phenyl) propanoic; 126 (3- { [2 '- (acetylamino) -4'-methyl-4, d-bi-1,3-thiazol-2-yl] amino} phenyl) -ethyl acetate; 27 N- [2- (allylamino) -4'-methyl-4,5'-b- 1, 3-thiazol-2'-yl] urea; 130 N- (2-anilino-4'-methyl-4, d-bi-1,3-thiazol-2'-yl) urea; 131 N-. { 2 - [(4-Hydroxyphenyl) aminoj-4'-methyl-4, d-bi-1,3-thiazol-2'-yl} urea; 133 (4- { [2 '- (acetylamino) -4'-methyl-4, d'-bi-1,3-thiazol-2-yl] amino.} - phenyl) acetic acid; d 134 N- (4- [2 '- (acetylamino) -4 * -methyl-4, d-bi-1,3-thiazol-2-yl] amino.} - benzoyl) beta-alanine; 136 N- (4- { [2 '- (acetylamino) -4'-methyl-4, d-bi-1,3-thiazol-2-yl] amino.} - benzoyl) glycine; 136 3- (3 { [2 '- (acetylamino) -4'-methyl-4, d-bi-1,3-thiazol-2-yl] amino} -0-phenyl) propanoic acid. The compounds of the present invention are useful as medicaments. They can be used for the preparation of a medicament for the prophylaxis and / or treatment of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplants, rejection of grafts or lung injuries. In one embodiment, the compounds of Formula (I) are useful for the treatment and / or prophylaxis of autoimmune diseases or inflammatory diseases such as multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, lung inflammation. , thrombosis or infection / inflammation of the brain such as meningitis or encephalitis.

In another embodiment, the compounds of Formula (I) are useful for the treatment and / or prophylaxis of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Huntington's disease, CNS trauma, stroke or ischemic conditions, d In yet another embodiment, according to the invention, the compounds of Formula (I) are useful for the treatment and / or prophylaxis of cardiovascular diseases such as atherosclerosis, cardiac hypertrophy, myocyte cardiac dysfunction, elevated blood pressure or vasoconstriction. In yet another embodiment according to the invention, the compounds of Formula (I) are useful for the treatment and / or prophylaxis of chronic obstructive pulmonary disease, anaphylactic shock fibrosis, psoriasis, allergic diseases, asthma, stroke or ischemic conditions. , ischemia-reperfusion, aggregation / activation of platelets, d atrophy / hypertrophy of the skeletal muscle, leukocyte recruitment in the cancerous tissue, angiogenesis, invasion by metastasis, in particular melanoma, Kaposi's sarcoma, acute and chronic bacterial and viral infections, sepsis, transplant, rejection of grafts, glomerulosclerosis, glomerulonephritis, progressive renal fibrosis, endothelial and epithelial lesions or in the lung or in general, inflammation of the airways of the lung. The thiazole derivatives exemplified in this invention can be prepared from readily available raw materials using the following general methods and procedures. It will be appreciated that where they provide typical or preferred experimental conditions (i.e., reaction temperatures, time, moles of reagents, solvents, etc.), other experimental conditions may also be used, unless otherwise specified. The optimum reaction conditions may vary with the reagents or solvents used, but such conditions can be determined by the person skilled in the art, using routine optimization procedures.

Synthesis of the compounds of the invention The novel bis-thiazole or oxazole-thiazole derivatives according to Formula (I) can be prepared from readily available raw materials, by various synthetic procedures, using both the chemical protocols in solution phase and in solid phase (Pirrung et al., J. Comb. Chem. 2001, 3.90-96). The examples of the synthetic trajectories for (sic) will be described. The following abbreviations refer to the following definitions: min (minute), hr (hour), g (gram),), MHz (Megahertz), ml (milliliter), mmol (millimole), mM (millimolar), ta (temperature environment), ATP (Adenoside Triphosphate), BSA (Bovine Seroalbumin), CDI (NN-carbonyldiimidazole), DCM (dichloromethane), DCC (dicyclohexylcarbodiimide), DIEA (di-isopropyl ethylamine), DMSO (Dimethyl Sulfoxide), EDC ( 1- (3-dimethylaminopropyl) -3-ethyl-carbodiimide hydrochloride), HPLC (Liquid Chromatography High Performance), Insl P (D-myo-inositol-1-phosphate), mCPBA (n-chloroperoxybenzoic acid), MS (mass spectrometry), NMR (Nuclear Magnetic Resonance), PBS (Phosphate-buffered Physiological Serum), Pls (Phosphoinositides), PI3K (Phosphoinositide 3-kinases), PI (3) P (Phosphatidylinositol 3-monophosphate), PI (3,4) P2 (Phosphatidylinositol 3,4-bisphosphonate), PI (3,4,5) ) P3 (Phosphatidylinositol 3,4,5-triphosphate), PI (4) P (Phosphatidylinositol 4-phosphate), PI (4,5) P2) (4,5-Phosphatidylinositol biphosphonate), Ptdlns (Phosphatidylinositol), SPA (Scintillation Proximity Assay), TEA (triethylamine), THF (tetrahydrofuran), TLC (Thin Layer Chromatography), UV (Ultraviolet). A synthetic procedure (Reaction Scheme 1 below) consists of reacting approximately equimolar amounts of a-bromoketone reagent (P1) with a thiourea, a dithiocarbamate, an alkyl, alkenyl or alkynyl ester of dithiocarbamic acid (P2), mixed in a solvent, preferably polar, such as an alcohol solvent, to provide a compound of Formula (I). The temperature of the reaction depends on the nature of (P1) and (P2), which varies between -20 ° C and that of reflux.

REACTION SCHEME 1 Pl P2 (i) Another synthetic process, described in Reaction Scheme 2 below, consists in reacting in the same way a free amine derivative (P1a), with a thiourea or a dithiocarbamate (P2), providing the bis-thiazole or the oxazol-thiazole corresponding to Formula (la).

REACTION SCHEME 2 Pia P2. ? a (I) The derivative (la) can be further substituted by a group -C (O) R4 to lead to a compound of Formula (I) using the conditions known to the person skilled in the art.

When the group -C (0) R4 is an acyl group, the corresponding acyl chloride is added to the intermediate (la) in the presence of a base, for example, pyridine, DIEA, TEA, etc. The corresponding carboxylic acid may also be added in the presence of an activating agent such as DCC, EDC, etc. A formyl group, ie, -C (0) R4 = -C (0) H, can be introduced by heating an intermediate (a) in formic acid or in any alkyl formate, with or without a cosolvent. A substituted urea is formed by the addition of an isocyanate, R8R9NC (0), to the intermediate (a) in the presence of a base, for example, DIEA, TEA, etc. The sequential addition of CDI and ammonia to the intermediate (la) provides a compound of Formula (1) with -C (0) R4 = -C (0) NH2. Other functionalities -C (0) R4 can be added to the intermediate (a), to provide a compound of Formula (1), as defined in the above description, using the reaction conditions known to the person skilled in the art. In the case of the compounds of the invention of Formula (I), wherein R1 = NR5R6, ie of Formula (Ib), the same procedures as those described above can be used, and wherein the derivatives of formula (P2) are the thiourea of formula (P2a) (Reaction Scheme 3 below).

REACTION SCHEME 3 Pl P2a (Ib) For the preparation of the compounds of Formula (Ib), approximately equimolar amounts of the reagent of the a-bromoketone (P1) and the substituted N-thiourea (P2a) are stirred as a solution or a suspension in a solvent, preferably polar, such as an alcohol solvent. When reagents (P1) or (P2a) are used as a salt, an excess of base, preferably triethylamine or pyridine (approximately 3 equivalents), is added to the reaction mixture. The temperature chosen for this reaction depends on the nature of (P1) and (P2a), which varies between -20 ° C and that of reflux. The desired bis-thiazole or oxazole thiazole of Formula (Ib) are then isolated as the HBr salt by filtration, if precipitated from the reaction mixture with cooling, or by evaporation of the solvents to obtain the raw product. This crude product can then be purified, if desired, by crystallization or by standard chromatographic methods. When R5 and R6 form a ring, the same procedures described above can be used.

Alternatively, the HBr released during the reaction can first be neutralized by the addition of an excess of base, preferably triethylamine or pyridine (approximately 3 equivalents). The desired bis-thiazole or oxazole thiazole of Formula (Ib) are then isolated by filtration d, if precipitated from the reaction mixture with cooling, and washed with water to remove the HBr salt from the base. added It can also be precipitated by the addition of water and isolated by filtration or extracted with organic solvents, such as EtOAc or DCM. The resulting crude product can then be purified, if desired, for example, by crystallization or by standard chromatographic methods. These reaction conditions described above and detailed in the following Examples can also be applied when the compounds (P1a) are used as raw materials. In this case, the d compounds of Formula (Ib) can be obtained with an additional step for the introduction of the group -C (0) R4, as defined above in the description, using conditions known to the person skilled in the art. When -C (0) R4 is an acyl group, the corresponding acyl chloride is added to the intermediate (la), wherein R1 = NR5R6, in the presence of a base, for example, pyridine, DIEA, TEA, etc. The corresponding carboxylic acid may also be added in the presence of an inactivating agent, such as DCC, EDC, etc.

A formyl group, ie, -C (0) R4 = -C (0) H, can be introduced by heating it, where R1 = NR5R6, in formic acid or in any alkyl formate with or without a cosolvent. A substituted urea is formed by the addition of an isocyanate, R8R9NC (0), to the intermediate (la), wherein R1 = NR5R6, in the presence of a base, for example, DIEA, TEA, etc. The sequential addition of CDI and ammonia to the intermediate (la), wherein R1 = NR5R6, provides a compound of the invention according to Formula (Ib) with -C (0) R4 = -C (0) NH2. Other functionalities -C (0) R4 can be added to the intermediate (la), wherein R1 = NR5R6, to provide a compound of the invention according to Formula (Ib), as defined above in the description, using the conditions of reaction known to the person skilled in the art. The thioureas (P2a) used in the above Synthetic Reaction Scheme 3 are commercially available from various sources or are synthesized using conditions known to the person skilled in the art. For example, thioureas (P2a) can be obtained by coupling a salt of an amine NHR5R6, preferably, HCl salt with potassium thiocyanate used in equimolarity in THF under reflux (Herr et al., J.

Synthesis, 2000, 1569-1574) as shown in Reaction Scheme 4 below, Trajectory A.

REACTION SCHEME 4 Path A R ° KSCN. THF Rs reflux R- N H.N. L H HCl Yr P2a Path B etoKfcarbonüo Fia Path C Thiocyanate of Bepzoyl thio? ammonium benzoyl chloride 80 ° C ? " S P2a Path D CH3 / NaHCO3 sa1, CI2SO P2a Trajectory E L THF, D? EA. CUSO P2a The NHR5R6 amine can be first activated with ethoxycarbonyl isothiocyanate by providing an ethoxycarbonyl thiourea intermediate, as presented above in Reaction Scheme 4, Path B (Hartmann et al., Prakt.Chemin.1973, 31d, 144-148). After deprotection under acidic conditions, for example, concentrated HCl, the desired thiourea (P2a) is released. The amine NHR5R6 can also be activated with benzoyl isothiocyanate, obtained by the addition of benzoyl chloride to ammonium thiocyanate, providing the benzoyl thiourea intermediate, as shown in Reaction Scheme 4, Trajectory C (Rasmussen et al., Synthesis, 1988, 4d6-4d9). After deprotection under basic conditions, for example, NaOH, the desired thiourea (P2a) is released. Alternatively, the amine NHR5R6 can be reacted with thiophosgene, followed by the addition of ammonia, as presented above in Reaction Scheme 4, Path D (Wilson et al., J. Bioorg, Med.Chem. Lett, 2001). , 11, 916-918; d Feldman et al, Tetrahedron Lett., 1991, 32, 87d). If the above set of synthetic methods is not applicable to obtain the substituted N-thiourea (P2a), suitable methods of preparation known to the person skilled in the art should be used. The amine NHR5R6 used in the above Synthetic Reaction Scheme 4 0 is commercially available from several sources or is synthesized as will be detailed below in the examples, using conditions known to the person skilled in the art. Thioureas (P2a) synthesized under the conditions described in trajectories A, B, C and D, or any other method reported in the literature, are either used directly in the synthesis of bis-thiazole or oxazole-thiazole.

Formula (I) or is first purified, if desired, for example, by crystallization or by standard chromatographic methods. The bis-thiazole or oxazol-thiazole derivatives of the invention, according to Formula (I), wherein R1 is S02R7, ie, compounds of Formula (I), can be obtained by various synthetic procedures. An example of such a procedure is described hereinafter. The bis-thiazole or oxazole-thiazole derivatives of the invention, according to Formula (I), wherein R1 is S02R7, ie, compounds of Formula (le) and wherein R7 is selected from optionally substituted C6 alkyl, optionally substituted C2-C6 alkenyl and optionally substituted alkynyl, can be obtained by the oxidation of the alkyl, alkenyl or alkynyl sulfide (P3), as shown below in Reaction Scheme d below.

REACTION SCHEME 5 P3 mCPBA M Id P3a "R'CO" for example, R'C (?) CI, etc.

M The oxidizing agents used in the transformation can be selected from m-peroxybenzoic acid, mCPBA, (Alvarez-lbarra et al., Heterocycles1991, 32, 2127-2137), KMn04 (Konno et al, Yakugaku 1990, 110, 105-114), H202 (Fukatsu et al, Heterocycles, 1989, 29, 1517-1528) and any other oxidative agent known to the person skilled in the art. The oxidation reaction can also be performed on the free amine (P3a) to drive the corresponding bis-thiazole or oxazole thiazole (Id) intermediate which can be further substituted by a -C (0) R4 group in a compound of the invention of Formula (le), using the conditions known to the person skilled in the art. When -C (0) R4 is an acyl group, the corresponding acyl chloride is added to the intermediate (Id) in the presence of a base, for example, pyridine, DIEA, TEA, etc. The corresponding carboxylic acid may also be added in the presence of an activating agent such as DCC, EDC, etc. A formyl group, -C (0) R4 = -C (0) H, can be introduced by heating the intermediate (Id) in formic acid or in any alkyl formate, with or without a cosolvent. A substituted urea is formed by the addition of an isocyanate, R8R9NC (0), to the intermediate (Id) in the presence of a base, for example, DIEA, TEA, etc. The sequential addition of CDI and ammonia to the intermediate (Id) provides a compound of the invention of Formula (le) with -C (0) R4 = -C (0) NH2. Other functionalities -C (0) R4 can be added to the intermediate (Id), to lead to a compound of the invention according to Formula (le), as defined above in the description, using the reaction conditions known to the person skilled in the art. The bis-thiazole or oxazol-thiazole derivatives of the invention, according to Formula (I), wherein R 1 is-SO 2 NR 10 R 11, ie, compounds of Formula (le) can be obtained in two steps, starting with a step of oxidative chlorination with Cl2 for the transformation of a sulfide derivative (P4) into the corresponding sulfonyl chloride (P6), as shown in Reaction Scheme 6 below. The second step is the addition of a suitable amine HNR10R11 to the sulfonyl chloride (P6) in the presence of a base, for example, DIEA, TEA, pyridine, etc., providing sulfonamide derivatives of the invention, according to the Formula (le), as shown in Reaction Scheme 6 below. Where R 0 and R 11 form a ring, the same procedures described above can be used.

REACTION SCHEME 6 OR, P4 P5 P6 (I read The passage of oxidative chlorination can be rced by a two-step process, which involves the oxidation of a sulfide (P4) in the corresponding sulfonic acid (P5) (Mazzone et al., II Drug Ed. Se. 1980, 36, 181- 196), followed by its chlorination in a sulfonyl chloride (P6). Different chlorination reagents can be used, such as for example PCI5, POCI3 or SOCI2 (Chanet al., Bioorg, Med.Chem. 1998, 6, 2301-2316, Kropf et al., J. Chem. Eng. Data 1988, 33, 537-638; El-Maghraby et al., Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry 1981, 20B, 256-267).

Methods for preparing the intermediates of the compounds of Formula (1) The intermediates (P3) and (P4) are obtained by the reaction of approximately equimolar amounts of the a-bromoketone (P1) with ammonium dithiocarbamate (P2b) or alkyl ester , alkenyl or alkynyl of dithiocarbamic acid (P2c) respectively, as shown below in Reaction Scheme 7 below.

REACTION SCHEME 7 Pl P2b P4 P2c P3 The mixture is stirred as a suspension or solution in a polar solvent, preferably an alcohol solvent, at a temperature which depends on the nature of (P1), (P2b) or (P2c) (Pattan et al., J. Indian Drugs 2002, 429-433). The desired bis-thiazole or oxazole thiazole of formula (P3) or (P4) respectively, is isolated by filtration, in the event that it is precipitated from the reaction mixture after cooling, or by evaporation of the solvents for get the raw product. This crude product can be purified, if desired, for example, by crystallization or by standard chromatographic methods. The compound (P3) can also be obtained by the direct alkylation of (P4) with R7Hal (where Hal is any leaving group such as halides (eg Cl, Br, I), alkyl sulfonyloxy or arylsulphonyloxy groups (for example , a tosyloxy group) in the presence of a base, for example, Mel or any other alkyl, alkenyl or alkynyl, alkyl, alkenyl or alkynylsulfonyloxy, alkyl or aryl halide in the presence of NaOH (Nair et al., J. Org Chem. 1976, 40, 1348-1349) Ammonium dithiocarbamate (P2b) can be obtained by adding ammonia to a solution of carbon disulfide in a solvent such as THF, as shown in Reaction Scheme 8 It can be further transformed into (P2c) using R7Hal, for example, dimethyl sulfate (Brandsma et al., Synthesis 1985, 948-949).

REACTION SCHEME 8 for example, dimethyl sulfate P2b P2c The a-bromoketone (P1) can be obtained in two steps, thiazole -acetyl-2-substituted amino (P5) as shown in Reaction Scheme 9 below.

REACTION SCHEME 9 P5 P6 • Br., Dioxane, 50 0 Pia Pl The functionalization of the primary amine in (P5) with a group -C (0) R4 as defined above in the description, can be performed first, using the conditions known to the person skilled in the art, to provide (P6). When -C (0) R4 is an acyl group, the corresponding acyl chloride is added to (Pd) in the presence of a base, for example, pyridine, DIEA, TEA, etc. The corresponding carboxylic acid may also be added in the presence of an activating agent such as DCC, EDC, etc. A formyl group -C (0) R4 = -C (0) H can be introduced by heating (Pd) in formic acid or in any alkyl formate, with or without a cosolvent. A substituted urea is formed by the addition of an isocyanate, R8R9NC (0), to the intermediate (Pd) in the presence of a base, for example, DIEA, TEA, etc. The sequential addition of CDI and ammonia to (P5) provides (P6) with -C (0) R4 = -C (0) NH2. Other functionalities -C (0) R4 can be added to the intermediate (P5), to provide an intermediate of formula (P6) as d was defined above in the description, using the reaction conditions known to the person skilled in the art. This step is followed by an a-bromination of the d-acetyl group to provide the intermediate (P1). These two steps can be done in the reverse order, by first performing bromination in the intermediate (P5) in the presence of an unprotected primary amine, providing an intermediate (P1 a), and then introducing a group -C (0) R4 as defined above in the description, using the conditions known to the person skilled in the art to provide an intermediary (P1). In both synthetic trajectories, different brominating agents can be used, such as Br2 (Bhatti et al., Indian J. Heterocyclic Chem. 2000.10, 81-84), in the optional presence of HBr (Lipinski et al., J.

Med. Chem. 1986, 29, 2164-2163), NBS (Sayed et al., Heteroatom Chemistry 1999, 10, 385-390). Intermediates according to the formula (P5) are commercially available from various synthetic processes, using both the chemical phase in solution and solid phase protocols (Kodomari et al., Tetrahedron Lett., 2002, 43, 1717-1720) . An example of a synthetic procedure for obtaining the intermediate (P5) is illustrated in Reaction Scheme 10 hereinafter.

REACTION SCHEME 10 for example, P6 A substituted bicyclet (P7) is halogen, using for example, Br2 for a bromination or thionyl chloride for a chlorination, providing an intermediate (P8). "Hal" in the intermediate (P8) can also be a tosyloxy group, which is introduced with suitable reagents such as hydroxy (tosyloxy) iodobenzene. The intermediate (P8) is then added to a solution of thiourea or urea in a suitable solvent, preferably a polar solvent, for example, EtOH to lead to an intermediate (P5). The specific reaction conditions, temperature, time, etc., depend on the nature of X and the substituents R2 and R3, according to the literature and as will be detailed below in the examples (Sayed et al., 1999, previous Dahiya et al., Indian J. Chem. 1986, 25B, 966; Lipinski et al., J.

Org Chem. 1984, 49, 666-670; WO96 / 01979; EP0117082; JP11209284; Óhler et al., Chem. Ber. 1986, 118, 4099-4130). The intermediate (P6) can be obtained directly from the reaction of (P8) with a suitable thiourea or urea (P9), substituted with a d group -C (0) R4 as defined above in the description. Thiourea or urea (P9) are commercially available or are obtained by the functionalization of the urea H2NC (0) NH2 or the thiourea H2NC (S) NH2 with -C (0) R4, as defined above in the description, using the conditions known to the person skilled in the art. When R3 = H, P7a is prepared in one step, as the sodium salt, by condensing a methyl ketone with ethyl formate, as described in Reaction Scheme 11 below. We joke directly below, providing the intermediate P8a, according to the literature and as will be detailed below in the examples (Lipinski et al., J. Org. Chem. 1984, 49, 566-570).

REACTION SCHEME 11 P7a P8a According to a further general procedure, the compounds of formula (I) can be converted to the alternative compounds of Formula (I), employing suitable interconversion techniques, well known to a person skilled in the art. If the set of the above synthetic methods are not applicable to obtain the compounds according to Formula (I) and / or the d intermediates necessary for the synthesis of the compounds of Formula (1), suitable, known preparation methods should be used. by a person with experience in the technique. In general, the synthetic trajectories for any individual compound of Formula (I) will depend on the specific substituents of each molecule and on the ready availability of the necessary intermediates; again such factors will be appreciated by those with ordinary skill in the art. For all methods of protection and deprotection, see Philip J. Kocienski, in "Protecting Groups", Georg Thieme Verlag Stuttgart, New York, 1994 and Theodora W. Greene and Peter GM Wuts in "Protective Groups in Organic Synthesis", Wiley Interscience, 3rd Edition 1999. The compounds of this invention can be isolated in association with solvent molecules by crystallization from the evaporation of an appropriate solvent. The pharmaceutically acceptable acid addition salts of the compounds of Formula (1), which contain a basic center, can be prepared in conventional manner. For example, a solution of the free base can be treated with a suitable acid, either neat or in a suitable solution, and the resulting salt isolated by filtration or by evaporation under vacuum of the reaction solvent. The salts of Pharmaceutically acceptable base addition can be obtained in an analogous manner by treating a solution of a compound of Formula (I) with a suitable base. Both types of salts can be formed or intertwined using ion exchange resin techniques. When employed as pharmaceuticals, the compounds of the present invention are typically administered in the form of a pharmaceutical composition. Thus, pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, diluent or excipient, are also within the scope of the present invention. A person skilled in the art is aware of a variety of such carrier compounds, diluents or excipients, suitable for formulating a pharmaceutical composition. The compounds of the invention, together with a conventionally employed adjuvant, carrier, diluent or excipient, may be placed in the form of pharmaceutical compositions and unit dosages thereof, and in such form that they may be employed as solids, such as tablets or capsules. filled, or liquids such as solutions, suspensions, emulsions, elixirs or capsules filled therewith, all for oral use, or in the form of sterile injectable solutions for parenteral (including subcutaneous use). Such pharmaceutical compositions and unit dosage forms thereof may comprise ingredients in conventional proportions, with or without additional active compounds or principles, and such unit dosage forms may containing any suitable effective amount of the active ingredient commensurate with the range of the daily dosage intended to be employed. Pharmaceutical compositions containing the thiazole derivatives of this invention can be prepared in a manner well known in the pharmaceutical art and comprise at least one active compound. Generally, the compounds of this invention are administered in a pharmaceutically effective amount. The amount of the compound administered will actually be determined typically by a physician, in light of the relevant circumstances, including the condition to be treated, the route of administration chosen, the actual compound administered, the age, weight and response of the individual patient, the severity of the patient's symptoms and similar. The pharmaceutical compositions of the present invention can be administered by a variety of routes including oral rectal, transdermal, subcutaneous, intravenous, intramuscular and intranasal. Compositions for oral administration may take the form of solutions or suspensions of bulk liquid or bulk powders. More commonly, however, the compositions are presented in unit dosage forms to facilitate accurate dosing. The term "unit dosage forms" refers to physically discrete units suitable as unit dosages for human subjects and other mammals, each unit containing a predetermined amount of calculated active material to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. Typical unit dosage forms include pre-filled ampoules or syringes, pre-measured liquid or pill compositions, tablets, capsules or the like, in the case of solid compositions. In such compositions, the thiazole derivative is usually a minor component (from about 0.1 to about 60% by weight or preferably about 1 to about 40% by weight), with the remainder being various carriers or carriers and processing aids, useful in forming the desired dosage form. Liquid forms suitable for oral administration can include a suitable aqueous or non-aqueous vehicle with buffers, suspending and dispersing agents, colorants, flavors and the like. The solid forms may include, for example, any of the following ingredients or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as msium stearate; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate or orange flavor. Injectable compositions are typically based on sterile injectable physiological saline or physiologically buffered saline or other injectable carriers known in the art. As mentioned above, the bis-thiazole derivatives of Formula (I) in such compositions are typically a minor component, which frequently varies between 0.05 to 10% by weight, with the remainder being the injectable carrier and the like. The components described above for orally administered or injectable compositions are simply representative. Additional materials, as well as processing techniques and the like are set forth in Part 5 of Remington's Pharmaceutical Sciences, 20th Edition, 2000, Marck Publishing Company, Easton, Pennsylvania, which is incorporated herein by reference. The compounds of this invention can also be administered in substance sustained release forms or sustained release drug delivery systems. A description of the representative sustained release materials can also be found in the materials incorporated in Remington's Pharmaceutical Sciences. In the following, the present invention will be illustrated by means of some examples, which are not considered as limiting the scope of the invention.

EXAMPLES The following commercially available intermediates were used: 5-Acetyl-2-amino-4-methylthiazole and 2,4-pentanedione have been used from a commercial source. The commercial amines that have been used as raw material for the synthesis of thiourea are the following: 4-aminobenzamide,. { 4 - [(4-benzylpiperazin-1-yl) carbonyl] phenyl} amine, morpholine, 1-methylpiperazine, ethyl piperidin-3-carboxylate, 2-piperidin-4-ylethanol, pyrrolidine, pyrrolidin-3-ol, 6-methoxypyridin-3-amine, 6-chloropyridin-3-amine, beta-alanine, 3-amino-2-fluoropyridine, N- (2-cyanoethyl) amine, 1-amino-3,3-diethoxypropane, aminoacetaldehyde of diethyl acetal, 2-aminoacetophenone, 3- amino-2-chloropyridine, 5- (3-aminophenyl) oxazole, 5- (3-aminophenyl) tetrazole, methyl 3-aminobutanoate, hydrochloride salt, 3-aminobenzyldehyde of ethylene acetal, (4-aminophenyl) acetic acid, N - (4-aminobenzoyl) -beta-alanine, N- (4-aminobenzoyl) glycine, 3- (3-aminophenyl) propanoic acid, 3- (4-aminophenyl) propanoic acid, (3-aminophenyl) acetic acid, 4- amino-N-pyridin-2-ylbenzenesulfonamide, 2- (2-aminophenyl) ethanol, (3-aminophenyl) methanol, 2- (4-aminophenyl) ethanol, 2 - [(3-aminophenyl) sulfonyl] ethanol, hydrochloride salt , 4-amino-N, N-dimethylbenzenesulfonamide, 3-aminobenzenesulfonamide, 2-chloropyridin-4-amino, 4-amino-N-methylbenzenesulfonamide, N- (5-aminopyridin-2-yl) acetamide, 2,3- dihydro-1-benzofuran-5-amine, [2- (1-methylpyrrolidin-2-yl) ethyl] amine, (2-pyrrolidin-1-ylethyl) amine, 1- (3-atminopropyl) pyrrolidin-2-one, N- (2-aminoethyl) acetamide, N, N-dimethyletan-1,2-diamine, 2-aminoethanol, 4- (2-aminoethyl) phenol, N, N-dimethylpropan-1,3-diamine, 3-aminopropan- 1-ol, [3- (1H-imidazol-1-yl) propylamine, beta-alaninamide, hydrochloride salt, (2-methylprop-2-en-1-yl) amine, 2-aminophenol, 3-aminophenol, 6 -fluoropyridin-3-amine, 2-fluoropyridin-3-amine, d-aminopyridine-2-carbonitrile, (3-methoxyphenyl) amine, (4-chlorophenyl) amine, 3-aminobenzamide, (2-nitrophenyl) amine, quinoline- 3-amine, quinolin-5-amine, quinolin-6-amine, cyclopentanamine, cyclopropanamine, (pyridin-3-ylmethyl) amine, 4-aminobutan-1-ol, [3- (methylsulfonyl) phenyl] amine, hydrochloride salt , 3-aminopropanitrile, (3-pyrrolidin-1-ylpropyl) amine, (1,1-dioxide-1-benzothien-6-yl) amine, [(1-ethylpyrrolidin-2-yl) methyl] amine, aminoacetonitrile, -methylpropan-1-amine, (2,2-dimethypropyl) amine, cis- (2-aminociclohexyl) methanol, s to hydrochloride, trans- (2-aminocyclohexyl) methanol, hydrochloride salt, sec-butylamine, (pyridin-4-ylmethyl) amine, [4- (morfoiin-4-ylsulfonyl) phenyl] amine, 3-amino-N- butyl benzenesulfonamide, (cyclopropylmethyl) amine, cyclobutanamine, 2,3-dihydro-1H-inden-2-ylamine, [2- (methylsulfonyl) phenyl] amine, hydrochloride salt, [2- (1 H-1, 2.4 -triazol-1-yl) ethyl] amine, 1- (3-aminophenyl) ethanol, methyl 4-aminobutanoate. The commercial thioureas used in the examples described below are as follows: 3 - [(aminocarbonothioyl) amino] benzoic acid, 4 - [(aminocarbonothioyl) amino] benzoic acid, N-benzylthiourea, N- (2-phenylethyl) thiourea, piperidin -1-carbothioamide, N-allylthiourea, N-pyridin-3-ylthiourea, N- pyridin-2-ylthiourea, N- (4-methoxyphenyl) thiourea, N- (4-hydroxyphenyl) thiourea, N- (4-nitrophenyl) thiourea, N- (4-cyanophenyl) thiourea, N- (4-chlorophenyl) thiourea , N- (2-chlorophenyl) thiourea, N- (2-methoxyphenyl) thiourea, N- (3-chlorophenyl) thiourea, N- (3-hydroxyphenyl) thiourea, N- (2-morpholin-4-ylethyl) thiourea, N- (2-piperidin-1-ylethyl) thiourea, N- (2-methoxyethyl) thiourea, N-cyclohexyl thiourea, N- (3-morpholin-4-ylpropyl) thiourea, N- (tetrahydrofuran-2-ylmethyl) thiourea, N-1 -benzofuran-d-ilthiourea, N-1-benzofuran-d-ilthiourea, N- (4-cyanophenyl) thiourea, N- (3-nitrophenyl) thiourea, N-allylthiourea, N-pyridin-3-ylthiourea, piperidin-1-carbothioamide, N-phenylthiourea, N- (4-hydroxyfenal) thourea, N-pyridin-3-ylthiourea. The HPLC, NMR and MS data provided in the examples described below were obtained as follows: HPLC: Waters Symmetry C8 column 60 x 4.6 mm, Conditions: MeCN / H20, 6 to 100% (8 minutes), max plot 230- 400 nm; Mass spectrum: PE-SCIEX API 150 EX (APCl and ESI), LC / MS spectrum: Waters ZMD (ES); 1 H NMR: Bruker DPX-300 MHz. Purification by preparative HPLC was performed with a Waters Prep LC 4000 HPLC system, equipped with Prep Nova-Pak®HR columns C186 μm 6? A, 40 x 30 mm (up to 100 mg) or with XTerra® Prep MS C8, 10 μm, 50 x 300 mm (up to 1 g ). All purifications were performed with a 0.09% MeCN / H20 TFA gradient. The reverse phase semipreparative HPLC was performed with the Parallex Flex Biotage System, equipped with Supelcosil ™ ABZ + Plus columns (26 cm x 21.2 mm, 12 μm); UV detection at 264 nm and 220 nm; flow of 20 mL / minute (up to 50 mg). TLC analysis was performed on Merck Precoated 60F254 plates. Purifications through Flash chromatography was performed on a SiO2 support, using mixtures of cyclohexane / EtOAc or DCM / MeOH as eluents. The chemistry of microwaves was carried out in a simpler microwave reactor Emrys ™ Optimiser by Personal Chemistry.

INTERMEDIARY 1 Preparation of N-, 5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl. Acetamide, hydrobromide salt (Intermediate (P1), where R2 is H, R3 and R4 are methyl and X is S) Intermediary 1 He passed N- (5-acetyl-4-methyl-1,3-thiazol-2-yl) acetamide (Intermediate (P6), wherein R2 is H, R3 and R4 are methyl v X is S) d-acetyl-2 -amino-4-methylthiazole (Pd) (12.35 g, 79 mmol) was suspended in a 3: 2 THF / DCM mixture (150 mL). The mixture was cooled to below 0 ° C and pyridine (16 mL) was added, followed by the dropwise addition. of acetyl chloride (8.43 mL, 119 mmol, 1.5 equivalents). The mixture was stirred 2 hours at 0 ° C. As the acetylation was complete, the reaction was quenched with the addition of water (70 mL) and diluted with EtOAc (100 mL). The two phases were separated and the organic phase was washed with a portion of a 10% citric acid solution. The organic layer was dried over MgSO4, filtered and evaporated. The resulting crude mass was purified by crystallization from a mixture of EtOAc / Cyclohexane to obtain N- (5-acetyl-4-methyl-1,3-thiazol-2-yl) acetamide (P6) as a colorless powder (13.13). g, 83.6% yield). 1 H NMR (DMSO-d 6) d: 2.17 (s, 3 H), 2.47 (s, 3 H), 2.56 (s, 3 H), 12. 44 (broad s, 1 H). M "(ESI): 197.3; M + (ESI): 199.3 HPLC, Retention time: 1.7 minutes (purity: 99.7%).

Step II N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-1-acetamide, hydrobromide salt. (Intermediate 1) A solution of Br2 (3.36 mL, 65.6 mmol) in 75 mL of dioxane was added dropwise to a solution of N- (5-acetyl-4-methyl-1,3-thiazole-2-yl). ) acetamide (P6), obtained in Step I, as described above, (10.40 g, 52.5 mmol) in 200 mL of dioxane. The resulting mixture was heated at 50 ° C for 19 hours. The solution turned from dark red to beige and remains a heterogeneous mixture. By analytical HPLC, only 2.8% of the raw material was detected. The suspension was filtered, washed with a 1: 2 mixture of EtOAc / hexanes (50 mL) and air-dried for 15 minutes, to provide Intermediate 1 as a beige solid (11.2 g, 60%). This was used in the synthesis of the bis-thiazole as the HBr salt or as the original compound, after 5 minutes of treatment with Amberlyst A21 in a DCM / MeOH mixture. 1 H NMR (DMSO-d 6) d: 2.04 (s, 3 H), 2.44 (s, 3 H), 4.62 (s, 2 H), 12.44 (broad s, 1 H). M "(ESI): 276; M + (ESI): 278. HPLC, Retention time: 2.2 minutes (purity: 97.4%).

INTERMEDIARY 2 Preparation of 1- (2-amino-4-methyl-113-thiazol-5-yl) -2-bromoethanone, hydrobromide salt (Intermediate (P1a), where R2 is H, R3 is methyl and X is S) Intermediary 2 The d-acetyl-2-amino-4-methylthiazole (Pd) (1.0 g, 6.4 mmol) was suspended in a 48% solution of HBr in water (20 mL, 6.4 mmol). The mixture was heated to 60 ° C and a Br2 solution (0.262) was added dropwise. mL, 5.12 mmol, 0.8 equivalents) in dioxane (20 mL). The mixture was stirred at 60 ° C for 3 hours. The progress of the reaction was followed by LC / MS. When complete, the solvents were evaporated, and the water was removed by azeotropic distillation with toluene. The resulting solid was recrystallized from a mixture of isopropanol / Et 0, providing Intermediate 2 as a colorless solid (890 mg, 74% yield). 1 H NMR (DMSO-d 6) d: 2.46 (s, 3 H), 4.50 (s, 3 H), 6.90 (broad s, 1 H), 9.18 (broad s, 2 H). M "(ESI): 234.1; M + (ESI): 236.1.

INTERMEDIARY 3 Preparation of N-.5- (bromoacetyl) -4-methyl-1,3-oxazol-2-yl-acetamide (Intermediate (P1), where R2 is H, R3 and R4 are methyl and X is O) Intermediary 3 Step I 3-Bromo-2,4-pentanedione (Intermediate (P8), where R2 is H, R3 is methyl and Hal is Br) A solution of bromine (56.9 g, 0.35 moles, 18 mL) in CCI (135 mL), was added during 80 minutes to a biphasic solution of 2,4-pentanedione (P7) (35 g, 0.35 mol, 36 mL) in a 1: 1 mixture of CCI4 / water (400 mL), keeping the temperature at 3-4 ° C. 40 minutes after the addition, both layers were separated and the organic phase was dried over MgSO4. Evaporation under reduced pressure afforded 3-bromo-2,4-pentanedione (P8) as a slightly yellowish liquid (54.01 g, 86%). 1 H NMR (DMSO-d 6) d: 2.32 (s, 6 H), 5.64 (s, 1 H).

Step II 1- (2-amino-4-methyl-1,3-oxazol-5-yl) ethanone (Intermediate (P5), where R2 is H, R3 is methyl and X is O) 3-Bromo-2,4 -pentandione (P8) (26.66 g, 148.93 mmoles) obtained in Step I as described above, was dissolved in acetone (87 mL). This mixture was added to a solution of urea (22.36 g, 372 mmol, 2.5 equivalents) in water (20 mL). The resulting mixture was heated in order to obtain a clear solution and distributed in 38 microwave tubes (3 ml each). The vials were heated at 100 ° C for 1200 seconds each in a microwave oven. All vials were combined, saturated NaHCO3 (100 mL) and EtOAc (100 mL) were added, the aqueous phase was saturated with NaCl and the phases were separated. The aqueous phase was extracted with EtOAc (4 times with 100 ml). The combined organic layers were dried over MgSO4, filtered and evaporated under reduced pressure to give 1- (2-amino-4-methyl-1,3-oxazol-5-yl) ethanone (P5) as an orange solid ( 12.09 g). This was further recrystallized from MeOH to give a brown solid (5.56 g, 27%). 1 H NMR (DMSO-d 6) d: 2.22 (s, 3 H), 2.25 (s, 3 H), 7.51 (s, 2 H).

He passed N- (5-acetyl-4-methyl-1,3-oxazol-2-yl) acetamide (Intermediate (P6), where R2 is H. R3 v R4 are methyl v X is O) La 1- (2- amino-4-methyl-1, 3-oxazol-d-yl) ethanone (Pd) obtained in the Step II as described above (12.55 g, 89.58 mmol, 1.00 equivalents), was dissolved in pyridine (300 ml). The solution was cooled to 0 ° C, and acetyl chloride (9.dd, 134.37 mmol, 1.50 equivalents) was added dropwise at a rate such that the temperature did not exceed 5 ° C. The mixture was stirred at room temperature overnight. A solution of HCl (1.0 M, 260 mL) was added, and the desired product was extracted with EtOAc (5 times, 100 mL). The combined organic layers were dried over MgSO4, filtered and evaporated to give the N- (5-acetyl-4-methyl-1,3-oxazol-2-yl) acetamide (P6) as a beige / brown solid (15.18). g, 93%). 1 H NMR (DMSO-d 6) d: 2.12 (s, 3 H), 2.34 (s, 3 H), 2.35 (s, 3 H), 11. 64 (s, 1 H).

Step IV N-r5- (bromoacetyl) -4-methyl-1,3-oxazole-2-acetamide (Intermediate 3) N- (5-acetyl-4-methyl-1,3-oxazol-2-yl) acetamide ( P6) obtained in the previous Step lll (13.29 g, 72.95 mmoles, 1.00 equivalents), was dissolved in Glacial acetic acid (250 ml) and 10 drops of hydrobromic acid were added to 62%. To the resulting solution, bromine (3.74 ml, 72.95 mmol, 1.00 equivalents) was added dropwise, and the mixture was stirred at room temperature for 2.5 hours. A beige precipitate formed. This was filtered, washed with cyclohexane and dried under reduced pressure to yield Intermediate 3 as a beige solid (14.89 g, 78%). 1 H NMR (DMSO-d 6) d: 2.14 (s, 3 H), 2.38 (s, 3 H), 4.46 (s, 2 H), 11.78 (s, 1 H). M "(ESI): 259.8; M + (ESI): 261.9 HPLC, Retention time: 1.3 minutes (purity: 97.6%).

INTERMEDIARY 4 Preparation of N-f5- (2-bromo-acetyl) -thiazole-2-ip-acetamide (Intermediate (P1), where R2 and R3 are H. R4 is methyl and X is S) Intermediary 4 He passed Sodium Acetoacetaldehyde (Intermediate (P7a), where R2 is H) Ethyl formate (5 g, 0.067 mol) was slowly added to a solution of NaOMe (3.64 g, 0.067 mol) in diethyl ether (30 mL) and acetone (5 mL). The mixture was stirred for 30 minutes. The resulting solid was collected by filtration, washed with ether, and then dried under vacuum to provide sodium acetoacetaldehyde (P7a) as a white solid (4.5 g, 61%).

Step II 2-Bromoacetoacetaldehyde (Intermediate (P8a), where R is H > d Sodium acetoacetaldehyde (P7a) (4.6 g, 0.041 mol) obtained in Step I as described above, was dissolved in DCM (45 mL). The resulting solution was cooled to -78 ° C and bromine (6.6 g, 0.041 mol) in DCM (3 mL) was added dropwise. The reaction mixture was stirred at -78 ° C for 24 hours and warmed to room temperature. The resulting solid was collected by filtration and recrystallized from ethyl acetate and petroleum ether to give the 2-bromo acetoacetaldehyde (P8a) as a pale yellow solid (5.4 g, 78%).

Step lll 1- (2-Amino-1,3-thiazol-5-yl) ethanone (Intermediate (P5), where R2 and R3 are H and X is S. The 2-Bromoacetoacetaldehyde obtained in Step II as described above ( 5 g, 0.03 mol), was dissolved in ethanol (60 mL), thiourea (2.76 g, 0.03 mol) was added, and the reaction mixture was stirred for 24 hours at room temperature and 3 hours under reflux. environment and the resulting solid was isolated by filtration, washed with EtOH and It was dried under vacuum. 1- (2-Amino-1,3-thiazol-5-yl) ethanone (Pd) was recovered as a white solid (2.5 g, 40%).

Step IV N- (5-acetyl-1,3-thiazol-2-yl) acetamide (Intermediate (P6), wherein R2 and R3 are H, R4 is methyl and X is S) 1- (2-Amino-1, 3-thiazol-d-yl) ethanone obtained in Step III as described above (2 g, 9.66 mmol), was dissolved in a mixture of THF (15 mL) and DCM (10 mL). The resulting solution was cooled to below 0 ° C. Acetyl chloride (1.1 g, 14.4 mmol) was added and the mixture was stirred at room temperature overnight. This was then diluted with water (50 mL), extracted with ethyl acetate (3 x 60 mL). The combined organic phase was washed with water, brine, dried over MgSO, filtered and evaporated to give the N- (d-acetyl-1,3-thiazol-2-yl) acetamide (P6) as a white solid ( 2.1 g, 87%).

Step V Nd- (2-bromo-acetyl) -thiazole-2-p-acetamide (Intermediate 4) The N- (d-acetyl-1,3-thiazol-2-yl) acetamide obtained in Step IV as described above (1.5 g, 6 mmol), dissolved in dioxane (50 mL). Bromine (0.96 g, 6 mmol) was added and the mixture was heated to 60 ° C. for 24 hours. The reaction mixture was concentrated. The resulting solid was isolated by filtration and recrystallized from ethyl acetate and petroleum ether, providing Intermediate 4 as a white, off-white solid (1.2 g, 60%). 1 H NMR (DMSO-d 6) d: 2.17 (s, 3 H), 4.76 (s, 2 H), 8.47 (s, 1 H), 12.67 (broad s, 1 H). M "(ESI): 261.09; M + (ESI): 263.14 HPLC, Retention time: 1.79 minutes (purity: 94.32%).

INTERMEDIARY 5 Preparation of N-r5- (2-bromo-acetyl) -4-trifluoromethyl-thiazole-2-yl-acetamide (Intermediate (P1), where R2 is H, R3 is CF3 and R4 is methyl v X is S) Intermediary 5 Step I 1 - . 1 - | "2-amino-4- (trifluoromethyl) -1, 3-thiazol-d-yl] ethanone (Intermediate (Pd), where R2 is H v R3 is CF3) Hydroxy (tosyloxy) iodobenzene (3 g, 7.7 mmol) to a solution of 1,1,1-trifluoropentane-2,4-dione (1 g, 6.4 mmol) in ACN (10 mL) The resulting mixture was heated under reflux for 45 minutes, then it was cooled below room temperature, and thiourea (0.59 g, 7.7 mmol) was added The mixture was heated under reflux for 4 hours and then allowed to stand overnight.The reaction mixture was concentrated and the residue was concentrated. recrystallized from ethyl acetate and petroleum ether to give 1- [2-amino-4- (trifluoromethyl) -1,3-thiazol-5-yl] ethanone (P8) as a white solid (1.2 g, 79%) .

Step II N- [d-acetyl-4- (trifluoromethyl) -1,3-thiazol-2-yl) acetamide (Intermediate (P6), where R2 is H, R3 is CF3, R4 is methyl and X is S) The 1- [2-amino-4- (trifluoromethyl) -1,3-thiazol-5-yl] ethanone obtained in Step I as described above (1 g, 5.7 mmol), was dissolved in a THF mixture ( 7.5 mL), DCM (7.5 mL) and pyridine (1 g, 12.8 mmol). The resulting solution was cooled to below 0 ° C and acetyl chloride (0.6 g) was added., 7.7 mmoles). The mixture was stirred overnight at room temperature. This was diluted with water (10 mL) and extracted with DCM (3 x 25 mL). The combined organic phase was washed with water, brine, dried over MgSO, filtered and concentrated. The resulting crude product, N- [5-acetyl-4- (trifluoromethyl) -1,3-thiazol-2-yl) acetamide, was used in the next step without further purification (1.1 g, 90%).

He passed 2-Acetylamino-4- (trifluoromethyl) -5-bromoacetyl-thiazole (Intermediate 5.) The N- [5-acetyl-4- (trifluoromethyl) -1,3-thiazol-2-yl) acetamide obtained in the Step II, as described above (1 g, 4.2 mmol), was dissolved in dioxane (60 mL). Bromine (0.67 g, 4.2 mmol) was added and the mixture was heated at 60 ° C for 24 hours. The reaction mixture was concentrated. He The crude compound obtained was recrystallized from ethyl acetate and petroleum ether to provide Intermediate d (0.8 g, 60%), which was mixed with a bis-brominated intermediate in a ratio of 4: 6. However, this was used as such in the reactions described hereinafter. 1 H NMR (DMSO-d 6) d: 2.22 (s, 3 H), 2.38 (s, 3 H), 4.73 (s, 2 H), 13.08 (s, 1 H). 19F NMR (DMSO-d6) d: -61.22. M "(ESI): 329.1; M + (ESI): 331.3 HPLC, Retention time: 2.90 minutes (purity: 41.47%).

INTERMEDIARY 6 Preparation of ethyl 2- (acetylamino) -5- (bromoacetyl) -1,3-thiazole-4-carboxylate (Intermediate (P1), where R2 is H, R3 is COOEt and R4 is methyl and X is S ) Intermediary 6 He passed Ethyl 5-acetyl-2-amino-1,3-thiazole-4-carboxylate (Intermediate (Pd), where R2 is H and R3 is COOEt) The dioxovalerate (2 g, 12.6 mmol) was dissolved in CCI4 (20). mL) and cooled below 0 ° C. SOCI2 (1.7 g, 17.7 mmol) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. The resulting residue was dissolved in absolute ethanol (20 mL). Thiourea (1.4 g, 18.9 mmoies) was added and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate (3 x 25 mL). The combined organic phase was washed with water, brine and dried over MgSO4. Filtration and evaporation of the solvents gave the 5-acetyl-2-amino-1,3-thiazole-4-carboxylate from ethyl as a white solid (0.8 g, 29%). This was used in the next step without further purification.

Step 11 Ethyl 5-acetyl-2- (acetylamino) -1,3-thiazole-4-carboxylate (Intermediate (P6), where R2 is H, R3 is COOEt, R4 is methyl and X is S) The ethyl 5-acetyl-2-amino-1,3-thiazole-4-carboxylate, obtained in Step I as described above (0.8 g, 3.7 min), it was dissolved in a mixture of THF (10 mL) and DCM (d mL) and pyridine (0.73 g, 9.3 mmol). The resulting solution was cooled to below 0 ° C and acetyl chloride (0.43 g, d.6 mmol) was added. The mixture was stirred overnight at room temperature. This was diluted with ethyl acetate (25 mL). The organic phase was washed with water, brine, dried over MgSO, filtered and concentrated. The resulting crude product was crystallized from ethyl acetate and petroleum ether, affording ethyl 5-acetyl-2- (acetylamino) -1,3-thiazole-4-carboxylate as a white solid (0.6 g, 62%).

Step lll Ethyl 2- (acetylamino) -5- (bromoacetyl) -1,3-thiazole-4-carboxylate (Intermediate 6) 5-Acetyl-2- (acetylamino) -1,3-thiazole-4-carboxylate Ethyl obtained in Step II as described above (0.6 g, 2.3 mmol), was dissolved in dioxane (50 mL). Bromine (0.37 g, 2.33 moles) was added and the mixture was stirred at 60 ° C for 24 hours. The reaction mixture was concentrated. The resulting crude compound was recrystallized from a mixture of ethyl acetate and petroleum ether, affording Intermediate 6 as a white solid (0.7 g, 90%). This was contaminated with 19% of the bis-brominated intermediate. However, this was used as such in the reactions described hereinafter. 1 H NMR (DMSO-d 6) d: 1.27 (m, 3 H), 2.19 (s, 3 H), 4.31 (m, 2 H), 4.74 (s, 2 H), 12.90 (broad s, 1 H). M "(ESI): 333.1; M + (ESI): 335.1 HPLC, Retention time: 2.66 minutes (purity: 70.54%).

INTERMEDIARY 7 Preparation of N- (5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] urea (Intermediate (P1), where R2 is H, R3 and R4 are methyl and X is S ) Intermediary 7 Step I N- (5-acetyl-4-methyl-1,3-thiazol-2-yl) urea (Intermediate (P6), where R2 is H, R3 is methyl, R4 is NH3 and X is S. The 2-Amino-4-methyl-d-acetylthiazole (3 g, 19.2 mmol) was dissolved in DMF (30 mL). CDI (3.5 g, 21.1 mmol) was added and the mixture was stirred at room temperature for 3 hours. 0.5 N ammonia in dioxane (60 mL, 30 mmol) was added, and the mixture was stirred for 2 days in a closed system. The resulting precipitate was recovered by filtration, washed with petroleum ether and dried under vacuum to give N- (5-acetyl-4-methyl-1,3-thiazol-2-yl) urea as a colorless solid (1.5 g, 39%).

Step II N- [5- (bromoacetyl) -4-methyl-1,3-thiazole-2-urea (Intermediate 7) A solution of (d-acetyl-4-methyl-thiazol-2-yl) urea, obtained in the Step I, as described above (1.5 g, 7.5 mmol), was dissolved in dioxane (200 mL). Bromine (1.2 g, 7.5 mmol) was added and the mixture was heated at 60 ° C overnight. The reaction mixture was concentrated and the resulting crude product was recrystallized from a mixture of ethyl acetate and petroleum ether, affording Intermediate 7 as a colorless solid (0.55 g, 26%). This was mixed with 7% of the bis-brominated intermediate and 55% of the raw material. However, this was used as such in the reactions described hereinafter. M "(ESI): 277.81; M + (ESI): 279.89. HPLC, Retention time: 1.78 minutes (purity: 36.29%).

Amina 1 Preparation of 5- (3-aminophenyl) -1,4,4-oxadiazo! -2-ol (Amin d (NHR 5 R 6), where R 5 is H and R 6 is 5-Phenyl-M, 3,41 -oxadiazol-2-ol ) 0 Amina 1 He passed Methyl 3-nitrobenzoate 3-Nitrobenzoic acid (1.00 g, d.98 mmol, 1.00 equivalents) was dissolved in toluene (16 ml). Trimethylsilyl diazomethane in toluene and MeOH (1/1) (8.98 ml, 2.00 M, 17.96 mmoles, 3.00 equivalents) was added dropwise. The solution was stirred at room temperature for 1.5 hours. Solvents were removed to give methyl 3-nitrobenzoate as a yellow powder (940.70 mg, 86.79%). 1 H NMR (DMSO-de) d: 3.92 (s, 3 H), 7.84 (m, 1 H), 8.35 (m, 1 H), 8.50 (m, 1 H), 8.62 (m, 1 H). HPLC, Retention time: 1.8 minutes (purity: 99.1%).

Step II 3-Nitrobenzohydrazide Methyl 3-nitrobenzoate (940.70 mg, 5.19 mmol, 1.00 equivalents) was dissolved in EtOH (24.00 ml). Hydrazine hydrate (4.04 ml, 83.09 mmoles, 16.00 equivalents) was added and the mixture was stirred at room temperature for 1 hour. This was stirred at 60 ° C for 6 hours and room temperature overnight. The formed precipitate was filtered and dried under vacuum to give the 3-nitrobenzohydrazide as a white off-white solid (815.90 mg, 86.73%). 1 H NMR (DMSO-de) d: 4.62 (s, 2 H), 7.76 (m, 1 H), 8.24 (m, 1 H), 8.36 (m, 1 H), 8.63 (s, 1 H), 10.15 ( s, 1 H).

Step lll - (3-nitrophenyl) -1,4,4-oxadiazol-2-ol 1,1-carbonyldiimidazole (641.18 mg, 3.95 mmol, 1.00 equivalents) was added to a solution at 0 ° C of 3-nitrobenzohydrazide (715.90) mg, 3.95 mmol, 1.00 equivalents) and triethylamine (822.18 μl, 5.93 mmol, 1.50 equivalents) in DMF (30.00 ml). The reaction mixture was stirred between 0 ° C and room temperature for 4 hours. The solvents were removed under vacuum, yielding an orange oil, which was solubilized in DCM and washed with 0.1 M HCl. The organic phase was concentrated. The resulting precipitate it was recovered by filtration to give 5- (3-nitrophenyl) -1,4,4-oxadiazol-2-ol as a white solid (469.90 mg, 58%). 1 H NMR (DMSO-d 6) d: 7.84 (s, 1 H), 8.19 (m, 1 H), 8.41 (m, 2 H), 12.91 (s, 1 H). HPLC, Retention time: 2.06 minutes (purity: 97.5%).

Step IV - (3-aminophenyl) -1,4,4-oxadiazol-2-ol (Amine 1) In a flask, 5- (3-nitrophenyl) -1,4,4-oxadiazol-2-ol was dissolved ( 369.90 mg, 1.79 mmol, 1.00 equivalents) in MeOH (20.00 ml) under an inert atmosphere. Palladium on carbon at 10% (190.03 mg, 0.18 mmol, 0.10 equivalents) was added, and the reaction mixture was stirred 5 minutes at room temperature. The mixture was then placed under atmospheric pressure of hydrogen. The reaction was completed after 2 hours. The mixture was filtered over celite and rinsed with MeOH. The solvents were evaporated under vacuum to give 5- (3-aminophenyl) -1,4,4-oxadiazol-2-ol as a white powder (283.30 mg, 89.55%). 1 H NMR (DMSO-d 6) d: 5.43 (s, 2 H), 6.70 (m, 1 H), 6.89 (m, 1 H), 7.08 (s, 1 H), 7.14 (m, 1 H), 12.44 ( s, 1 H).

Amina 2 Preparation of 5- (3-aminophenyl) -1,4,4-thiadiazol-2-amine (Amines (NHR5R6), wherein R5 is H and R6 is 5-Phenyl-_1.3.4.thiadiazol-2-ylamine, Amina 2 Thiosemicarbazide (465.69 mg, 5.00 mmol); 1.00 equivalents) and 3-aminobenzonitrile (590.69 mg, 5.00 mmol, 1.00 equivalents) were heated in TFA (2.50 ml) at 60 ° C for 4 hours. The mixture became a thick yellowish solution. The reaction mixture was poured into ice-water (15 mL) and neutralized with an aqueous solution of saturated NaHCO 3. The resulting precipitate was filtered to give 5- (3-aminophenyl) -1,3,4-thiadiazol-2-amine as a white, off-white solid (291.00 mg, 30.27%). The aqueous layers were extracted with ethyl acetate (3 x 16 mL). The combined organic layers were washed with a saturated solution of NaCl, dried over sodium sulfate, filtered and concentrated to provide a 1: 1 mixture of the d- (3-aminophenyl) -1,4,4-thiadiazole- 2-amine and N- [3- (5-Amino- [1, 3,4] thiadiazol-2-yl) -phenyl] -2,2,2-trifluoroacetamide (526.00 mg). The undesired trifluoroacetamide can be deprotected in a quantitative yield by dissolving it in a 2N solution of ammoniacal methanol (30 equivalents), and stirred at room temperature for 3 hours. 1 H NMR (DMSO-d 6) d: 5.29 (broad s, 2H), 6.59 (m, 1 H), 6.85 (m, 1 H), 6.96 (m, 1 H), 7.06 (t, J = 8 Hz, 1H), 7.28 (broad s, 2H). M "(ESI): 191.3; M + (ESI): 193.3.

Amina 3 General procedure for the esterification of the amino acid of formula (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid: for example, Preparation of methyl 3-Aminopropanoate (Amine (NHR5R6), wherein R5 is H and R6 is propanoate of methyl) Amine 3 A mixture of beta-alanine (2.00 g, 22.45 mmol, 1.00 equivalents) in MeOH (20.00 ml) was cooled to 5 ° C. Thionyl chloride (3.26 ml, 44.90 mmol, 2.00 equivalents) was slowly added over 16 minutes under vigorous stirring. After the addition was complete, the reaction mixture was heated under reflux overnight. The reaction mixture it was concentrated under vacuum. The resulting oil was treated with dry ether to afford the methyl 3-aminopropanoate as a white solid (2.48 g, 79.08%). 1 H NMR (DMSO-d 6) d: 2.71 (m, 2 H), 2.97 (s, 2 H), 3.62 (s, 3 H), 8.22 (s, 2 H, NH 2).

Preparation of thiourea (P2a): Procedure A The appropriate amine R5R6NH (1 equivalent), as well as the salt of HCl and KSCN (1.5 equivalents) were heated under reflux in THF (0.5 M). When the reaction was complete, the mixture was diluted with H 0 and extracted with EtOAc (3 portions). The combined organic phases were washed with HCl 1 N, brine and dried over Na S0. After filtration and concentration, the isolated thiourea (P2a) was used in the synthesis of the bis-thiazole or of the oxazole-thiazole, following the general procedure 1 described below.

Preparation of thiourea (P2a): Procedure B The appropriate amine R5R6NH (1 equivalent) was dissolved in acetone (1M). This solution was added to a mixture of ethoxycarbonyl isothiocyanate (0.8 equivalents) in acetone (0.5 M). The progress of the reaction was followed by LC-MS. When complete, 18% aqueous HCl was added, and the mixture was extracted with two portions of EtOAc. The combined organic phases were dried over MgSO, filtered and evaporated. The products were, in usual, pure enough to be used directly for hydrolysis in thioureas or possibly purified by flash chromatography. The resulting N-ethoxycarbonyl thiourea was heated at 100 ° C in concentrated HCl (0.1 M). When the deprotection was complete, the mixture was diluted with water, basified with a solution of NH4OH and extracted with EtOAc (3 portions). The combined organic phases were dried over MgSO4. Thiourea (P2a) isolated, evaporated and filtered, was then used in the synthesis of the bis-thiazole or the oxazole-thiazole, following the general procedure 1 described below.

Preparation of thiourea (P2a): Procedure C Benzoyl chloride (1.1-1.4 equivalents) was added during d minutes to a fresh solution prepared of NH4SCN (1.1-1.4 equivalents) in acetone reactive grade (0.1 M, endothermic), and the The mixture was heated under reflux for approximately 15 minutes. The heating was stopped and the appropriate amine R5R6NH (1 equivalent), either pure or in acetone, was added as fast as possible while maintaining a vigorous reflux. After the addition, the mixture was heated under reflux for 15 to 30 minutes, then poured into an excess of crushed ice with vigorous stirring. The resulting solid was collected and washed abundantly with H20, followed by cold H20 / MeOH (1: 1) or MeOH. The products were, in usual manner, sufficiently pure to be used directly for hydrolysis in the thioureas or possibly purified by flash chromatography.

The resulting N-benzoylthiourea was added in one portion to a preheated solution, with stirring (approximately 80 ° C) of 5% aqueous NaOH (0.5 M). When the deprotection was complete, the mixture was poured into ice containing an excess of aqueous HCl. The pH was adjusted to 8-8.5 with NH4OH. The desired thiourea was filtered and washed with NH OH and water, or extracted with EtOAc (3 portions), and dried over MgSO4. The isolated thiourea (P2a) was then used in the synthesis of the bis-thiazole or the oxazole-thiazole, following the general procedure 1 described below.

Preparation of thiourea (P2a): Method D The appropriate amine R5R6NH (1 equivalent) was added to a 1: 1 mixture of chloroform / water (0.1M). A saturated solution of NaHCO 3 in water (3 equivalents) was added dropwise, followed by thiophosgene (1.1 equivalents) at 0 ° C. The biphasic mixture was stirred overnight at room temperature. The progress of the reaction was followed by TLC. After completion, the organic phase was separated, washed with water and dried over MgSO4. A saturated solution of ammonia in ethanol (1 volume) was added to the chloroform solution, and stirred overnight at room temperature. The reaction mixture was concentrated to provide the expected thiourea, which was kept as a crude product or recrystallized in a suitable solvent. The isolated thiourea was used in the synthesis of the bis-thiazole or the oxazol-thiazole, following the general procedure 1 described below.

Preparation of Thiourea (P2a): Procedure E The appropriate amine R5R6NH (1 equivalent), was dissolved in THF (0.06 to 0.1 M). N, N-diisopropylethylamine (1 equivalent) was added and the mixture was cooled to below 0 ° C. Thiophosgene (1 equivalent) was added dropwise. The reaction was maintained at 0 ° C. Its progression was followed by LC-MS. After completion, 2M ammonia in ethanol (d equivalents) was added, and the reaction mixture was stirred at room temperature. When the conversion was complete, the solvents were removed under reduced pressure, providing the expected thiourea (P2a), which was maintained as a crude product or recrystallized from a suitable solvent.

The isolated thiourea was used in the synthesis of the bis-thiazole or the oxazol-thiazole, following the general procedure 1 described below.

Synthesis of bis-thiazole or oxazole-thiazole: General Procedure 1 Intermediate P1 or P1a was dissolved in EtOH (0.5 M) and the appropriate thiourea (1 equivalent) was added. When P1 or P1a is used as a salt, TEA (3 equivalents) is added before the addition of thiourea. The mixture was stirred for 1 to 24 hours at temperatures ranging from -20 ° C to reflux. When the reaction was finished, TEA (2-3 equivalents) was added. The desired product (la) or (Ib) was isolated as indicated in the following examples.

EXAMPLE 1 3- (R 2 - (Acetylamino) -4-methyl-415-bi-1,3-thiazol-2-ylamino} benzoic acid, hydrobromide salt (i) According to the general procedure, 1, 3 - [(amidocarbonothioyl) aminojbenzoic acid (Aldrich) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole-2- il] acetamide (Intermediate 1) in EtOH. The mixture was stirred at room temperature for 30 minutes. The desired product was filtered from the reaction mixture, and washed with cold EtOH. Compound (1) was isolated as a persimmon solid (68%). 1 H NMR (DMSO-de, 300 MHz) d 2.13 (s, 3 H), 2.51 (s, 3 H), 6.93 (s, 1 H), 7.44 (m, 1 H), 7.49 (m, 1 H), 7.92 (m, 1 H), 8.25 (m, 1 H), 10.49 (s, 1 H), 11.83 (broad s, 1 H). M '(ESI): 373; M + (ESI): 375. HPLC, Retention time: 2.6 minutes (purity: 92.8%).

EXAMPLE 2 Acid 4-. { f2- (acetylamino) -4-methyl-4,5-bi-1,3-thiazole-2 -pamino} benzoic, hydrobromide salt (2) According to general procedure 1, 4 - [(aminocarbonothioyl) aminojbenzoic acid (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl. ] acetamide (Intermediate 1) in EtOH. The mixture was stirred at room temperature for 30 minutes.

The desired product was filtered from the reaction mixture and washed with cold EtOH.

The compound (2) was isolated as a white solid (67%). 1 H NMR (DMSO-de, 300 MHz) d 2.13 (s, 3 H), 2.49 (m, 3 H), 7.00 (s, 1 H), 7.73 (d, J = 9 Hz, 2H), 7.90 (d, J = 9 Hz, 2H), 10.71 (s, 1 H), 12.07 (s, 1 HOUR). M "(ESI): 373; M + (ESI): 375. HPLC, Retention time: 3 minutes (purity: 9d%).

EXAMPLE 3 N-r2- (benzylamino) -4-methyl-4,5-bi-1,3-thiazole-2-inacetamide (3) According to general procedure 1, it was added N-benzylthiourea (Lancaster) to a solution of N- [5- (bromoacetyl) -4-methyl-1, 3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 1.5 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. Compound (3) was isolated as a light yellow solid (34%). 1 H NMR (DMSO-de, 300 MHz) d 2.27 (s, 3 H), 2.56 (s, 3 H), 4.61 (m, 2 H), 6.78 (s, 1 H), 7.49 (m, 5 H), 8.40 (m , 1 H), 12.14 (s, 1 H). M "(ESI): 343; M + (ESI): 345. HPLC, Retention time: 2.79 minutes (purity: 99.6%).

EXAMPLE 4 N-. { 4-methyl-2-f (2-phenylethyl) amino1-4,5-bi-1,3-thiazol-2-yl > acetamide According to general procedure 1, N- (2-phenylethyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 1.5 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. Compound (4) was isolated as a light yellow solid (74%). 1 H NMR (DMSO-de, 300 MHz) d 1.93 (s, 3 H), 2.25 (s, 3 H), 2.70 (t, J = 7.5 Hz, 2 H), 3.26 (m, 2 H), 6.43 (s, 1 H ), 7.07 (m, 5H), 7.64 (m, 1 H), 11.79 (s, 1 H). M "(ESI): 357; M + (ESI): 359. HPLC, Retention time: 2.79 minutes (purity: 93.3%).

EXAMPLE 5 N-.4-methyl-2-piperidin-1-yl-4,5-bi-1,3-thiazol-2-yl) acetamide (5) According to general procedure 1, piperidin-1-carbothioamide (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 1.5 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. Compound (d) was isolated as a colorless solid (82%). 1 H NMR (DMSO-d 6, 300 MHz) d 1.46 (m, 6 H), 1.98 (s, 3 H), 2.29 (s, 3 H), 3.29 (m, 4 H), 6.64 (s, 1 H), 11.86 (s) , 1 HOUR). M "(ESI): 321; M + (ESI): 323. HPLC, Retention time: 2.73 minutes (purity: 95.2%).

EXAMPLE 6 N-_2- (aHlamino) -4-methyl-4,5-bi-1,3-thiazole-2-ipacetamide (6) According to general procedure 1, N-allylthiourea was added (Fluka) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 1.5 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (6) was isolated as a light green solid (65%). 1 H NMR (DMSO-dβ, 300 MHz) d 2.14 (s, 3 H), 2.44 (s, 3 H), 3.90 (m, 2 H), 5.13 (dd, J = 3 Hz, J = 12 Hz, 1 H), 5.28 (dd, J = 3 Hz, J = 18 Hz, 1 H), 5.94 (m, 1 H), 6.65 (s, 1 H), 7.89 (m, 1 H), 11.99 (s, 1 H). M "(ESI): 293; M + (ESI): 295. HPLC, Retention time: 1.99 minutes (purity: 98.7%).

EXAMPLE 7 N-.4-Methyl-2- (pyridin-3-ylamino) -4,5-bi-1,3-thiazole-2 -pacetamide (7) According to general procedure 1, N-pyridin-3-ylthiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (2 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. Compound (7) was isolated as a yellow-orange solid (91%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.18 (s, 3 H), 2.53 (m, 3 H), 7.01 (s, 1 H), 7.41 (m, 1 H), 8.17 (m, 1 H), 8.22 (m, 1 H), 8.89 (d, J = 3 Hz, 1 H), 10.57 (s, 1 H), 12.11 (s, 1 H). M- (ESI): 330; M + (ESI): 332. HPLC, Retention time: 1.97 minutes (purity: 98%).

EXAMPLE 8 N-f4-Methyl-2- (pyridin-2-ylamino) -4,5-bi-1,3-thiazole-2-acetamide (8) According to general procedure 1, N-pyridin-2-ylthiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (8) was isolated as a yellowish beige solid (51%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.17 (s, 3 H), 2.51 (s, 3 H), 6.98 (m, 1 H), 7.05 (s, 1 H), 7.12 (m, 1 H), 7.75 (m, 1H), 8.35 (m, 1 H), 11.49 (s, 1 H), 12.07 (broad s, 1 H). M "(ESI): 330; M + (ESI): 332. HPLC, Retention time: 2.07 minutes (purity: 98.2%).

EXAMPLE 9 N-. { 2- (4-methoxyphenyl) amino-1-4-methyl-4,5-bi-1,3-thiazol-2-yl > acetamide P) According to general procedure 1, N- (4-methoxyphenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-metii-1,3-thiazol-2-yl] acetamide (Intermediary 1) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (9) was isolated as a brown solid (60%). 1 H NMR (DMSO-de, 300 MHz) d 2.25 (s, 3 H), 2.54 (s, 3 H), 3.82 (s, 3 H), 6.68 (s, 1 H), 6.94 (m, 2 H), 7.57 (m , 2H). M "(ESI): 359; M + (ESI): 361. HPLC, Retention time: 3.29 minutes (purity: 96.3%).

EXAMPLE 10 N-. { 2-r (4-hydroxyphenyl) amino-1-4-methyl-4,5-bi-1,3-thiazol-2-yl > acetamide (10) According to general procedure 1, N- (4-hydroxyphenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. Compound (10) was isolated as a light pink solid (50%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.17 (s, 3 H), 2.50 (s, 3 H), 6.79 (m, 3 H), 7.43 (m, 2 H), 9.19 (s, 1 H), 9.98 (s) , 1 H), 12.07 (s, 1 H). M- (ESI): 345; M (ESI): 347. HPLC, Retention time: 2.52 minutes (purity: 99%).

EXAMPLE 11 N-. { 4-methyl-2-r (4-nitrophenyl) amino1-4,5-bi-1,3-thiazol-2-yl acetamide (11) According to general procedure 1, N- (4-nitrophenyl) thiourea (Aldrich) was added to a solution of N- [d- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide ( Intermediary 1) in EtOH. The mixture was stirred at reflux for 20 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (11) was isolated as an orange solid (40%). 1 H NMR (DMSO-de, 300 MHz) d 2.13 (s, 3 H), 2.49 (s, 3 H), 7.10 (s, 1 H), 7.83 (, 2 H), 8.23 (m, 2 H), 11.10 (s, 1 H), 12.09 (s, 1 H). M "(ESI): 374; M + (ESI): 376. HPLC, Retention time: 3.69 minutes (purity: 100%).

EXAMPLE 12 4-. { r2- (acetylamino) -4-methyl-4,5-bi-1,3-thiazole-2 -pamino} benzamide (12) According to general procedure 1, 4 - [(aminocarbonothioyl) amino] benzamide (obtained from 4-aminobenzamide from Aldrich following procedure C) was added to a solution of N- [5- (bromoacetyl) - 4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 1.5 hours. Then TEA (2 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. This was then purified by flash chromatography. The compound (12) was isolated as a light beige solid (29%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.14 (s, 3 H), 2.49 (s, 3 H), 6.97 (s, 1H), 7.16 (s broad, 1H), 7.70 (m, 2H), 7.85 (m, 3H), 10.60 (s, 1H), 12.07 (s, 1 H). M "(ESI): 372; M + (ESI): 374. HPLC, Retention time: 2.73 minutes (purity: 99.5%).

EXAMPLE 13 N-r2- ( {4-R (4-benzylp '? Peracin-1-ipcarbonyl-1-phenyl) -amino) -4-methyl-4,5-bi-1,3-thiazole-2-ipacetamide, salt of trifluoroacetate (13) According to general procedure 1, N- was added. { 4 - [(4-benzylpiperazin-1-yl) carbonyl] phenyl} thiourea (obtained from the commercial. {4 - [(4-benzylpiperazin-1-yl) carbonyl] phenyl} amine, following procedure C) to a solution of N- [5- (bromoacetyl) -4 -methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by preparative HPLC. The compound (13) was isolated as a beige solid (42%). 1 H NMR (DMSO-de, 300 MHz) d 2.13 (s, 3 H), 2.49 (s, 3 H), 3.25 (m, 6 H), 3.88 (m, 2 H), 4.36 (m, 2 H), 6.98 (s, 1 H), 7.47 (m, 7 H), 7.73 (m, 2 H), 9.90 (s broad, 1 H), 10.60 (s, 1 H), 12.08 (s, 1 H). M "(ESI): 531; M + (ESI): 533. HPLC, Retention time: 2.76 minutes (purity: 99.9%).

EXAMPLE 14 N- (2-amino-4-methyl-4,5-bi-1,3-thiazol-2-yl) acetamide (14) According to general procedure 1, thiourea (Fluka) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at room temperature for 1.5 hours. Then TEA (2 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (14) was isolated as a beige solid (81%). 1 H NMR (DMSO-de, 300 MHz) d 2.17 (s, 3 H), 2.47 (s, 3 H), 6.62 (s, 1 H), 7.18 (s broad, 2 H), 12.02 (s, 1 H). M '(ESI): 253; M + (ESI): 25d. HPLC, Retention time: 1.21 minutes (purity: 99.9%).

EXAMPLE 15 N- (2-anilino-4-methyl-4,5-bi-1,3-thiazol-2-yl) acetamide (fifteen) According to general procedure 1, N-phenylthiourea (Aldrich) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt ( Intermediary 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The compound (15) was isolated as a brown green solid (quantitative). 1 H NMR (DMSO-d 6, 300 MHz) d 2.13 (s, 3 H), 2.48 (s, 3 H), 6.68 (s, 1 H), 6.96 (m, 1 H), 7.32 (, 2 H), 7.63 (m , 2H), 10.29 (s, 1 H), 12.00 (s, 1H). M "(ESI): 329; M + (ESI): 331. HPLC, Retention time: 3.46 minutes (purity: 96.6%).

EXAMPLE 16 N- (4-methyl-2-morpholin-4-yl-4,5-bi-1,3-thiazol-2-yl) acetamide (16) According to general procedure 1, morpholin-4-carbothioamide (obtained from the Fluka morpholine following procedure B) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole -2-Isoxamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The compound (16) was isolated as a light beige solid (74%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.14 (s, 3 H), 2.46 (s, 3 H), 3.42 (m, 4 H), 3.74 (m, 4 H), 6.89 (s, 1 H), 12.03 (s) , 1 HOUR). M "(ESI): 323; M * (ESI): 325. HPLC, Retention time: 2.5 minutes (purity: 99.6%).

EXAMPLE 17 N-.4-Methyl-2- (4-methylpiperazin-1-yl) -4,5-bi-1,3-thiazole-2-yl acetamide, trifluoroacetate salt (17) According to general procedure 1, 4-methylpiperazine-1-carbothioamide (obtained from Fluka 1-methylpiperazine following procedure B) was added to a solution of N- [d- (bromoacetyl) -4-methyl-1 , 3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by preparative HPLC. The compound (17) was isolated as a green oil (67%). 1 H NMR (CDCl 3, 300 MHz) d 2.36 (s, 3 H), 2.58 (s, 3 H), 2.86 (s, 3 H), 3.10 (m, 2 H), 3.83 (m, 6 H), 6.71 (s, 1 H) , 14.92 (broad s, 1 H). M "(ESI): 336; M + (ESI): 338. HPLC, Retention time: 1.71 minutes (purity: 93%).

EXAMPLE 18 1-f2- (Acetylamino) -4-methyl-4,5-bi-1,3-thiazol-2-ylpiperidine-3-carboxylic acid methyl ester (18) According to general procedure 1, ethyl 1- (aminocarbonothioyl) piperidine-3-carboxylate (obtained from ethyl piperidine-3-carboxylate of Fluka following procedure B) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The compound (18) was isolated as a light yellow solid (61%). 1 H NMR (DMSO-de, 300 MHz) d 1.72 (m, 3 H), 2.01 (m, 1 H), 2.16 (s, 3H), 2.47 (s, 3H), 2.73 (m, 1 H), 3.22 (m, 1 H), 3.37 (m, 1H), 3.68 (s, 3H), 3.71 (m, 1 H) , 4.00 (m, 1 H), 6.86 (s, 1 H), 12.05 (s, 1 H). M "(ESI): 379; M + (ESI): 381. HPLC, Retention time: 3.11 minutes (purity: 90.8%).

EXAMPLE 19 N- (2-r4- (2-hydroxyethyl) piperidin-1-ip-4-methyl-4,5-bi-1,3-thiazol-2-yl> acetamide (19) According to general procedure 1, 4- (2-hydroxyethyl) piperidine-1-carbothioamide (obtained from 2-piperidin-4-ylethanol from Aldrich following procedure B) was added to a solution of N- [5- ( bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The compound (19) was isolated as a beige solid (48%). 1 H NMR (DMSO-de, 300 MHz) d 1.25 (m, 2 H), 1.44 (m, 2 H), 1.68 (m, 1 H), 1.79 (m, 2 H), 2.16 (s, 3 H), 2.47 (s) , 3H), 3.05 (m, 2H), 3.51 (m, 2H), 3.92 (m, 2H), 4.43 (t, J = 6 Hz, 1 H), 6.82 (s, 1 H), 12.04 (s, 1 HOUR). M "(ESI): 365; M + (ESI): 367. HPLC, Retention time: 2.25 minutes (purity: 95.9%).

EXAMPLE 20 N- (4-methyl-2-pyrrolidin-1-yl-4,5-bi-1,3-thiazol-2-yl) acetamide (twenty) According to general procedure 1, pyrrolidin-1-carbothioamide (obtained from Fluka pyrrolidine following procedure B) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole -2-iljacetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The compound (20) was isolated as a light yellow solid (50%). 1 H NMR (DMSO-de, 300 MHz) d 2.00 (m, 4H), 2.14 (s, 3H), 2.45 (s, 3H), 3.41 (m, 4H), 6.72 (s, 1 H), 12.00 (s) , 1 HOUR). M "(ESI): 307; M + (ESI): 309. HPLC, Retention time: 1.83 minutes (purity: 98.8%).

EXAMPLE 21 N-f2- (3-hydroxypyrrolidin-1-yl) -4-methyl-4,5-bi-1,3-thiazole-2-acetamide (twenty-one) According to general procedure 1, 3-hydroxypyrrolidin-1-carbothioamide (obtained from pyrrolidin-3-ol from Aldrich following procedure B) was added to a solution of N- [5- (bromoacetyl) -4-methyl- 1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The compound (21) was isolated as a light beige solid (54%). H NMR (DMSO-d6, 300 MHz) d 1.85-1.96 (m, 1 H), 2.0-2.14 (m, 1 H), 2.11 (s, 3 H), 2.42 (s, 3 H), 3.27 (m, 1 H), 3.41-3.56 (m, 3H), 4.40 (broad s, 1 H), 5.05 (d, J = 3 Hz, 1 H), 6.69 (s, 1 H), 11.97 (s broad, 1 H) . M "(ESI): 323.2; M + (ESI): 325.2 HPLC, Retention time: 1.4 minutes (purity: 98.4%).

EXAMPLE 22 N-f2- (tert-butylamino) -4-methyl-4,5-bi-1,3-thiazole-2-inacetamide (22) According to general procedure 1, N- (tert-butyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, salt of hydrobromide (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 1.6 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The compound (22) was isolated as a dark yellow solid (quantitative). 1 H NMR (DMSO-de, 300 MHz) d 1.38 (s, 9 H), 2.10 (s, 3 H), 2.42 (s, 3 H), 6.56 (s, 1 H), 7.43 (s, 1 H), 11.70 ( s, 1 H). M "(ESI): 309.3; M + (ESI): 311.3 HPLC, Retention time: 2.5 minutes (purity: 96.7%).

EXAMPLE 23 N-. { 2-f (6-methoxypyridin-3-yl) amino-1-4-methyl-4,5-bi-113-thiazol-2-yl} acetamide (2. 3) According to general procedure 1, N- (6-methoxypyridin-3-yl) thiourea (obtained from 6-methoxypyridin-3-amine from Aldrich following procedure C) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazoI-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (23) was isolated as a brown-beige solid (73%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.15 (s, 3 H), 2.49 (s, 3 H), 3.85 (s, 3 H), 6.86 (d, J = 9 Hz, 1 H), 6.89 (s, 1 H), 7.91 (dd, J = 3, 9 Hz, 1 H), 8.63 (d, J = 3 Hz, 1 H), 10.24 (s, 1 H), 12.06 (s, 1 H). M "(ESI): 360.3; M + (ESI): 362.2 HPLC, Retention time: 2.6 minutes (purity: 97.6%).

EXAMPLE 24 N-. { 2-r (6-chloropyridin-3-yl) amino-1-4-methyl-4,5-bi-1,3-thiazol-2-yl) acetamide (24) According to general procedure 1, N- (6-chloropyridin-3-yl) thiourea (obtained from 6-chloropyridin-3-amine from Aldrich following procedure C) was added to a solution of N- [ d- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (24) was isolated as a light beige solid (72%). 1 H NMR (DMSO-de, 300 MHz) d 2.16 (s, 3 H), 2.50 (s, 3 H), 7.02 (s, 1 H), 7.51 (d, J = 9 Hz, 1 H), 8.13 (dd, J = 3, 9 Hz, 1 H), 8.79 (d, J = 3 Hz, 1 H), 10.70 ( s, 1 H), 12.09 (s, 1 H). M "(ESI): 364; M + (ESI): 366. HPLC, Retention time: 3.3 minutes (purity: 98.7%).

EXAMPLE 25 N-. { 2 - "(4-cyanophenyl) amino-4-methyl-4,5-bi-1,3-thiazol-2-yl} acetamide (25) According to general procedure 1, N- (4-cyanophenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (26) was isolated as a beige solid (72%). 1 H NMR (DMSO-de, 300 MHz) d 2.13 (s, 3 H), 2.50 (s, 3 H), 7.05 (s, 1 H), 7.78 (m, 4H), 10.85 (s, 1 H), 11.95 (s, 1 H). M "(ESI): 354.3; M + (ESI): 356.3 HPLC, Retention time: 3.5 minutes (purity: 99.5%).

EXAMPLE 26 N - ^^^ - ChlorophenylJaminol ^ -methyl ^ S-bi-l ^ -thiazole ^ -i-Acetamide (26) According to general procedure 1, N- (4-chlorophenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (26) was isolated as a beige solid (47%). 1 H NMR (DMSO-de, 300 MHz) d 2.13 (s, 3 H), 2.47 (s, 3 H), 6.92 (s, 1 H), 7.37 (m, J = 9 Hz, 2H), 7.66 (m, J = 9 Hz, 2H), 10.43 (s, 1 H), 11.85 (s, 1 H). M "(ESI): 363; M + (ESI): 365. HPLC, Retention time: 3.9 minutes (purity: 99.9%) EXAMPLE 27 N-. { 2 - [(2-chlorophenyl) amino-1-4-methyl-4,5-bi-1,3-thiazol-2-yl} acetamide (27) According to general procedure 1, N- (2-chlorophenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, Hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (27) was isolated as a brown solid (59%). 1 H NMR (DMSO-de, 300 MHz) d 2.12 (s, 3 H), 2.45 (s, 3 H), 6.93 (s, 1 H), 7.06 (m, 1 H), 7.34 (m, 1 H), 7.48 (m, 1 H), 8.30 (m, 1 H), 9.73 (s, 1 H), 12.10 (s) , 1 HOUR). M "(ESI): 363; M + (ESI): 365. HPLC, Retention time: 3.8 minutes (purity: 97.7%).

EXAMPLE 28 N-. { 2 - [(2-methoxyphenyl) amino1-4-methyl-4,5-bi-1,3-thiazol-2-yl} acetamide (28) According to general procedure 1, N- (2-methoxyphenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (28) was isolated as a white solid (69%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.12 (s, 3 H), 2.46 (s, 3 H), 3.85 (s, 3H), 6.84 (s, 1 H), 6.91-7.05 (m, 3H), 8.33 (m, 1 H), 9.59 (s, 1 H), 11.85 (s, 1 H). M "(ESI): 359; M + (ESI): 361. HPLC, Retention time: 3.5 minutes (purity: 100%).

EXAMPLE 29 N-. { 2-f (3-chlorophenyl) amino-1-4-methyl-4,5-bi-1,3-thiazol-2-yl} acetamlda (29) According to general procedure 1, N- (3-chlorophenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (29) was isolated as a beige solid (81%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.13 (s, 3 H), 2.50 (s, 3 H), 6.95 (s, 1 H), 7.00 (m, 1 H), 7.33 (m, 1 H), 7.40 (m, 1 H), 8.00 (s, 1 H), 10.52 (s, 1 H), 12.10 (s) , 1 HOUR). M- (ESI): 363; M + (ESI): 365. HPLC, Retention time: 3.9 minutes (purity: 99.8%).

EXAMPLE 30 N-. { 2 -. (3-hydroxyphenyl) amino-4-methyl-4,5-bi-1,3-thiazol-2-yl} acetamide (30) According to general procedure 1, N- (3-hydroxyphenyl) thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was filtered and washed with water. The compound (30) was isolated as a persimmon solid (79%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.12 (s, 3 H), 2.47 (s, 3 H), 6.38 (m, 1 H), 6.86 (s, 1 H), 7.01-7.09 (m, 3H), 9.36 (s, 1 H), 10.15 (s, 1 H), 11.85 (s, 1 H). M "(ESI): 345; M + (ESI): 347. HPLC, Retention time: 2.9 minutes (purity: 99.6%).

EXAMPLE 31 N-. { 4-methyl-2-r (2-morpholin-4-ylethyl) amino1-4,5-bi-1,3-thiazol-2-yl > acetamide, hydrochloride salt (31) According to general procedure 1, N- (2-morpholin-4-ylethyl) thiourea (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl. ] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 4 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then precipitated as the HCl salt. The compound (31) was isolated as a pastel pink solid (42%). 1 H NMR (DMSO-de, 300 MHz) d 2.14 (s, 3 H), 2.45 (s, 3 H), 3.18 (m, 2 H), 3.39 (m, 3 H), 3.73 (m, 3 H), 3.81 (m, 2H), 3.98 (m, 2H), 6.74 (s, 1 H), 8.04 (broad s, 1 H), 10.56 (s broad, 1 H), 12.04 (s, 1 H). M "(ESI): 366; M + (ESI): 368. HPLC, Retention time: 1.6 minutes (purity: 96.8%).

EXAMPLE 32 N ^ -methyl ^ - ^ - piperidin-1-ylethyldaminol ^ .d-bi-l ^ -thiazole ^ -i ^ acetamide, hydrochloride salt (32) According to general procedure 1, N- (2-piperidin-1-ylethyl) thiourea (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole- 2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 4 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then precipitated with the HCl salt. The compound (32) was isolated as a mauve solid (74%). 1 H NMR (DMSO-d 6, 300 MHz) d 1.33 (m, 1 H), 1.62-1.87 (m, 5 H), 2.08 (s, 3 H), 2.39 (s, J = S Hz, 3 H), 2.92 (m , 2H), 3.23 (m, 2H), 3.49 (m, 2H), 3.6-3.8 (m, 2H), 6.68 (s, 1H), 7.98 (broad s, 1H), 9.74 (broad s, 1H), 11.98 (s, 1 H). M "(ESI): 364; M + (ESI): 366. HPLC, Retention time: 1.8 minutes (purity: 97.4%).

EXAMPLE 33 N-. { 2-r (2-methoxyethyl) amino-1-4-methyl-4,5-bi-1,3-thiazol-2-yl} acetamide (33) According to general procedure 1, N- (2-methoxyethyl) thiourea (Transwld) was added to a solution of N- [d- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, salt of hydrobromide (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 4 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The compound (33) was isolated as a dark green (quantitative) oil. 1 H NMR (CDCl 3, 300 MHz) d 2.16 (s, 3 H), 2.50 (s, 3 H), 3.37 (s, 3 H), 3.52 (m, 2 H), 3.60 (m, 2 H), 5.82 (broad s, 1 H), 6.40 (s, 1 H), 10.97 (s broad, 1 H). M "(ESI): 311; M + (ESI): 313. HPLC, Retention time: 1.6 minutes (purity: 97.7%).

EXAMPLE 34 N-r2- (cyclohexylamino) -4-methyl-4,5-bi-13-thiazol-2-yl-1-acetamide (3. 4) According to general procedure 1, N-cyclohexyl thiourea (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1 ) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 4 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The compound (34) was isolated as a green foam (89%). 1 H NMR (CDCl 3, 300 MHz) d 1.16-1.44 (m, 5 H), 1.55-1.83 (m, 3 H), 2.07 (m, 2 H), 2.13 (s, 3 H), 2.49 (s, 3 H), 3.30 ( m, 1 H), 5.62 (d, J = 9 Hz, 1 H), 6.39 (s, 1 H), 10.98 (broad s, 1 H). M "(ESI): 335; M + (ESI): 337. HPLC, Retention time: 2.5 minutes (purity: 93%).

EXAMPLE 35 N-. { 4-methyl-2-f (3-morpholin-4-ylpropyl) amino1-4,5-bi-1,3-thiazol-2-yl} acetamide, hydrochloride salt (35) According to general procedure 1, N- (3-morpholin-4-ylpropyl) thiourea (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole- 2-yl] acetarnide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 4 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then precipitated as the HCl salt. The compound (35) was isolated as a purple solid (82%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.05 (m, 2H), 2.14 (s, 3H), 2.44 (s, 3H), 2.98-3.26 (m, 4H), 3.31-3.64 (m, 4H), 3.79 (m, 2H), 3.98 (m, 2H), 6.69 (s, 1 H), 8.00 (s broad, 1 H), 10.70 (s broad, 1 H), 12.04 (s, 1 H). M "(ESI): 380; M + (ESI): 382. HPLC, Retention time: 1.3 minutes (purity: 98.5%).

EXAMPLE 36 N-. { 4-methyl-2-f (tetrahydrofuran-2-ylmethyl) aminol-4,5-bi-1,3-thiazol-2-yl > acetamide (36) According to general procedure 1, N- (tetrahydrofuran-2-ylmethyl) thiourea (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide. , hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 4 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The compound (36) was isolated as a light green solid (quantitative). 1 H NMR (CDCl 3, 300 MHz) d 1.59-1.70 (m, 1 H), 1.86-2.07 (m, 3 H), 2.15 (s, 3 H), 2.24 (s, 3 H), 3.28 (m, 1 H), 3.56 (m, 1 H), 3.76 (m, 1 H), 3.87 (m, 1 H), 4.14 (m, 1 H), 5.96 (broad s, 1 H), 6.38 (s, 1 H), 11.01 (s broad, 1 H). M "(ESI): 337.3; M + (ESI): 339.3 HPLC, Retention time: 1.8 minutes (purity: 94.4%).

EXAMPLE 37 N- (2-R (2-hydroxy-2-phenylethyl) aminol-4-methyl-415-bi-1,3-thiazol-2-yl> acetamide, trifluoroacetate salt (37) According to general procedure 1, N- (2-hydroxy-2-phenylethyl) thiourea (prepared from 2-amino-1-phenylethanol (Fluka) was added, following procedure C) to a solution of N- [5 - (bromoacetyl) -4-methyl-1, 3-thiazol-2-yl-acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at reflux for 2 hours. Then TEA (3 equivalents) was added. The solvents were evaporated and the desired product was purified by preparative HPLC. The compound (37) was isolated as a yellow solid (32%). 1 H NMR (DMSO-de, 300 MHz) d 2.14 (s, 3 H), 2.45 (s, 3 H), 3.31 (d, J = 9 Hz, 1 H), 3.51 (d, J = 6 Hz, 1 H) , 4.48 (s broad, 1 H), 4.88 (d, J = 6 Hz, 1 H), 6.64 (s, 1 H), 7.22-7.47 (m, 6H), 7.98 (s broad, 1 H), 12.01 (s, 1 H). M " (ESI): 373; M + (ESI): 375. HPLC, Retention time: 2.3 minutes (purity: 97.2%).

EXAMPLE 38 N-r2- (1-benzofuran-5-ylamino) -4-methyl-4,5-bi-1,3-thiazole-2-acetamide, trifluoroacetate salt (38) According to general procedure 1, N-1-benzofuran-5-ylthiourea (Bionet) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl. ] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 1 hour. Then TEA (3 equivalents) was added. The solvents were evaporated and the desired product was purified by preparative HPLC. The compound (38) was isolated as a light pink solid (36%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.13 (s, 3 H), 2.49 (s, 3 H), 6.84 (s, 1 H), 6.89 (m, 1 H), 7.45 (m, 1 H), 7.55 (m, 1 H), 7.95 (m, 1 H), 8.01 (m, 1 H), . 26 (s, 1 H), 12.04 (s broad, 1 H). M "(ESI): 369; M + (ESI): 371. HPLC, Retention time: 3.6 minutes (purity: 99.8%).

EXAMPLE 39 N-. { 2-f (3-cyanophenyl) amino-1-4-methyl-415-bi-1,3-thiazol-2-yl} acetamide (39) According to general procedure 1, 1- (3-cyanophenyl) -2-thiourea (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred at room temperature for 17 hours. Then TEA (3 equivalents) was added. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (39) was isolated as a light yellow solid (43%). 1 H NMR (DMSO-de) d: 2.13 (s, 3 H), 2.49 (s, 3 H), 6.99 (s, 1 H), 7.40 (m, 1 H), 7.53 (m, 1 H), 7.80 (m , 1 H), 8.24 (m, 1 H), 10.70 (s, 1 H), 12.07 (s, 1 H). M "(ESI): 356; M + (ESI): 354. HPLC: Retention time: 3.5 minutes (purity: 95.79%).

EXAMPLE 40 .4-Methyl-2- (pirtdin-3-ylamino) -4,5-bi-1,3-thiazol-2-yl.formamide (40) Step I: 4-methyl-N-2-pyridin-3-yl-4,5-bi-1,3-thiazole-2,2-diamine According to general procedure 1, 3-pyridyl thiourea ( Lancaster) to a solution of 1- (2-amino-4-methyl-1,3-thiazol-5-yl) -2-bromoethanone, hydrobromide salt (Intermediate 2) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 2 hours. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The 4-methyl-N-2-pyridin-3-yl-4,5-bi-1,3-thiazole-2,2-diamine was isolated as a light yellow solid in 95% yield. M "(ESI): 288.2; M + (ESI): 290.1 HPLC, Retention time: 1.2 minutes (purity: 99.6%).

Step II [4-methyl-2- (pyridin-3-ylammon) -4,5-bi-1,3-thiazole-2-pformamide (40) In a microwave tube, the 4-methyl-N -2-pyridin-3-yl-4,5-bi-1,3-thiazole-2,2-diamine obtained in Step I as described above (58.0 mg, 0.20 mmol, 1.00 equivalents), was dissolved in acid Formic (2.00 ml).

The mixture was heated twice at 130 ° C for 30 minutes in a microwave. A 50% conversion was provided. The solvents were evaporated and the desired product was isolated by preparative HPLC. Compound (40) was isolated as a dark yellow solid (13 mg, 21% yield). 1 H NMR (DMSO-d 6, 300 MHz) d 2.53 (s, 3 H), 7.06 (s, 1 H), 7.55 (m, 1 H), 8.20 (m, 1 H), 8.27 (m, 1 H), 8.48 (s, 1 H), 9.01 (s, 1 H), 10.77 (s, 1H), 12.00 (s, 1 H). M + (ESI): 316.3; M + (ESI): 318.3. HPLC, Retention time: 1.9 minutes (purity: 97.4%).

EXAMPLE 41 N- ( { R2 (- (allylamino) -4-methyl-4,5-bi-1,3-thiazole-2-ynyamino} carbonyl) -beta-alaninate ethyl (41) Step N-2-allyl-4-methyl-4,5-bi-1,3-thiazole-2,2-d-amines According to general procedure 1, N-allylthiourea (Fluka) was added to a solution of 1- (2-amino-4-methyl-1,3-thiazol-5-yl) -2-bromoethanone, hydrobromide salt (Intermediate 2) and TEA (3 equivalents) in EtOH. The mixture was stirred at room temperature for 1 hour. Then TEA (3 equivalents) was added. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. This was then purified by flash chromatography. The N-2-allyl-4-methyl-4, d-bi-1,3-thiazole-2,2-diamine was isolated as a colorless solid (176 mg, 70% yield).

M + (ESI): 263.1. HPLC, Retention time: 1.5 minutes (purity: 92.0%).

Step ll N - (([2- (allylamino) -4-methyl-4,5-bi-1,3-thiazol-2-ylmethyl) carbonyl) -ethanolaninate (41) To a solution of N-2 allyl -4-metii-4,5-bi-1,3-thiazole-2,2-diamine obtained in Step I as described above (60.60 mg, 0.18 mmol, 1.00 equivalents) in DCM (2.00 ml), was added to commercial N-ethyldiisopropylamine (0.07 ml, 0.40 mmoles, 2.20 equivalents) and commercial ethyl 3-isocyanatopropionate (26.03 mg, 0.18 mmoles, 1.00 equivalents). The mixture was stirred under reflux for 5 hours, and the solvents were evaporated. The resulting product was purified by preparative HPLC. The purified fraction was diluted with EtOAc and washed with NaHCO 3, affording compound (41) as a dark oil (28.2 mg, 39%). 1 H NMR (DMSO-d 6) d: 1.18 (m, 3 H), 2.35 (s, 3 H), 2.50 (m, 2 H), 3. 36 (m, 2H), 3.86 (m, 2H), 4.04 (m, 2H), 5.11 (m, 1 H), 5.24 (m, 1 H), 5.90 (m, 1 H), 6.52 (s, 1 H), 6.68 (m, 1 H), 7.83 (m, 1 H), 10.29 (broad s, 1 H). M "(ESI): 394; M + (ESI): 396. HPLC, Retention time: 2.5 minutes (purity: 98. 36%).

EXAMPLE 42 N-. { 4-methyl-5-f2- (pyridin-3-ylamino) -1,3-thiazol-4-ill-1,3-oxazol-2-yl > acetamide, trifluoroacetate salt (42) According to general procedure 1, 3-pyridyl thiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-oxazol-2-yl] acetamide (Intermediate 3) in EtOH. The mixture was stirred 17 hours at -20 ° C, then 5 hours at room temperature. The desired product was filtered from the reaction mixture. This was further purified by preparative HPLC. The compound (42) was isolated as a yellow solid (d%). 1 H NMR (Methanol-d 4) d: 2.21 (s, 3 H), 2.52 (s, 3 H), 7.07 (s, 1 H), 7.93 (m, 1 H), 8.43 (m, 3 H), 9.55 (s, 1 HOUR). M "(ESI): 314; M + (ESI): 316. HPLC, Retention time: 1.5 minutes (purity: 96.03%).

EXAMPLE 43 N - ^ - ^ - fluoropyridine-S-iDaminol ^ '- methyl ^ .d'-bi-I.S-thiazole ^' - iiyacetamide, bis-hydrochloride salt (43) According to general procedure 1, N- (2-fluoropyridin-3-yl) thiourea (prepared from 3-amino-2-fluoropyridine (Asymchem) was added, following procedure D) to a solution of N- [ 5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred for 2 hours at room temperature. After the addition of water, the desired product was filtered and washed with water. The N-. { 2 - [(2-fluoropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamida was isolated as a pale yellow solid (67%). The hydrochloride salt of an N- batch was prepared. { 2 - [(2-fluoropyridin-3-yl) amino] -4'-methyl-4, d-bi-1,3-thiazol-2'-yl} acetamide (200.00 mg, 0.57 mmol, 1.00 equivalents). This was suspended in MeOH (10.00 ml) and hydrogen chloride (2.29 ml, 1.25 M, 2.86 mmoles, 5.00 m) was added. equivalents) in methanol. The mixture was stirred for 20 minutes at room temperature and filtered. The yellow powder obtained was washed with diethyl ether and dried under vacuum, yielding compound (43) in 79% yield. 1 H NMR (DMSO-d 6, 300 MHz) d 2.13 (s, 3 H), 2.47 (s, 3 H), 3.15 (s, 2H), 7.01 (s, 1 H), 7.36 (m, 1 H), 7.77 (m, 1 H), 8.94 (m, 1 H), 10.39 (s, 1 H), 12.07 (s, 1 HOUR). M- (ESI): 347.8; M + (ESI): 349.8. HPLC, Retention time: 3.0 minutes (purity: 100%).

EXAMPLE 44 N - ^ - ^ - CyanoetiDamino ^^ '- meti. S'-bi-I.S-thiazole ^' - illacetamide (44) According to general procedure 1, N- (2-cyanoethyl) thiourea (prepared from N- (2-cyanoethyl) amine (Lancaster) was added, following procedure D) to a solution of N- [5- ( brornoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred for 30 minutes at room temperature. The solvents evaporated and the The desired product was purified by flash chromatography. The compound (44) was isolated as a light orange solid (29%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.11 (s, 3 H), 2.42 (s, 3 H), 2.84 (m, 2 H), 3.51 (m, 2 H), 6.68 (s, 1 H), 8.06 (t , J = 3 Hz, 1 H), 11.98 (s, 1H). M "(ESI): 306; M + (ESI): 308. HPLC, Retention time: 1.86 minutes (purity: 97.5%).

EXAMPLE 45 N-. { 2-r (3,3-diethoxypropyl) amino1-4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide (45) According to general procedure 1, N- (3,3-diethoxypropyl) thiourea (prepared from 1-amino-3,3-diethoxypropane (Acros) was added, following procedure D) to a N solution. - [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred for 60 minutes at room temperature. The solvents were evaporated and the desired product was purified by preparative HPLC. The compound (45) was isolated as a dark yellow foam (56%). 1 H NMR (DMSO-d 6, 300 MHz) d 1.22 (t, 6 H), 2.03 (m, 2 H), 2.20 (s, 3 H), 2.50 (s, 3 H, COCH 3), 3.50 (m, 4 H), 3.67 ( m, 2H), 4.62 (t, J = 9 Hz, 1 H), 5.73 (m, 1 H), 6.41 (s, 1 H). M "(ESI): 383; M + (ESI): 385. HPLC, Retention time: 2.42 minutes (purity: 97.7%).

EXAMPLE 46 N - ^ - ^^ - Diethoxy Diethyloxy-methyl-S'-bi- S-thiazole ^ -acetamide According to general procedure 1, N- (3,3-diethoxypropyl) thiourea (prepared from the aminoacetaldehyde of diethyl acetal (Fluka), following procedure D) was added to a solution of N- [5- (bromoacetyl) - 4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred for 3 hours at room temperature. The solvents evaporated. DCM was added and washed with a saturated solution of NH 4 Cl and brine. This organic phase was dried over MgSO, filtered and evaporated. The desired product was purified by flash chromatography to afford compound (46) as an orange solid (44%). 1 H NMR (DMSO-de, 300 MHz) d 1.25 (m, 6H), 2.22 (s, 3H), 2.53 (s, 3H), 3.48 (m, 2H), 3.60 (m, 2H), 3.76 (m, 2H), 4.70 (m, 1 H), 5.50 (m, 1 H), 6.44 (s, 1 H). M "(ESI): 369; M + (ESI): 371. HPLC, Retention time: 2.45 minutes (purity: 95.3%).

EXAMPLE 47 N-f4, -methyl-2-r (2-oxo-2-phenylethyl) amino1-4,5'-bi-1,3-thiazol-2'-il > acetamide (47) According to general procedure 1, N- (2-oxo-2-phenylethyl) thiourea (prepared from 2-aminoacetophenone (Fluka), following procedure D) was added to a solution of N- [5- (bromoacetyl ) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred for 1 hour at room temperature. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (47) was isolated as a colorless solid (71%). 1 H NMR (DMSO-de, 300 MHz) d 2.18 (s, 3 H), 2.61 (s, 3 H), 4.83 (s, 2 H), 7.33 (m, 1 H), 7.43 (m, 2 H), 7.63 (m , 2H), 7.67 (s, 1 H), 12.56 (s, 1 H). M "(ESI): 372; M + (ESI): 374. HPLC, Retention time: 3.72 minutes (purity: 99.2%).

EXAMPLE 48 N-r2-r (2-chloropyridin-3-yl) aminol-4'-methyl-415'-bi-1,3-thiazol-2'-il > acetamide (48) According to general procedure 1, N- (2-chloro-3-pyridinyl) thiourea (prepared from 3-amino-2-chloropyridine (Fluka) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in EtOH. The mixture was stirred for 1 hour at room temperature. The solvents were evaporated and the desired product was purified by flash chromatography. The compound (48) was isolated as a pink solid (64%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.12 (s, 3 H), 2.45 (s, 3 H), 7.02 (s, 1 H), 7.65 (m, 1 H), 8.03 (m, 1 H), 8.83 (m, 1 H), 9.96 (s, 1 H), 12.06 (s, 1 H). M "(ESI): 364; M + (ESI): 366. HPLC, Retention time: 3.16 minutes (purity: 99.8%).

EXAMPLE 49 N- (4'-methyl-2- (r3- (1,3-oxazol-5-yl) phenylamino> -4,5'-bi-1,3-thiazole-2'- Dacetamide (49) According to general procedure 1, N- [3- (1, 3-oxazoI-5-yl) phenyl] thiourea (prepared from d- (3-aminophenyl) oxazole (Maybridge) was added, following the procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in a mixture of EtOH Acetone 2: 1. The mixture was stirred for 5 hours at room temperature. The solvents are evaporated and the desired product was purified by preparative HPLC. The compound (49) was isolated as a beige solid (11%). 1 H NMR (DMSO-de, 300 MHz) d 2.16 (s, 3 H), 2.48 (s, 3 H), 6.93 (s, 1 H), 7.38 (m, 3 H), 7.66 (s, 1 H), 8.47 ( s, 1 H), 8.50 (s, 1 H), 10.50 (s, 1 H), 12.06 (s, 1 H). M "(ESI): 396; M + (ESI): 398. HPLC, Retention time: 3.69 minutes (purity: 99.1%).

EXAMPLE 50 N- (4, -methyl-2-fr3- (1H-tetrazol-5-yl) phenylamino.) -4.5'-bi-1,3-thiazole-2'- Qacetamide, potassium salt (fifty) According to general procedure 1, N- [3- (1 H-tetrazol-5-yl) phenyl] thiourea (prepared from 5- (3-aminophenyl) tetrazole (Avocado) was added, following procedure E) a a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred for d hours at room temperature. The solvents were evaporated and the desired product was purified by preparative HPLC. The N- (4'-methyl-2- { [3- (1 H-tetrazol-5-yl) phenyl] amino} -4, d-bi-1,3-thiazole-2'-yl ) acetamide was isolated as the TFA salt. One sample (120.20 mg, 0.30 mmol, 1.00 equivalents) was dissolved in a mixture of THF (5.00 ml) / MeOH (2 mL). PS-DIEA (Argonaut, 78.76 mg, 0.30 mmol, 1.00 equivalents) was added and the mixture was stirred for 15 minutes. The resin was filtered and rinsed with a DCM / MeOH 2: 1 mixture. The filtrate was evaporated, providing (50) as the original compound (105.3 mg, 88%). This was dissolved in THF (100 ml) and water (100 ml), and a solution of potassium hydroxide in water (469.07 μl, 0.50 M, 0.23 mmoles, 1.00 equivalents) was added. The mixture was filtered on cotton and freeze-dried, yielding compound (50) as a beige powder (103.6 mg, quantitative yield). 1 H NMR (DMSO-de, 300 MHz) d 2.12 (s, 3 H), 2.50 (s, 3 H, COCH 3), 6.87 (s, 1 H), 7.31 (m, 1 H), 7.56 (m, 1 H) , 7.76 (m, 1 H), 7.99 (s, 1 H), 10.31 (s, 1 H), 12.07 (s, 1H). M "(ESI): 397; M + (ESI): 399. HPLC, Retention time: 2.98 minutes (purity: 98.3%).

EXAMPLE 51 N- (4, -methyl-2- { R4- (1 H-tetrazol-5-yl) phenylamino -4.5, -bi-1,3-thiazole-2'- Dacetamide (51) The N-. { 2 - [(4-cyanophenyl) amino] -4-methyl-4,5-b- 1, 3-thiazol-2-yl} acetamide (25) obtained in Example 25 as described above (150.00 mg, 0.42 mmol, 1.00 equivalents), was dissolved in anhydrous DMF (10.00 ml). Tributyltin chloride (457.89 μl, 1.69 mmol, 4.00 equivalents) and sodium azide (109.74 mg, 1.69 mmol, 4.00 equivalents) were successively added. The mixture was heated at 130 ° C for two days. After cooling below room temperature, the black solution was poured into an ice / water mixture and acidified with a 5N HCl solution. The solvents evaporated. The resulting solid was washed with Et20 to remove the excess of Bu3SnCI. This was finally purified by preparative HPLC, yielding (51) as a brown powder (12.0 mg, 7.14%). 1 H NMR (DMSO-ds, 300 MHz) d 2.09 (s, 3 H), 2.45 (s, 3 H), 6.99 (s, 1 H), 7.86 (d, J = 8 Hz, 2 H), 7.99 (d, J = 8 Hz, 2H), 10.72 (s, 1 H), 12.07 (s, 1 HOUR). M "(ESI): 397; M + (ESI): 399. HPLC, Retention time: 2.97 minutes (purity: 93.2%).

EXAMPLE 52 N-. { 4'-Methyl-2-r2- (1H-tetrazol-5-yl) -ethylamino-1-r4,5'-1-biazolyl-2, -il > -acetamide, potassium salt (52) The N-. { 2 - [(2-Cyanoethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide (44) obtained in Example 44 as described above (225.00 mg, 0.73 mmol, 1.00 equivalents), was suspended in dry toluene (5.00 ml). Trimethylsilyl azide (481.33 μl, 3.66 mmol, 5.00 equivalents) and dibutyltin oxide (91.10 mg, 0.37 mmol, 0.50 equivalents) were added. The mixture was heated overnight under reflux. As the reaction was not terminated, dibutyltin oxide (18.22 mg, 0.07 mmol, 0.10 equivalents) and trimethylsilyl azide (192.53 μl, 1.46 mmol, 2.00 equivalents) were added, and the mixture was further refluxed for 24 hours.

The solvents were evaporated and the crude mixture was purified by preparative HPLC to give the N-. { 4'-Methyl-2- [2- (1 H-tetrazol-5-yl) -ethylamino] - [4,5 '] -thiazolyl-2'-yl} -acetamide (62) as the TFA salt (192.30 mg; 56.57%). This was dissolved in THF (22.00 ml). PS-DIEA (Argonaut, 118.91 mg, 0.46 mmol, 1.10 equivalents) was added, and the mixture was stirred for 1 hour 16 minutes. The resin was filtered and rinsed with a THF / MeOH 2: 1 mixture. The filtrate was evaporated giving (62) as the original product (146.2 mg, quantitative). This was dissolved in a 1: 1 THF / water mixture (20.00 ml), and potassium hydroxide (800.00 μl, 0.50 M, 0.40 mmole, 0.97 equivalent) was added. The mixture was filtered on cotton and dried by freezing, providing (52) as a light yellow powder (133.2 mg, 82.8%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.09 (s, 3 H, CH 3), 2.42 (s, 3 H, COCH 3), 2.92 (t, J = 6, 2 H), 3.47 (m, 2 H), 6.57 (s) , 1 H), 7.73 (t, J = 6, 1 H), 11.90 (broad s, 1 H). M "(ESI): 349; M + (ESI): 351. HPLC, Retention time: 1.54 minutes (purity: 98.6%).

EXAMPLE 53 N- (2- { R3- (5-hydroxy-1,3,4-oxadiazol-2-yl) phenylamino.} -4'-methyl-4,5 '-bi-1, 3- thiazol-2'-yl) acetamide, potassium salt 0 (53) According to general procedure 1, N- [3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl] thiourea (prepared from d- (3-aminophenyl)) was added. -1, 3,4-oxadiazol-2-ol (Amine 1), following procedure E) ad a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediary 1) in EtOH. The mixture was stirred for d hours at room temperature. A precipitate formed. This was filtered, yielding N- (2- { [3- (d-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl] amino.} -4'-metif-4, d ' -bi-1,3-thiazol-2'-yl) acetamide (63) as the original product (pale yellow solid, 139.70 mg, 29.86%). This was dissolved in a mixture of THF (4.00 ml) and water (4.00 ml). A solution of potassium hydroxide (660.63 μl, 0.50 M, 0.33 mmole, 0.98 equivalents) was added and the reaction mixture was stirred for 20 minutes at room temperature. This was finally dried by freezing, providing (53) as a pale yellow solid (152.54 mg, quantitative yield). 1 H NMR (DMSO-de, 300 MHz) d 2.11 (t, 3 H), 2.48 (s, 3 H), 6.87 (s, 1 H), 7.21 (m, 1 H), 7.31 (m, 1 H), 7.72. (m, 2H), 10.35 (s, 1 H), 12.04 (s, 1 H). M "(ESI): 413; M + (ESI): 415. HPLC, Retention time: 3.25 minutes (purity: 99.4%).

EXAMPLE 54 N- (2- (r3- (5-amino-1, 3,4-thiadiazol-2-yl) phenanamino > -4, -methyl-4,5'-bi-1,3-thiazole - 2'-yl) acetamide, trifluoroacetate salt (54) According to general procedure 1, N- [3- (5-amino-1, 3,4-thiadiazol-2-yl) phenyl] thiourea (prepared from d- (3-aminophenyl) -1 was added, 3,4-thiadiazol-2-amine (Amina 2), following procedure E) to a solution of N- [6- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH.

The mixture was stirred for 5 hours at room temperature. The solvents are evaporated and the desired product was purified by preparative HPLC to give (54) as a light beige solid (75.00 mg, 33%). 1 H NMR (DMSO-dβ, 300 MHz) d 2.16 (s, 3 H), 2.51 (s, 3 H), 6.95 (s, 1 H), 7.39 (m, 4 H), 7.54 (m, 1 H), 8.31 (s) broad, 1 H), 8.71 (broad s, 1 H), 10.52 (broad s, 1 H), 12.10 (broad s, 1 H). M "(ESI): 428; M + (ESI): 430. HPLC, Retention time: 2.97 minutes (purity: 95.13%).

EXAMPLE 55 N- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-beta-alanine, trifluoroacetate salt (55) Step 1 Preparation of methyl N-f2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-yn-beta-alaninate According to general procedure 1, N- was added (aminocarbonothioyl) -beta-alaninate methyl (prepared from 3- methyl aminopropanoate (amine 3), following procedure D) to a solution of N- [d- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in a 2: 1 EtOH / Acetone mixture. The mixture was stirred for 6 hours at room temperature. The solvents were evaporated and methyl N- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alaninate was used in the next step without additional purification.

Step 2 Preparation of N-r2 '- (acetylamino) -4'-methyl-4, d-bi-1,3-thiazole-2-n-beta-alanine, trifluoroacetate salt (dd) To the N-solution - [2 '- (acetylamino) -4'-methyl-4, methyl d'-bi-1, 3-thiazol-2-yl] -beta-alaninate obtained above (300.00 mg, 0.88 mmol, 1.00 equivalents) in MeOH (10.00 ml), sodium hydroxide (17.62 ml, 1.00 M, 17.62 mmol, 20.00 equivalents) was added and the mixture was stirred at room temperature. After 3 hours, the reaction mixture was acidified to pH = 1 with a 1N HCl solution, and extracted with AcOEt (3 times). The combined organic layers were washed with water, brine and dried over magnesium sulfate. After filtration and evaporation of the solvents, the crude product was purified by preparative HPLC, yielding (56) as a colorless solid (22.6 mg, 8%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.11 (s, 3 H), 2.42 (s, 3 H), 2.56 (m, 2 H), 2.43 (m, 2 H), 3.90 (s, 2 H), 6.62 (s, 1 H), 7.78 (s, 1 H), 11.98 (s, 1 H). M "(ESI): 325; M + (ESI): 327. HPLC, Retention time: 1.49 minutes (purity: 93.3%).

EXAMPLE 56 5- (2- 2 '- (Acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-ylamino ethyl) -1,3,4-oxadiazole-2-olate, salt of potassium (56) Step 1 Preparation of N- (3-hydrazino-3-oxopropyl) thiourea The methyl 3 - [(aminocarbothioyl) amino] propanoate (500.00 mg; 3. 08 mmoles; 1.00 equivalents) (prepared from methyl 3-aminopropanoate (Amine 3), following procedure D), was dissolved in MeOH (25.00 ml). Hydrazine hydrate (2.38 ml, 48.89 mmoles; equivalents) and the mixture was stirred under reflux for 5 hours, then at room temperature overnight. A white precipitate formed. This was filtered and washed with MeOH to give the N- (3-hydrazino-3-oxopropyl) thiourea as a colorless solid (490.7 mg, 98%).

Step 2 Preparation of N- [2 - [(4-hydrazino-4-oxo-butyl) amino-1-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide N- (3-hydrazino-3-) oxopropyl) thiourea obtained in Step 1 as described above (200.00 mg, 1.23 mmol, 1.00 equivalents), was dissolved in MeOH (30.00 ml) with triethylamine (512.02 μl, 3.70 mmol, 3.00 equivalents). The resulting solution was cooled to below 0 ° C. Intermediary 1 (340.23 mg, 1.23 mmoles, 1.00 equivalents) dissolved in MeOH (2 mL) was added. The reaction mixture was stirred overnight at 0 ° C. The solvents evaporated, providing the N-. { 2 - [(4-Hydrazino-4-oxobutyl) amino] -4'-methyl-4, d-bi-1,3-thiazol-2'-yl} acetamide as a yellow solid, which was used in the next step without further purification. M "(ESI): 339; M + (ESI): 341. HPLC, Retention time: 1.16 minutes (purity 81.5%).

Step 3 Preparation of 5- (2- { F2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-pamino) ethyl) -1, 3,4-oxadiazole -2-olate, potassium salt (66) 5 The N-. { 2 - [(4-Hydrazino-4-oxobutyl) amino] -4'-methyl-4, d-bi-1,3-thiazol-2'-yl} Acetamide obtained in Step 2 as described above (419.73 mg, 1.23 mmoles, 1.00 equivalents), was dissolved in a 1: 1 mixture of THF / DMF (18 mL). Triethylamine (0.26 ml, 1.85 mmol, 1.50 equivalents) was added, and the resulting solution was cooled to below 0 ° C. 0 1, 1 '-carbonyldiimidazole (399.85 mg, 2.47 mmol, 2.00 equivalents) in THF (8.00 ml) was added. The reaction was stirred at 0 ° C for 5 hours. The solvents were evaporated and the resulting crude product was purified by preparative HPLC to provide d- (2 { [2 '- (acetylamino) -4'-methyl-4,5'-b-1, 3- thiazol-2-yl] amino.} ethyl) -1,4,4-oxadiazole-2-olate (66) as the TFA salt (227.1 mg, d 50% yield). 1 H NMR (DMSO-d 6, 300 MHz) d 2.11 (s, 3 H), 2.42 (s, 3 H), 2.86 (m, 2 H), 2.64 (m, 2 H), 6.64 (s, 1 H), 11.98 (s) , 1 H), 12.07 (s, 1 H). M "(ESI): 365; M + (ESI): 367. HPLC, Retention time: 1.67 minutes (purity: 95.3%). 5- (2 { [2 '- (acetylamino) -4' was dissolved. -methyl-4, d'-bi-1, 3-thiazol-2-yl] amino] ethyl) -1, 3,4-oxadiazol-2-olate, trifluoroacetate salt (227.1 mg, 0.473 mmol) in DMF PS-DIEA (Argonaut, 123.00 mg, 0.6d mmoles, 1.37 equivalents) was added and the mixture was stirred for 1 hour.The reaction mixture was filtered, rinsed with DMF and evaporated to provide (66) as he original product (173 mg, quantitative yield). M "(ESI): 365; M + (ESI): 367. HPLC, Retention time: 1.73 minutes (purity: 97.5%) This was dissolved in a 1: 1 mixture of THF / water (173 mg, 0.473 mmol in 10 mL) A solution of potassium hydroxide (1047.33 μl, 0.50 M, 0.52 mmol, 0.98 equivalents) was added and the reaction mixture was stirred for 20 minutes at room temperature.The reaction mixture was filtered over cotton and dried by freezing, providing (56) as a pale pink solid (216.4 mg, 90.37%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.10 (s, 3 H), 2.43 (s, 3 H), 2.66 (t, J = 8 Hz, 2H), 3.47 (m, 2H), 6.63 (s, 1 H), 7.79 (t, J = 8 Hz, 1 H), 12.06 (s, 1 H), M "(ESI): 365; M + (ESI): 367. HPLC, Retention time: 1.88 minutes (purity: 95.0%).

EXAMPLE 57 Acid 4-. { r2 '- (acetylamino) -4'-methyl-4,51-bi-1,3-thiazol-2-ylamino > butanoic, potassium salt (57) Step 1 Preparation of 4 - ([2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-ipamino} methyl butanoate According to general procedure 1, 4 - Methyl (aminocarbothioyl) amino] butanoate (prepared from methyl 3-aminobutanoate, hydrochloride salt (Fluka), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl- 1, 3-thiazol-2-yl-acetamide, hydrobromide salt (Intermediate 1) and TEA (3 equivalents) in a 2: 1 EtOH / Acetone mixture The mixture was stirred for 5 hours at room temperature. the desired product was suspended in water, filtered and dried under vacuum. 4- [{[2 '- (acetylamino) -4'- methyl-4,5'-bi-1,3-thiazol-2-yl] amino} Methyl butanoate was isolated as a yellow solid (166.00 mg, 83.63%). 1 H NMR (DMSO-d 6, 300 MHz) d 1.82 (m, 2 H), 2.10 (s, 3 H) 2.37 (m, 2 H), 2.41 (s, 3 H), 3.22 (m, 2 H), 3.58 (s, 3 H) ), 6.60 (s, 1 H), 7.74 (m, 1H), 11.98 (s, 1 H). M "(ESI): 353; M + (ESI): 355. HPLC, Retention time: 1.92 minutes (purity: 90.2%).

Step 2 Preparation of the acid 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-ipamino} butanoic, potassium salt (57) To a solution of 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-b- 1, 3-thiazol-2-yl] amino} Methyl butanoate obtained above (164.00 mg, 0.46 mmol, 1.00 equivalents) in MeOH (5.00 ml), sodium hydroxide (9.25 ml, 1.00 M, 9.25 mmoles, 20.00 equivalents) was added and the mixture was stirred at 35 ° C. . After 2 hours, the reaction mixture was acidified to pH = 1 with a 1N HCl solution and the solvents were removed by freeze drying. The resulting solid was dissolved in DMF and filtered to remove the NaCl salt. After evaporation of DMF and treatment with ether, acid 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} Butanoic was obtained as a solid (73.00 mg, 46.35%). This was suspended in a 1: 1 water / THF mixture (4.00 ml) and potassium hydroxide (428.87 μl, 0.50 M, 0.21 mmoles, 1.00 equivalents) was added. The resulting solution was filtered through of cotton and dried by freezing, providing (57) as a light orange powder (78.70 mg, 96.96%). 1 H NMR (DMSO-d 6, 300 MHz) d 1.69 (m, 2 H), 1.97 (m, 2 H), 2.10 (s, 3 H), 2.40 (s, 3 H), 3.11 (m, 2 H), 6.53 (s, 1 H), 8.94 (s, 1 H), 12.01 (s, 1 H). M "(ESI): 339; M + (ESI): 341. HPLC, Retention time: 1.58 minutes (purity: 98.8%).

EXAMPLE 58 N- (2- (r3- (5-hydroxy-1,3,4-oxadiazol-2-yl) propynamine > -4'-methyl-4,5'-bi-1,3-thiazole-2'- il) acetamide, potassium salt (58) Step 1 Preparation of N- (4-hydrazino-4-oxobutyl) thiourea The methyl 4 - [(aminocarbothioyl) amino] butanoate (176.24 mg, 1.00 mmol, 1.00 equivalents) (prepared from the 3-aminobutanoate of methyl, hydrochloride salt (Fluka), following procedure D), was dissolved in MeOH (10.00 ml). Hydrazine hydrate (2.97 ml, 48.89 mmoles, 48.89 equivalents) was added. The reaction mixture was stirred for 5 hours under reflux and overnight at room temperature. The solvents evaporated. The resulting oil was dissolved in MeOH and EtOH was added. A white product precipitated. This was filtered and washed with EtOH to give N- (4-hydrazino-4-oxobutyl) thiourea (128.5 mg, 72.91%). HPLC, Retention time: 6.50 minutes (purity: 86.9%).

Step 2 Preparation of N- (2-f (4-hydrazino-4-oxobutyl) amino-1-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl> acetamide N- (4 -hydrazine-4-oxobutyl) thiourea (128.50 mg, 0.73 mmol, 1.00 equivalents) was dissolved in MeOH (7.00 ml) and triethylamine (0.30 ml, 2.19 mmoles, 3.00 equivalents), the solution was cooled to below 0 ° C and Intermediate 1 (201.20 mg, 0.73 mmol, 1.00 equivalents) was added as a solid The mixture was stirred 2 hours at room temperature The solvents were evaporated and the N-. {2 - [(4-hydrazino-4- oxobutyl) amino] -4'-methyl-4,5'-bi- 1, 3-thiazol-2'-yl.} acetamide was used in the next step without further purification M "(ESI): 353; M + (ESI): 355. HPLC, Retention time: 1.19 minutes (purity: 95.3%).

Step 3 Preparation of N- (2- { F3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) propypamino} -4'-methyl-4,5'-bi- 1,3-thiazol-2'-yl) acetamide, potassium salt (58) CDI (236.74 mg, 1.46 mmol, 2.00 equivalents) was added to a solution at 0 ° C of N-. { 2 - [(4-Hydrazino-4-oxobutyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide (258.75 mg, 0.73 mmol, 1.00 equivalents) in DMF (5.00 ml) and triethylamine (0.15 ml, 1.10 mmol, 1.50 equivalents). The mixture was stirred at 0 ° C for 3 hours. As the reaction was finished, the solvents evaporated. The crude mixture was purified by preparative HPLC; providing N- (2- {[3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) propyl] amino} -4'-methyl-4,5'-bi-1 , 3-thiazol-2'-yl) acetamide (58) as the TFA salt (matt white solid, 259 mg, 71.8%). M "(ESI): 379; M + (ESI): 381. HPLC, Retention time: 1.72 minutes (purity: 99.3%) This was dissolved in DCM PS-DIEA (150.43 mg, 0.58 mmol, 1.10 equivalents) was added. ) and the mixture was stirred for 15 minutes.The resin was filtered and washed with DCM and a mixture of DCM / MeOH.The filtrate was evaporated, yielding (58) as the original product (192 mg, 96%). suspended in water and potassium hydroxide (1.01 ml, 0.50 M, 0.50 mmole, 0.96 equivalents) was added The mixture was stirred for 5 minutes and dried by freezing, yielding (58) as a beige solid (189.4 mg; %). 1 H NMR (DMSO-d 6, 300 MHz) d 1.88 (m, 2 H), 2.14 (s, 3 H, CH 3), 2.44 (s, 3 H, CH 3), 2.56 (s, 2 H), 3.28 (m, 2H), 6.64 (s, 1 H), 7.81 (m, 1 H, NHCH2), 12.04 (s, 1 H, NHCOCH3). M "(ESI): 379; M + (ESI): 381. HPLC, Retention time: 1.73 minutes (purity: 99.5%).

EXAMPLE 59 3- (r2 '- (acetylamino) -4, -methyl-4,5, -bi-1,3-thiazole-2-inamino-N-hydroxybenzamide (59) The acid 3-. { [2- (acetylamino) -4-methyl-4,5-bi-1,3-thiazol-2-yl] amino} benzoic acid, hydrobromide salt (1) obtained as described above in Example 1 (81.80 mg, 0.22 mmol, 1.00 equivalents), was dissolved in dry DMF (3.00 ml). N-ethyldiisopropylamine (201.68 μl, 1.09 mmol, 5.00 equivalents), HATU (99.68 mg, 0.26 mmol, 1.20 equivalents) and hydroxylamine hydrochloride (30.36 mg, 0.44 mmol, 2.00 equivalents) were added and the mixture was stirred at room temperature. After 3 hours, the reaction was complete. The solvents were evaporated and the crude mixture was purified by preparative HPLC to give (59) as a beige solid (19.60 mg, 23.04%). 1 H NMR (DMSO-d 6, 300 MHz) d 2.13 (s, 3 H), 2.52 (s, 3 H, COCH 3), 6.92 (s, 1 H), 7.36 (m, 2 H), 7.91 (m, 2 H), 10.44 ( s, 1H), 11.16 (s, 1H), 12.06 (s, 1 H). M "(ESI): 388; M + (ESI): 390. HPLC, Retention time: 2.41 minutes (purity: 89.8%).

EXAMPLE 60 Acid 3-. { r2 '- (acetylamino) -4, -methyl-4,5'-bi-1,3-thiazol-2-ylamino} -N-hydroxybenzenecarboximide (60) Triethylamine (0.99 ml, 7.03 mmoles, 5.00 equivalents) was added to a suspension of hydroxylamine hydrochloride (488.76 mg, 7.03 mmoles, 5.00 equivalents) in DMSO (10.00 ml). After 15 minutes, an insoluble material (Et3N.HCl) was filtered and washed with THF. The filtrate was concentrated in vacuo to remove THF. The N-. { 2 - [(4-cyanophenyl) amino] -4-methyl-4,5-b- 1, 3-thiazol-2-yl} acetamide (25) obtained as described above in Example 25 (500.00 mg, 1.41 mmol, 1.00 equivalents) was added, and the The mixture was stirred overnight at 75 ° C. The reaction mixture was diluted with water and extracted with EtOAc. The aqueous phase was dried by freezing. Water was added and the resulting precipitate was filtered, washed with ether, yielding (60) as a beige powder (425.20 mg, 65.67%). , 1 H NMR (DMSO-de, 300 MHz) d 2.09 (s, 3 H), 2.45 (s, 3 H), 5.68 (s broad, 2H), 6.85 (m, 1 H), 7.28 (m, 2H), 7.77 (m, 2H), 9.58 (s, 1 H), 10.35 (s, 1 H), 12.02 (s, 1H) ). M '(ESI): 387; M + (ESI): 389. HPLC, Retention time: 2.07 minutes (purity: 84.4%).

EXAMPLE 61 N- (2- (r3- (5-Hydroxy-1,2,4-oxadiazol-3-yl) phenylamino> -4'-methyl-4,5'-bi-1,3-thiazole- 2'-il) acetamide, potassium salt (61) 2-Ethylhexyl chloroformate (101.22 μl; 0. 51 mmoles; 1.00 equivalents) to an ice-cooled mixture of 3- acid. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -N-hydroxybenzene-carboximide (60) obtained as described above in Example 60 (200.00 mg, 0.51 mmoles, 1.00 equivalents) and anhydrous pyridine (41.56 μl, 0.51 mmoles, 1.00 equivalents) in DMF (2.00 ml). The resulting mixture was stirred at 0 ° C for 30 minutes. This was diluted with water and extracted with EtOAc (3 times). The extracts were washed with water and dried over NaSO4. The solvents were evaporated and the resulting crude intermediate was suspended in xylene (2 mL) and heated at 150 ° C for 2 hours. The solvents were evaporated and the resulting crude product was purified by flash chromatography to provide N- (2 { [3- (5-hydroxy-1, 2,4-oxadiazol-3-yl) phenyl] amino. .4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide (61) as the original product (134.90 mg, 64.70%). One sample (88.00 mg, 0.21 mmol, 1.00 equivalents) was suspended in water (2.50 ml) and THF (2.50 ml) and a solution of potassium hydroxide (416.15 μl, 0.50 M, 0.21 mmol, 0.98 equivalents) were added. The resulting solution was filtered through cotton and dried by freezing, providing (61) as a brown powder (82.8 mg, 91.58%). 1 H NMR (DMSO-de, 300 MHz) d 2.12 (s, 3 H), 2.52 (s, 3 H, COCH 3), 6.88 (s, 1 H), 7.34 (m, 2 H), 7.84 (m, 2 H), 10.34 (s, 1 H). M + (ESI): 413; M + (ESI): 415. HPLC, Retention time: 3.09 minutes (purity: 97.6%).

EXAMPLE 62 N-r2 - ((3-r (Z) - (2,4-dioxo-1,3-thiazoyldin-5-ylidene) met.phenyl)> 4-methyl-4,5 ' -bi-1, 3-thiazol-2'-il.acetamide, acetate salt (62) Step 1 Preparation of (2- (F3- (1, 3-dioxolan-2-yl) phenylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide According to In general procedure 1, N- [3- (1,3-dioxolan-2-yl) phenyl] thiourea (prepared from 3-aminobenzyldehyde of ethylene acetal (Alfa) was added, following procedure D) to a solution of N - [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. N- (2- {[3- (1, 3-dioxolan-2-yl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole-2 ' -yl) acetamide was isolated as a beige solid (320 mg, 88%). HPLC, Retention time: 3.26 minutes (purity: 90.29%).

Step 2 Preparation of the N-.2- ,. { 3 -. (Z .- (2,4-dioxo-1, 3-thiazo [idin-5-ylidene) methylphenyl) amino) -4'-methyl-4,5'-bi-1.S-thiazole ^ - illacetamide, acetate salt (62) A solution of N- (2- {[[3- (1, 3-dioxolan-2-yl) phenyl] amino} -4'-methyl-4 , 5'-bi-1,3-thiazol-2'-yl) acetamide obtained in Step 1 as described above (290.00 mg, 0.72 mmol, 1.00 equivalents), 2,4-thiazolidinedione (151.90 mg, 1.30 mmol; 1.80 equivalents) and beta-alanine (115.55 mg, 1.30 mmol, 1.80 equivalents) in AcOH (6.00 ml), was heated at 100 ° C for 1 hour 30 minutes. Water was added and the precipitate was filtered and washed with Et20, providing (62) as a yellow solid (35 mg, 9%). 1 H NMR (DMSO-d 6, 300 MHz) d 1.92 (s, 3 H), 2.14 (s, 3 H), 2.50 (s, 3 H), 6.98 (s, 1 H), 7.22 (d, J = 7.91 Hz, 1 H), 7.50 (t, J = 7.91 Hz, 1 H), 7.73 (s, 1 H), 7.80 (d, J = 7.91 Hz, 1 H), 7.85 (s, 1 H), 10.59 (s, 1 H), 11.92 (s, 1 H), 12. 06 (s, 1 H), 12.60 (s, 1 H). M "(ESI): 456; M + (ESI): 458. HPLC, Retention time: 3.52 minutes (purity: 93.0%).

EXAMPLE 63 N-4'-methyl-2- (. {4-f (pyridin-2-ylamino) sulfoninophenylamino) -4,5, -bi-1,3-thiazole-2'-acetamide (63) According to general procedure 1, 4 - [(aminocarbonothioyl) amino] -N-pyridin-2-ylbenzenesulfonamide (prepared from 4-amino-N-pyridin-2-ylbenzenesulfonamide (Sigma) was added, following the procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole-2-itjacetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (63) was isolated as a beige solid (25.25 mg, 25%). M + (ESI): 487.2. HPLC, Retention time: 6.89 minutes (purity: 85.8%).

EXAMPLE 64 N- (2- (r 2 - (2-hydroxy-ethenamine > -4, -methyl-4,5, -bi-1,3-thiazol-2'-yl) acetamide (64) According to general procedure 1, N- [2- (2-hydroxyethyl) phenyl] thiourea (prepared from 2- (2-aminophenyl) ethanol (Aldrich) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (64) was isolated as a beige solid (43.71 mg, 56%). M + (ESI): 375.2. HPLC, Retention time: 8.21 minutes (purity: 90.26%).

EXAMPLE 65 N- (2- (r3- (hydroxymethyl) phenylamino> -4'-methyl-45, -bi-1,3-thiazol-2'-yl) acetamide (65) According to general procedure 1, N- [3- (hydroxymethyl) phenyl] thiourea (prepared from (3-aminophenyl) methanol (Aldrich), following procedure D) was added to a solution of N- [ 5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (65) was isolated as a beige solid (18.89 mg, 18%). M + (ESI): 361. HPLC, Retention time: 7.13 minutes (purity: 96.88%).

EXAMPLE 66 N- (2- (r4- (2-hydroxyethyl) phenylamino> -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide (66) According to general procedure 1, N- [4- (2-hydroxyethyl) phenyl] thiourea (prepared from 2- (4-aminophenyl) ethanol (Aldrich) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (66) was isolated as a beige solid (57.25 mg, 52%). M + (ESI): 375.2. HPLC, Retention time: 7.08 minutes (purity: 98.7%).

EXAMPLE 67 N-r2 - ((3-r (2-hydroxyethyl) sulfoninphenyl) amino) -4] -methyl-4,5, -bi-1,3-thiazole-2'-ylkacetamide (67) According to general procedure 1, N- was added. { 3 - [(2-hydroxyethyl) sulfonyl] phenyl} thiourea (prepared from 2 - [(3-aminophenyl) sulfonyl] ethanol, hydrochloride salt (Aldrich), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1, 3 -thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (67) was isolated as a beige solid (21.50 mg, 35%). M + (ESI): 439. HPLC, Retention time: 6.57 minutes (purity: 95.3%).

EXAMPLE 68 N-r2 - ((4 - ^ (dimethylamino) sulfoninphenyl) - amino) -4'-methyl-4,5'-bi-1,3-thiazol-2, - illacetamide (68) According to general procedure 1, 4 - [(aminocarbonothioyl) amino] -N, N-dimethylbenzenesulfonamide (prepared from 4-amino-N, N-dimethylbenzenesulfonamide (Bionet), following procedure D) was added. to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (68) was isolated as a beige solid (36.04 mg, 28%). M + (ESI): 438. HPLC, Retention time: 8.972 minutes (purity: 94.344%).

EXAMPLE 69 N- (2- (r3- (aminosulfonyl) phenylamino> -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl.acetamide (69) According to general procedure 1, 3 - [(aminocarbonothioyl) amino] benzenesulfonamide (prepared from 3-aminobenzenesulfonamide (Maybridge), following procedure D) was added to a solution of N- [5- (bromoacetyl) -4 -methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (69) was isolated as a beige solid (25.11 mg, 44%). M + (ESI): 410. HPLC, Retention time: 6.9 minutes (purity: 96.9%).

EXAMPLE 70 N-. { 2-R (2-chloropyridin-4-yl) amino-1-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide (70) According to general procedure 1, N- (2-cyoropyridin-4-yl) thiourea (prepared from 2-chloropyridin-4-amine (Aldrich), following procedure A) was added to a solution of N- [ 5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (70) was isolated as a beige solid (57.51 mg, 6%). M + (ESI): 366. HPLC, Retention time: 7.37 minutes (purity: 91.5%).

EXAMPLE 71 N-r 4'-methyl-2- 4-r (methylamino) sulfonylphenyl > amino) -4,5, -bi-1,3-thiazole-2'-illacetamide (71) According to general procedure 1, 4 - [(aminocarbonothioyl) aminoj-N-methylbenzenesulfonamide (prepared from 4-amino-N-methylbenzenesulfonamide (Fluorochem), following procedure D) was added to a solution of N- [5] - (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (71) was isolated as a beige solid (25.14 mg, 21%). M + (ESI): 424. HPLC, Retention time: 6.9 minutes (purity: 96.9%).

EXAMPLE 72 N- (5-p2 '- (acetylamino) -4'-methyl-415'-bi-1,3-thiazol-2-amino-pyridine-2-Dacetamide (72) According to general procedure 1, N- was added. { 5 - [(aminocarbonothioyl) amino] pyridin-2-yl} acetamide (prepared from N- (5-aminopyridin-2-yl) acetamide (Fluorochem), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole -2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (72) was isolated as a beige solid (29.20 mg, 22%). M + (ESI): 389.2. HPLC, Retention time: 6.13 minutes (purity: 96.13%).

EXAMPLE 73 N-r2- (2,3-dihydro-1-benzofuran-5-ylamino) -4, -methyl-4,5'-bi-1,3-thiazole-2'- iHacetamide (73) According to general procedure 1, N- (2,3-dihydro-1-benzofuran-5-yl) thiourea (prepared from 2,3-dihydro-1-benzofuran-5-amine ( Bionet), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (73) was isolated as a beige solid (37.35 mg, 46%). M + (ESI): 389.2. HPLC, Retention time: 8.96 minutes (purity: 95.34%).

EXAMPLE 74 N- (4'-methyl-2- (r2- (1-methylpyrrolidin-2-yl) ethanamide> -4,5'-bi-1,3-thiazole-2'- Dacetamide (74) According to general procedure 1, N- was added. { 2- (1-methylpyridinidin-2-yl) ethyl] thiourea (prepared from [2- (1-methylpyrrolidin-2-yl) ethyl] amine (Aldrich), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (74) was isolated as a beige solid (6.82 mg, 5%). M + (ESI): 366. HPLC, Retention time: 5.77 minutes (purity: 93.52%).

EXAMPLE 75 N-. { 4'-methyl-2-r (2-pyrrolidin-1-ethyl) amino1-4,5'-bi-1,3-thiazol-2'-il > Acetamida (75) According to general procedure 1, N- (2-pyrrolidin-1-ylethyl) thiourea (prepared from the (2-pyrrolidin-1-ylef? L) amine (Aldrich) was added, following the procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (75) was isolated as a beige solid (22.99 mg, 31%). M + (ESI): 352. HPLC, Retention time: 6.05 minutes (purity: 94.7%).

EXAMPLE 76 N- (4, -methyl-2- { R3- (2-oxopyrrolidin-1-yl) propylamino) -4,5'-bi-1,3-thiazol-2'-yl) acetamide (76) According to general procedure 1, N- [3- (2-oxopyrrolidin-1-yl) propyl] thiourea (prepared from 1- (3-aminopropyl) pyrrolidin-2-one (Lancaster) was added. , following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (76) was isolated as a beige solid (12.72 mg, 12%). M + (ESI): 380. HPLC, Retention time: 5.89 minutes (purity: 91.2%).

EXAMPLE 77 N- (2- { F2- (acetylamino) ethylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide According to general procedure 1, N- was added. { 2 - [(aminocarbonothioyl) amino] ethyl} acetamide (prepared from N- (2-aminoethyl) acetamide (Lancaster), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediary 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. The compound (77) was isolated as a light yellow oil (31.28 mg, 65%). M + (ESI): 340. HPLC, Retention time: 5.56 minutes (purity: 64%).

EXAMPLE 78 N- (2- { F2- (dimethylamino) ethylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide (78) According to general procedure 1, N- [2- (dimethylamino) ethyl] thiourea (prepared from N, N-dimethyletan-1,2-diamine (Fluka) was added, following procedure C) a a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (78) was isolated as a beige solid (34.30 mg, 38%). M + (ESI): 326. HPLC, Retention time: 5.93 minutes (purity: 95.7%).

EXAMPLE 79 N- (2-R (2-hydroxyethyl) amino-1-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl> acetamide (79) According to general procedure 1, N- (2-hydroxyethyl) thiourea (prepared from 2-arninoethanol (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl -1, 3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (79) was isolated as a beige solid (5 mg, 43%). M + (ESI): 299.2. HPLC, Retention time: 5.6 minutes (purity: 94.9%).

EXAMPLE 80 N- (2- (r2- (4-hydroxyphenyl) ethyl-amino) > -4'-methyl-4,5, -bi-1,3-thiazol-2'-yl) acetamide (80) According to general procedure 1, N- [2- (4-hydroxyphenyl) ethyl] thiourea (prepared from 4- (2-aminoethyl) phenol (Fluka) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-, 3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (80) was isolated as a beige solid (49.18 mg, 47%). M + (ESI): 375.2. HPLC, Retention time: 6.84 minutes (purity: 97.9%).

EXAMPLE 81 N- (2- {3- (dimethylamino, propynyl-4'-methyl-4,5'-bi-1,3-thiazole-2'-Qacetamide (81) According to general procedure 1, N- [3- (dimethylamino) propylthiourea (prepared from N, N-dimethylpropan-1,3-diamine (Fluka) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-metii-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (81) was isolated as a light yellow oil (35.39 mg, 34%). M + (ESI): 340. HPLC, Retention time: 5,595 minutes (purity: 94.41%).

EXAMPLE 82 N-. { 2-R (3-hydroxypropyl) aminol-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide (82) According to general procedure 1, N- (3-hydroxypropyl) thiourea (prepared from 3-aminopropan-1-ol (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (82) was isolated as a beige solid (38.17 mg, 4%). M + (ESI): 313.2. HPLC, Retention time: 5.67 minutes (purity: 97.1%).

EXAMPLE 83 N- (2 - (.3- (1 H-imidazol-1-yl) propylamino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide (83) According to general procedure 1, N- [3- (1 H-imidazol-1-yl) propyl] thiourea (prepared from [3- (1 H-imidazol-1-yl) propyl) was added. ] amine (Aldrich), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyI-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. The compound (83) was isolated as a light yellow oil (50.3 mg, 50%). M + (ESI): 363.2. HPLC, Retention time: 5.6 minutes (purity: 94.336%).

EXAMPLE 84 N-3-r2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-beta-alaninamide (') According to general procedure 1, N-3- (aminocarbonothioyl) -beta-alaninamide (prepared from beta-alaninamide, hydrochloride salt (Novabio), following procedure D) was added to a solution of N - [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. The compound (84) was isolated as a light yellow oil (11.25 mg, 13%). M + (ESI): 323. HPLC, Retention time: 6.62 minutes (purity: 65.495%).

EXAMPLE 85 N-. { 4'-methyl-2 -. (2-methy1prop-2-en-1-yl) amino, -4,5'-bi-1,3-thiazol-2'-yl} acetamide (85) According to general procedure 1, N- (2-methylprop-2-en-1-yl) thiourea (prepared from (2-methylprop-2-en-1-yl) amine) was added (Acros ), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (85) was isolated as a beige solid (15.75 mg, 70%). M + (ESI): 309.2. HPLC, Retention time: 7.54 minutes (purity: 97.43%).

EXAMPLE 86 N-. { 2 - [(2-hydroxyphenyl) amino1-4'-methyl-4,5'-bi-1,3-thiazol-2'-il > acetamide (86) According to general procedure 1, N- (2-hydroxyphenyl) thiourea (prepared from 2-aminophenol (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl -1, 3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (86) was isolated as a light yellow oil (23.66 mg, 49%). M + (ESI): 347.2. HPLC, Retention time: 8.04 minutes (purity: 91.8%).

EXAMPLE 87 N ^ - ^ e-fluoropyridin-S-iDaminol ^ '- methyl ^ S'-bi-l ^ -thiazole ^' - illacetamide (87) According to general procedure 1, N- (6-fluoropyridin-3-yl) thiourea (prepared from 6-fluoropyridin-3-amine (Asymchem) was added, following procedure D) to a solution of N- [ 5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (87) was isolated as a beige solid (34.15 mg, 33%). M + (ESI): 350. HPLC, Retention time: 8.25 minutes (purity: 96.053%).

EXAMPLE 88 N-. { 2-f (4-cyanophenyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-il > acetamide (88) According to general procedure 1, N- (4-cyanophenyl) thiourea (Fluka) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (88) was isolated as a beige solid (17.23 mg, 5%). M + (ESI): 356. HPLC, Retention time: 9.13 minutes (purity: 93.3%).

EXAMPLE 89 N ^ - ^ e-cyanopyridin-S-iDaminol ^ '- methyl ^ .d'-bi-l ^ -thiazole ^' - i ^ acetamide (89) According to general procedure 1, N- (6-cyanopyridin-3-yl) thiourea (prepared from 5-aminopyridine-2-carbonitrile (Aldrich) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (89) was isolated as a beige solid (28.71 mg, 29%). M + (ESI): 357.2. HPLC, Retention time: 7.96 minutes (purity: 92.6%).

EXAMPLE 90 N-. { 2-f (3-methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide (90) According to general procedure 1, N- (3-methoxyphenyl) thiourea (prepared from (3-methoxyphenyl) amine (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (90) was isolated as a beige solid (19.63 mg, 12%). M + (ESI): 361.2. HPLC, Retention time: 10.03 minutes (purity: 94.8%).

EXAMPLE 91 3-. { 2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-aminoamid > benzamide (91) According to general procedure 1, 3 - [(aminocarbonothioyl) aminojbenzamide (prepared from 3-aminobenzamide (Fluka), following procedure D) was added to a solution of N- [5- (bromoacetyl) -4-methyl -1, 3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (91) was isolated as a beige solid (25.49 mg, 33%). M + (ESI): 374. HPLC, Retention time: 15.27 minutes (purity: 97.8%).

EXAMPLE 92 N-. { 4'-meth1l-2-r (2-nitrophenyl) amino1-4,5'-bi-1,3-thiazol-2'-il > acetamide (92) According to general procedure 1, N- (2-nitrophenyl) thiourea (prepared from (2-nitrophenyl) amine (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (92) was isolated as a beige solid (12.69 mg, 15%). M + (ESI): 376. HPLC, Retention time: 11.55 minutes (purity: 94.5%).

EXAMPLE 93 N-f4'-methyl-2-r (3-nitrophenyl) amino1-4,5'-bi-1,3-thiazol-2'-yl acetamide (93) According to general procedure 1, N- (3-nitrophenyl) thiourea (Fluka) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (93) was isolated as a beige solid (67.80 mg, 63%). M + (ESI): 376. HPLC, Retention time: 9.94 minutes (purity: 93.93%).

EXAMPLE 94 N-r4, -methyl-2- (quinolin-3-ylamino) -4,5'-bi-1,3-thiazole-2'-acenamide (94) According to general procedure 1, N-quinolin-3-Itiourea (prepared from quinolin-3-amine (Aldrich), following procedure A) was added to a solution of N- [5- (bromoacetyl) - 4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (94) was isolated as a beige solid (29.83 mg, 25%). M + (ESI): 382. HPLC, Retention time: 7 minutes (purity: 98.2%).

EXAMPLE 95 N-r 4, -methyl-2- (quinolin-5-ylamino) -4,5'-bi-1,3-thiazol-2'-yl-1-acetamide (95) According to general procedure 1, N-quinolin-5-ylthiourea (prepared from quinolin-5-amine (Fluka) was added, following procedure A) to a solution of N- [5- (bromoacetyl) -4 -methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (95) was isolated as a beige solid (15.45 mg, 19%). M + (ESI): 382. HPLC, Retention time: 6.11 minutes (purity: 95.3%).

EXAMPLE 96 N-r4'-methyl-2- (quinolin-6-ylamino) -4,5'-bi-1,3-thiazole-2'-spathimide (96) According to general procedure 1, N-quinolin-6-ylthiourea (prepared from quinolin-6-amine (Fluka), following procedure A) was added to a solution of N- [5- (bromoacetyl ) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by preparative HPLC. The compound (96) was isolated as a beige solid (39.67 mg, 45%). M + (ESI): 382. HPLC, Retention time: 6.37 minutes (purity: 98.9%).

EXAMPLE 97 N- [2- (Cyclopentylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-acetamide (97) According to general procedure 1, N-cyclopentylthiourea (prepared from cyclopentanamine (Fluka), following procedure C) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1, 3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (97) was isolated as a beige solid (44.41 mg, 54%). M + (ESI): 323.2. HPLC, Retention time: 8.14 minutes (purity: 91.8%).

EXAMPLE 98 N-r2- (cyclopropylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2, -yl1acetamide According to general procedure 1, N-cyclopropyl thiourea (prepared from cyclopropanamine (Aldrich), following procedure C) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole -2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (98) was isolated as a beige solid (65.7 mg, 62%). M + (ESI): 295.2. HPLC, Retention time: 6.86 minutes (purity: 98%).

EXAMPLE 99 N ^ '- methyl ^ - ^ pyridin-S-ilmethi-aminol ^^' - bi-I.S-thiazole ^ '- illacetamide (99) According to general procedure 1, N- (pyridin-3-methyl) thiourea (prepared from (pyridin-3-ylmethyl) amine (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (99) was isolated as a light yellow oil (10 mg, 12%). M + (ESI): 346. HPLC, Retention time: 5.69 minutes (purity: 86.5%).

EXAMPLE 100 N 2-r.4-hydroxybutyl) amino1-4'-methyl-4,5 '3Í-1,3-thiazole-2-acetamide (100) According to general procedure 1, N- (4-hydroxybutyl) thiourea (prepared from 4-aminobutan-1-ol (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (100) was isolated as a light yellow oil (26.2 mg, 16%). M + (ESI): 327.2. HPLC, Retention time: 5.71 minutes (purity: 92.9%).

EXAMPLE 101 N- (4, -methyl-2- (r3- (methylsulfonyl) phenylamino> -4.5'-bi-1,3-thiazole-2'-Qacetamide (101) According to general procedure 1, N- [3- (methylsulfonyl) phenyl] thiourea (prepared from [3- (methylsulfonyl) phenyl] amine, hydrochloride salt (Acras) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (101) was isolated as a beige solid (24.2 mg, 20%). M + (ESI): 409.2. HPLC, Retention time: 7.87 minutes (purity: 93.13%).

EXAMPLE 102 N-l ^ -methyl ^ - ^ - pyrrolidin-1-ylpropiDamino ^ '- bi-I.S-thiazole-S'-illacetamide (102) According to general procedure 1, N- (3-pyrrolidin-1-ylpropyl) thiourea (prepared from (3-pyrrolidin-1-ylpropyl) amine (Lancaster) was added, following procedure D ) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (102) was isolated as a beige solid (14.18, 16%). M + (ESI): 366. HPLC, Retention time: 5.85 minutes (purity: 94.398%).

EXAMPLE 103 N- (2-r (1,1-dioxido-1-benzothien-6-yl) amino-1-4'-methyl-4,5'-bi-1,3-thiazole-2'-in acetamide (103) According to general procedure 1, N- (1,1-dioxide-1-benzothien-6-yl) thiourea (prepared from (1,1-dioxide-1-benzothien-yl) amine) was added. (Maybridge), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (103) was isolated as a beige solid (58.6 mg, 40%). M + (ESI): 419.2. HPLC, Retention time: 8.1 minutes (purity: 93.69%).

EXAMPLE 104 N- (2- { R (1-ethylpyrrolidin-2-yl) methypamino> -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide (104) According to general procedure 1, N - [(1-ethylpyrrolidin-2-yl) methyl] thiourea (prepared from [(1-ethylpyrrolidin-2-yl) methyljamine (Acros) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (104) was isolated as a light yellow oil (47.24 mg, 46%). M + (ESI): 366. HPLC, Retention time: 6.227 minutes (purity: 97.59%).

EXAMPLE 105 N ^ - Cyanomethyaminamin ^ '- methyl ^ d-bi-l ^ -thiazole ^' - illacetamide (105) According to general procedure 1, N- (cyanomethyl) thiourea (prepared from aminoacetonitrile (Sigma), following procedure D) was added to a solution of N- [5- (bromoacetyl) -4-methyl -1, 3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. The compound (105) was isolated as a light yellow oil (3.96 mg, 5%). M + (ESI): 294. HPLC, Retention time: 6.86 minutes (purity: 85%).

EXAMPLE 106 N-f2- (isobutylamino) -4'-methyl-4,5'-bi-1,3-f.iazol-2'-ureaethamide (106) According to general procedure 1, N-isobutylthiourea (prepared from 2-methylpropan-1 -amine (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4methyl-1 , 3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (106) was isolated as a beige solid (50.82 mg, 57%). M + (ESI): 311.2. HPLC, Retention time: 7.9 minutes (purity: 90.6%).

EXAMPLE 107 N ^^ - dimethylpropiQaminol ^ '- methyl ^. S'-bi-l ^ -thiazole-S'-illacetamide (107) According to general procedure 1, N- (2,2-dimethylpropyl) thiourea (prepared from (2,2-dimethylpropyl) amine (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (107) was isolated as a beige solid (35.87 mg, 38%). M + (ESI): 325.2. HPLC, Retention time: 8.8 minutes (purity: 97.7%).

EXAMPLE 108 N- (2-fflcis) -2- (hydroxymethyl) cyclohexinamino > -4'-methyl-4,5, -bi-1,3-thiazol-2, ^ il) acetamide (108) According to general procedure 1, N - [(cis) -2- (hydroxymethyl) cyclohexylthiourea (prepared from cis- (2-aminocyclohexyl) methanol, hydrochloride salt (Acros) was added, following procedure D ) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (108) was isolated as a light yellow oil (24.3 mg, 5%). M + (ESI): 367.2. HPLC, Retention time: 6.23 minutes (purity: 75%).

EXAMPLE 109 N ^ - ttrans ^ -dihydroxymethiQciciohexinamino ^ '- methyl? S'-bi-I.S-thiazol-2'-yl, acetamide (109) According to general procedure 1, N - [(trans) -2- (hydroxymethyl) cyclohexyl] thiourea (prepared from trans- (2-aminocyclohexyl) methanol, hydrochloride salt (Acras) was added, following the procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (109) was isolated as a beige solid (34.5 mg, 61%). M + (ESI): 367.2. HPLC, Retention time: 6.79 minutes (purity: 94.4%).

EXAMPLE 110 N-, 2- (sec-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl, acetamide (110) According to general procedure 1, N- (sec-buty!) Thiourea (prepared from sec-butylamine (Avocado) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4- methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (110) was isolated as a beige solid (67.01 mg, 75%). M + (ESI): 311.2. HPLC, Retention time: 7.68 minutes (purity: 90.2%).

EXAMPLE 111 N ^ '- methyl-S-rfPiridin ^ -ylmethiDaminol ^ S'-bi-l ^ -thiazole-S'-illacetamide (111) According to general procedure 1, N- (pyridin-4-ylmethyl) thiourea (prepared from (pyridin-4-ylmethyl) amine (Aldrich) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (111) was isolated as a light yellow oil (38.54 mg, 7%). M + (ESI): 346. HPLC, Retention time: 5.72 minutes (purity: 91.8%).

EXAMPLE 112 N- (4'-methyl-2- (r 4 - (morpholin-4-ylsulfonyl) phenylamino> -4,5'-bi-1,3-thiazole-2'- Dacetamide (112) According to general procedure 1, N- [4- (morpholin-4-ylsulfonyl) phenyl] thiourea (prepared from [4- (morpholin-4-ylsulfonyl) phenyl] amine (Maybridge) was added, following Procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (112) was isolated as a beige solid (24.82 mg, 19%). M + (ESI): 480. HPLC, Retention time: 8.55 minutes (purity: 96%).

EXAMPLE 113 N-r2 - ((3-R (butylamino) sulfoninphenyl). Amino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-ill acetamide (113) According to the general procedure, 1, 3 - [(aminocarbonothioyl) amino] -N-butylbenzenesulfonamide (prepared from 3-amino-N-butylbenzenesulfonamide (Aldrich), following procedure D) was added to a solution of N- [5- (Bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by preparative HPLC. Compound (113) was isolated as a beige solid (26.42 mg, 20%). M + (ESI): 466. HPLC, Retention time: 10.31 minutes (purity: 99.1%).

EXAMPLE 114 N-. { 2-r (cyclopropylmethyl) amino-1-4'-methyl-4,5, -bi-1,3-thiazol-2, -yl) -acetamide (114) According to general procedure 1, N- (cyclopropylmethyl) thiourea (prepared from (cyclopropylmethyl) amine (Fluka) was added, following procedure C) to a solution of N- [5- (bromoacetyl) -4 -methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (114) was isolated as a beige solid (39.26, 32%). M + (ESI): 309.2. HPLC, Retention time: 7.3 minutes (purity: 97.5%).

EXAMPLE 115 N-f2- (Cyclobutylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-illacetamide (115) According to general procedure 1, N-cyclobutyl thiourea (prepared from cyclobutanamine (Fluka), following procedure C) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazole- 2-Iketatamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (115) was isolated as a beige solid (73.20 mg, 84%). M + (ESI): 309.2. HPLC, Retention time: 7.68 minutes (purity: 90.2%).

EXAMPLE 116 N-2- (2,3-Dihydro-1 H -inden-2-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamida (116) According to general procedure 1, N- (2,3-dihydro-1 H-inden-2-yl) thiourea (prepared from 2,3-dihydro-1 H-inden-2-ylamine) was added ( Maybridge), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (116) was isolated as a beige solid (6 mg, 6%). M + (ESI): 371.2. HPLC, Retention time: 9.83 minutes (purity: 90.8%).

EXAMPLE 117 N- (4'-methyl-2- { R2- (methylsulfonyl) phenyl-amino) > -4,5'-bi-1,3-thiazol-2'-yl) acetamide (117) According to general procedure 1, N- [2- (methylsulfonyl) phenyl] thiourea (prepared from [2- (methylsulfonyl) phenyljamine, hydrochloride salt (Acras), following procedure A) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. The compound (117) was isolated as a light yellow oil (5.93 mg, 10%). M + (ESI): 409. HPLC, Retention time: 9.5 minutes (purity: 83.4%).

EXAMPLE 118 N- (4'-methyl-2- { R2- (1H-1, 2,4-triazol-1-yl) ethinylamine> -4.5'-bi-1,3-thiazole-2 '- IOacetamide (H8) According to general procedure 1, N- [2- (1 H-1, 2,4-triazol-1-yl) ethyl] thiourea (prepared from [2- (1H-1, 2 , 4-triazol-1-yl) ethyl] amine (Ostwest), following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide ( Intermediary 1) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (118) was isolated as a beige solid (6.51 mg, 3%) M + (ESI): 350. HPLC, Retention time: 5.699 minutes (purity: 91.43%).

EXAMPLE 119 N- (2-fr3- (1-hydroxyethyl) phenylamino> -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide (119) According to general procedure 1, N- [3- (1-hydroxyethyl) phenyl] thiourea (prepared from 1- (3-aminophenyl) ethanol (Aldrich) was added, following procedure D) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH. The mixture was stirred 5 hours at room temperature. After the addition of water, the desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. Compound (119) was isolated as a light yellow oil (41.06 mg, 50%). M + (ESI): 375.2. HPLC, Retention time: 7.62 minutes (purity: 88.4%).

EXAMPLE 120 (4- { R2 '- (Acetylamino) -4'-methyl-415'-bi-1,3-thiazol-2-ylamino.} Phenyl) methyl acetate (120) The methyl ester of (4-aminophenyl) acetic acid (Lancaster) is obtained using the etherification conditions described above for the amines (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid. It is transformed into its corresponding thiourea, following procedure D. The resulting thiourea,. { 4- [(aminocarbonothioyl) aminojphenyl} Methyl acetate, is added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH, according to the general procedure 1. The The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (120) was isolated as a beige solid (10 mg, 9%). M + (ESI): 403. HPLC, Retention time: 9.3 minutes (purity: 90.7%).

EXAMPLE 121 N- (4- { R2 '- (acetylamino) -4'-methyl-4,5, -bi-1,3-thiazole-2-amino acid &benzyl) -beta-alaninate methyl The N- (4-aminobenzoyl) -beta-alanine methyl ester (Aldrich) is obtained using the etherification conditions described above for the amines (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid. It is transformed into its corresponding thiourea, after the procedure D. The resulting thiourea, N- (4-aminobenzoyl) -beta-alaninate methyl, is added to a solution of N- [5- (bromoacetyl) -4-methyl-1 , 3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH, according to the general procedure 1. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (121) was isolated as a beige solid (22.39 mg, 23%). M + (ESI): 460. HPLC, Retention time: 7.2 minutes (purity: 90%).

EXAMPLE 122 N- (4-, 2 ^ acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-ylamino} benzoyl) methyl glycinate (122) The N- (4-aminobenzoyl) glycine methyl ester (Aldrich) is obtained using the etherification conditions described above for the amines (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid. It is transformed into its corresponding thiourea, after procedure D. The resulting thiourea, N-. { 4 - [(aminocarbonothioyl) aminojbenzoyl} Methyl glycinate is added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH, according to the general procedure 1. The mixture it was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (122) was isolated as a beige solid (35.35 mg, 18%). M + (ESI): 446. HPLC, Retention time: 7.05 minutes (purity: 91.5%).

EXAMPLE 123 3- (3- (r2 '- (Acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-pamino) phenyl) propanoate methyl (123) The 3- (3-aminophenyl) propanoic acid methyl ester (Lancaster) is obtained using the etherification conditions described above for the amines (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid. It is transformed into its corresponding thiourea, after the procedure D. The resulting thiourea, 3-. { 3- [(aminocarbonothioyl) amino] phenyl} Methyl propanoate is added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH, according to the general procedure 1. The mixture is stirred for 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (123) was isolated as a beige solid (12.3 mg, 11%). M + (ESI): 417.2. HPLC, Retention time: 10,285 minutes (purity: 93%).

EXAMPLE 124 3- (4 - (.2 '- (Acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-ylamino} phenyl) propanoic acid (124) The methyl ester of 3- (4-aminophenyl) propanoic acid (Lancaster) is obtained using the etherification conditions described above for the amines (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid. It is transformed into its corresponding thiourea, after the procedure D. The resulting thiourea, 3-. { 4- [(aminocarbonothioyl) amino] phenyl} Methyl propanoate is added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl-acetamide (Intermediate 1) in EtOH, according to the general procedure 1. The mixture is stirred for 5 hours at room temperature. The resulting ester was hydrolyzed under the reaction condition. The solvents were evaporated and the desired product was purified by crystallization. The compound (124) was isolated as a solid beige (11 mg, 8%). M + (ESI): 403. HPLC, Retention time: 10.09 minutes (purity: 91.4%).

EXAMPLE 125 4-. { methyl r2, - (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-amino-butanoate (125) According to general procedure 1, methyl 4- (aminocarbonothioyl) amino] butanoate (prepared from methyl 4-aminobutanoate (Fluka), following procedure D) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH.

The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (125) was isolated as a beige solid (9.61 mg, 5%). M + (ESI): 356.

HPLC, Retention time: 7,678 minutes (purity: 96.506%).

EXAMPLE 126 (3- { F2 '- (Acetylamino) -4'-methyl-4,5'-b- 1,3-thiazole-2-ynyamino> phenyl) methyl acetate (126) The methyl ester of (3-aminophenyl) acetic acid (Aldrich) is obtained using the etherification conditions described above for (NHR5R6), wherein R5 is H and R6 contains a carboxylic acid. It is transformed into its corresponding thiourea, after the procedure D. The resulting thiourea,. { 3 - [(aminocarbonothioyl) amino] phenyl} methyl acetate, is added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] acetamide (Intermediate 1) in EtOH, according to the general procedure 1. The The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (126) was isolated as a beige solid (4.47 mg, 6%). M + (ESI): 403.2. HPLC, Retention time: 7.7 minutes (purity: 90%).

EXAMPLE 127 N-r2- (Allylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-il.urea (127) According to general procedure 1, N-allylthiourea (Lancaster) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] urea (Intermediate 7) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (127) was isolated as a beige solid (14.3 mg, 18%). M + (ESI): 296. HPLC, Retention time: 8.95 minutes (purity: 93.08%).

EXAMPLE 128 N-r ^ -methyl ^ -pyridin-S-ylaminoM ^ '- bi-I.S-thiazole ^' - inurea (128) According to general procedure 1, N-pyridin-3-ylthiourea (Fluka) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] urea (Intermediate 7) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (128) was isolated as a beige solid (32.63 mg, 35%). M + (ESI): 333.2. HPLC, Retention time: 5.71 minutes (purity: 98.09%).

EXAMPLE 129 N- (4, -methyl-2-piperidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) urea (129) According to general procedure 1, piperidine-1-carbothioamide (Transwld) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] urea (Intermediate 7) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (129) was isolated as a beige solid (28.38 mg, 30%). M + (ESI): 324. HPLC, Retention time: 8.7 minutes (purity: 98.1%).

EXAMPLE 130 N- (2-anilino-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) urea According to the procedure generated! 1, N-phenylthiourea was added (Transwld) to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] urea (Intermediate 7) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (130) was isolated as a beige solid (30.17 mg, 32%). M + (ESI): 332. HPLC, Retention time: 8.37 minutes (purity: 94.42%).

EXAMPLE 131 N - ^ - r ^ -hydroxyphenamino'-methyl ^ S'-bi-l ^ thiazole-S'-illurea (131) According to general procedure 1, N- (4-hydroxyphenyl) thiourea (Aldrich) was added to a solution of N- [5- (bromoacetyl) -4-methyl-1,3-thiazol-2-yl] urea (Intermediate 7) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. The compound (131) was isolated as a beige solid (70.42 mg, 68%). M + (ESI): 348. HPLC, Retention time: 6.14 minutes (purity: 96.82%).

EXAMPLE 132 N-, 2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazole-2'-ipacetamide (132) According to general procedure 1, N-pyridin-3-ylthiourea (Lancaster) was added to a solution of N- [5- (2-bromo-acetyl) -thiazol-2-yl] -acetamide (Intermediate 4 ) in EtOH. The mixture was stirred 5 hours at room temperature. The solvents were evaporated and the desired product was purified by crystallization. Compound (132) was isolated as a beige solid (37.28 mg, 42%). M + (ESI): 318. HPLC, Retention time: 6 minutes (purity: 94.96%).

EXAMPLE 133 Acid (4- { R2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-pamino} phenyl) acetic acid (133) Methyl (4- {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) acetate ( 122) was dissolved in a mixture of 1 N MeOH / NaOH (0.1 M) and stirred 4 hours at room temperature. The reaction mixture was concentrated and acidified to pH 4 with 1.5 N HCl. The resulting solids were filtered, washed with water and dried under vacuum. The compound (133) was isolated as a beige solid (6.72 mg, 50%). M + (ESI): 389.2. HPLC, Retention time: 7.19 minutes (purity: 80.67%).

EXAMPLE 134 N- (4- (r2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-imamino> benzoyl) -beta-alanine (134) The N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino) benzoyl) -beta-alaninate methyl ( 123) was dissolved in a mixture of 1 N MeOH / NaOH (0.1 M) and stirred 4 hours at room temperature. The reaction mixture was concentrated and acidified to pH 4 with 1.5 N HCl. The desired product was extracted with EtOAc (3 fractions) and dried over MgSO4. The combined organic phases were filtered and evaporated. The compound (134) was isolated as a light yellow oil (5.77 mg, 48%). M + (ESI): 446. HPLC, Retention time: 6.07 minutes (purity: 68.2%).

EXAMPLE 135 N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-pamino> benzoyl) glycine The N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) glycinate methyl (124 ) was dissolved in a mixture of 1 N MeOH / NaOH (0.1 M) and stirred 4 hours at room temperature. The reaction mixture was concentrated and acidified to pH 4 with 1.5 N HCl. The resulting solid was filtered, washed with water and dried under vacuum. Compound (135) was isolated as a beige solid (12.02 mg, 82%) M '"(ESI): Non-ionizing, HPLC, Retention time: 14.49 minutes (purity: 98.5%).

EXAMPLE 136 3- (3- { R2, - (Acetylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2-ylamino} phenyl) propanoic acid (136) The methyl 3- (3. {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) propanoate (125 ) was dissolved in a mixture of 1 N MeOH / NaOH (0.1 M) and stirred 4 hours at room temperature. The reaction mixture was concentrated and acidified to pH 4 with 1.5 N HCl. The resulting solid was filtered, washed with water and dried under vacuum. Compound (136) was isolated as a beige solid (7.84 mg, 63%). M + (ESI): 403.2. HPLC, Retention time: 7.94 minutes (purity: 94.21%). The following compounds can be synthesized according to the general reaction schemes proposed herein and are commercially available: N-. { 2 - [(4-ethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 4'-methyl-2 - [(4-methylphenyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole- 2'-il} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl} phenyl) amino] -4,5'-bi-1,3-thiazole-2 ' -il} acetamide; N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] propanamide; N-. { 2 - [(4- {[[2,6-dimethoxypyrimidin-4-yl) amino] sulfonyl] phenyl) amino] -4'-methyl-4,5'-bi-1, 3-thiazole-2'-il} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl} phenyl) aminoj-4,5'-bi-1,3-thiazole-2 '-il} propanamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole- 2'-il} propanamide; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) acetamide; N-. { 2 - [(4-aminophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-ethylphenyl) aminoJ-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-methylphenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 2 - [(4-bromophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-i !} acetamide; N-. { [4- (aminosulfonyl) phenyljamino} -4'-methyl-4,5'-bi-1,3-thiazole-2'-l) acetamide; N-. { 2 - [(2,5-dimethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-Acetylphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { [4- (dimethylamino) pheny] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 4'-methyl-2 - [(3-nitrophenol) amino] -4,5'-bi-1,3-thiazole-2'-yl} acetamide; acid 3-. { [2 '- (acetylamino) -4-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -benzoic.

EXAMPLE 137 Biological assays The compounds of the present invention can be subjected to the following tests a) High performance assay of the PI3K lipid kinase (binding assay) The effectiveness of the compounds of the invention in inhibiting the phosphorylation of the lipid induced by P13K can be tested in the following binding assay.

The assay combines scintillation proximity assay technology (SPA, Amersham) with the ability of neomycin (a polycationic antibiotic) to bind phospholipids with high affinity and specificity. The Scintillation Proximity Assay is based on the properties of weakly emitting isotopes (such as 3H, 125l, 33P). The coating of SPA beads with neomycin allows the detection of phosphorylated lipid substrates after incubation with recombinant PI3K and radioactive ATP in the same well, capturing the radioactive phospholipids with the SPA beads through their specific binding to neomycin. A 384 MTP wells containing 5 μl of the test compound of Formula (I) (solubilized in 6% DMSO to provide a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.001 μM of the test compound), the following test components are added. 1) 5 μl (58 ng) of GST-PI3K? human recombinant (in 40 mM Hepes, pH 7.4, 1 mM DTT and 5% ethylene glycol) 2) 10 μl of lipid micelles and 3) 10 μl of kinase buffer ([33 P]? - ATP 45 μM / 60 nCi, MgCl 2 30mM, 1mM DTT, 1mM ß-glycerophosphate, 00μM Na3V04, 0.3% Na cholate, in 40mM Hepes, pH 7.4). After incubation at room temperature for 180 minutes, with gentle agitation, the reaction is stopped by the addition of 60 μl of a solution containing 100 μg of PVON SPA beads coated with neomycin in PBS containing 10 mM ATP and 5 mM EDTA. . The assay is further incubated at room temperature for 60 minutes with gentle agitation to allow binding of the phospholipids to the SPA beads with neomycin. After precipitation of SPA PVT beads coated with neomycin, for 5 minutes at 1500 x g, Ptdlns (3) P is quantified by scintillation counting in a Wallac MicroBeta ™ plate counter. The values indicated in Table I below refer to the IC5o (nM) with respect to the PI3K ?, that is, the amount needed to achieve the 50% inhibition of the target. The values show a considerable inhibitory potency of the thiazole compounds with respect to PI3K ?. Examples of inhibitory activities for the compounds of the invention are set forth in Table I below.

TABLE I b) Cell-based ELISA to verify inhibition of PI3K The efficacy of the compounds of the invention for inhibiting Akt / PKB phosphorylation induced by PI3K can be tested in the following cell-based assay. Measurement of Akt / PKB phosphorylation in macrophages after stimulation with Complement 5a: Untreated 264: Untreated macrophages 264-7 (cultured in DMEM-F12 medium containing 10% fetal calf serum and antibiotics) plaque at 20O00 cells / well in 96 MTP 24 hours before cell stimulation. Before stimulation with 50 nM of the Complement 5a for 5 minutes, cells and serum were deprived of nutrients for 2 hours, and pretreated with inhibitors for 20 minutes. After stimulation the cells were fixed in 4% formaldehyde for 20 minutes and washed 3 times in PBS containing 1% Triton X-100 (PBS / Triton). The endogenous peroxidase is blocked by a 20 minute incubation in 0.6% H202 and 0.1% Sodium Azide in PBS / Triton and washed 3 times in PBS / Triton. The cells were then blocked by a 60 minute incubation with 10% fetal calf serum in PBS / Triton. Next, the phosphorylated Akt / PKB was detected by overnight incubation at 4 ° C with the first antibody (antiphosfoserin 473 Akt IHC, Cell Signaling) diluted 800-fold in PBS / Triton, containing 5% fetal calf serum (BSA). After 3 washes in PBS / Triton, the cells were incubated for 60 minutes with peroxidase-conjugated goat anti-hook antibody (1/400 dilution in PBS / Triton, containing 5% BSA), washed 3 times in PBS / Triton, and 2 times in PBS and were further incubated in 100 μl of the substrate reagent solution (R & D) for 20 minutes. The reaction was stopped by the addition of 50 μl of 1 M S04H2 and the absorbance was read at 450 nm. The values indicated in Table II below reflect the percentage inhibition of AKT phosphorylation compared to the basal level. The values show a clear effect of the thiazole compounds in the activation of AKT forsphorylation in macrophages.

Examples of the inhibitory activities for the compounds of the invention are set forth in the following Table II TABLE II IC50 values of the thiazole derivatives in the Cellular Assays EXAMPLE 138 Model of cellular recruitment in the peritoneal cavity induced by thioglycollate The in vivo efficacy of the compounds of the invention to inhibit the migration of leukocytes after intraperitoneal exposure of thioglycolate to inhibit the migration of leukocytes after intraperitoneal exposure of thioglycolate can be tested with the following assay.

Experimental protocol: Female C3H mice aged 8-10 weeks were fasted for 18 hours. 15 minutes before the intraperitoneal injection of thioglycollate (1.5%, 40 ml / kg), the mice were treated orally with Piridin methylene thiazolidinediones of formula (I). The control mice received CMC / Tween as the vehicle (10 ml / kg). The mice were then sacrificed by CO 2 inhalation and the peritoneal cavity was washed twice with 5 ml ice cold PBS / 1 mM EDTA. Probe feeding was done 4 hours or 48 hours after exposure to thioglycolate to evaluate the recruitment of neutrophils or macrophages, respectively. Leukocytes (neutrophils, lymphocytes or macrophages) were counted using a Beckman Coulter®; A ° T 5diff ™. Dexamethasone was used as a reference drug.

EXAMPLE 139 Preparation of a pharmaceutical formulation The following formulation examples illustrate the representative pharmaceutical compositions according to the present invention, not being restricted thereto.

Formulation 1 - Tablets A compound of Formula (I) was mixed as a dry powder with a dry gelatin binder in an approximate weight ratio of 1: 2.

A minor amount of magnesium stearate was added as a lubricant. The mixture was formed into tablets of 240-270 mg (80-90 mg) of the active thiazole compound per tablet) in a tablet press.

Formulation 2 - Capsules A compound of Formula (I) was mixed as a dry powder with a starch diluent in an approximate weight ratio of 1: 1. The mixture was filled into 250 mg capsules (125 mg of the active thiazole compound per capsule).

Formulation 3 - Liquid A compound of Formula (I) (1250 mg), sucrose (1.75 g) and xanthan gum (4 mg) were combined, passed through an E.U.A. No. 10 mesh, and then mixed with a previously prepared solution of microcrystalline cellulose and sodium carboxymethyl cellulose (11: 89, 50 mg) in water. Sodium benzoate (10 mg), flavor, and color were diluted with water and added with shaking. Then, enough water was added to produce a total volume of 5 mL.

Formulation 4 - Tablets A compound of Formula (I) was mixed as a dry powder with a dry gelatin binder in an approximate weight ratio of 1: 2.

A minor amount of magnesium stearate was added as a lubricant. The mixture was formed into tablets of 450-900 mg (150-300 mg of the thiazole active compound) in a tablet press.

Formulation 5 - Invention A compound of Formula (I) was dissolved in an aqueous sterile buffered saline injectable medium at a concentration of about 5 mg / ml.

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A thiazole derivative according to Formula (I), (!) wherein R1 is a portion of the formula -NR5R6; R2, R3 and R5 are independently selected from H, CrC6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl; R4 is selected from H; C6 alkyl; C2-C6 alkenyl and C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, C6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl; C 1 -C 6 alkylalkoxycarbonyl and C 6 C alkylaxyloxy, R 6 is selected from d-C 6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; C6 alkylalkoxy, aryl, heteroaryl, C3-C8 cycloalkyl; C3-C8 heterocycloalkyl; C6 alkyl alkylaryl; C-C6 alkylheteroaryl; C3-C8-C3-C8-cycloalkyl alkyl; C 3 -C 8 -heterocycloalkyl alkyl, C 6 alkylacyl, CrC 6 alkylcarboxy, C 1 -C 6 alkylamino, C 6 alkylaminocarbonyl, C 6 alkylalkoxycarbonyl and C 5 -C 6 alkylacylamino, or R 5 and R 6, With the carbon atoms to which they are attached form a saturated ring or a 5-8 membered aromatic ring, optionally containing one or more heteroatoms selected from O, N and S, X is selected from O and S; as well as the isomers and mixtures of these to be used as a medicine.

2. A thiazole derivative according to Formula (1), (i) wherein R1 is a portion of the formula -NR5R6; R2, R3 and R5 are independently selected from H, CrC6 alkyl, C2-C2 alkenyl and C2-C6 alkynyl; R4 is selected from H; CrC6 alkyl; C2-C6 alkenyl and C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, C-? -C6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl; C 1 -C 6 alkylalkoxycarbonyl and C 6 C alkylaxyloxy, R 6 is selected from C 1 -C 6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; C6 alkylalkoxy, heteroaryl, C3-C8 cycloalkyl; C3-C8 C-i-C3-cycloalkyl alkyl; C 1 -C 6 alkyl heterocycloalkyl C 3 -C 8 alkyl, C 6 alkyl alkylac, C 1 C 6 alkylcarboxy, C C β alkylamino, CrC 6 alkylaminocarbonyl, C 6 alkylalkoxycarbonyl and C 5 -C 6 alkylacylamino, or R 5 and R 6, together with the carbon atoms to which they are attached, they form a saturated ring or a 5-8 membered aromatic ring, optionally containing one or more heteroatoms selected from O, N and S, X is selected from O and S; as well as these isomers.

3. The thiazole derivative according to claim 1 or 2, further characterized in that R is H.

4. The thiazole derivative according to claim 1 or 2, further characterized in that R3 is methyl.

5. The thiazole derivative according to any of the preceding claims, further characterized in that R4 is selected from C6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl.

6. The thiazole derivative according to any of the preceding claims, further characterized in that R5 is H and R6 is selected from C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6 alkylalkoxy and alkyl. of C C6 C3-C8 cycloalkyl and C-C6 alkyl C3-C8 heterocycloalkyl.

7. The thiazole derivative according to any of claims 1 to 4, further characterized in that R5 is H and R6 is selected from C6 arylalkyl and C6 heteroarylalkyl.

8. The thiazole derivative according to any of claims 1 to 4, further characterized in that R5 is H and R6 is selected from aryl and heteroaryl.

9. - The thiazole derivative according to any of claims 1 to 4, further characterized in that R5 is H and R6 is selected from phenyl and pyridine.

10. The thiazole derivative according to any of claims 1 to 4, further characterized in that R5 and R6, together with the carbon atoms to which they are attached, form a saturated ring or an aromatic ring of 5-8. members, optionally containing one or more heteroatoms selected from O, N and S.

11. The thiazole derivative according to any of claims 1 to 10, further characterized in that R1 is -NR5R6; R2 is H; R3 is methyl; R4 is selected from C -? - C6 alkyl; C2-C6 alkenyl, C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, C6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl and C6 alkylalkoxycarbonyl, R5 is H and R6 is selected from C6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; C- | -C6 alkylalkoxy, C-C6 alkylacyl; CrC6 alkylcarboxy; alkylacylamino of CrC6, alkylamino of CrC6, alkylaminocarbonyl of C C6, alkylalkoxycarbonyl of C C6; CrC6-C3-C8 cycloalkyl alkyl; and C 1 -C 6 alkylheterocycloalkyl and X is S.

12. The thiazole derivative according to any of claims 1 to 10, further characterized in that R 1 is -NR 5 R 6; R2 is H; R3 is methyl; R4 is selected from CrC6 alkyl; C2-C6 alkenyl, C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, C-C-alkyl, C2-C6-alkenyl; C2-C6 alkynyl and C 1 -C 6 alkylalkoxycarbonyl, R 5 is H and R 6 is selected from Cr C 6 alkylaryl and C 6 C alkylheteroaryl and X is S.

13. The thiazole derivative according to any of claims 1 to 10, further characterized in that R 1 is -NR5R6; R2 is H; R3 is methyl; R 4 is selected from C 1 -C 2 alkyl; C2-C6 alkenyl, C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, CrC6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl and alkylalkoxycarbonyl of CrC6, R5 is H and R6 is selected from aryl and heteroaryl and X is S.

The thiazole derivative according to any of claims 1 to 10, further characterized in that R1 is - NR5R6; R2 is H; R3 is methyl; R4 is selected from optionally substituted C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, C6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl and alkylalkoxycarbonyl of CrC6, R5 is H and R6 is selected from heterocycloalkyl and C3-C8 cycloalkyl and X is S.

15. The thiazole derivative according to any of claims 1 to 10, further characterized because R1 is -NR5R6; R2 is H; R3 is methyl; R4 is selected from optionally substituted C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from H, C-rC6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl and C6 alkylalkoxycarbonyl, R5 and R6, together with the carbon atoms to which they are attached, form a saturated ring or a 5-8 membered aromatic ring, optionally containing one or more heteroatoms selected from O, N and S, and X is S.

16. The thiazole derivative according to claim 1, further characterized by being selected from the following group: acid 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino} benzoic; 4- acid. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino} benzoic; N- [2- (benzylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-isocacetamide; N-. { 4'-methyl-2 - [(2-phenylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-metii-2-piperidin-1-yl-4,5'-b, -1,3-thiazole-2'-yl) acetamide; N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4'-methyl-2- (pyridin-2-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(4-methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-hydroxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(4-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; 4-. { [2 '- (acetylamino) -4-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino} benzamide; N- [2- ( { 4 - [(4-benzylpiperazin-1-yl) carbonyljphenyl] amino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl ] acetamide; N- (2-anilino-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (4'-methyl-2-morpholin-4-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [4'-methyl-2- (4-methylpiperazin-1-yl) -4,5'-b, -1,3-thiazol-2'-yl-acetamide; 1- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] piperidine-3-carboxylic acid methyl ester; N-. { 2- [4- (2-Hydroxyethyl) piperidin-1-ylj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2-pyrrolidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2- (3-hydroxypyrrolidin-1-yl) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [2- (tert-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(6-methoxypyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; N-. { 2 - [(6-chloropyridin-3-yl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-cyanophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-hydroxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-morpholin-4-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-piperidin-1-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-methoxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N - [(2- (cyclohexylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. {4'-methyl-2 - [(3-morpholin-4-ylpropyl) amino] -4,5'-bi-1,3-thiazol-2'-yl.} Acetamide; N-. {4'-methyl-2- [( tetrahydrofuran-2-ylmethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl.} acetamide; N-. {2 - [(2-hydroxy-2-phenylethyl) amino] 4'-methyl-4,5'-bi-1,3-thiazol-2'-yl.} Acetamide; N- [2- (1-benzofuran-5-ylamino) -4'-methyl-4, 5'-bi-1,3-thiazol-2'-yl] acetamide; N-. {2 - [(3-cyanophenyl) amino] -4'-methyl-4,5'-bi-1, 3- thiazole-2'-.l. acetamide; [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-ylformamide; ( { [2- (Allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino} -carbonyl) -beta-alaninate ethyl; N-. {4-methyl-5- [2- (pyridin-3-ylamino) -1,3-thiazol-4-yl] -1,3-oxazol-2-yl} acetamide; - {2 - [(2-fluoropyridin-3-yl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl.} Acetamide; N-. 2 - [(2-cyanoethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl.} Acetamide; N-. {2 - [(3.3 -dietoxypropyl) amino] -4'-methyl-4,5'-bi-1, 3 -thiazole-2'-il} acetamide; N-. { 2 - [(2,2-diethoxyethyl) amino] -4'-methyl-4,5'-bi- 1,3-thiazole-2'-il} acetamide; N-. { 4'-methyl-2 - [(2-oxo-2-phenylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2 { [3- (1, 3-oxazol-5-yl) phenyl] amino} -4,5'-bi-1,3-thiazole-2 ' -yl) acetamide; N- (4'-methyl-2- { [3- (1 H -tetrazol-5-yl) phenyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl acetamide; N- (4'-methyl-2- { [4- (1 H -tetrazol-5-yl) phenyl] amino.} -4,5'-bi-1,3-thiazole-2'-; l) acetamide; N-. { 4'-Methyl-2- [2- (1 H-tetrazol-5-yl) -ethylamino] - [4,5 '] -thiazolyl-2'-yl} -acetamide; N- (2- {[3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl] amino} -4'-metii-4,5'-bi-1, 3 -thiazol-2'-yl) acetamide; "N- { [3- (5-amino-1, 3,4-thiadiazol-2-yl) phenyl] amino.}. 4'-methyl-4, 5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2 '- (acetylamino) -4'-methyl-4,5'-b- 1, 3-thiazole-2-yl -beta-alanine; 5- (2- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} ethyl) - 1, 3,4-oxadiazole-2-olate, 4- {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino}. butanoic, N- (2- { [3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) propyl] amino.}. 4'-methyl-4,5'-bi-1 , 3-thiazol-2'-yl) acetamide; 3 { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} .-N-hydroxybenzamide: 3- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} - N-hydroxybenzenecarboximide N- (2- {[3- (5-hydroxy-1, 2,4-oxadiazol-3-yl) phenyl] amino} -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; N- [2- (. {3 - [(Z) - (2,4-dioxo-1,3-thiazolidin-5-ylidenemethyl] phenyl}. amino) -4'-methyl-4,5'-bi-1,3-thiazole-2 '-yljacetamide; N- [4'-methyl-2- ( { 4 - [(pyridin-2-ylamino) sulfonyljphenyl]. Amino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (2- {[2- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-b¡-1,3-thiazol-2'-yl) acetamide; N- (2- {[3- (hydroxymethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[4- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2- ( { 3 - [(2-hydroxyethyl) sulfonyl] phenyl} amino) -4'-methyl-4,5'- bi-1, 3-thiazol-2'-yl] acetamide; N- [2- ( { 4 - [(dimethylamino) sulfonyl] phenyl} amino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (2- {[[3- (aminosulfonyl) pheny] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(2-chloropyridin-4-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [4'-methyl-2- (. {4 - [(methylamino) sulfonylj-phenyl} amino) -4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- (5- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Pyridin-2-yl) acetamide; N- [2- (2,3-dihydro-1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4'-methyl-2- { [2- (1-methylpyrrolidin-2-yl) ethyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N-. { 4'-methyl-2 - [(2-pyrrolidin-1-ylethyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2 { [3- (2-oxopyrrolidin-1-yl) propyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N- (2- { [2- (acetylamino) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[2- (dimethylamino) ethyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl) acetamide; N-. { 2 - [(2-hydroxyethyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamida; N- (2- { [2- (4-hydroxyphenyl) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[[3- (dimethylamino) propyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(3-hydroxypropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { [3- (1 H-imidazol-1-yl) propyljamino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N -3- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alaninamide; N-. { 4'-methyl-2 - [(2-methylprop-2-en-1-yl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2 - [(2-hydroxyphenyl) amino] -4'-methyl-4,5'-b- 1, 3-thiazol-2'-yl.} Acetamide; N-. {2- [2- (6-fluoropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl.} Acetamide; N- { 2 - [(4- cyanophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl.} acetamide; N-. {2 - [(6-cyanopyridin-3-yl) amino] ] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl.} Acetamide; N-. {2 - [(3- methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamida; 3-. { [2'- (acetylamino) -4'-methyl-4,5'-b'-1,3-thiazol-2-yl] amino} benzamide; N-. { 4'-methyl-2 - [(2-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamida; N-. { 4'-methyl-2 - [(3-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [4'-methyl-2- (quinolin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [4'-methyl-2- (quinolin-5-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4'-methyl-2- (quinolin-6-ylammon) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [2- (Cyclopentylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [2- (cyclopropylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-carboxytamide; N-. { 4'-methyl-2 - [(pyridin-3-ylmethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-Hydroxybutyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2-. {[[3- (methylsulfonyl) phenyl] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 4'-methyl-2 - [(3-pyrrolidin-1-ylpropyl) amino] -4,5'-bi-1,3-thiazole-2'-yl} acetamida; N-. { 2 - [(1,1-dioxido-1-benzothien-6-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[[(1-ethylpyrrolidin-2-yl) methyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(Cyanomethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2- (isobutylaminoH'-metiM.d'-bi-I .S-thiazole-yl-acetamide; N-. {2 - [(2,2-dimethylpropyl) amino] -4'-methyl-4 , 5'-bi-1, 3-thiazoI-2'-yl.} Acetamide, N - ([(cis) -2- (hydroxymethyl) cyclohexyl] amino} -4'-methyl-4,5'-bi -1, 3-thiazol-2'-yl) acetamide; N- { [(Trans) -2- (hydroxymethyl) cyclohexyl] amino.}. 4'-methyl-4.5'-bi-1, 3- thiazol-2'-yl) acetamide; N- [2- (sec-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 4'-methyl-2 - [(pyridin-4-ylmethyl) amino] -4,5'-b, -1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2 { [4- (morpholin-4-ylsulfonyl) phenyl] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2- ( { 3 - [(butylamino) sulfonyl] phenyl} amino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(c.propylmethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2- (Cyclobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [2- (2,3-dihydro-1 H -inden-2-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4'-methyl-2 { [2- (methylsulfonyl) phenyl] amino.} -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4 '-methyl-2- { [2- (1 H-1, 2,4-triazol-1-yl) ethyl] amino3-4,5'-bi-1,3-thiazole-2'-yl) acetamide; N- (2- {[3- (1-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl) acetamide (4- {[[2'- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) methyl acetate; N- ( 4-. {- [methyl 2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) -beta-alaninate; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-b- 1, 3-thiazol-2-yl] amino.} Benzoyl) glycinate methyl; - (3- {[2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) propanoate of methyl; (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} phenyl) propanoic; 4- { [2' - (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} - methyl butanoate; (3- {[2 '- (acetylamino) -4 methyl-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} phenyl) acetate; N- [2- (allylamino) -4'-methyl-4,5'- bi-1, 3-thiazoI-2'-yl] urea; N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl-urea; N- (4'-methyl-2-piperidin-1 -yl-4,5'-bi-1,3-thiazol-2'-yl) urea; N- (2-anilino-4'-methyl-4,5'-b- 1, 3-thiazol-2'-yl) urea; N-. { 2 - [(4-hydroxyphenyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} urea; N- [2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} phenyl) acetic acid; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) -beta-alanine; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) glycine; 3- (3 { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) propanoic acid; N-. { 2 - [(4-Ethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(4- methylphenyl) amino] -4,5'-bi-1,3-thiazole-2'-iI} acetamide; N-. { 2 - [(4- {[[4,6-d.methylpyr] mymid] -2-yl) amino] sulfonyl} phenyl) amino] -4'-methyl-4,5-bi-1 , 3-thiazole-2'-il} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl, phenyl) aminoj-4,5'-b, -1,3-thiazole-2 ' -il} acetamide; N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-ylpropanamide; N-. { 2 - [(4- {[[2,6-d¡methoxypyrimidin-4-yl) amino] sulfonyl} phenyl) -amino] -4'-methyl-4,5'-bi-1, 3 -thiazole-2'-il} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl] phenyl] amino] -4,5'-bi-1, 3-thiazole-2'-il} propanamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl) aminoj-4, -methyl-4,5'-bi-1,3-thiazole -2'-il} propanamide; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} phenyl) -acetamide; N-. { 2- (4-aminophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-Ethylphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-methylphenyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-Bromophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[4- (aminosulfonyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(2,5-dimethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-acetylfenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- (2- {[4- (dimethylamino) phenylamino} -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl) acetamide.

17. The thiazole derivative according to claim 2, further characterized in that it is selected from the following group: N- [4'-methyl-2-piperidin-1-yl-4,5'-bi-1, 3- thiazol-2'-yl) acetamide; • N- [4'-methyl-2-pyridin-3-ylammon) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4-methyl-2- (pyridin-2-ylammon) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4'-methyl-2-morpholin-4-yl-4,5'-bi-1,3-thiazole-2'- il) acetamide; N- [4'-methyl-2- (4-methyl-piperazin-1-yl) -4,5'-bi-1,3-thiazol-2'-yl-acetamide; Methyl 1 - [2- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] piperidine-3-carboxylate; N-. { 2- [4- (2-hydroxyethyl) piperidin-1-yl] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2-pyrrolidin-1-yl-4,5'-bi-1,3-thiazoI-2'-yl) acetamide; N- [2- (3-hydroxypyrrolidin-1-yl) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [2- (tert-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(6-methoxy-pyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; N-. { 2 - [(6-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4-methyl-2 - [(2-morpholin-4-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-piperidin-1-ylethyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-methoxyethyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamida; N- [2- (cyclohexylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-alkylamide; N-. { 4'-methyl-2 - [(3-morpholin-4-ylpropyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2- [(tetrahydrofuran-2-ylmethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2- (1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] formamide; N-. { 4-Methyl-5- [2- (pyridin-3-ylamino) -1,3-thiazol-4-yl-1, 3-oxazol-2-yl} acetamide; N-. { 2 - [(2-fluoropyridin-3-yl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-Cyanoethyl) aminoj-4'-methyI-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3,3-diethoxypropyl) amino] -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2,2-diethoxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-oxo-2-phenylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alanine; 4- acid. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -butanoco; N-. { 2- [(2-chloropyridin-4-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (5-. {2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} pyridin-2-yl) acetamide; N- [2- (2,3-dihydro-1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4'-methyl-2- { [2- (1-methylpyrrolidin-2-yl) ethyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N-. { 4'-methyl-2 - [(2-pyrrolidin-1-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2 { [3- (2-oxopyrrolidin-1-yl) propyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N- (2- { [2- (acetylamino) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[[2- (dimethylamino) ethyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(2-hydroxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; N- (2- {[[3- (dimethylamino) propyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(3-hydroxypropyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N -3- [2 '- (acetylamino) -4 * -methyl-4,5'-bi-1,3-thiazol-2-ylj-beta-alaninamide; N-. { 2 - [(6-cyanopyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [4'-methyl-2- (quinolin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4'-methyl-2- (quinolin-5-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4'-methyl-2- (quinolin-6-ylamino) -4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [2- (Cyclopentylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [2- (cyclopropylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(4-hydroxybutyl) amino] -4'-methyl-4,5'-b, -1,3-thiazole-2'-yl} acetamide; N-. { 4'-methyl-2 - [(3-pyrrolidin-1-ylpropyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(1,1-Dioxy-1-benzothien-6-yl) aminoj-4'-methyl-4,5'-b, -1,3-thiazol-2'-yl} acetamide; N- (2- {[[(1-ethylpyrrolidin-2-yl) methyl] amino} -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(Cyanomethyl) amino] -4'-methyl-4,5'-b, -1,3-thiazole-2'- il} acetamide; N- [2- (isobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(2,2-dimethylpropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- { [(Cis) -2- (hydroxymethyl) cyclohexyl] amino} -4'-methylene-4,5'-bi-1,3-thiazole-2'- il) acetamide; N- (2- { [(Trans) -2- (hydroxymethyl) cyclohexyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2- (sec-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 2 - [(cyclopropylmethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2- (Cyclobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [2- (2,3-dihydro-1 H -inden-2-ylamino) -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl-acetamide; 4- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} methyl butanoate; N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] urea; N- (4'-methyl-2-piperidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) urea.

18. The use of a thiazole derivative according to formula (I): 0) wherein R1 is a portion of the formula -NR5R6; R2, R3 and R5 are independently selected from H, CrC6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl; R4 is selected from H; C-rC6 alkyl; C2-C6 alkenyl and C2-C6 alkynyl and -NR8R9, wherein R8 and R9 are independently selected from CrC6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl; R6 is selected from H, C C6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; C 1 -C 7 alkylalkoxy, aryl, heteroaryl, C 3 -C 8 cycloalkyl; C3-C8 heterocycloalkyl; A C6 arylalkyl; C-C6 alkylheteroaryl; C3-C6-C3-C8-cycloalkyl and C3-C8-C6-C6-alkylcycloalkyl, or R5 and R6, together with the carbon atoms to which they are attached, form a saturated, partially unsaturated or aromatic ring of 8 members, optionally containing one or more heteroatoms selected from O, N and S, X is selected from O and S; as well as the isomers and mixtures thereof for the preparation of medicaments for the prophylaxis and / or treatment of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplants, rejection of grafts or lung injuries.

19. The use as claimed in claim 18, wherein said diseases are selected from the group including Alzheimer's disease, Huntington's disease, CNS trauma, stroke or ischemic conditions.

20. The use as claimed in claim 18, wherein the diseases are selected from the group including multiple sclerosis, psoriasis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, inflammation of the lung, thrombosis or infection / inflammation of the brain, such as meningitis or encephalitis.

21. - The use as claimed in claim 18, wherein the diseases are selected from the group that includes atherosclerosis, cardiac hypertrophy, cardiac myocyte dysfunction, elevated blood pressure or vasoconstriction.

22. The use as claimed in claim 18, wherein the diseases are selected from the group including chronic obstructive disease, anaphylactic shock fibrosis, psoriasis, allergic diseases, asthma, stroke or ischemic conditions, ischemia-reperfusion, aggregation / activation of platelets, atrophy / hypertrophy of skeletal muscle, recruitment of leukocytes in cancerous tissue, angiogenesis, invasion by metastasis, in particular melanoma, Kaposi's sarcoma, acute and chronic bacterial and viral infections, sepsis, graft rejection, glomerulosclerosis, glomerulonephritis, progressive renal fibrosis, endothelial and epithelial lesions in the lung or, in general, inflammation of the airways of the lung.

23. The use as claimed in any of claims 18 to 22, for the modulation, in particular, for the inhibition of the activity of the PI3 kinase.

24. The use as claimed in claim 23, wherein the PI3 kinase is a PI3? Kinase.

25. The use as claimed in claims 18 to 24, wherein the compound is selected from the group: acid 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino} benzoic; 4- acid. { [2 '- (acetylamino) -4'-methyl- 4,5'-bi-1,3-thiazol-2'-yl] amino} benzoic; N- [2- (benzylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 4'-methyl-2 - [(2-phenylethyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- (4'-methyl-2-p-peridin-1-yl-4,5'-b, -1,3-thiazol-2'-yl) acetamide; N- [2- (allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [4'-methyl-2- (pyridin-2-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(4-methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-hydroxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-meth1l-2 - [(4-nitrophenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl-acetamide; 4-. { [2 '- (acetylamino) -4-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino} benzamide; N- [2- ( { 4 - [(4-benzylpiperazin-1-yl) carbonyl] phenyl} amino) -4'-methyl-4,5'-bi-1,3-thiazole-2 ' -yl] acetamide; N- (α-amino-4'-methyl-4,5'-b, -1,3-thiazol-2'-yl) acetamide; N- (2-anilino-4'-methyl-4,5'-b, -1,3-thiazol-2'-yl) acetamide; N- (4'-methyl-2-morpholin-4-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [4'-methyl-2- (4-methylpiperazin-1-yl) -4,5'-b- 1, 3-thiazol-2'-yl] acetamide; 1 - [2 '- (Acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] piperidin-3-carboxylic acid methyl ester; N-. { 2- [4- (2-hydroxyethyl) p.peridin-1-ylj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2-pyrrolidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2- (3-hydroxypyrrolidin-1 -yl) -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl-acetamide; N- [2- (tert-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 2 - [(6-methoxypyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(6-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-cyanophenyl) amino-4'-methy1-4,5'-b, -1,3-thiazol-2'-yl} acetamida; N-. { 2 - [(4-chlorophenyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-chlorophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2- methoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; N-. { 2 - [(3-chlorophenyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-hydroxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazole-2'-i1} acetamide; N-. { 4'-methyl-2 - [(2-morpholin-4-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-piperidin-1-ylethyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-methoxyethyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N - [(2- (cyclohexylamino) -4'-methyl-4,5'-bi-1,3-thiazole-2'-yl-acetamide; N-. {4'-methyl-2 - [(3-morpholine 4-ylpropyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl.} Acetamide; N-. {4'-methyl-2- [(tetrahydrofuran-2-ylmethyl) aminoj -4,5'-bi-1, 3-thiazol-2'-yl.} Acetamide; N-. { 2 - [(2-hydroxy-2-phenylethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2- (1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 2 - [(3-cyanophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] formamide; N- ( { [2- (Allylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] amino.} - carbonyl) -beta-alaninate ethyl; N-. { 4-Methyl-5- [2- (pyridin-3-ylamino) -1,3-thiazol-4-yl-1, 3-oxazol-2-yl} acetamide; N-. { 2 - [(2-fluoropyridin-3-yl) aminoj-4'-methyl-4,5'-bi-1,3-thiazole-2'-yl} acetamide; N-. { 2 - [(2-Cyanoethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3,3-diethoxypropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2,2-diethoxyethyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-oxo-2-phenylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-chloropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2 { [3- (1, 3-oxazol-5-yl) phenyl] amino} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N- (4'-methyl-2 { [3- (1 H-tetrazol-5-yl) phenyl] amino.} -4,5'-bi-1,3-thiazole-2'-! l) acetamide; N- (4'-methyl-2 ~ { [4- (1 H-tetrazol-5-yl) phenyl] amino.} -4,5'-bi-1,3-thiazole- 2'-yl) acetamide; N-. { 4'-Methyl-2- [2- (1 H-tetrazol-5-yl) -ethylamino] - [4,5 '] -thiazolyl-2'-yl} -acetamide; N- (2- {[3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) phenyl] amino} -4'-methyl-4,5'-bi-1, 3 -thiazole-2'-yl) acetamide; N-. { [3- (5-amino-1, 3,4-thiadiazol-2-yl) phenyljamino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-ylj-beta-alanine; 5- (2- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Ethyl) -1, 3.4 -oxadiazole-2-olate; 4- acid. { [2 '- (acetylamino) -4'-methyl-4,5'-b, -1,3-thiazol-2-yl-amino} butanoic; N- (2- { [3- (5-hydroxy-1, 3,4-oxadiazol-2-yl) propylamine.) -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} -N-hydroxybenzamide; acid 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} -N-hydroxybenzenecarboximide; N- (2- { [3- (5-hydroxy-1, 2,4-oxadiazol-3-yl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole -2'-il) acetamide; N- [2- ( { 3 - [(Z) - (2,4-dioxo-1, 3-thiazolidin-5-ylidenemethyl] phenyl} amino) -4'-methyl-4,5'- bi-1, 3-thiazol-2'-yl-acetamide; N- [4'-methyl-2- (. {4 - [(pyridin-2-ylamino) sulfonylphenyl] amino) -4, 5'-bi- 1, 3-thiazol-2'-yl] acetamide; N- (2- {[2- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4,5 '-bi-1, 3-thiazol-2'-yl) acetamide, N- (2- {[[3- (hydroxymethyl) phenyl] amino} -4'-methyl-4,5'-bi- 1,3-thiazol-2'-yl) acetamide, N- (2- {[[4- (2-hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl) acetamide; N- [2- (. {3 - [(2-hydroxyethyl) sulfonyl] phenyl} amino) -4'-methyl-4,5'-bi -1, 3-thiazol-2'-yl] acetamide, N- [2- (. {4 - [(dimethylamino) sulfonyljphenyl] amino) -4'-methyl-4,5'-bi-1, 3-thiazol-2'-yl] acetamide; N- (2- {[[3- (aminosulfonyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazole; 2'-yl) acetamide: N- {2 - [(2-chloropyridin-4-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl. acetamide; N- [4'-methyl-2- (. {4 - [(methylamino) sulfonyl] -phenyl} amino) -4,5'-bi-1,3-t-azole-2 '-yl] acetamide, N- (5- { [2' - ( acetyl amino) -4'-methyl- 4,5'-bi-1,3-thiazol-2-yl] amino} pyridin-2-yl) acetamide; N- [2- (2,3-dihydro-1-benzofuran-5-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4'-methyl-2- { [2- (1-methylpyrrolidin-2-yl) ethyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N-. { 4 '~ methyl-2 - [(2-pyrrolidin-1-ylethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2 { [3- (2-oxopyrrolidin-1-yl) propyl] amino.} -4,5'-bi-1,3-thiazole-2'-yl) acetamide; N- (2- { [2- (acetylamino) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[[2- (dimethylamino) ethyl] -amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(2-hydroxyethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamida; N- (2- { [2- (4-hydroxyphenyl) ethyl] amino.} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- (2- {[[3- (dimethylamino) propyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(3-hydroxypropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { [3- (1 H-imidazol-1-yl) propyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-3- [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] -beta-alaninamide; N-. { 4'-methyl-2 - [(2-methylprop-2-en-1-yl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-hydroxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(6-fluoropyridin-3-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-cyanophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(6-cyanopyridin-3-yl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-methoxyphenyl) aminoj-4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; 3-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} benzamide; N-. { 4'-methyl-2 - [(2-nitrophenyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(3-nitrophenyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [4'-methyl-2- (quinolin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [4'-methyl-2- (quinolin-5-ylamino) -4,5'- bi-1, 3-thiazol-2'-yl-acetamide; N- [4'-methyl-2- (quinolin-6-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- [2- (Cyclopentylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [2- (cyclopropylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N-. { 4'-methyl-2 - [(pyridin-3-ylmethyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-Hydroxybutyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2-. {[[3- (methylsulfonyl) phenyl] amino} -4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 4'-methyl-2 - [(3-pyrrolidin-1-ylpropyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(1,1-dioxido-1-benzothien-6-yl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[[(1-ethylpyrrolidin-2-yl) methyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(Cyanomethyl) amino] -4'-methy1-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- [2- (S-butylamino) -4'-methyl-4,5'-b, -1,3-thiazol-2'-yl] acetamide; N-. { 2 - [(2,2-dimethylpropyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { [(cis) -2- (hydroxymethyl) cyclohexyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { [(trans) -2- (hydroxymethyl) cyclohexyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N- [2- (sec-butylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N-. { 4'-meth1l-2 - [(pyridin-4-ylmethyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (4'-methyl-2- { [4- (morpholin-4-ylsulfonyl) phenyl] amino} -4,5'-b, -1,3-thiazol-2'-yl) acetamide; N- [2- ( { 3 - [(butylamino) sulfonyl] phenyl.}. Amino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetam gives; N-. { 2 - [(cyclopropylmethyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide-, N- [2- (cyclobutylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-acetamide; N- [2- (2,3-dihydro-1 H -inden-2-ylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4'-methyl-2 { [2- (methylsulfonyl) phenyl] amino.} -4,5'-bi-1,3-thiazol-2'-yl] acetamide; N- (4 '-methyl-2- { [2- (1 H-1, 2,4-triazol-1-yl) ethyl] amino3-4,5'-bi-1,3-thiazole-2'-yl) acetamide, N- (2- { [3- (1- hydroxyethyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; (4- {[[2'- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) -acetate methyl; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) -beta-alaninate methyl; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) glycinate methyl; 3- (3- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) propanoate methyl; 3- (4 { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} phenyl) propanoic acid; 4-. { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} methyl butanoate; (3- {[2 '- (Aethylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino} phenyl) -acetate methyl; N- [2- (allylamino) -4'-methyl-4,5'-b, -1,3-thiazole-2'-yl-urea; N- [4'-methyl-2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] urea; N- (4'-methyl-2-piperidin-1-yl-4,5'-bi-1,3-thiazol-2'-yl) urea; N- (2-anilino-4'-methyl-4,5'-b- 1, 3-thiazol-2'-yl) urea; N-. { 2 - [(4-hydroxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl-urea; N- [2- (pyridin-3-ylamino) -4,5'-bi-1,3-thiazol-2'-yl] acetamide; (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} phenyl) acetic acid; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-b- 1, 3-thiazol-2-yl] amino.} Benzoyl) -beta-alan na N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Benzoyl) glycine; 3- (3 { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl-amino} phenyl) propanoic acid; N-. { 2 - [(4-Ethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamida; N-. { 4'-methyl-2 - [(4-methylphenyl) amino] -4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) amino] sulfonyl} phenyl) amino] -4'-methyl-4,5-bi-1,3-thiazole -2'-ii} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl} phenyl) aminoj-4,5'-bi-1,3-thiazole-2'- il} acetamide; N- [2- (allylamino) -4'-methyl-4,5 * -bi-1,3-thiazole-2'-ylpropanamide; N-. { 2 - [(4- {[[2,6-d¡methoxypyrimidin-4-yl) amino] sulfonyl} phenyl) - aminoj-4'-methyl-4,5'-bi-1,3-tiazole-2'-yl} acetamide; N-. { 4'-methyl-2 - [(4. {[[(5-methylisoxazol-3-yl) amino] sulfonyl, phenyl) amino] -4,5'-bi-1,3-thiazole-2 ' -il} propanamide; N-. { 2 - [(4- {[[4,6-dimethylpyrimidin-2-yl) aminojsulfonyl} phenyl) aminoj-4, -methyl-4,5'-bi-1,3-thiazole-2'- L} propanamida; N- (4- { [2 '- (acetylamino) -4'-methyl-4,5'-bi-1,3-thiazol-2-yl] amino.} Phenyl) -acetamide; N-. { 2- (4-aminophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(2-Ethylphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 4'-methyl-2 - [(2-methylphenyl) aminoj-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(4-Bromophenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[4- (aminosulfonyl) phenyl] amino} -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl) acetamide; N-. { 2 - [(2,5-dimethoxyphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N-. { 2 - [(3-Acetylphenyl) amino] -4'-methyl-4,5'-bi-1,3-thiazol-2'-yl} acetamide; N- (2- {[4- (dimethylamino) phenylamino} -4'-methyl-4,5'-bibl-1,3-thiazol-2'-yl) acetamide.

26. A pharmaceutical composition, characterized in that it contains at least one derivative according to any of claims 1 to 17 and a pharmaceutically acceptable carrier, diluent or excipient thereof.