MXPA06007440A - PYRROLO[2,3-b]PYRIDINE DERIVATIVES ACTIVE AS KINASE INHIBITORS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM - Google Patents

Abstract

Compounds which are pyrrolo[2,3-b]pyridine derivatives or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed;these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, cell proliferative disorders, Alzheimer's disease, viral infections, auto-immune diseases and neurodegenerative disorders;also disclosed is a process under SPS conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

Description

DERIVATIVES OF PLRROL? R2,3-b1PiRlDlNA ACTIVE AS INHIBITORS OF KINASE, PROCEDURE FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT COMPRISE THEM INTERREFERENCE TO RELATED REQUESTS The present application claims the benefit of British Patent Application Number 0330043.1 filed on December 24, 2003.

FIELD OF THE INVENTION The present invention relates to pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors and, more particularly, relates to pyrrolo [2,3-b] pyridine derivatives further substituted at the 5-position, with a process for their preparation, with combinatorial libraries thereof, with pharmaceutical compositions comprising them and with their use as therapeutic agents, particularly in the treatment of diseases related to poorly regulated protein kinases.

BACKGROUND OF THE INVENTION The malfunction of protein kinases (PK) is the key element of numerous diseases. A large amount of the oncogenes and proto-oncogenes involved in human cancers code for PK. Increased PK activities are also implicated in many non-malignant diseases such as benign prostatic hyperplasia, familial adenomatosis, polyposis, neurofibromatosis, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis and postsurgical stenosis and restenosis. PKs have also been implicated in inflammatory conditions and in the multiplication of viruses and parasites. PKs are also considered to play a major role in the pathogenesis and development of neurodegenerative disorders. For a general reference to malfunction or lack of PK regulation, see, for example, Current Opinion in Chemical Biology 1999, 3, 459-465.

BRIEF DESCRIPTION OF THE INVENTION An object of the invention is to provide compounds that are useful in therapy as agents against a group of diseases caused by, and / or related to, a poorly regulated activity of the protein kinase.

Another objective is to provide compounds that are endowed with protein kinase inhibitory activity. The present inventors have now discovered that some pyrrolo [2,3-b] pyridine derivatives are endowed with protein kinase inhibitory activity and therefore may be useful in therapy in the treatment of diseases related to poorly regulated protein kinases. More specifically, the compounds of this invention are useful in the treatment of a variety of cancers including, but not limited to: carcinoma such as cancer of the bladder, breast, colon, kidney, liver, lung that includes lung cancer of small cells, esophagus, gallbladder, ovary, pancreas, stomach, cervix, thyroid, prostate and skin that include squamous cell carcinoma; hematopoietic tumors of the lymphoid line including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgking's lymphoma, non-Hodgkin's lymphoma, hairy cell leukemia and Burkett's lymphoma, myeloid line hematopoietic tumors including leukemia acute and chronic myelogens, myelodysplastic syndrome and promyelocytic leukemia; tumors of mesenchymal origin that include fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system that include astrocytoma, neuroblastoma, glioma and schwannomas; other tumors that include melanoma, seminoma, keratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, follicular thyroid cancer, and Kaposi's sarcoma.

Due to the key role of PKs in the regulation of cell proliferation, these pyrrolo [2,3-b] pyridine compounds are also useful in the treatment of a variety of proliferative cell disorders such as, for example, benign prostatic hyperplasia, familial adenomatosis, polyposis, neurofibromatosis, psoriasis, proliferation of vascular smooth cells associated with asterosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis and postoperative stenosis and restenosis. In addition, the compounds of the invention are useful in the treatment of Alzheimer's disease, as suggested by the fact that cdkd is involved in the phosphorylation of tau protein (J. Biochem., 17, 741-749, 1995). . The compounds of this invention, as modulators of apoptosis, are useful in the treatment of cancer, viral infections, prevention of the development of AIDS in HIV-infected individuals, autoimmune diseases and neurodegenerative disorders. The compounds of this invention are also useful for inhibiting tumor angiogenesis and metastasis, as well as the treatment of rejection of organ transplantation and reverse rejection disease. The compounds of the invention also act as an inhibitor of other protein kinases, for example cylindrical kinases (cdk) such as cdk2 and cdkd, protein kinase C in different isoforms, Met, PAK-4, PAK-5, ZC-1, STLK-2, DDR-2, Aurora 1, Aurora 2, Bub-1, PL, Chk1, Chk2, HER2, rafl, MEK1, MAPK, EGF-R, PDGF-R, FGF-R, IGF-R, PI3K, Wheel kinase, Src, Abl, Akt, MAPK, ILK, MK-2, IKK-2, Cdc7, Nek and therefore is effective in the treatment of diseases associated with other protein kinases. The compounds of the invention are also useful in the treatment and prevention of alopecia induced by radiotherapy or induced by chemotherapy.

DETAILED DESCRIPTION OF THE INVENTION Pyrrolopyridine derivatives are widely known in the art. As an example, the compound 3-carboxamido pyrrolo [2,3-b] pyridine has been reported as a synthetic intermediate in Chemical Abstracts C.A. 93 (1980): 168162. Some other N-substituted pyrrolopyridine 3-carboxamide derivatives additionally by indolyl groups are described as 5-HT2C / 2B antagonists (see WO 96/11929); the above 3-carboxamide derivatives further substituted by N- (isoquinolylethylcyclohexyl) groups are described as antipsychotic agents (see WO 00/24717, WO 00/21951, WO 00/21950, WO 98/50364); 3-carboxamidopyrrolopyridine compounds N-substituted by azabicyclo rings are also described as synthetic intermediates in the preparation of tropyl derivatives having antitussive properties.

In addition, the pyrrolopyridine 3-hydrazide derivatives are described as synthetic intermediates for preparing more complex protein kinase inhibitors, as reported in WO 00/71537. The 7-azaindoles as inhibitors of N-terminal C-JUN kinases and therefore useful in the treatment of neurodegenerative disorders are also described in WO 03/082868. However, none of the pyrrolopyridine derivatives of the prior art results in presenting an additional amino group, optionally additionally functionalized in the 5-position of the pyrrolopyridine backbone. The pyrrolo [2,3-b] pyridine compounds of broad general formula endowed with therapeutic activity also include protein kinase inhibitory activity and are also described in WO 00/71537; WO 01/01986; WO 01/58869; WO 99/32111; WO 99/37637; WO 97/03069; WO 99/58496 and WO 95/28400. The 3-alkenylpyrrolo [2,3-b] pyridine derivatives as inhibitors of protein kinase are also described in WO 01/98299 in the name of the applicant itself. Accordingly, the present invention provides a method for treating diseases caused by and / or associated with altered protein kinase activity, for administration to a mammal in need thereof, an effective amount of a compound represented by the formula (I) wherein R is selected from the group consisting of -Ra, -CORa, -CONRa, -S02Ra or -COORa; R-i is a group -NRcRd or -ORc; wherein Ra, Rb, Rc and Rd are the same or different and are each hydrogen or an optionally substituted group, which is selected from linear or branched alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms linear or branched carbon, linear or branched alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms or cycloalkylalkyl of 1 to 6 carbon atoms, aryl or arylalkyl of 1 to 6 carbon atoms or heterocycle or heterocycloalkyl of 1 to 6 carbon atoms or, taken together with the nitrogen atom to which they are attached, either Ra and Rb as well as Rc and Rd can form an optionally substituted 4- to 7-membered heterocycle, which optionally contains a heteroatom or a group additional heteroatom that is selected from S, O, N or NH; or isomers, tautomers, carriers, metabolites, prodrugs and pharmaceutically acceptable salts thereof. In a preferred embodiment of the method described in the foregoing, the disease caused by and / or associated with an altered protein activity kinase is selected from the group consisting of cancer, proliferative cell disorders, Alzheimer's disease, viral infections, autoimmune diseases and neurodegenerative disorders. The specific types of the compounds of the present invention are useful for treatment and include, but are not limited to, carcinoma, squamous cell carcinoma, hematopoietic tumors of the myeloid or lymphoid lines, tumors of mesenchymal origin, tumors of the central nervous system and peripheral, melanoma, seminoma, keratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, follicular thyroid cancer and Kaposi's sarcoma. In another preferred embodiment of the method described in the foregoing, the proliferative cell disorder is selected from the group consisting of benign prostatic hyperplasia, familial adenomatosis, polyposis, neurofibromatosis, psoriasis, proliferation of vascular smooth cells related to atherosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis and postoperative stenosis and restenosis. The present invention further provides a compound represented by the formula (I) where R is selected from the group consisting of -Ra, -CORa, -CONRaRb, -S02Ra or -COORa; RT is a group -NRcRd or -ORc; wherein Ra, Rb, Rc and Rd are the same or different and each is independently hydrogen or an optionally substituted group, which is selected from linear or branched alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 atoms linear or branched carbon or linear or branched 2 to 6 carbon atoms alkynyl, cycloalkyl of 3 to 6 carbon atoms or cycloalkylalkyl of 1 to 6 carbon atoms, aryl or arylalkyl of 1 to 6 carbon atoms or heterocycle or heterocycloalkyl from 1 to 6 carbon atoms or, taken together with the nitrogen atom to which they are attached, either Ra and Rb as well as Rc and Rd can form a heterocycle of 4 to 7 members optionally substituted, which optionally contains a heteroatom or an additional heteroatom group which is selected from S, O, N and NH; or isomers, tautomers, carriers, metabolites, prodrugs and pharmaceutically acceptable salts thereof. Unless otherwise specified, when reference is made to the compounds of formula (I) by themselves, as well as with any pharmaceutical composition thereof or any therapeutic method of treatment comprising them, the present invention includes the entire of the hydrates, solvates, complexes, metabolites and prodrugs of the compounds of this invention. The prodrugs are any compound covalently linked which releases the medicament of active origin, according to formula (I) in vivo. If a chiral center or other form of an isomeric center is present in a compound of the present invention, all forms of said isomer or isomers, including the enantiomers and diastereomers, are intended to be covered therein. The compounds containing a chiral center can be used as a racemic mixture or as an enantiomerically enriched mixture, or the racemic mixture can be separated using well-known techniques and a single enantiomer can be used alone. In cases where there may be compounds in tautomeric form, such as the keto-enol tautomers, each tautomeric form is contemplated as being included within this invention either existing in equilibrium or predominantly in one form. In the present description, unless otherwise indicated, the term straight or branched alkyl of 1 to 6 carbon atoms is intended to be any group such as, for example, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, secbutyl, tertbutyl, n-pentyl, n-hexyl and the like. Examples of linear or branched alkenyl or alkynyl of 2 to 6 carbon atoms include any of the unsaturated alkenyl or alkynyl groups with from 2 to 6 carbon atoms, for example including but not limited to vinyl, halo, 1- propenyl, isopryloyl, 1-, 2- or 3-butenyl, pentenyl, hexenyl, ethynyl, 1- or 2-propynyl, butynyl, pentynyl, hexynyl and the like.

The term cycloalkyl of 3 to 6 carbon atoms is defined as any of the 3- to 6-membered carbocyclic rings, such as, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl and the like. Unless otherwise specified, by the term "aryl" is meant a monocyclic or bicyclic, either a carbocycle as well as a heterocycle with one or two ring portions either fused or linked together by single bonds, wherein at least one of the carbocyclic or heterocyclic rings is aromatic; but which also includes 1 or 2 ring portions, where all of the rings are aromatic. Unless otherwise specified, the heterocycle is a 4 to 7 membered ring with 1 to 3 heteroatoms or heteroatom groups which are selected from N, NH, O, and S. The non-limiting examples of aryl groups of the invention are, for example, phenyl, indanyl, biphenyl, V- or 3-naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, imidazopyridyl, 1,2-methylenedioxyphenyl, thiazolyl, isothiazolyl, pyrrolyl, pyrrolylphenyl, furyl, phenylfuryl, benzotetrahydrofuranyl, oxazolyl, isoxazolyl, pyrazolyl, chromenyl, thienyl, benzothienyl, isoindolinyl, benzoimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, benzofurazanyl, 1, 2,3- triazolyl, 1-phenyl-1, 2,3-triazolyl and the like. The term heterocycle (e.g. heterocyclyl) or heterocyclic group is a 4- to 7-membered heterocycle which embraces aromatic heterocyclic groups also known as heteroaryl groups and currently covered by the term aril. As well as the saturated or partially unsaturated heterocyclic groups having from 1 to 3 ring heteroatoms or heteroatom groups selected from N, NH, O and S. Examples of these 4 to 7 membered heterocyclic groups are, example, 1,3-dioxolane, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidin, pyrazoline, piperidine, piperazine, morpholine, tetrahydrofuran, hexamethyleneimine, 1,4-hexahydrodiazepine, azetidine and the like. When referring to the compounds of formula (I), wherein R is a group -CONRaR and / or R, is a group -NRcRd and Ra and Rb and / or Rc and Rd are taken together with the nitrogen atom at which are attached, they can also form an optionally substituted 4- to 7-membered heterocycle containing an additional ring heteroatom or a heteroatom group of S, O, N or NH. According to the meanings provided for Ra, Rb, Rc, Rd any of the above groups is unsubstituted or may be optionally further substituted at any of its free positions by one or more groups, for example 1 to 6 groups which are selected from: halogen, nitro, oxo groups (= 0) , carboxy, cyano, alkyl, polyfluorinated alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl; aril; heterocyclic, amino groups and derivatives thereof such as, for example, alkylamino, dialkylamino, arylamino, diarylamino, ureido, alkylureido or arylureido; carbonylamino groups and derivatives thereof such as, for example, formylamino, alkylcarbonylamino, alkenylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino, hydroxy groups and derivatives thereof, such as, for example, alkoxy, aryloxy, alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy or alkylidenaminoxy; carbonyl groups and derivatives thereof, such as, for example, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl; sulphurated derivatives such as, for example, alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, aryisulfinyl, arylsulfonyloxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl. In turn, when appropriate, each of the above substituents may additionally be further substituted by one or more of the groups mentioned above. In the present description, unless otherwise specified, the term "halogen" is a fluorine, chlorine, bromine or iodine atom. The term polyfluorinated alkyl is intended to be an alkyl group of 1 to 6 straight or branched carbon atoms as defined above, wherein more than one hydrogen atom is substituted by fluorine atoms such as, for example, trifluoromethyl , 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 1,1,1,3,3-hexafluoropropyl-2-yl and the like. From all of the foregoing, it is evident to a person skilled in the art that any group whose name has been identified as a compound name such as, for example, cycloalkylalkyl, arylalkyl, heterocyclylalkyl, alkoxy, alkylthio, aryloxy, arylalkyloxy, alkylcarbonyloxy and similar, should be considered as conventionally constructed as part of the parts from which it is derived. Heretofore, as an example, the term "heterocyclylalkyl" denotes a linear or branched which is further substituted by a heterocyclic group as defined above. The term "pharmaceutically acceptable salts" encompasses salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical with the condition that it is pharmaceutically acceptable. Suitable pharmaceutically acceptable acid addition salts of the compounds of the present invention are preferably prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are acids: hydrochloric, hydrobromic, hydriodic, nitric, carbonic, sulfuric and phosphoric. Suitable organic acids are preferably selected from the classes of organic acids aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carbocyclic and sulphonic, examples of which are the acids: formic, acetic, trifluoroacetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic , toluenesulfonic, 2-hydroxyethanesulfonic, sulphanilic, stearic, cyclohexylaminosulfonic, algenic, hydroxybutyric, galactárico and galacturónico. The addition salts of Suitable pharmaceutically acceptable bases of the compounds of the present invention include metal salts made of aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made of N, N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts are preferably prepared by conventional means from the corresponding compounds of the present invention, for example by reacting them with the appropriate acid or base. A first class of preferred compounds of the invention is represented by the derivatives of formula (I) wherein R is a group -CORa and Ri is a group -NRcRd, wherein Ra, Rc and Rd are as defined above. Another class of preferred compounds of the invention is represented by the derivatives of formula (I) wherein R is -CONRaRb and R-i is a group -NRcRd, wherein Ra, Rb, Rc and Rd are as defined above. Another class of preferred compounds of the invention is represented by the derivatives of formula (I) wherein R is a group -S02Ra and R-i is a group -NRcRd wherein Ra, Rc and Rd are as defined above. Another class of preferred compounds is represented by the derivatives of formula (I) wherein R is a group -COORa and R-i is a group -NRcRd wherein Ra, Rc and Rd are as defined above.

Another class of preferred compounds of the invention is represented by the derivatives of formula (I) wherein R is as defined in formula (I) and R-i is an -ORc group wherein Rc is as defined above. Another class of preferred compounds is represented by the derivatives of formula (I) wherein R is a group Ra and R ^ is a group -NRcRd wherein Ra, Rc and Rd are as defined in the above. Preferably, within the above classes, Ra, Rb, Rc and Rd are selected, each independently, according to the meanings reported in tables I, II of the experimental section. For a reference to specific examples of compounds of formula (I) of the invention, optionally in the form of pharmaceutically acceptable salts, see the experimental section. As stated in the above, a further objective of the present invention is a process for preparing the compounds of formula (I). Therefore, the compounds of formula (I) and the pharmaceutically acceptable salts thereof are obtained using standard techniques known to a person ordinarily skilled in the art. For example, they are obtained by a process comprising: a) reacting 1- (phenylsulfonyl) -1H-pyrrolo [2,3-b] pyridine-3-carboxylic acid methyl ester with nitrate of tetrabutylammonium (TBAN) in the presence of trifluoroacetic anhydride (TFAA) so that a compound of formula (II) is obtained b) reacting the compound of formula (II) under basic or acid hydrolysis conditions so as to obtain a compound of formula (III) or a salt thereof c) reacting the compound of formula (III) with a carboxy protective agent, for example an esterifying agent, so as to obtain a compound of the formula: wherein Alk denotes alkyl, for example methyl; d) reacting the compound of formula (IV) with tin (II) chloride and N-methyl-α-pyrrolidinone (NMP) so that a compound of formula (I) is obtained where Alk is as defined in the foregoing and optionally, reacting it according to any of the alternative stages (e.1), (e.2), (e.3) or (e.4) e.1) with any of the compounds of formula (V), (VI), (VII) or (VIII) RaCOZ (V); RaNCO (VI); RaS02Z (Vil); RaOCOZ (VIII) wherein Ra is as defined in the above and Z is a halogen atom, so that the compound of formula (I) is obtained wherein Alk is as defined in the above and R is a group -CORa, -CONHRa, -S02Ra or -COORa, respectively; or e.2) with a suitable amine of formula (IX) in the presence of triphosgene or a suitable chloroformate HNRaRb (IX) so as to obtain the above compound of formula (I) wherein R is a group -CONRaRb; or e.3) with an appropriate aldehyde or ketone derivative of formula (X) under reductive operating conditions Ra-CO-Ra (X) wherein each Ra is the same or different as defined above, so that the compound is obtained above of formula (I) wherein R is a group -CH (Ra) Ra; or e.4) with an iodine or aromatic bromine of formula (XI) or (Xll) Ra-I (XI) Ra-Br (Xll) in the presence of a suitable palladium catalyst and a ligand, so as to obtain a compound of formula (I) wherein R is Ra and the latter represents a carbocyclic or heterocyclic aromatic group; and, optionally f) converting the compound of formula (I) that has been obtained with any of steps (d), (e.1), (e.2), (e.3) or (e.4) into another compound of formula (I) and / or in a pharmaceutically acceptable salt thereof. The above procedure is an analogy procedure which can be carried out according to well-known methods.

According to the stage (a) of the procedure, the nitration of! 1- (Phenylsulfonyl) -1H-pyrrolo [2,3-b] pyridine-3-carboxylic acid methyl ester to provide the compound of formula (II) is carried out with tetrabutylammonium nitrate (TBAN) in the presence of a trifluoroacetic anhydride (TFAA). The reaction is carried out in a suitable solvent, for example a halogenated hydrocarbon such as dichloromethane, by treatment at a temperature ranging from 0 ° C to room temperature and for a time ranging from about 10 hours to about hours. According to step (b) of the process, the compound of formula (II) undergoes hydrolysis under basic or acidic conditions.

Preferably, the reaction is carried out in the presence of aqueous sodium hydroxide and 2,2,2-trifluoroethanol (TFE) at a temperature ranging from room temperature to about 90 ° C and for a time from 4 hours to a day. According to the operating conditions that are used, the compound of formula (III) can be obtained either in its acid form or, alternatively, as a salt. Preferably, the hydrolysis reaction is carried out under basic conditions, for example in the presence of sodium hydroxide, so that the corresponding disodium salt is obtained, as indicated in the experimental section (see example 2). According to step (c) of the process, the compound of formula (Mil) is esterified according to operating conditions well known in the presence of suitable alcohols. As an example, this reaction is carried out in the presence of methanol so that the corresponding carboxymethyl ester derivative of formula (II) is obtained wherein Alk denotes methyl. Alternatively, the compound of formula (IV) of the step (c) wherein Alk indicates methyl is prepared by direct hydrolysis of the compound of formula (II) according to known methods, for example in the presence of potassium trimethylsilanolate in tetrahydrofuran (THF) or of triethylamine (TEA) in methanol. According to step (d) of the process, the nitro group of the compound of formula (IV) is reacted with the corresponding amino derivative. The reduction is preferably carried out in the presence of tin (II) chloride and NMP according to well-known methods. Clearly, any of the various methods known in the art for reducing nitro groups to amino groups, which for example comprises catalytic hydrogenation, can also be used successfully. From the foregoing, it is evident to a person skilled in the prior art technique of step (d) that a compound of formula (I) is obtained wherein R is a hydrogen atom and Ri is an -ORc group wherein Rc is exactly the alkyl group which is introduced through step (c) of the process, for example methyl. The compound of formula (I) obtained in this way can optionally be converted into a variety of formula derivatives (I) when working as described in any of the stages from (e.1) to (e.4) of the procedure, according to well-known methods. Typically, the compound of formula (I) of step (d) having an amino group in the 5-position can be reacted; with a compound of formula (V) so as to obtain the corresponding carboxyamido derivative wherein R is -CORa and Ra is as defined above; with a compound of formula (VI) such that the corresponding ureido derivative is obtained wherein R is -CONHRa and Ra is as defined above; with a compound of formula (VII) such that a sulfonamido derivative is obtained wherein R is -S02Ra and Ra is as defined above; with a compound of formula (Vil) such that a carbamate derivative is obtained wherein R is -COORa and Ra is as defined above; with a compound of formula (IX) and triphosgene or a suitable chloroformate so that a ureido derivative is obtained wherein R is -CONRaRb and Ra and Rb are as defined above; with a compound of formula (X) under reductive operating conditions so that a derivative is obtained in which R is -CH (Ra) Ra and each Ra, same or different and independently from each other, are as defined in the above . Any of the above reactions is carried out according to conventional methods normally used in the preparation of functionalized amino derivatives from the corresponding amine.

Within the compounds of formulas (V), (Vil) or (V I) of step (e.1), in paticular, Z represents a halogen atom and even more preferably a chlorine atom. In this regard, the compound of formula (I) of step (d) is dissolved in a suitable solvent such as dichloromethane, dimethylformamide, tetrahydrofuran, dioxane or the like and a suitable base such as triethylamine, diisopropylethylamine, sodium carbonate or the like is add to it. The compound of the general formula (V), (Vil) or (VIII) is then added and the mixture is stirred for a time from about 2 hours to about 15 hours, at a temperature ranging from about 20 ° C to about 80. ° C. When an isocyanate of general formula (VI) is used, the reaction conditions are the same as those reported in the above except that it may not be required in the base. In all of these reactions, a suitable catalyst such as dimethylaminopyridine can optionally be used. According to step (e.2) of the process, the compound of formula (I) obtained in step (d) can be reacted with an amino derivative of formula (X) in the presence of a triphosgene or a chloroformate suitable such as, for example, 4-nitrophenyl chloroformate. The reaction is carried out in a suitable solvent such as a halogenated hydrocarbon, preferably dichloromethane, in the presence of a base such as, for example, diisopropylethylamine or triethylamine and by working at room temperature.

According to the stage (e.3) of! In the process, the compound of formula (I) of step (d) is reacted under reductive conditions with an aldehyde or ketone derivative of formula (X) so as to obtain the corresponding compound of formula (I) wherein R is as defined in the above. From the foregoing, it is evident that for a person skilled in the art that by using an aldehyde derivative of formula (X) wherein one of the two Ra is a hydrogen atom, the corresponding derivative can be obtained wherein R is -CH2Ra. Similarly, by using a ketone derivative, compounds having R as -CH (Ra) Ra can be obtained wherein each Ra is, independently of each other, as stated in the above but different from hydrogen. According to step (e.4) of the process, the compound of formula (I) of step (d) is converted into the corresponding arylated derivative of formula (I) with R as Ra and wherein Ra is an aryl group, and therefore, encompasses carbocyclic or heterocyclic aromatic groups. The reaction is carried out according to known methods, with any suitable iodide or aryl bromide of formula (XI) or (Xll), in the presence of a suitable catalyst, for example, a palladium catalyst such as palladium acetate or Pd2 (dba) 3, and of a suitable ligand. For a general reference to the above arylation reaction and operating conditions thereof (also including solvents, catalysts and ligands), see, for example J. Am. Chem. Soo, (2003), 125, 6653-55; JOC (2001), 66, 2560-2565; and JOC (2002), 67, 6479-6486. In addition to the foregoing, it is also evident to a person skilled in the art that, whenever desired, any of the above compounds of formula (I) prepared in this manner can be further converted to other derivatives of formula (I), as is established in stage (f) by worked according to conventional methods. As an example, the compounds of formula (I) wherein R is any of the groups mentioned above and Alk represents a given alkyl, for example methyl, can be converted into the compounds of formula (I): g) wherein R is as defined in the foregoing and R ^ is -ORc, wherein Rc is different from methyl, by transesterification reactions that are carried out according to well-known methods, for example with a suitable compound of formula (XIII) R ° -OH (XIII) under acidic or basic conditions, optionally in the presence of a suitable metal-based catalyst, such as dibutyltin oxide or titanium alkoxides, such as, for example, titanium (IV) ethoxide, titanium sopropoxide (IV) and the like; h) wherein R is as defined in the above and R-i is an -OH group, by acid or basic hydrolysis. As a further example, the compounds of formula (I), wherein R is as defined above and Ri is an -ORc group wherein Rc is an alkyl group which can also be converted to the corresponding amido derivatives of the formula (I) i) wherein R-] is -NRcRd, with Rc and Rd as defined above, by treatment with ammonia with a suitable amine of formula (XIV) or (XV) RC-NH2 (XIV); RcRdNH (XV) Optionally in the presence of suitable catalysts such as, for example, 2-hydroxypyridine, potassium iodide, sodium cyanide or dimethylaminopyridine. Likewise, the compounds of formula (I), wherein R is as defined above and Ri is a group -ORc wherein Rc is hydrogen, optionally converted to the corresponding amido derivatives of formula (I) by treatment as established in the stage (i) optionally in the presence of a suitable condensing agent by Examples are dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide (EDC), O-benzotriazolyltetramethylisouronium tetrafluoroborate (TBTU) or benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP). From all of the above, it is also evident to a person skilled in the art that if a compound of formula (I) prepared according to the above process is obtained as a mixture of isomers, its separation into unique isomers of formula (I) , carried out according to conventional techniques, is still within the scope of the present invention. Likewise, conversion to the free compound (I) of a corresponding salt thereof, according to methods well known in the art, is still within the scope of the invention. When the compounds of formula (I) are prepared according to any variant of the process, all of which are intended to be within the scope of the invention, the optional functional groups within the starting materials, the reactants or the intermediates of they and which may give rise to unwanted side reactions, need to be adequately protected according to conventional techniques. Likewise, the conversion of the latter to the free deprotected compounds can be carried out according to known procedures.

The starting materials of the subject process of the present invention, which encompass any possible variant as well as any reagent thereof, are known compounds and, if not commercially available by themselves, can be prepared according to well-known methods. As an example, the compound methyl ester of 1- (phenylsulfonyl) -1H-pyrrolo [2], 3-b] pyridine-3-carboxylic acid can be prepared as described in Tetrahedron Letters 40 (1999), 5853-5854. Likewise, the compounds of formula (V), (VI), (VII), (VIII), (IX), (X), (XII), (XIII), (XIV) and (XV) are known or they are easily obtained according to known methods. The intermediate compound of formula (III) of the process represents a further objective of the invention. In addition to the foregoing, the compounds of formula (I) of the invention are advantageously prepared according to combination chemistry techniques well known in the art, by carrying out the aforementioned reactions between the intermediates in a serial manner and the work under conditions of solid phase synthesis (SPS). As an example, the intermediate compounds of formula (III) which are obtained according to step (b) of the process, can be easily supported on a polymeric resin, for example through the formation of a carboxamide group, and the intermediate supported from this way it can be reacted subsequently according to the Remaining stages of the procedure. Preferably, the above resin is a polystyrene resin commercially available including, for example, Wang resin, resin Trityl, Cl-trityi resin, Rink amide resin, Tentagel OH resin, resins formyl and derivatives thereof.

According to a preferred embodiment of the invention, the polystyrene resin is a derivatized formyl polystyrene resin which can be obtained by reacting a commercially available formyl polystyrene resin, for example 4- (4-formyl-3-methoxyphenoxy) butyryl AM resin, with a suitable amino derivative under reducing conditions, for example in the presence of sodium borohydride and derivatives thereof, substantially as follows: NaBH (OAc) 3 (P) -CHO + R-NH2 ^ (P) _CH2_NHR The reaction is preferably carried out in a suitable solvent such as dichloromethane and in the presence of acetic acid.

Amino derivatives supported on polymer obtained from this way, particularly those which are referable as the resin former derivatized polystyrene formyl are widely known in the art technique.

In general, amines loaded on formyl polystyrene resins also known as methoxybenzaldehyde polystyrene resins sensitive to acid "AMEBA resins" are prepared by standard reductive amination in the presence of an excess of amine in TMOF / DCE and NaBH (OAc) 3 or AcOH / DMF and NaCNBH3, for example as reported in Tetrahedron Letters (1997), 38, 7151-7154; J. Am. Chem. Soc. (1998), 120, 5441; and Chem. Eur. J. (1999), 5, 2787. Therefore, a further objective of the present invention is to provide a process for preparing the compounds of formula (I) and pharmaceutically acceptable salts thereof, which process comprises: j) reacting the compound of formula (III) which is prepared according to step (b) with a derivatized formyl polystyrene resin of formula (XVI) (P) -CH2-NHR ° (XVI) wherein (P) is the resin and Rc is as defined in the above, so that a compound of formula (XVII) is obtained k) reacting the compound of formula (XVI!) according to step (d) and optionally with any of steps (e.1), (e.2), (e.3) or (e.4) so that a compound of formula (XVIII) is obtained (XVIII) where (P), R and R ° are as defined in the above; I) separating the resin of the compound of formula (XIII) under acidic conditions so that a compound of formula (I) is obtained wherein R is as defined in the above, and Ri is a group -NHRC, wherein Rc is as defined in the above; and, optionally m) converting the compound thus obtained of formula (I) into another compound of formula (I) and / or pharmaceutically acceptable salts thereof. According to step (j) of the process, the reaction is carried out in a suitable solvent, for example N-methylpyrrolidone (NMP), dimethylformamide (DMF) or dichloromethane (DCM) in the presence of diisopropylethylamine (DIEA) and a suitable condensing agent such as, for example, 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide (EDC), dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), dimethylaminopyridine (DMAP) or tetrafluoroborate O-benzotriazolyl tetramethylisouronium (TBTU).

According to step (k) of the process, the supported compound of formula (XVII) is first reduced as in step (d) of the process so that the amino derivative is obtained, and optionally reacted further as indicated above, so as to give rise to a variety of compounds functionalized at the 5-position of the pyrrolo [2,3-b] pyridine ring. The operating conditions are essentially those indicated above by treatment under homogeneous operating conditions. The separation of resin according to step (I) can be carried out under acidic conditions in the presence of suitable acids such as, for example, hydrochloric or trifluoroacetic acids. Clearly, a plurality of compounds of formula (I) can be obtained by working according to the combination chemistry techniques as indicated above. Therefore, a further objective of the present invention is a library of two or more compounds of formula (I) wherein: R is selected from the group consisting of: -Ra, -CORa, CONRaRb, -S02Ra, -S02Ra or -COORa; Ri is a group -NRcRd or -ORc; wherein Ra, Rb, Rc and Rd are the same or different, and each is independently hydrogen or an optionally substituted group, which is selected from linear or branched alkyl of 1 to 6 carbon atoms, alkenyl from 2 to 6. linear or branched carbon atoms, linear or branched alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms or cycloalkylalkyl of 1 to 6 carbon atoms, aryl or arylalkyl of 1 to 6 carbon atoms or heterocycle or Heterocycloalkyl from 1 to 6 carbon atoms or, taken together with the nitrogen atom to which they are attached, either Ra and Rb as well as Rc and Rd can form a heterocycle of 4 to 7 members optionally substituted, which optionally contains an additional ring heteroatom or a heteroatom group which is selected from S, N O NH; or isomers, tautomers, carriers, metabolites, prodrugs and pharmaceutically acceptable salts thereof. According to a preferred embodiment of the invention, the library mentioned above comprises the compounds of formula (I), wherein R is a group Ra and Ri is a group -NRcRd wherein Ra, Rc and Rd are as defined in previous. Within another embodiment, the library mentioned above comprises compounds of formula (I) wherein R is a group -CORa and R-i is a group -NRcRd, wherein Ra, Rc and Rd are as defined above.

Within another embodiment, the library mentioned above comprises compounds of formula (I) wherein R is a group -CONRaRb and Ri is a group -NRcRd, wherein Ra, Rb, Rc and Rd are as defined above. Within another embodiment, the library mentioned above comprises compounds of formula (I) wherein R is a group S02Ra and R-i is a group -NRcRd wherein Ra, Rc and Rd are as defined above. Within another embodiment, the library mentioned above comprises compounds of formula (I) wherein R is a group -COORa and R-i is a group -NRcRd wherein Ra, Rc and Rd are as defined above. Within another embodiment, the library mentioned above comprises compounds of formula (I) wherein R is an as defined in formula (I) and R-i is a group -ORc, wherein Rc is as defined above. For a general reference to the above libraries of the compounds of formulas (I) see the experimental section. From all of the foregoing, it is evident to a person skilled in the art that once the library of pyrrolo [2,3-b] pyridine derivatives has been prepared, for example consisting of a few thousand compounds of formula (I ), the library can be used very advantageously for screening in search of given kinases, as previously reported.

For a general reference to libraries of compounds and use thereof as screening tools in the determination of biological activities see J. Med. Chem. 1999, 42, 2373-2382; and Bioorg, Med. Chem. Lett. 10 (2000), 223-226.

Pharmacology The compounds of formula (I) are active as inhibitors of protein kinase and are therefore useful, for example, in limiting the unregulated proliferation of tumor cells. In therapy, they are used in the treatment of various tumors such as those reported above, as well as in the treatment of other proliferative cell disorders such as psoriasis, vascular smooth cell proliferation associated with atherosclerosis and postsurgical stenosis and restenosis, and in the treatment of Alzheimer's disease. The inhibitory activity of the putative cdk / cyclin inhibitors and the potency of the selected compounds is determined by an assay method based on the use of SPA technology (Amersham Pharmacia Biotech). The assay consists in the transfer of a phosphate portion radioactively labeled by the kinase to a biotinylated substrate. The biotinylated product labeled with the resulting 33P is allowed to bind to SPA beads coated with streptavidin (biotin capacity, 130 pmol / mg) and the light emitted is measured in a scintillation counter.

Assay of inhibition of cdk2 / cyclin A activity Kinase reaction: Biotinylated in the laboratory, ATP is added to each well of a 96-well plate in a U-bottom 4 μM of histone H1 substrate (Sigma # H-5505) 10 μm (0.1 μCi of P33? -ATP) 1.1 nM cyclin A / CDK2 complex, inhibitor in a final volume of 30 μl buffer (TRIS 10 mM HCl, pH 7.5, 10 mM MgCl 2, 7.5 mM DTT + 0.2 mg / ml BSA).

After incubation for 60 min at room temperature, the reaction is stopped by the addition of 100 μl of PBS buffer containing EDTA. 32 mM, cold ATP 500 μM, Triton X-100 0.1% and 10 mg / ml of SPA spheres coated with streptavidin. After 20 min of incubation they are extracted 110 μl of suspension and transferred to OPTIPLATE of 96 wells containing 100 μl of 5 M CsCl. After 4 hours, the plates are read for 2 min in a Packard TOP-Count radioactivity reader. Cl50 Determination: Inhibitors were tested at different concentrations ranging from 0.0015 to 10 μM. The experimental data is analyzed by the computer program GraphPad Prizm using the logistic equation of four parameters: y = lower + (upper-lower) / (1 + 10 ((l09 CI5 ° -? Rpendiente)) where x is the logarithm of the inhibitor concentration, and it is the response, and starts at the bottom and advances towards the top with a sigmoid shape.

Experimental method: The reaction is carried out in buffer (10 mM Tris, pH 7.5, 10 mM MgCl 2, 0.2 mg / ml BSA, 7.5 mM DTT) containing 3.7 nM enzyme, histone and ATP (constant ratio of cold ATP / marked 1/3000). The reaction is stopped with EDTA and the substrate is retained in a phosphomembrane (Millipore Multiscreen 96-well plates). After extensive washing, the multiscreen plates are read on a top counter. The control (time zero) is measured for each concentration of ATP and histone. Experimental design: The reaction rates are measured at four concentrations of ATP, substrate (histone) and inhibitor. A concentration matrix of 80 points is designed around the respective values of ATP and Km of substrate, and Cl50 values of inhibitor (0.3, 1, 3, 9 times the Km or Cl50 values). A preliminary experiment of time course in the absence of inhibitor and at different concentrations of ATP and substrate allows the selection of a single endpoint time (10 min) in the linear range of the reaction for the Ki determination experiment. Kinetic parameter calculations: Kinetic parameters are calculated by simultaneous non-linear least squares regression using [equation 1] (competitive inhibitor with respect to ATP, random mechanism) using the complete data set (80 points): v = Ka R a m Ka * Kb -t-a * Kcf B + a »Kb»? +? »B + cif * - • J» (Kb + -) Ki ß [Equation 1] where A = concentration of ATP, B = concentration of substrate, I = concentration of inhibitor, Vm = maximum velocity, Ka, Kb, Ki constants of dissociation of ATP, substrate and inhibitor, respectively. The symbols a and ß are the factor of cooperativity between the substrate and the ATP binding and between the substrate and the inhibitor binding, respectively. In addition, the selected compounds are characterized in a panel of ser / thre kinases strictly related to the cell cycle (cdk2 / cyclin E, cdkl / cyclin B1, cdk5 / p25, cdk4 / cyclin D1) and also for specificity in MAPK, PKA , EGFR, IGF1-R, Aurora-2 and Cdc 7.

Inhibition assay of cdk2 / cyclin E activity Kinase reaction: 10 μM of histone H substrate (Sigma # H-5505) biotinylated in the laboratory, ATP is added to each well of a 96 well plate in the bottom in U-shape. 30 μm (0.3 μCi of P33? -ATP), 4 ng of 1.1 nM GST-cyclin E / CDK2 complex, inhibitor in a final volume of 30 μl buffer (10 mM TRIS HCl, pH 7.5, 10 mM MgCl 2, 7.5 DTT mM + 0. 2 mg / ml BSA). After incubation for 60 min at room temperature the reaction is stopped by the addition of 100 μl of PBS buffer containing 32 mM EDTA, 500 μM cold ATP, 0.1% Triton X-100 and 10 mg / ml of SPA spheres coated with streptavidin. After 20 min of incubation, 110 μl of suspension is extracted and transferred to OPTIPLATE of 96 wells containing 100 μl of 5M CsCl. After 4 hours, the plates are read for 2 min in a Packard TOP-Count radioactivity reader. Determination of CI5o: see above Assay of inhibition of cdkl / cyclin B1 activity Kinase reaction: Biotinylated in the laboratory, ATP is added to each well of a 96-well plate in the bottom in U 4 μM of histone H1 substrate (Sigma # H-5505) 20 μM (0.2 μCi of P33? -ATP), 3 ng of cyclin B / CDK1 complex, inhibitor in a final volume of 30 μl of buffer (TRIS 10 mM HCl, pH 7.5, 10 mM MgCl2, 7.5 mM DTT + 0.2 mg / ml BSA). After 20 min of incubation at room temperature the reaction is stopped by the addition of 100 μl of PBS + 32 mM EDTA + 0.1% Triton X-100 + 500 μM ATP containing 1 mg of SPA spheres. Then a volume of 100 μl is transferred to Optiplate. After incubation for 20 min for substrate retention, 100 μl of 5 M CsCl is added to allow stratification of the spheres at the top of the Optiplate and allowed to stand 4 hours before the radioactivity count on a Top-Count instrument. Cl50 determination: see above Cdk5 / p25 activity inhibition assay The cdk5 / p25 activity inhibition assay is performed according to the following protocol.

Kinase reaction: 100 μM biotinylated, 30 μm ATP (0.3 μCi of P33? -ATP), 15 ng of protein, are added to each well of a 96-well plate in the U-bottom substrate of histone H1 (Sigma # H-5505). CDK5 / p25 complex, inhibitor in a final volume of 30 μl of buffer (10 mM TRIS HCl, pH 7.5, 10 mM MgCl 2, 7.5 mM DTT + 0.2 mg / ml BSA). After 35 min of incubation at room temperature the reaction is stopped by the addition of 100 μl of PBS buffer containing 32 mM EDTA, 500 μM cold ATP, 0.1% Triton X-100 and SPA spheres coated with 10 mg / ml streptavidin. . After 20 min of incubation, 110 μl of suspension is extracted and transferred to OPTIPLATE of 96 wells containing 100 μl of 5M CsCl. After 4 hours the plates are read for 2 minutes in a Packard Top-Count radioactivity reader. Cl50 determination: see above Inhibition assay of cdk4 / cyclin D1 activity Kinase reaction: Mouse wells of a 96-well plate are added to the bottom of the mouse substrate GST-Rb (769-921) (# sc-4112 of Santa Cruz) 0.4 μM, ATP 10 μm (0.5 μCi of P33? -ATP), 100 ng of GST-CDK4 / GST-cyclin D1, expressed in baculovirus, suitable concentrations of inhibitor in a final volume of 50 μl of buffer (TRIS HCl 10 mM , pH 7.5, 10 mM MgCl 2, 7.5 mM DTT + 0.2 mg / ml BSA). After 40 min at 37 ° C incubation, the reaction is stopped by the addition of 20 μl of 120 mM EDTA.

Retention: 60 μ! Are transferred! from each well to the MultiScreen plate to allow attachment of the substrate to the phosphocellulose filter. The plates are then washed 3 times with 150 μl / well of PBS, free of Ca ++ / Mg ++ and filtered through the MutiScreen filtration system. Detection: The filters are allowed to dry at 37 ° C, then 100 μl / well of scintillation liquid is added and the Rb-labeled Rb fragment is detected by radioactivity counting in the Top-Count instrument. Determination of IC50: see above MAPK activity inhibition assay Kinase reaction: 10 μM, biotinylated in the laboratory, 15 μM ATP (0.15 μCi) are added to each well of a 96 well plate in the bottom on a substrate MBP (Sigma # M-1891). of P33? -ATP), 30 ng of GST-MAPK (Upstate Biotechnology # 14-173), inhibitor in a final volume of 30 μl of buffer (10 mM TRIS HCl, pH 7.5, 10 mM MgCl 2, 7.5 mM DTT + 0. 2 mg / ml BSA). After incubation for 35 min at room temperature, the reaction is stopped by adding 100 μl of PBS buffer containing 32 mM EDTA, 500 μM cold ATP, 0.1% Triton X100 and SPA spheres coated with 10 mg / ml streptavidin. After 20 min of incubation, 110 μl of suspension is extracted and transferred in OPTIPLATE of 96 wells containing 100 μl of 5 M CsCl. After 4 hours the plates are read for 2 min in a Packard Top-Count radioactivity reader.

Determination of C! 50: see above PKA activity inhibition assay Kinase reaction: 10 μM, biotinylated in the laboratory, 10 μM ATP (100 μM ATP histone substrate H1 (Sigma # H-5505) is added to each well of a 96-well plate in a U-bottom. 0.2 μCi of P33? -ATP), 0.45 U of PKA (Sigma # 2645), inhibitor in a final volume of 30 μl of buffer (TRIS 10 mM HCl, pH 7.5, 10 mM MgCl2, 7.5 mM DTT + 0.2 mg / ml of BSA). After incubation for 90 min at room temperature the reaction is stopped by adding 100 μl of PBS buffer containing 32 mM EDTA, 500 μM cold ATP, 0.1% Triton X100 and SPA spheres coated with 10 mg / ml streptavidin. After 20 min of incubation, 10 μl of suspension are removed and transferred into OPTIPLATE of 96 wells containing 100 μl of 5 M CsCl. After 4 hours the plates are read for 2 min in a Packard Top-Count radioactivity reader. Cl50 determination: see above EGFR activity inhibition assay Kinase reaction: 10 μM, biotinylated in the laboratory, 2 μM ATP (0.04 μCi) are added to each well of a 96-well plate in the bottom on a substrate MBP (Sigma # M-1891). of P33? -ATP), 36 ng of insect cells expressing GST-EGFR inhibitor in a total volume of 30 μl of buffer (Hepes, 50 mM, pH 7.5, 3 mM MgCl 2, 3 mM MnCl 2, 1 mM DTT, NaV03 3 μm + 0.2 mg / ml BSA). After incubation for 20 min at room temperature, the reaction is stopped by adding 100 μl of PBS buffer containing 32 mM EDTA, 500 μM cold ATP, 0.1% Triton X100 and SPA spheres coated with 10 mg / ml streptavidin. After 20 min of incubation, 110 μl of suspension is extracted and transferred in OPTIPLATE of 96 wells containing 100 μl of 5 M CsCl. After 4 hours the plates are read for 2 min in a Packard Top-Count radioactivity reader. Cl50 determination: see above IGF1-R activity inhibition assay The IGF1-R activity inhibition assay is performed according to the following protocol. Enzyme activation: IGF-1 R must be activated by autophosphorylation before starting the experiment. Just before the test, a concentrated enzyme solution (694 nM) is incubated for half an hour at 28 ° C in the presence of 100 μM ATP and then diluted to the working dilution in the indicated buffer. Kinase reaction: Biotinylated IRS1 peptide substrate (PRIMM) is added to each well of a 96-well plate in a U-bottom. μM, inhibitor 0-20 μM, ATP 6 μM, 1 μCi P33? -ATP and GST-IGF1-R 6 nM (preincubated for 30 min at room temperature with cold 60 μM cold ATP) in a final volume of 30 μl buffer (50 mM Hepes, pH 7.9, MgCI 3 mM, 1 mM DTT, 3 μM NaVo3). After incubation for 35 min at room temperature, the reaction is stopped by adding 100 μl of PBS buffer containing 32 mM EDTA, 500 μM cold ATP, 0.1% Triton X100 and SPA spheres coated with 10 mg / ml streptavidin. After 20 min of incubation, 110 μl of suspension is extracted and transferred in OPTIPLATE of 96 wells containing 100 μl of 5 M CsCl. After 4 hours the plates are read. for 2 min in a Packard Top-Count radioactivity reader.

Aurora-2 activity inhibition assay Kinase reaction: A biotinylated peptide (4 repeat sequences of LRRWSLG) 8 μM, 10 μM ATP (0.5 μCi of P33?) Is added to each well of a 96-well plate at the bottom. -ATP), Aurora inhibitor 2 7.5 ng in a final volume of 30 μl buffer (Hepes, 50 mM, pH 7.0, 10 mM MgCl 2, 1 mM DTT, 0.2 mg / ml BSA and 3 μM orthovanadate). After 60 minutes of incubation at room temperature the reaction is stopped and the biotinylated peptide is retained by adding 100 μl of slurry suspension. Stratification: 100 μl of 5 M CsCI2 is added to each well and allowed to stand 4 hours before the radioactivity count is performed on the Top-Count instrument. Cl50 determination: see above Inhibition assay of Cdc7 / dbf4 activity The inhibition assay of Cdc7 / dbf4 activity is carried out according to the following protocol. The biotin-MCM2 substrate is transphosphorylated by the Cdc7 / dbf4 complex in the presence of ATP labeled with? 33-ATP. The substrate of phosphorylated biotin-MCM2 is then retained by spheres of SPA coated with streptavidin and the degree of phosphorylation is evaluated by β-counting. The Cdc7 / dbf4 activity inhibition assay is performed in 96-well plates, according to the following protocol. To each well of the plate are added: 10 μl of substrate (biotinylated MCM2, final concentration 6 μM) 10 μl of enzyme (Cdc7 / dbf4, final concentration 17.9 nM) 10 μl of test compound (12 concentrations increasing in the interval nM to μM to generate a dose-response curve) 10 μl of a mixture of cold ATP (final concentration 2 μM) and radioactive ATP (molar ratio with cold ATP 1/5000) which is then used to initiate the reaction which is allowed carried out at 37 ° C. The substrate, enzyme and ATP are diluted in 50 mM HEPES, pH 7.9, containing 15 mM MgCl 2, 2 mM DTT, 3 μM NaV03, 2 mM glycerophosphate and 0.2 mg / ml BSA. The solvent for the test compounds also contains 10% DMSO.

After incubation for 60 minutes, the reaction is stopped by adding to each well 100 μl of PBS, pH 7.4 containing 50 mM EDTA, 1 mM cold ATP, 0.1% Triton X100 and SPA spheres coated with 10 mg / ml streptavidin. After 20 min of incubation, 110 μl of suspension is extracted and transferred to OPTIPLATE of 96 wells containing 100 μl of 5M CsCl. After 4 hours the plates are read for 2 min in a Packard Top-Count radioactivity reader. Cl50 determination: see above. The compounds of formula (I) of the present invention, suitable for administration to a mammal, for example to humans, are administered by the usual routes and the dosage level depends on the age, weight, conditions of the patient and route of administration. For example, a suitable dosage adopted for oral administration of a compound of formula (I) preferably ranges from about 10 to about 500 mg per dose, from 1 to 5 times daily. The compounds of the invention can be administered in a variety of dosage forms, for example orally, in the form of tablets, capsules, sugar or film-coated tablets, liquid solutions or suspensions; rectally in the form of suppositories; parenterally, for example intramuscularly or by intravenous and / or intrathecal and / or intraspinal injection or infusion.

In addition, the compounds of the invention can be administered either as single agents or, alternatively in combination with known anticancer treatments such as radiation, therapy or chemotherapy regimen in combination with cytostatic or cytotoxic agents, antibiotic type agents, agents alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-like agents, cyclooxygenase inhibitors (for example COX-2 inhibitors), metalomatrizprotease inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents , anti-HER agents, anti-EGFR agents, antiangiogenesis agents, farnesyltransferase inhibitors, inhibitors of the ras-raf signal transduction pathway, cell cycle inhibitors, other cdks inhibitors, tubulin binding agents, topoisomerase I inhibitors , topoisomerase II inhibitors and the like, optionally n of liposomal formulations thereof. If formulated as a fixed dose, such combination products utilize the compounds of this invention within the dosage range described above and other pharmaceutically active agents within the approved dosage range. The compounds of formula (I) can be used sequentially with known anticancer agents when a combined formulation is inappropriate.

The present invention also includes pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable excipient (which can be a carrier or a diluent). The pharmaceutical compositions containing the compounds of the invention are usually prepared following conventional methods and administered in a pharmaceutically suitable form. For example, solid oral forms may contain, together with the active compound, diluents such as, for example, lactose, dextrose, sucrose, cellulose, corn starch or potato starch; lubricants, for example silica, talc, stearic acid, magnesium or calcium stearate and / or polyethylene glycols; binding agents, for example starches, gum arabic, gelatin, methylcellulose, carboxymethylcellulose or polyvinylpyrrolidone; disaggregation agents, for example a starch, alginic acid, alginates or sodium starch glycolate; effervescent mixtures; colorants; sweeteners; wetting agents such as lecithin, polysorbates, lauryl sulfates and in general non-toxic and pharmacologically inactive substances used in pharmaceutical formulations. Such pharmaceutical preparations can be made using known techniques, for example by mixing, granulating, tabletting, sugar coating or film coating processes. Liquid dispersions for oral administration also include, for example, syrups, emulsions and suspensions.

It is preferred that the syrups include, for example, sucrose or sucrose with glycerin and / or mannitol and / or sorbitol as the carrier. It is preferred that the suspensions and emulsions may contain, for example, a natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose or polyvinyl alcohol. The suspension or solutions for intramuscular injections optionally and preferably contain, together with the active compound, a pharmaceutically acceptable carrier, for example sterile water, olive oil, ethyl oleate, glycols, for example propylene glycol, and if desired, an adequate amount of lidocaine hydrochloride. The solutions for intravenous injections or infusion optionally and preferably contain as carrier, for example, sterile water or preferably they can be in the form of sterile aqueous isotonic saline solutions or they can contain propylene glycol as a carrier. It is preferred that the suppositories contain together with the active compound a pharmaceutically acceptable carrier, for example cocoa butter, polyethylene glycol, a polyoxyethylene sorbitan fatty ester surfactant or lecithin. The following examples are intended herein to better illustrate the present invention without presenting any limitation thereto.

Experimental section General Methods Flash chromatography is performed on silica gel (Merck grade 9395, 60A). The retention times of high pressure liquid chromatography (CLAP, t.r.) are determined by: Method 1 (CLAP 1): Instruments: Hewlett Packard 1312A binary pump; Gilson 215 autosampler coupled with a 1 ml syringe, Polymer Labs PL1000 evaporative light scattering detector (ELSD) and a Micromass ZMD mass spectrometer operating in the positive ionization mode of electrospray. The LC eluent is divided and approximately 200 μl / min enters the mass spectrometer and 800 μl / min into the ELS. Chromatographic condition: the mobile phases of CLAP consist of 0.1% trifluoroacetic acid in CLAP grade water (A) and 1% trifluoroacetic acid in CLAP grade acetonitrile (B). The CLAP gradient is shown in the following table.

Travel time: 2.4 minutes Flow rate: 1 ml / min Injection volume: 3 μl Column temperature: ambient (20 ° C) Column: 50 x 2.0 mm Hypersil C18 BDS; 5 μm ELS detector: Nebulizer temperature 80 ° C Evaporation temperature, 90 ° C Gas flow 1.5 l / h MS detector: m / z 150-800 at 0.5 seconds / - exploration, 0.1 second delay between exploration 25V cone voltage, 140 ° C source temperature Drying gas 350 l / h The retention times in ELSD (CLAP, tr) are given in minutes. The masses are provided as a ratio m / z. Method 2 (CLAP_2): Instrumentation: Waters 2790 CLAP system equipped with a 996 Waters PDA detector and a single quadrupole mass spectrometer Micromass mod. ZQ equipped with an electrospray ion source (ESI). Chromatographic condition: column RP18 Waters x Terra (4.6 x 50 mm, 3.5 μm); mobile phase A is 5 mM ammonium acetate buffer (pH 5.5 with acetic acid / acetonitrile 95: 5) and mobile phase B is H20 / acetonitrile (5:95). The gradient of 10 to 90% of B in 8 minutes, retention of 90% of B for 2 minutes. UV detection at 220 nm and 254 nm. Flow rate, 1 ml / min. injection volume 10 μl. Full scan, mass range from 100 to 800 urn. Hair voltages of 2.5 KV; source temperature is 120 ° C; the cone is 10 V. Retention times (CLAP, t.r.) are given in minutes at 220 nm or at 254 nm. The mass is given as m / z ratio. When necessary, the compounds were purified by preparative CLAP on a Waters Symmetry C18 column (19 x 50 mm, 5 μm) using preparative Waters 600 CLAP equipped with a 996 Waters PDA detector and a Micromass mod single quadrupole mass spectrometer. ZQ, ionization of electron spray in the positive mode. Mobile phase A is water, trifluoroacetic acid (TFA) 0.01% and mobile phase B is acetonitrile. The gradient of 10 to 90% of B in 8 minutes, retention of 90% of B for 2 min. Flow rate of 20 ml / min. The 1H NMR spectrometry is performed on a single-bay Bruker AVANCE 400MHz instrument with gradients. It is equipped with a QNP probe (interchangeable 4-core probe - H, 13C, 19F and 31P) (NMR method 1) on a Mercury VX instrument operating at 400.45 MHz equipped with a 5 mm double resonance probe [1 H ( 15N-31 P) ID_PFG Varian] (NMR method 2). As indicated above, various pyrrolopyridine derivatives of formula (I) of the invention have been synthesized in parallel, (also briefly identified as azaindoles) according to the combinational chemistry techniques. In this regard, some compounds prepared in this way have been identified conveniently and unequivocally, as well as the coding system of tables III and V to VIII, together with the retention times of CLAP (methods 1 and 2) and mass. Table IV, instead, refers to analytical NMR data for some representative compounds of the formula (I) of the library. Each code, which identifies a single specific compound of formula (I) consists of three A-M-B units. A represents any substituent R-r [see formula (I)] and is attached to the remainder of the azaindole portion through the carbon atom so that azaindole derivatives are obtained which are substituted at the position 3- (A-M-B); each radical (substituent) A is represented in the following Table I. B represents any substituent R- [see formula (I)] and is attached to the remainder of the azaindole portion through the nitrogen atom so that azaindole derivatives are obtained which are substituted at position 5 (AMB); each radical (substituent) B is represented in the following Table II. M refers to the central nucleus of the divalent 3-carboxyazaindole portion having the -N- group at position 5, substituted by groups A and B.

M For ease of reference, each of groups A or B of Tables I and II has been identified with the appropriate chemical formula that also indicates the point of attachment to the remainder of the molecule M. As an example only, the compound A21-M-B10 of frame V (see entry 3162) represents an azaindol M which is substituted at position 5 by group B10 and at position 3 (through group -NH-) by group A21; likewise, compound A10-M-B70 in Table III (see entry 2083) represents an azaindol M which is substituted at position 5 by group B70 and at position 3 (through group -NH-) by the group A10: A21- -B10 A10-M-B70 TABLE F - GROUPS A TABLE G - GROUPS B EXAMPLE 1 Preparation of methyl 5-nitro-1- (phenylsulfonyl) -1H-pyrrolor2,3-b1pyridin-3-carboxylate To an ice-cooled solution of 187.7 g (0.616 moles) of tetrabutylammonium nitrate in 2.07 I of dichloromethane is added trifluoroacetic anhydride (87.5 ml), 0.616 mmoles) over a period of 25 minutes, under nitrogen. This mixture is transferred slowly, by means of a cannula, to a preformed solution of 150.0 g (0.474 moles) of 1- (phenylsulfonyl) -1H-pyrrolo [2,3-b] pyridine-3-carboxylic acid methyl ester in 2.7 I of dichloromethane at + 4 ° C. The reaction mixture is stirred at + 4 ° C for 4 hours and then maintained at this temperature for an additional 23 hours. The cold reaction mass is poured into 2.3 I of water and stirred for 1 hour. The aqueous layer is separated and extracted again with 1 g of dichloromethane. The combined organic extracts are concentrated under vacuum to a thick yellow suspension which is treated with 1.05 I of methanol. The suspension is cooled to 0 ° C and stirred for an additional 1 hour before it is filtered, washed with methanol and dried to give 128 g of the pure title compound as a fluffy yellow solid (yield = 74.7%). p.f. = 195-196 ° C 1H NMR-method 2 (DMSO): 3.91 (s, 3H), 7.64-7.69 (m, 2H), 7.76-7.81 (m, 1 H), 8.25-8.27 (m, 2H), 8.74 (s, 1 H), 8.96 (d, 1 H, J = 2.58 Hz), 9.27 (d, 1 H, J = 2.58 Hz).

EXAMPLE 2 Preparation of 5-nitro-1H-pyrrolor2,3-b1pyridine-3-carboxylate disodium To a suspension of 95.7 g (0.265 mol) of the compound of Example 1 in 1.34 I of 2,2,2-trifluoroethanol is added 0.545 I of 17% NaOH over a period of 40 minutes under vigorous stirring. The yellow-orange mixture is refluxed for 16 hours and then cooled to 0 ° C and stirred for an additional 2 hours. The precipitate is filtered off, washed with acetone and dried to give 79.8 g of the title compound as an orange crystalline solid (yield = 93.1% as tetrahydrate). p.f. > 230 ° C. 1 H NMR-method 2 (DMSO): 7.83 (broad s, 1 H), 8.89 (d, 1 H, J = 2.80 Hz), 9.07 (broad s, 1 H).

EXAMPLE 3 Preparation of 5-nitro-1H-pyrrolor-2,3-b1-pyridine-3-carboxylic acid To a clear solution of the compound of Example 2 (88.10 g, 0.35 mmol) in 2.65 I of water is added dropwise concentrated HCl (52.6 mL, 0.526 mol) diluted with 105 mL of water over a period of 50 minutes under efficient agitation to room temperature. The resulting suspension is cooled to + 4 ° C and stirred for an additional 1 hour. The above is separated by filtration, washed with water and finally dried to provide 55.6 g of the compound of the title as a light yellow powder (yield = 98.5% (title 95%)). p.f. = 282-285 ° C, with 1H NMR decomposition-method 2 (DMSO): 8.41 (d, 1 H, J = 2.83 Hz), 9.00 (d, 1 H, J = 2.59 Hz), 9.16 (d, 1 H , J = 2.59 Hz), 12.5-13.0 (broad s, 1H), 13.14 (s, 1 H).

EXAMPLE 4 Loads of isoamylamine (corresponding to fragment A32 of Table I) on a methoxybenzaldehyde polystyrene resin sensitive to acid (AMEBA resin) The resin 4- (4-formyl-3-methoxyphenoxy) butyryl Am [copoly (styrene-1% dvb) 100-200 mesh] (1.5 g, 1 equivalent, loaded 0.94 mmol / g) is expanded in DCM and then filtered . A mixture of THF / DCM (4: 1, 15 ml), 6 equivalents of isoamylamine and 6 equivalents of AcOH is added. After 15 minutes NaBH (OAc) 3 is added and the reaction is stirred overnight at room temperature. After filtration the resin is washed with methanol (x3), DMF / DCM (1: 1) (x3) and DCM (x5).

EXAMPLE 5 Preparation of A32-M-B47 Step (a): loaded with the 7-azaindole scaffold (the title compound of example 3) on the resin of example 4 To the resin of Example 4 (10 g, 0.77 mmol / g) in 100 ml of anhydrous DMF is added 3-carboxy-5-nitro-7-azaindole (2.39 g, 11.55 mmol), TBTU (3.71 g, 11.55 mmol) and DIPEA (2.92 g, 23.10 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 100 ml of DMF, 100 ml of DCM, 100 ml of DMF, 100 ml of DCM, 100 ml of MeOH, 100 ml of DCM, 100 ml of MeOH, 100 ml of DCM, 100 ml of MeOH. and TBME (100 ml x 2) and dried under vacuum to provide 11.30 g of 7-azaindole bound to resin.

Verification of resin loading The verification of resin loading is carried out to demonstrate the complete loading of the building block on the resin and that no oligomerization has occurred while coupling with TBTU. Benzoyl chloride is used in order to top off the amine loaded with unreacted resin (ie isoamylamine for example 5) and to acylate 1-NH-azaindole. The absence of bezamide (ie, isoamylbenzamide for example 5) in the separate mixture demonstrates the quantitative loading of the scaffold on the resin. The presence of 1-N-benzoylazaindole or 1-NH-azaindole demonstrates that it has not occurred as a coupling of 3-carboxy-5-nitro-7-azaindole during the resin loading step. To the resin obtained after the procedure described in Example 5 (step a) (0.035 g, 0.027 mmol) in 1 ml of DCM, DIPEA (0.035 g, 0.265 mmol) and benzoyl chloride (0.038 g, 0.265) are added. mmoles). The reaction mixture is stirred for 4 hours and the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of eOH, 1 ml of DCM, 1 ml of MeOH. and TBME (1 ml x 2) and then air-dried. The product is separated from the resin (1 ml of 60% TFA / DCM for 20 minutes) to give an off white solid (0.008 g, 80%). LCMS (shows a mixture of 1-N-benzoylated azaindole and 1-NH-azaindole): m / z 277 [M + H] +, m / z 318 [M + MeCN + H] + (17% pure 215 nm) and m / z 381 [M + H] +, m / z 322 [M + MeCN + H] + and m / z 761 [2M + H] + at t.r. 2.04 min (74% purity at 215 nm).

Step b: reduction of the nitro group To the resin obtained in step (a) (11 g, 7.5 mmol) in 100 ml of NMP is added tin chloride (II) dihydrate (15.94 g, 77 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 100 ml of DMF, 100 ml of DCM, 100 ml of DMF, 100 ml of DCM, 100 ml of MeOH, 100 ml of water, 100 ml of MeOH, 100 ml of DCM, 100 ml of MeOH. and TBME (100 ml x 2) and dried under vacuum to provide 11.05 g of 7-azaindole bound to resin. 0.01 g of resin is separated with 1 ml of 60% TFA / DCM for 20 minutes to give an off white solid (0.014 g, 74%). LCMS: m / z 247 [M + H] + and m / z 288 [M + MeCN + Hf at t.r. 1.35 min (96% purity at 215 nm).

Stage c: topped with acid chlorides To the resin of step (b) (0.11 g, 0.075 mmole) in 1 m! of DCM is added Hunig's base (0.050 g, 0.385 mmoles) second by 4-methoxybenzoyl chloride (corresponding to fragment B47 of Table II, 0.065 g, 0.385 mmoles). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1 ml of DMC, 1 ml of MeOH and TBME (1 ml x 2) and then air-dried. The resin is stirred in an acetonitrile / ammonia solution (1 ml, 4: 1) for 4 hours and then isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1.ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH, 1 ml of DMC, 1 ml of MeOH and TBME (1 ml x 2) and then air-dried. The product is separated from the resin (60% TFA / DCM, 3 x (3 x 0.5 ml)) to give an off white solid (0.016 g, 55%) of formula (I) corresponding to A32-M-B47 (see entry 964 of table III below). NMR 1H-method 1 (MeOH d-4): 8.75 (1 H, d, 2.3 Hz), 8.67 (1H, s), 7.97 (1 H, s), 7.87 (2H, d, 8.8 Hz), 6.92 ( 2H, d, 8.9 Hz), 3.75 (3H, s), 3.39 (2H, t, 7.5 Hz), 1.62-1.52 (1 H, m), 1.44-1.37 (2H, m), 0.85 (6H, d, 6.6 Hz), the indole and amide NH are not observed. LCMS (HPLC: m / z 381 [M + H] + at t.r. 1.24 min (100%, ELS detection).

Following the procedure described in the above, that is, from any suitable amino derivative that is supported on the resin according to example 4 and when working as in the previous steps of subsections (a) to (c) of the example 5 in the presence of any suitable acyl chloride derivative, the following compounds of Table III (ie, the library) are prepared: Métotfo t.r. niradaj C-ompuesltoj ... nira-da Compound Method] t, r. CLAP frnírt} í CLAP - ((m, n) 29 A14- -B30 HPLC 1 1.16 359 A13-M-8-42 HPLC_1_1 341 A1 -M-B31 HPLC 1 1.1 373? 3- A13-M-B 3 HPLC 11.27 425 3Í A14-M-B32 H LG 1 383 74 A13 / Í-B44 JHPLC 1J 1.0-3 329-32 A14- -B33 HPLC 1 0-86 305 75 A13- -B45 -ÍPLC 1 1.02 397 33 A14-M-B3-4 HPLC 1 1.17 407 A13-M-B46 IHPLC i 0.91 287 34 A14-M-B35 HPLC 10.98 383 77 A1J-M-B47 HPLC 1 1.06 353 A14-M-B36 H LC 1 1.28 3S5 78 i A13-M-B37 ÍHPLC 1 0.86 275 36 A1S-M-825 HPLC 1, 0.9S 331 A13- -838 HPLC 0.9 314 37 A1ß-M-B26 ÍHPL.C 1 0.95 3-01 80 A14- -B39 JHPLC "1.06 369 3S A15-M-g27. | HPLC..1 1.02 335 81 A14-M-B40 ÌHPf.C 1? 1.05 | 353 3? A15-M-B2S HPLC 1 327 82 A14-R? -B41 HPLC 1 333 40 A15-M-B29 HPLC 1 0.74 259 83 A144W-B4Z IHPLC 1.02 357 41 A15-M-B30 HPLC 1 H.18 3 1 84 A14-M-B43 HPLC 1 1.18 441 42 At5-M-B31 MPLO 1 1.13 355 85 A14-M-B44 HPLC 1 0.94 345 43 A15- -B32 HPLC 1 f.03 365 SS A14-M-B 59JPLC 1 0.94 413 44 A1-y.M-B33lHP.LC_ 0.87 237 87 A14-M-B46 HPLC 1 0.83 303 45 A15-M-B34 NPLC 1 1.2 3SS 88 4-M- &47 HPLC 0.99 ¡369 46 A15-M-B35 HPLC. , 1 365 89 Af4-M-B3T] HPLC ~ 0.77 291 A15-M-B36 HPLC 1 1.3 i 377? FQ A1 - -B3S ¡H¡PLC 0.S1 330 A16-M-B25 iHPLC 1 1.23 401 91 A15- -B39 IH LC 1 1.09 35149 AI € -M-KS HPLC i 1.29 407 92 A15-M-B41 HPLC 1 1.03 315 50 A16-M-B23 PLC 1 339 33 A15-M-B 2 HPLG 1 1.04 339 51 A16- -S3Q IHPLC .1 1.39 421 94 A15-IV.-B4 NC 1 0.97 327 A16-M-B31 HPLC 1 1.34 435 95 A15-M-B45, HPLC 1. i se 3S5 j A16-MW332JHPLC 1 1.24 445 36 A15-MB 6 HPLC 1 0.S4 285 54 A15-M-833 HPLC 1.1.14 367 37 A15-M-B47 HPLC. 1.02 i 351 -55 A16-M-B34IHPLC 1 1.39 469 98 A15-M-B371HPLC 0.79 273 56 A17- -25 HPLC 1 1.27 385 99 A1S-M-B38HPLC 1 0.B4 312 S? A17-M-B26 PLC 1 1.26 365 100 A16-M-B40 HPLC 1 1.3 415 SE A17- S27 WP C 1.29 399 101 Atß-MU34l HPLC 1 1.27 395 59 A17-M-B28 HPLC 1 1.34 301 102 A16-M-B42HP C "» 1.27 419 80 A17-M-B2ß H LC 1 1.05 323 103 A16-M-B44 HPLC 1 / í.22 407 61 í A17-M-ß30 H LC 1 1.43 405 304 ÍPLC 1 1.1B 475 62 A17-M-B31 NPLC 1.38 4W 105 A 6-M-B46 HPLC 1 1.11 3S5 63 A17- -B32 HPLG 1.29 429 106 A16-M-B47 HPLC 1 1.24 431 64 A17- -B33 HPLC 1 LIS 351 107 A1-6-M-B37 HPLC 1.1.07 353 65 A17-M-B34 jHPLC 1 1.43 453 108 A17-M-B39 HPLC 1 1.34? 4Í5 66 A17- S35 HPLC 1 1.28 429 109 A17-M-B41 [HPLC 1 1.32 379 67 A12- -B37 HPLC 1 1.07 341 110 A17-EVÍ-B42 HPLC 1 1.32 403 68 A12-M-S38 tiPLC 1 1.11 380 ¡11 A17-M-B43 HPLC 1 1.45 4S7 Á13- -B39 jHF C 1 1.14 353 12 A17-1VLÉ 4 NPLC 1 1.27 331 7Q A13 * M * B4Ü HPLC 1.14 337 113 A17-M-B45 HPLC 1 122 459 71 A13-M-B4 yt C 1 | 1.09 317 114 < A17-M-B46 HPLC .16 349 ^. Method t.r. Entry. Compound Ci A Input 'Method .t. Compound (mtnWCM * HT CLAP Í! 2ííll t *? P 201 A17-M-B59 HPLC 1 1.36 429 244 A12 Í3 ~ B80 HPLC 1 132 504 202 A17-M-B62 iHPLC 1 13 419 24a A13 4-881 lOd 397 203 A17-M-B60 HPLC 1 í.22 363 246 A13-M-B71 HPLC 1 1.07 357 204 Al7-y-B6B H C. 129 475 2 £ L A13-M-872 HPLC 1 1.4 459 205 A17-M-B69 HPLC 1 133 421 248 A13-M-673 HPLC 1 1.22 345 208 A17-M-B3S HPLCJ S.52 441 249 A134? -B74 1HPLC 1 1.07 401 207 A18-M-B27 HPLC Í 1.2 391 250 A 3-M-B75 HPLC 1 102 343 208 A18-M-B28 1.24 3B3 (251 A13? -B76 ÍHPLC 1 1.22 379 20S A18-M-B29 HPLC 1 G.92 315 252 A13-M-877 HP C 1 | 104 348 210 A18- -B32 HPLC 1 119 421 253 A13? -B78 ÍHPLG 1 1.33 385 211 A18- -B33 HPLC 1 107 343 254 A13-M-B7S lHPLC 1 1.12; 367 212 A18-M-B34 HPLCJ 136 445 255 A 3-M-BS0"1HPLC. 1 | 1,16 438 213 A13- > 835 HPLC. 1 118 421 256 A14-M-B81.HPLC 1 1 413 214 A12-M-B39 HPLG 1 1.3 419 257 I A14-M-B71 H LC J 0.99 383 215 A12-M-B40 HPLCJ 1.3 403 258 A144A-B72 HPLCJ 1.32 475 216 A12-M-B41 HPLCJ 1.27 383 259 A14? -B73 HPLC 1 114 361 217 A12-M-S42 HPLCJ 127 407 260 A14-M-B74 [HPLC 1 0.9S 417 218 A12-M-B43 IHPLCJ 141 491 261 A14-M-B75 HPLC 1 0.95 359 219 A12- -B44 HPLC 1 122 395 262 A14-W-B76 HPLC 1 1.14 395 220 A12- -B4S HPLCJ 1.19 463 2B3 A14-M-B77 HPLC 1 0.95 364 221 A12- -B46 HPLC 1 1.11 353 264 I A14-M-B7B HPLC 1 12ß 41 1 222 A12-M-B47 HPLC 125 419 265 j A144? -B79 HPLC 1 10 l 383 223 A21-M-B34 jHPLC J 1.37 433 266 A-? 4-M-B82 HPLC? 106? 432 224 A21-M-B3S HPLC 1 124 429 267 A14-M-SSQ HPLC 1.08; 454 225 A19-M-B26 iHPLC I 126 365 268 A15-Y? -8S1 HPLC .1 1 03 395 226 A19-M-B27 HPLC 1 1.29 399 269 | At5 4-B71 IHPLC .1 1 02 365 227 A1S- -B28 HPLCJ 133 391 270 A16-M-B72 HPLC 1 1.35 457 i A17-M-B66 IHPLC 132 403 271 A1S-M-B73 H C 1 1.17 34 229 TA17-M-B70 HPLCJ 126 365 272 A15-M-B75 H C 1 0.97 341 230 I A1B-M-B62 H C J 1.2 411 273 Al5 / f-B7β HPLC 1 1.17 377 231 A18-W-B53 HP.LC_1 1.19 402 274 A15-M-B77 HPLC 1 0.98 346 232 A184? -B64 HPLCJ 1.37 445 275 A15-M.-B79 HPLC 1 107 365 [233 ~ f A1B- -866 HPLC ... 1 1 2 4S7 276 A15-M-B80 HPLC \ 11 43S 254 A1S-M-B68 HPLC 1 1.23. 395 277 A16 / I-881 iPLC 1 1.24 475 235 A12- -B7T HPLCJ 1.24 433 278 A1 &M-B71 HPLC 1; 1.24 445 236 A12-M-B72 HPLC 1 1.52 525 279 A16-.-B72 HPLC 1 1.52 537 237 A12-M-B73 HPLCJ 13B 411 280 AI64? -B73 HPLC 1 139 423 238 A12-M-B74 iHPLC 1 1.24 487 281 A16-M-B74 HPLC 1 1.24 479 2-39 A12-M-B75 HPLC 1 121 409 282 AÍ6-M-B78 HPLCJ 146 473 240 A12- -B7S HPLC 1.37 445 283 A16- I-BS0 HPLC 1 1 32 515 241 A12-M-B77 HPLC 1 122 414 284 A17-M-BS1 HPLQ..1 128 459 242 A12-M-B78 HPLC 1 146. 461 285 A17-WI-B71 HPLC Í 429 243 A12-M-B7 & HPLC Jl 1.28 433 286 \ A17-M-B72 | HPLC .1 156 521! firtétü-do tr. Method t.r. polished Compound iSnt aífjf Compound CLAP m +? ¡* CLAP fm¡n) j W + Hj ~ 631 A23-M-B86 HPLCJ 0.99 462 674 A284? -B35 HPLC 1 112! 381 632 A23-M-B87 HPLG 1: 1.03 675 A26- -B36 1HPLC 1 137 393 633 A23- -B90 HPLCJ 1.01 426 676 A27-M-B25 HPLC 1 1.25 1 405 634 A24-M-B83 HPLC 1 0.93 444 677 A27-M-B26JHPLC T 1.2 385 635 A24-M-B86 HPLC 1 Ü.9S 476 Jli A27-M-B27 HPLC 1 127 1 419 679 A27-M-B 28 HPLC_1 131 636 A25? -383 HPLGJ 1.05 $ 59? XL B37 A25-M-B84 HPLC 1 121 4.0.1 ... 680 A27-4? -B29 HPLC 1 1.05 343" 538 A2S-M-B94 HP C 1 132 391 681 A27-M-B30 HP C 1 139 425 639 A A25-M-B85 HPLCJ 0.95 313 682 A27-M-B31 H LC 1, 35 439 6 0 A2.5-M-B86 HPÍ & 1.12 391 683 A27-3.-B32.HPLC 1 1.26 149 641 A25-M-B68 HPLCJ 115 409 684 A27-M-B33 HPL J 1.17 371 642 A25-fvt-B35 HPLC 1 1.38 4S5 685 A27-M-B34 | HPLC 1 14 473 643 A25JW-B80 HPLG ..1 1.12 355 68 A27-M-B35 | HPLC "1j 125 449 A254 / 5-B93 HPLC Í 1.19 371 687 A27-M-B36 1HPLC 1 148 461 A25-M-891 HPLC Í 1.13 329 688 A2fl-M ~ B25 H LC Í 1.19 38 & 846 A25-M-B92 HPLC I 113 ML 689 A28-M-B26 IHPLC. ,, 1 1.16 369 690 A28- -B27 HPLC .... 1 1.2 403 §47 A21-M-BS3 HPLCJ 1.24 421 648 A21-M-B84 HPLC Í 137 463 691 A28-M-B28 HP 1.24 395 27 S49 A21-WI-B94 HPLCJ 147 453 692 A28-M-B29 fiH? PLC 1 0.97 3 650 AZÍ-M-B85 JHPLG 1 113 375 693 A28? -B30JHPLC 1 1.33 409 651 A21-M-B86JHPLCJ 13 453 694 A28-M-B31 HPLC J .29 423 652 A21-M-S87 HPLG_ 1.32 494 695 A28-M-B32 NPLC 1 1.2 433 09 355 653 A2 frB89 HPLC. 1.5 527 696 A26- -833 [HPLC ._. 1 1 65 A21- -BBP. HPLC 1 128 417 697 A28-M-B34 HPLC 134 457 655 'A21 W-B93 HPLC 1 1.35 433 693 A28-M-.B35 HPLC 11 9 433 656 A21-M-B91 IHPLC 1 13 699 A2B-M-B36. HPLC 11 1.43 445 657 A21-M-B92 HPLCJ 134 700 A29-IM-B25 HPLC "íl 1.18 401 658 A19- -83 HPLC 1 127 421 701 A29-M-B2T HPLC! 115 381 559 | A19-M-B84 HPLC 1 1.4 483 702 A29-W-B27 HPLC 1, 1.19 415 sso A19-M-S85 HPLG 1 1.17 375 703 A29-M-B26 HPLC 1 123 407 661 A1 S-M-B86 HPLCJ 134 453 704 A29-M-B29 HPLC 1. 0.96 339 A29-M-B30 HPLC 1 132 421 662 A19-M-B87 [HPLC 11 1.34 494 705 S63 A19 ~ M¡-BBS HPLCJ 1.35 471 70S A28-M-B31 HPLC 1 127 435. 707 A29-M-B32 HPLC 1 1.19. { • 5' 684 A2B-M-B25. HPLCJ 11 337 665 A26-M-B26 HPLC 1 108 317 708 A29-M-B33 HPLC 1 1.09 367 666 A2S-M-B27 HPLCJ 113 351 709- A2T-M-B34 HPLC 1 133 469 667 A264? -B28 HPLCJ 1.17 343 710 A28-M-B35 HPtC J 1.18 445 711 A29-M-B36 HPLCJI 141 668 A26-M-B29 HPLC 0.87 275 28 569 A26-M-B3Q HPLC 127 357 712 A30-NI 325 HPLC 11 1 570 A26-M-831 HPLCJ 1.22 371 713 A30-M-B26 HPLC 13 126 345 A30-M-B27 HPLC 13 13 379 671 A2S-M-S32 H-PLG 1 1.13 381 714 72 A26-IV5-833 HPLCJ 1.01 303 715 A30- -B28 HPLC 1.34 371 673 A26-M-334 H LC 1 128 405 716 A30-M-B29 Ih'PLC 12 1.08 303 Method t.r. Method t, c Entry! Compound CLAP Emrad_ Compound? HS CLAP (JDÍ?) [M + Kj " 975 A28-íü5-B68 HPLC 1 127 4Q7 1 018 A31- -BT1 HPLC 1 1.02 319 376 A28- -70 HPLC 1, 1.21 359 1019 A31-M-B6B HPLG 1 1.23 441 977 A29-M-B59 HPLC 1 131 445 1 020 j A31-M-B69 iHPLC 1 1.27 1 387 978 A23-M-B62 HPLCJ 124 435 1021 A31- -BB6 HPLC 1 1.27 369 979 A29- -B63 HPLCJ 1 22 426 1 022 A31-M-B70 HPLC 1 12 331 980 A29-M-BS0- H HPLCJ 1.14 1023 A324? -B59 HPLC. 1 961 A29-M-B64 HPLCJ, 139 1024 A32-M-B62 HPLC 1 982 A29-M-B65 H LC 1 1.3 437 1025 A32- -B67 HPLC .1 1.39 415 9B3 A29- -B61 HPLC 1 102 369 1026 A324? -B63 IHPLC 124 376 984 A29-M-B68 HPLCJ 122 491 1027 A3.24y. ~ B60 HPLC 1 1.16 329 985 A29-M-B69 IHPLC 1 125 437 1028 A3-2- -B64 iHPLC i 1.42 419 986! A29- -B6S HPLC 1 126 41B 1029 A32-M-B65 HPLC 1 | 1.32 387 987 294 -B70 HPLC 1 119 381 1030 A32- -B61 HPLC 1, 04 319 988 A3s-? .-S5? HPLC I 142 409 1031 A32-M-868 HPLC 1 1.2 441 989 A3Q- -B62 H CJ 1.36 399 1032 A32-M-B69 HPLC 1 1.28 1 387 990 A30-M-B67 HP CJ 147 429 1033 A32-M-B6S HPLC 1 128 _ 369 331 A30-M-B63 HPLC J 134 390 1034 A32-IW-B70 HPLC 1 122 331 992 A3O- -B60 HPLC 1 1.27 343 1035 A264? -B81 HPLC 1 i .18 411 993 A30-M-B64 HPLC 1 1.49 433 1036 A26-M-B71 HPLC. 1 1 .17 381 934 A30-M-B65 [HPLC 1 1.42 401 1037 1 A26- -72 HPLC 1 1.48 I 473 995 A30-M-S61 HPLC 1 114 333 1038 A2é-M-B7S HPLC 1? 1.33 f 359 S36 A30-M-B68 iHPLC 1 133 455 1039 I A26-M-B74 HPLC Jl 117 415 997 A30-M-S69 H LC 1 1.37 401 1040 A26-M-B75 HPLC 1 | 113 357 998 A3P-M-866 JHPLC. .1 1.38 383 1041 A2S-M-B76 HPLC 1 133 393 999 A3O-M-B70 HPLC 1 1.32 345 1042 A26-M «B77 HPLC 1 114 362 1000 A33-M-B59 [HPLC 1 141 421 1043 A26-M-B78 HPLC 1 1 .43 409 1001 A33-M-B62 [HPLC 1 134 41 1? 64 TA26-B71? HP LC 1 122 381 10u2 A33- -BS7 HPLC 1 1 47 441 1Q45 26-M-B82 HPLC 125 430 1003 A33-M-B63 HPLC 1 132 402 1046 A26-M'B80 ÍHP LC 1 1.26 452 1004 A33-M-B60 HPLC 1j 1.25 355 1047 A27-M-B81 HPLC 1 133 479 10O5 A33-M-BS4 JHPLC 1 1.48 445 1048 I A27? -B71 H LC ^?] 132 i 449 1006 A33- »B65 IHPLC 1 1.4 413 1049 A27? -B72 HPLG 1I S9 541 10O7 A33-M-BS1 IHPLC 1 112 345 1050 A27-IW-B73 HPLC 1 147 427 1008 A33-M-B68 H C 1 132 467 1051 A274? -B74 HPLC 1 134 1 483 1009 A33-- -B89 HPLCJ, 136 413 1052 A27-M-B75 HPLC 1 13 425 1010 A33-M-S66 HPLC. 1 136 395 1 &53 A27-M-B76 HPLC 1 1 46 461 1011 A33-M-B70 'HPLC 1 1.29 357 1054 A29-M-B73 HPLC 1 139 423 1012 A31-M- &59 HPLC 1 133 395 1055 A29-M-B74 HPLC 1 124 479 1013? A31-M-B62 HPLC 1 124 385 1056 A29-M-B75 HPLC 1 1.21 421 1014 A31- -B67 HPLC 1 1.39 415 1057 A294 / I-B76 HPLC 1 138 457 1015 A31- -B63 HPLC 1 1.23 376 1053 A29-M-B77 HPLC 1 1.22 42Í 1016! A31- -B60 IHPLC 1 1 15 32 & 1059 A29-M-878 HPLC 11 147 473 1017 ¡A31-M-B65 HPLC 1 132 387 1060 * A29- -379 HPLC 1M.29 445 Eñtt-a Method to Compound I Method t.r. Mr¿daj Composite t.r. CLAP [M * r CLAP (min) t? Sj 1147 A33-663 HPLCJ 132 413 1190 A35-M-B25 IHPLC 1 1.19 415 1148 A33-BS4 HPLCJ 1.45 455 1181 A35-M-B26 SHPLC 1 115 395 1149 A33-M-B94 HPLC 1 1.55 445 1192 A38-M-S27 HPLC 1 1.21 429 1150 A33 - ?? - B85 HPLCJ 121 367 1193 A35-M-B28 iHPLC 1 125 421 1151 A334M-Bß6 W H: PLC 1 138 445 1184 A35-M-B29 HPLC 0.97 3S3 1152 A33-M-B87 HPLC 1¡ 1.39 486 1195 A35- -B30 HPLC 1 1.35 435 1153 A33-M-BJ58 HPLC..1) 1.39 463 .1196 A35-M-B31 HPLC 1 131 449 1154 A 3-M-BS3 HPLC 111531 519 Í? 197 A35- -B32 HPLC 1 121 459 1155 A33-ÍV.-B9Ü HPLC 1! 135 409 11198 A35-M-B33 jHPLCJ 109 381 1156 A33-M-B93 HPLC 1 142 425 1199 A36-M-B26 fHPLC i 0.93 372 1157 A33-891 ÍHPLCJ 138 \ 383 1200 A36-M-B33 HPLC 1 0.87 358 1158 A33-M-892 ÍHPLC 1.41 35 1201 A36-M-630 HPLC 1.26 44S 1159 A31- -83 IHPLC 1j .22 387 1202 A37-M-B2S HPLC 1 9.92 _372 A31- -B84 HPLCJ 136 429 1203 A374 / I-B26 fHPLC 1 0.87"352 5161 A31- -84 HPLC 1 1.47 419 1204 A374? -B27 HPLC 1 0.S4 386 1162 A31-M-BS5 HPLC 1 112 341 1205 A37- -B28_ HPLC.Jj 0.97 378 H163 A31-M-B86 HPLC 1 129 419 1206 A37 ~ fyf-B29 H C 0.7 l 310 1164 A31-M-BB7HPLC J 13 46O 1207 A37-M-B30 HPLC 1 1.07 392 1165 A31- -B59 HPLCJ 151 493 1208 fA37-M-B31ÍHPLG 1 102 405 1166 A31-EV1B90 HPLC 1 127 383 1209 A37 vlB32 HPLC 1 0.96 418 1167 A31- -BS3HPLC 1 1.34 399 1210 A37-M-B33 HPLC 1 0.81 333 188 A31-M-B91 HPLC 1 1.29 357 121 A37-M-B34 HPLC 1 109 440 1169 I A314.4-B92 Hp C 1 1.33 409 1212 A37-M-635 HPLC Ji .92, 4-16 1170 A32-M-B83 HPLCJ 1.24 387 1213 A37-M-8 6 jHPLC "í i 1.19 428 * 1171 A32 A-B94HPLC- 1 147 419 1214 A38-M-B25 HPL = J 0.9 372 1172 A32-M-BB5HPLC 1 1.12 341 1215 i A38-M-B2S [HPLCJ 0-85 j 352 1173 | A324? -BB6 HPLC 1- 1.3 419 1216 A38-A.-827 iHPLC. 1 0.331 385 1174 [A32- ~ B87 RTc ~? 132 460 1217 A38-Ü.1828 HPLC J j 0.97) 378 1175 A32-M-BB8 HPLC 1 132 437 1218 A38-M-B29 HPLC 1 0.69 310 1176 A32-M-889 HPLC 1 1,521 493 1219 A38-M-B30 HPLC 1.1.06 392 1177 A32- -89D HPLCJi 1281 383 1220 Á38- M ~ B3ITHPLC .1, J.02 406 1178 A32-M-BS3.HPLCJ 1.3S 399 1221 A38-M-B32 HPLC 1 0.94 41S 1179 A32-M'B91. | HPLC_11 1.3 I 357 1222 A38-M-633 H C j 0.8 338 1180 A32-M-B92 KPLCJ 134 409 1223? A38-M-B34 HPLCJ. IOS] 440 1181 A34-M-B25 HPLC 1 13 399 1224 A38-M-S35 HPLC 1 416 1182 A34-M-B27 HPLCJ 132 413 1225 A39-AI-826 HPLC t 0.91 360 1133 A34-M-B28 HPLC 1.36 405 1226 A3945-B32 MFLC 1 0.99 424 1184 A34? -B29 HPLC 1 109 337 1227 A34-M-B39 HPLCJ 1.37 429 = 155 A34-M-BS0 HIPLC 1 145 419 1228 A34-M-B42 HPLC 1 137 417 1185 A34-M-B3Z HPLG 1 132 443 1229 A34-M-B43TÜPLC 1.}. ]., '. _ 501 A34- -B33 HPLCJI.1.21 365 1230 A34-M-B95 HPLC. 1 (1.37 478) 1188 A34-M-834 HPLC l [~ 145 467 1231 A34-M-B44 [HPLC 111.37 405 1189 A34-M-B36.KPLC.Jl..154 455 1232 A34-M-B45 IHPLC 1? 137 473 Entry ¿ompuesto méte < ia. CLAP Compound Entry ... «all tr. (ln) | IM + CLAP "l¡ [M + Hf 1319 A28 ~ M * B78 HPLC 1 149 461 1362 A41-M-BS8 HPLC 1 (0.99 380 1320 A28-W-B79 HPLC 1 1 - 433 1363 A36-M-B51 HPLC 1 0.86 358 1321 A28-W-B80 HPLC 1 134 504 1364 A36- -B52 HPLC 1 0.94 372 1322 A29-M-B81 HPLC 1 125 475 1365 A3S-NI-B53 HPLC 1 106 452 1323 A29 ^ M-B71 HPLC 1f 1.24 445 1366 ¡A36- -856 HPLC 1 40S 1324 A2T-M-B90 HP CJ 127 433 1367 A38-M-B57 HPLC 1 0.97 384 1325 A29-M-B93 HPLCJ 133 449 1368 A36 _-B5S iHPLC 1 OS 420 132S A29-M-B91 HP C 1 128 407 1369 .A37-M-B48 HPLC 408 1327 A28-M-BB2 HP G 11132 469 1370 A37- «B49 JHPLG 1 0.37 402 1328 A30-M-BB3 HPLC 1 134 401 1371 A37-M-850 H C 1 0.83 391 1329 A30-M-B84 HPLC 1 1.46 443 1372 A374? -B51 H HPLC 1 0.8 338 1330 A30- -B94 HPLC 1 156 433 1373 A37-W-B52 HPLC 1 0.88 352 1331 A30-M-B85 HPLC 1 | 124 355 1374 | A37-IW-e5 HPLC 1 0.91 390 1332 A30-M-BS6 IHPLC ... 1 139 433 137.5 j A37- -B55 HPLC..1.0.94 408 1333 A30- -B87 HPLC 1 14 474 1378 A37-M-B57 H NiPLC 1 0.91 384 1334 A304W-BS8 H LC 1 141 451 1377 A37-M-B58 HPLC 1 4 ^ 0 Í335 A35- -B? 4 HPLC 1 1.36 483 137T A38- -B48 HP C 1 408 1336 A35-M-B3-6 HPLCJI 144 471 1379 A38- -B49 HPLC 1 O.Sß | 402 1337 A40- -25 HPLC 1 0.89 309 1380 A384Í-S50 HPLC 1 0.82 3S1 1338 A 0-VM328 HPLCJ; 1.05 315 1381 A384? -B51 HPLC 1 0.79 338 1339 A40-M-B31 HPLC 1, 111 343 1362 A38-IV-B52 HPLC 1 0.87 352 1340 A41- -B26 HPLG 1 0.87 332 1383 A38? -B53 HPLC 1 432 1341 A34-M-B53 HPLC 1 1.37 459 1384 A38-M-B54 NPLC., 1 0.9 390 1342 A34- -B54 HP C 1.32 417 1385 A38-M-85S HPLC 1 0.94 4D8 1343 A34-M-B55 HPLC 1.35] 435 1386 A38- -856 HPLC 1 084 386 1344 A34-M-B57 [HPLC 1 1.32 351 1387 A38-M-B57, HPLC i 0.91 Í 3 3¡6 = .. 4 1345 A34-M-B5S iHPLC 1 1.37 427 138S A3 &- -B58 HPLC 1 0.99 400 1346 A35-M.B4E HP.LC 1 1.29 451 1389 A39-M-B51 HPLC 1 084 346 1347 A35-IU-B49 HPLC 1 1.25 445 1390 A394-BS7 HPLC 1 0.961 372 1348 A35-M-850 HPLCJ 1.13 434 1391 A39-M-B5T HPLC 1 1.04 | 408 1349. A35-M-B51 HPLCJ 111 381 1352 A34- -B59, HPLC 1 13T 43 1350 A35-W-B52 HPLC 1 117? 395 1393 A34-M-66e HPLC 1 1.31 4 £? 9 1351 A35-M-B53 HPLC 1¡ 1,271 475 1394 A34-tVf-B69.HPLC 1 135 435 1352 A35-M-B54 HPLC 1 12 433 1395 A34- -B70 HPLC 1j 129 379 1353. A35-M-B55 HPLC í 124 451 1396 A35-M-859 HPLC 11123 45'9 135? | A35-M-B56 1PLC.1 1.23 429 1397 A35-M-B62 HPLC 1 122 -as. 1355, A3S-M-B57 HPLC 1 1.21 407 1398 A3S- -B64 HPLC 1 137 483 1356 A35-M-B58 HPLC 1 1.27 443 1399 A3S? -B65 HPLC 1 .28 451 1357 l A40- -BS8 JHFLC, 1 1.1 337 1400 A35-M-BS6 HPLC 1 1.24 433 135B.A41-MBS1 HPLC 1 0.79 318 1401 A414? -S60 HPLC 1 0.84 330 13591 A 14.T-B52 HPLC 1 0.87 332 1402I 41-M-B70HPLC 1 0.89- 332 1360 | A41 .1B53.HPLG 1 412 1403 A36- -B68 HPLC 1 0.99 482 1361 j A41-M-857 IHPLC J O.S 344 1404 A37-M859 HPLC 1 101 t.r. Input Com.:..resto ¡nßtßíto E-? Tratl-. Compiles .0 motocto t.r. CLAP w CLAP. { míplIjJ? + HT 1491 A37-M-B87 HPLC 1 0.99 481 1534 A4S-M-B32 H LC 1.0 $ I 39? 1492 A37-M-B88 ÍHPLC 1 0.97 458 1535 A 5-M.B33 HPLC 1 0.96 319 1493 A37-M-B 89 BHPLC 1 1.2 514 1536 A45-M-B34 HPLC 1 125 421 1494 1 A37- -B90 PLC 1 0.97 404 1537 A45-M-B36 H C 1 133 409 1455 I A37-M-B93 IHPLC 1 104 420 1538 A 6-M-B25 HPLC 11 1.21 389 1496 í A37-M * B91 jHPLC 1 0.97 378 1539 A464A-B27 fHPLC 1 122 403 1497 [A37-M-B92 HPLC 1 1.04 430 1540 A464? -B29 HPLC 1 0.97 327 1498 A38-M-683 HPLC 1 0.89 408 1541 A1 -B26 dPLC 1 122 343 1499 A38-WS-B84 HPLC 1 1.04 4S0 1542 A1- -B29 HPLC 1 1.01 301 1500 A38-M-394 HPLC 1 112 440 1543 A1- -B3Q HPLC 1 1.4 383 f 1501 A3S-M-SS5 HPLC 1 0.82 362 1544 A1-M-B33 HPLC 11 114 329 1502 A3a * M * B-87 [HPLC 1 0.98 481 1545 A1-M-B34 HPLC 1f 1.41 431 1503 ASa-M-BSQ HPLC 1 0.98 404 1546 A1-M-836 HPLC 1 15 419 150 > 4 A38-M-B52 IHPLC tj 104 430 1547 A2-M-B25 HPLC 1 122 j 371 1505 A3 &-M-B86 HPLC 1 1 448 1548 A2-IU-B29 HPLC 1 0.98 309 1506 A39- -90 HPLC 11 1.01 412 1549 A2-M-B31 jHPLC. 1¡ 1.33 405 l 1S07 | A42-M-B2S .HPLC .111.2-6 407 1 1550 A2-M-B32 HPLC 1 1.24 415 1508 A42"M-B26jJ-fPLC" l 125 387 J551 A2-M-B33 HPLCJ 1.12 337 150ß A42-M-B27 H LC 29 421 1552 A2-M-B35 HP C 1 1.23 415 1510 A42-M-B28 PLC 1 133 413 1553 A2-ÍV.-B36 IHPLC 1 1.48 427 1511 A42-M-T29 HPLC 1 1.08 345 1554 A42-M-B39 HPLC 1 133 437 1512 A42-M-B30 HPLC 1 1.4 427 1555 A42-M-B40 HPLC 1j 1.34 421 1513 A42-M-B32 HPLC 1 1.28 451 1556 _ A42-M-341 HPLC 1.}. 1 3 401 1514 A42-M-B33 HPLC 1- 1161 373 1557 f A42-M-B43 HPLC 1 1.44 509 1515 A42-M-B34 HPLC 11 139 1 475 1558 A42-M-844 HPLC 1 1.26 413 1516 A42-IW-836 HPLC 11 149! 463 1559 A42-4? -B45 HPLC 1 122 481 1517 A43-M-825 HPLC 1 104 365 1560 A42-W-B46 HPLC 1 115 371 1518 A43-Í 1826 HPLC 11 1.01 345 15S1 A42-M-B47 HPLC 1 128 437 1519 A43-M-B28 HPLC 1 | 1.1 1 371 15S2 A424M-B37 HPLC 1 1.11 359 1520 A43-M-B29 HPLC 16 0.8 3.03 j 15S3 A42-M-B3B HPLC 1 114 398 152 1 A43-M-S30 HPLCJM .22 385 1554 A43-M-B39 HPLC 1 11 395 I 1522 1 A43-M-B32 HPLCJl 107 409 1565 A43-MB40 HPLC 1 112 379 1523 A43-M-S33 HPLC 1 0.94 331 1566 A43-M-B41 HPLC 11 1.07 359 1524 A43-R? -S34 f HFIPLC 1.23 433 1557 A43-M-842 HPLC 1 IOS 383 1525 A43- -B36 ÍHPLC '133 421 1568 A43-M-B43 HPLC 1 1.23 457 1526 A44-IM-B25_JHPLC 1 1.22 391 1569 A43- -B95 HPLC 1 105 444 1527 A44-W-B29 HPLC 1. 329 1570 A43-M-B44 HPLCJ 102 371 1528 A44-M-B32 t HtPLG 1 1.24 435 1571 A43- -B45 HPLC 1 439 i 1529 A45- -825 HPLC 106 353 1572 A43-ÍM-B46 HP CJ 0.9 329 1530 A45-M-B26.HPLC 1. 1.02 333 1573 A43-M-B47 HPLC 1 | 1.07 j 395 1531 A45-M-B27 tHPiC _1 | 108 367 1574 A43-M-837 HPLG 1 0 66 i 317 1532 A45-M-B29 j HHPF LC 1. 0.82 291 1575 A43-M-S38 HPLC 1 0.891 356 1533 A4S-M-B30 M [HP.LC 1 | 1.22 373 1576. A44- -B39 HPLC 1.28 421 Entities Compound method l.t. E rad? CLAP Compound method? .r, WrriirÜ IM + Hj CLAP [M + Hf 1921 A44? -B40 132 419 1964 AI114? -B4S HPLC 1 117 371 1922 A4-M-B41 HPLC 1 1.28 393 1965 A11-M-B4B HPLC 11.12 365 1923 A4-M-S44 HPLC, 1 124 411 1966 A114? -B50IHPLC 1 0.99 354 1924 A4-M-B45 HPLCJ 1,2 479 1967JA11-M-B5 JHPLC 1 0.96 301 1925 A4-M-B4S IHPLC.1 115 3S9 1968 A11-M-B52 HPLC 1 1.03 315 1926 A3-M-B39 HPLC 1 1.27 437 1969 A11-M-B54 HPLC 1 1.07 353 1927 A3-M-841 HPLC 1 1.23 401 J970 A11-M-B55 HPLC 1 | 111 37 1328 A3-M-B43 HPLC. , 1,1.35 50S 1971 1971 A4-M-B49 HPLC 1 13 435 1929 A3-M-B44 JHFLC. 1J1.1! 413 1972 A44? -B50 HPLC 1 1.19 424 1930 A3-W-B4S HPLC 1,16 481 1973 A4- -BS1 JHPLC 1 1.1B 371 1931 A3-M-B46 JHP.LC. 1.09 i 371 1574 A4- -B52 IHPLC 1.23 385 M932 A3-M-B4? HPLC 1 1211 437 1975 A4-M-B53- HPLC 1¡ 1.32 465 1933 A3-M-B37 F H HPf LC 1 1.06 359 197B A4-M-654 HPLC 126 423 1934 A5- -B39 HPLCJ 1.23 445 1977 A4-M-B55 HPLC 1 1.3 441 1935 A5-M-840 HPLC 1 122 429 1S78 A4- -85 & HPLC 1.29 419 A5- -45 HPLC 1 1.14 489 1979 A4-M-857 JHPLC 1 1.27 397 A5-M-846 HPLCJ 108 379 1980 A4-M-B5a IHPLC 1 1.32 433 1938 A9- -B39 I.HPLC 1 1.02 436 1881 A3-M-B4S HPLC 1 1.3 443 1939 A9 »-B44 HPLC" 1 0.98 4-P2 1982 A3- -B49 HPLC 1.26 437 1940 A94.-B4S g-tPLC 1¡ 0.86 370 1S83 A3- -B50 »HPLC 1 1.14 42S 1941 A10-M-939 HPLC 1 1.US 397 1984 A3-M-B51 HPLC 111.12 373 1942 A10-M-B42 HPLCJ 107. 385 19S5 A3-M-852 HPLC 11 LIS 367 194- A10-IV.-B95 HPLC 1 oH 446 1986 A3-M-B54 HPLC.111.21 425 1944 A1044-544 HP C 1 1,021 373 1587 A3-M-BSS HPLC 1 125 443 1945 A1Q4 / 1-B48 HPLC 0.931 331 isßß A3- -B56 H C, 1 124 421 1948 A10-M-B47 HPLC. 105, 397 1989 A3- -B57 H C 1 1.21 3S9 1947 A1U-M-B37 jHPLC 1 0.9 319 1390 A3-ÍV.-B58 HPLC. 435 ' } 1S48 i A10-M-B3S HPLC 1 0.92 358 1991 A5- -B51 ÜPLC 1,11 381 1S49 A7-M-B49 H HPPLLCJ 1.18 3S7 1992 A5- -B52 HPLC 1 1.17 395 950 A7-M-B51 I HWP PLLC 1 1.02 303 1993 A5-M-B53 HPLC? .Ss 475 1951 A74? -B52 HPLC. JJ .09 317 1S94 A5-M-B54 IHPLC 1 1.19 433 1952 A7-M-B54 iHPLC 1) 1.13 355 1995 A5-M-857 HPLC 119 407 1S53 A7-M-B55 HPLCJ 116 373 1996 A5-M-B5S jHPLC .1 (1.26 443 1954 A7- -B57 ÍHPLC 1 1.12 329 1997 A9-M-849 HPLC 1 101 436 1955 A8-M-B4B IHPLC 111 357 1998 A9-.VS-B50 HPLC 0.89 42S 1956 A8-M-849 HPLC 1 1.07 351 1999 A9-M-B51 jHPLCJ 0.8B 372 1957 AB-M-B50 HPLC 1 0.93 340 200Ó A9-M-B52 HPLC 0.94 3S6 1358 AB- -B51 HPLC 1 0.9 2§L 2001 AS- -B53 HPLCJ 1.04 465 1959 AB- -B52 HPLC 1 a.98 301 2002 A94? -BS4 HPLC 1: 0.95 424 1-960 HPLC 1 1.01 339 2003 AO-M-B5S HPLC 1 0.9S 442 1961 A8-M-B55 HPLC 1105 357 2004 A9-M-B56 HPLG. 1 | 0.09 420 1962 AB-M-B57 HPLC 1 | 1.01 313 J 2005 A9- -B57 HPLC 110.96 398 19S3 A8- -B58 iHPLC. | 1.1 34JLJ 2006 A94? -B5S HPLC .04 34 I Compound Input method i. method í.r. GLAP nlraeía - (min) fflt + Hf Compound CLAP (ruin) [M + H] j 1 2179 A5-M-683 HP C 1 124 451 2222 A15-M-BS0 HPLC 1 0.91 340 J 2160 A5-M-B84 HPLC 1 137 403 2223 A16-M-B48 HPLC 1 1.34 437 2181 A5-M-BBS HPLC 1 1.14 i 405 2224 A15-M-B49 HPLC 1.29 431 | _2182 A5-W.-B87 HPLC 1.32 524 2255 A16-M-B50 HPLC "1.1i 420 1 2183 Ad-JVL-BSB HPLC 1.61 S57 222S 16-M-BS1 jHPLC 1 114 367 2184 AS-M-890 HPLC .. 129 447 2227 A16-M-B53 μ HPLC 1 1.31 4S1 2185 A5-M-B93 JHPLC. 135 463 2228 A16-M-BS5 -HPLC 1 12d 437 2186 A..5-M-S9 ___1____ JH -PL-C. __J__ 1.31 421 2229 AI6'M-BSB HPLC 1 127 415 i 2187 A5-M-B92 HPLC 1 134 473 2230 A164? -B68 HPLC 1 1.3 429 21SB I A9-M-B83 H C 11 0.98 442 2231 A17-M-B48 HPLC 1 137 42J 2189 A9-M-B84 HPLC 1 1.13 454 2232 A17-M * B53 HPLC 1 135 44g j 2190 A9-M-B94 | H C, 1 123 474 2233 A1S-M-B48 | HPLC._1 | 128 413 2191 A9-M-BS5 HPLC 1 0.89 398 2234 A1B-M * B50 HPLC 1 11 398 2152 AS-M-B86 HPLC 1 104 474 2235 A1B-M-BS1 HPLG 1, 107 343 2133 9-M-BS7 [HPLC. 108 515 2236 A18-M-B54 HPLC 1 1.19 395 2194 | A9-M-B89 IHPLC 129 548 2237 A18-M-B55 HPLC 1 1.22 413 2195 A & -M-B90 HPLC 1 105 43H 223S A18-M-B56 HPLC 1 1.22 391 2196 A9-W1-B93 HPLC 1¡ 112 454 223B A1S-M-B57 HPLC 1 1.18 369 219? A48-S? -B28 iHPLCJ 127 40? 2240 A12-M-B62 HPLC 1.26 423 2198 A48- -B33 IHPLC 1 11 3S7 2241 A12-M-B67 HPLC 1? 1.39 453 2159 A16-M-B27 HPLC 1 125 415 2242 A15-M-B64 H C 1 I 122 389 2200 A48-M-B44 HPLC 1 118 407 2243 A1S-M-B65 HPLC 1.11 357 2201 A48-M-845 HPLC I 118 475 2244 A16-M-B59 HPLC 1.33 445 2202 A48.fi/lB46 HPkC 1 108 365 22 5 A16-M-B62 HPLC 1 126 435 2203 A48-M-B47 HPLC 1 1.22 431 2246 A16-M-B60 HPLC 1 118 379_ [220 A48 .1-B37 HPLC 1 103 353 2247 A16-M-B61 HPLC 1 105 369 l 220 $ A15-WWB40 HPLC 1 108 335 2246 A16-M-B6B H LC 1 1.24 491 2206 A16-M-B39 HPLC 1 13 431 2249. A16-M-B70. HPLC 1 123 381 220? A16-M-B43 HPLC 1 142 503 2250 A13-M-B59 iHPLC 1 12S 421 220B 17-M-B 0 HPLC 134 399 2251 A16-M-B85 HPLG 1 1.27 413 2209 A18-M-B39 HPLC 1, 125 407 2252 A18-M-BS9 HPLC I 123] 413 2210 A18-W-B40 HPLC 1 125 391 2253 A48-M-B73 HPLC 1 135 423 221 1 A18- -42 HPLC 1 122 395 2254 A48-M ^ B74 HPLG 1 1.21 473 2212 A1 ß-M-846 HPLC 1 104 341 2255 A404? -B76 HPLC 1 134 457 2213 A1B-M'B47 HPLC 1 1.19 407 2256 A154? -87S .HPLC. 129 393 2214 A48- -B50 HPLC .. 1I 113 420 2257 A15-M-B; a2 H PLG V 11 414 2215 A48- M-BS1 HPLC 1 1.1 357 225S A16-M-B7 755 H HPf LC 1 121 421 2216 A48-WI-B52 HPLC 1! 118 381 2259 A16- -B77 HPLC 1 1.21 426 2217 A48-M-B-54 HPLC 1 1.21 41S 22S0 A1B-M-BB2 HPLC 1. 131 494 2218 A48- -B55 H LC 1 124 437 2261 A1S-M-B72 jHPLCj 148 513 2219 A48-M-B57 HPLC t 12 393 22 &2 A18-M-673 HPLC 1 134 399 32220 A14-ME53 HPLC 399 2263 A18-M-B74 HPLC 1 119 455 2221 A15-M-S40 HPLC 1 1.06 351 2264 A12-M-B93 HPLG 1 134 437 Cor.ipa.oat- ».Helado i.f. Entrßíls COrtliStlCS.O method t.r. Eptraiíai CLAP fm.rt) Mi? J 2437 A1-M-B77 HPLC 1 1.2 388"2480 A7- -B40 HPLC 1 (119 351 2436 A1M-B 435 2481 A7? -B42 HPLGJ 1.16 355 -78 J ^ ^ H ^ PLC_ - * "ff f -l" -4 '. -5 A1-M-B82 HPLCJ 1.3 _5§_ 2482 A74Í-B45 HPLC., 1.08 411 2439 2440 A424? -B91 HPLCJ 131 413 24S3 A74? -B37 HPLC 1 0.97 289 2441 A43-M-B87 HPLC 1 1.09 474 2484 AB4-B41 HPLC 1 104 315 2442 A44-M-BS3 HPLGJ 1.19 427 2485 AS / S- &42 HPLCJ 106 339 2443 A444 ^ 3S4JHPLCJ 133 469 2486 A844-B43 HPLC 1 121 423 2444 A444? -S89 HPLC .1 145 533 2487 A8-M-B37 HPLC 1 0.85 273 2445 A44-M-BS0 IHPLCJ 1.23 423 2488 A11-M-B39 iHPLCJ! 1.14 365 2446 A44-M-B93 HPLC 1 13 439 Í4S9 A11? -341 HPLCJ} 11 329 2447 A45- -Bß9 HPLCJ 132 495 249Q A1144-042 HPLC 1 1.1 353 5448 JA45- -B _.HPLSJ 115 42S 2491 A11-M-B43 HPLC..1 124 437 2449 A46-M-BS4 HPLC Í 1.32 467 2492 A11 - M-B45 iHPLCJ 103 409 2450 A46-M-B94 FIPLCJ 1.42 457 2493 A114 -837 HPLC 1 0.92 287 il 0.94. 326 2451 A46- -B86 ÍHPLC 1.21 457 2434 A11-M-B38HPLC. 2452 A 6r BBTEtPLC, 1 122 498 2495 A4- -B39 jHPLC 1 131 435 T 531 249S A4-M-B42 HPLC 111.28 423 2453 A464-BS9 N LCJ 1.4 2454 A46-M-B90 H C; 1.2 421 2497 A4-ÍVÍ-84 [HPLC 11139 507 H 2455 A46-M-B93 JHPLGJ 128 437 249S A4-M-B47 435 2456 A464? -B91 jHFLC 124 395 2499 fPLC 1 | 1.25 A4-M-B3S. ÍHPLC 1 | 1.15 396 2457 A464? -B92 'LC 1 1.28 447 2500 A3-M-B42 HPLC 1J1.24 425 2458 A1-M-B83 HPLC 1 121 3B9 2501 A5-M-B41 HPLC 1 | 122 409 3459: A1-M-B84 H.PLC 1 135 2502 AS-M-B42. HPLC 1j 122 433 2460 A14? -B94 HPLG 1.1.45 431 2503- A5-M-B47 HPLC 1J 1.19 445 2461 A1-M-BS1 HPLCJ 1.27 2504 A544 B37 jHPLC 1,104 367 2462 j A2-MJJB4 HPLC 1 1.32 2505 A5-M-B38 iHPLC - • - 1..1i107 _406. 2463! A2-M-BB9 HPLCJ 1.44 513 2506 A9-M-84.1.jHPLC Jj? .99 400 A2-M-B90 HPLC..1 123 403 2507 A9-M-B43 HPLC, 111.11 508 2464 0.95 485 2465 A2-M-B83 HPLGJ 1.3 419 2508 A9-M-S95 H C 11 246S A7? -B31 JHPLGJ 129 | 371 2509 A9-M-B45 HPLC.110-94- 480 5467 A7-M-B35 ÍHPLC., 1 1.17 381 2510 A9 ÚLB37 iHPLC 1 | 0.8S 358 24S8 AB- «-B31 HPLGJ 1.18 355 2511 A10-M841 HPLC. 11.07 361 2489 A11-M-B35J1PJ-S. 112 379 2512 A1D-M-B45 HPLC "1I101 441 2470 131 405 2513 A7-U-B48 HPLC 11.22. 373 2471 A4 -S31 ÍHPLC J 1.42 439 2514 A7-M-850 HPLC 1 104 366 2472 A44Í-332 HPLCJ 132 A43 2515 A741853 HPLC .111.2 397 S2473 A4- -B35 HPLCJ 1.31 44 $ 2516 A7-M-B58 HPLCJ.1.1.9 365 2474 A3- -B31 HPLCJ 1.37 441 2517 AB- -B53 HPLCJ '1.1 1 3B1 2518 AS4? -B56 HPLC 1 05 335 2475 A5.M-B28 F C 1 421 2476 A54A-830 HPLC 1 1.39 435 2519 AT1-M-B53 HPLC 1 | US 1 395 ¡2477- A5-M-B34 HPLC 1 14 4B3 2w520 A 1 3-856 HPLC 11 349 2478 A5-M-B35 HPLC 1 L48 471 12521 A11-M-B57 HPLC 1 1,071 327 2479 A104 -B26 HPLC 1 1.04 _347 j [2522 A11 Í-B58 HPLC 1 1.15! 363 Entr.i_t.ai Compound method t-f, Enter *! Compound mélodc. CLAP l (mtn flfH-Hf CLAP '(mjri) [M + Hf 2609 I 17- -B49 HPLC ll 133 415 2652 IA40- -B9S HPLC 1 137 388 2ß10fA17- -B55i JPLC 1113 1 421 2663IA34-M-BS0HPLC 1 125 i 418 2611 | A1Z-M-B63 HPLC 1.24 414 2654 A404VI-B50 HPLC..1J 0.92 328 2612 'A124 / 1864 j-iPLCJ} 14 457 2655 A40-M-BS4 HPLC 1 1 327 2613Í 12-M-B86; (PLC .1 i! »2S 40? 26S6 A4tWtf-B55 HPLC 11105 345 261 J A4S4? -660 HPLC 114 379 2657 A 0? -B56 HPLC 11104 323 2615 t A4B- -B61 HPLC 1 101 369 26S8 A344? -B67 JKPLC 1,145 463 2616 A4S-M-BS8 fHPLC 122 491 2659 A3WB63 HPLC, 1j 1.31 424 2617 I A48- -S69 J JHHPfLC .11125 437 2660 A34-M-B64 jHPLC 1f 146 467 2615 j A16-M-B64 t H-iPeLCJ 1.41 459 2661 A34-W-565 HPLC 111.39 2619 A16-M-665ÍHPLC13 132 437 2S62 A34-M-B68 MPLC 1.1.35 417 2620 A16-M-B69 HPLC 1 128 437 2683 A35-M-S67 INPLC 1Í1.36 479 2621 A16-M-B66 HPLC 1 128 419 2664 A35-M-B63 NPLC 1 1.19 440 2622 A17-M-B67 IHPLC..1 143 44S 266-5 A404 ^ -B59 HPLCJI 11 353 2623 A17-M-B65 HPLC 1 135 421 2666 A4D-IW 363 HPLC 1.0.99 334 2624 A17-M-B611HPLC.11109 353 2667 A4O-M-B60 jH LC 1 0.92 287 2625 A18-M-B61 HPLC 0.97 545 26M A40-M-B6 1HPLC 1 119 377 2626 A12- -BT2 HPLG 1 1.31 482 268 * 1 A404J-B.65 JH LCJ, 1.09 345 2627 A13- -.B82 HPLC 114 415 2670 A40- -BS8 HPLC 1 101 399 2628 f A15-M-B74 JHPLCJ 101 399 2671 A40-M-869 jHPLC 103 345 2629. A17-M-B82 HPLC 135 478 2672 A404lB6S IHPLC 1 1.03 327 2630 l A12-M-SJ4 HPLC 1.42 457 2673 A36.M-B59JHPLC 1 107 436 2631 j A48-M-BB7 HPLC ... 1 12 ¿510 2674 A34- -B7fi IHPLC 1 143 455 2632 A14-M-B90 HPLC 1 105 371 2675 A34-M-BB2HPLC 1 1.39 492 2633 A15-M-B83HPLCJ 1.01 357 267ß A3S-M-B76] HPLCJ, 135 471 2634? 15-M-B84HPLC 1 US 399 A3S-M-BB2 HPLC. 1M.29 sofí 2635 A15-A? -B9 HPLCJ 127 389 2678 A40 .1B72 JH LC 1 1.37 445 2538 A15-M-B8? HPLC 111 430 2679 A4Ü-JW-B73 HPLC Í 1.21 331 2637 A16-M-B86 HP C 129 469 2680 A40-M-878 [K LCJ 1.31 381 2638 A174? -B94 [HPLC 1 148 453 2681 A40? -B82 H G 1 1.13 402 2639 A17-M-B90 H LC 1 13-1.1 417 2682 A404 -8ß0- | HPLCUl 1.14 424 264Ú A18-M-B83 HPLC ..1111 B. 413 2683 A37-M-Bs £ JHPLCJJ 1.02 465 2641 A18-M-B85 HP C 1 | 108 367 2684 A33-MB74 HPLG 1Í0.99 458 2642 A18-M-B91 HPLCJ 125 383 2685 A34-M-B84 HPLC 11.43 477 2643 A274? -B38 HPLC 1 11? 396 2686 A34-W-BS6 H LC 1 137 467 2644 A2B- -B3B IHPLC 1 09 380 2087 A34-M-B91 HPLG 1.37 405 2645 A2941B38 HPLCJ 1.0B 3S2 26SS A354? -B94 HPLG 1 1.43 483 2648 A33-M-BS6 JBPLC, 13 391"268 * 9 A354? -B86 HPLC 1 1.25 483 264?" A27-M-B80JHPLC 1 1.4 520 650 A35-M-B90 H 124 447 264B A284 /.- 8B2 iHPLC Ji 1.33 482 2S81 A4Q- -B83 HPLC 1 0.98 345 2649 A33- -B78 HPLC 1 1.55 449 2692 A40-M-B85 IH LC. 0.89 299 A344? -B26 HPLC 1.28 379 2693 A40-M-B8? HPLC 1.08 418 A34-M-B31 JHPLC ll 141 i 433 | 2594 I 40-M-BS1 HPIC 11,06 315 m < .to «to t.r. Come in.-. Compubsto ¡eptratla Campußsro méíp or CL.AP (m¡n [M-HíT CSLAP (in) j EM-H-if 2691 A40-M-B92 IHPLC 1 1.12 367 2738 A42-fVS-B84 HPLCJ 138 4S5 2696 A41 VS-BS7 H'PLC.1 0.99 461 2739 A44-M.-B94. HPLC, 1 14 459 269. 1. A42-WS-B31 HPLC 137 441 2740 A444? -B8S HPLC 1 1.25 459 2698 A47-M-S33 H LC 1 j 1.13. 399 2741 A44-S5 |? | HPLC ~ 125 397 2699 A47-M-835 HPLCJ 11 3S9 2742 A44-M-B92 PLC 1.29 449 2700 A43-M-B31 HPLCJ 1.16 399 2743 A1-M-892 HPLC .1 132 421 2701 A44-M-B28 jHPLC 1 1.29 367 2744 A2-fv.-Bd1 HPLC .1 125 377 2702 A44-M * 'B30 IHPLGJ 137 411 274S A2-M-B92.JHPLCJ! 129 429 2703 A44-M-B34 HPLC 1 137 459 2746 A7-W-B36 NPLC .1 t.44 393 2704. A44- -B35 HPLCJJ122 435 2747 A5-M-831 HPLCJ 1.35 449 2705 A45- »S31 HPLCJ 1.17 387 2748 AS-M-B34 HPLC.1 117 474 2706 A46-M-BS0 HPLC 1 1.34 f 409. 2749 A7-M-B95 HPLCJ 111 416 2707 A46- 'B3.5 ÍHPLC 1 1.44 433 2750 A7-W-B47 H CJ 1.14 367 2708 A1-M-B32 HPLCJ 1.25 407 2751 AB44-B95 HPLCJ 400 2709 A1M-835 HPLCJ 1.25 407 2752 A114? -89S NPLC.1 1.06 414 2710. A2-M-S27.HJP_LC_ 124 365 2753 A4-M-B37 C 1.12 357 2711 A2-M-B2B HPLCJj 1.29 377 2754 A3-M-B40 HPLC 1 127 421 2712 A2-M-B34 HPLC_1 1.39 439 2755 A34-B38 HPLCJ 1.08 396 2713. A42-M-B 2 H CJ 13 425 2756 A5-M-B95 H _1 1.17 494 2714 A444 ^ -B95 HPLC 1 1.24 470 2757 A5-M-B44 HPIC..J 116 421 2715 j A444 -B38 jHFLCJ 1.09 362 2758 A9-M-B42 HPLC. 0.39 424 2716 I A47-M-B57 JHPLCJ 1.06 347 2759 AS-M-B33"HPLC" 0.85 397 2711 A44-ÍU.-B50 lHPLC_1. 112 410 2760 A7-M-B56 iHPLC 1 116 351 2718 A46- -B 9 HPLCJ 29 425 2761 A5- -B56 JHPLCJ. 122 429 2719 A42-M-B64 jHPLC J.1 1.43 f 475 2762 A541B55 HPLC 1 1.26 451 2720 A42-MB68 HPLC 1 1,271 497. 2763 A9-M-B69 ÍHPLC 1 0.99 442 2721 47-M-BS2 HPLC J 1,11 f 389 2764 A5-M-B73 IHPLC..1 1.35 437 2722 A47-M-B63 HP Ji 1091 380 2765 A5-M-B76 HPLC 1.34 471 2723 A47-M-B64 [HPLC J .1281 453 2766 A9- -B74 HPLC 1 0.99 484 2724 A47 -B &5 IHPLCJ 1,191 391 2767 A9-IYÍ-B76 [HPLCJ 1.13 462 2725 A47-M-B81 iHPLC 0.87 j 323 2768 AS-M-B82 HPLCJ 1.05 499 i 2726 A444 -B62 FHPLC 1,1,24 425 2769 A7- -B94 HPLCJ 142 405 2727 A44-M-B57 IHPLG 1 138 455 2770 A8- -BS4 HPLCJ 12 399 ! 2728 A44-.W-B63 HPLC 2771 A11-M-BB5 HPLC._1 1.17 403 j I2723 A44-M-868 IH.FLCJ 2772 A11-M-687 HPLC. 1.2 444 -2730 A46-M-888 iHPLCJ, 127 479 27731 A5-M-B86 fHPLGJ 1.31 483 2731 .A2-M-B63 JHPLGJ. 122 396 2774 A2-M-B146. | HPLC_2 | 4.87 403 2732 A24J-B65 [HPLCJ 13 407 - 2, -7 / 75 A2-M-B147 iKPL_C_2 | 5.76 445 2733 A47-I ^ B7 1HPLCJ 1.09 3 &T 277S A2-M-B148 HPLC 2i 3.16 394 2734 A47- -B72 H.PLCJ 1.39 491 2777 ^^ B149_ i LC? 4.88 423 2735 A47? -. B74 IHPLC 1 109 433 2778 A2-M-S? 50 JH LcTlI 4.15 369 ^ 2736 A44-MB32 JHPLC 127 4S4 2779 A24-B151 HPLC 2 4,47 450 2737 A46-M-B73 HFLCJ 1.39! 411 2780 A2-M-S152 IHPLCJ 5,6 454 For entries from 2774 to 2813 of Table III, 1H-NMR was also performed where (NMR method 2) and the data are presented in the following Table IV. TABLE IV EXAMPLE 6 Preparation of A32-M-B13 By working as described in Examples 4 and 5 and carrying out the capped reaction with 2-trifluoromethylbenzenesulfonyl chloride (corresponding to fragment B13 of Table II) instead of the acyl chloride derivative, the title in accordance with the following operating conditions. To the resin obtained in step (b) of example 5 (0.11 g, 0. 075 mmoles) in 1 ml of DCM are added pyridine (0.030 g, 0.385 mmol), DMAP (0.001 g, 0.0077 mmol) and 2-trifluoromethylbenzenesulfonyl chloride (0.094 g, 0.385 mmol). The reaction mixture is stirred at temperature environment for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH, TBME (1 ml x 2) and then air-dried. The product is separated from the resin (60% TFA / DCM, 3 x (3 x 0.5 ml)) to give an off white solid (0.02 g, 55%) corresponding to the compound A32-M-B13 (see entry 3364 of the table) V next). LCMS (HPLCJ): m / z 455 [M + H] + and 496 [M + MeCN + H] + at t.r. of 1.36 min (97.5% by detection of ELS). By working in accordance with any previous example, that is, by starting from any supported amino derivative on a suitable resin and by carrying out the capped reaction with any suitable sulfonyl chloride derivative in this manner, the following compounds are obtained from box V (that is, library).

TABLE V í -poto So Eniriva-. Corrtp - «_. S .. or method CLAP JÜBJ-li £ Í EWr * da |; .Ca * P" »> '» CLAP PV »f HT 2910 A8-M-B13 fHPLC 1 1.17 425 2853 | Al -M-B 16 HPLC 1 134 449 2911 A3-J? -B13 HPLC 1 .34 511 N S54 A2- -B18 HPLC 1 .J? 457 2912 A4-M-B13 HPLC 1 139 1 509 2955 A7-M-S18 HPLC 1 1.27 423 2913 A11-M-B1 3 HPLC 1 1.21 439 1 2955 A & -M-S18 HPLC 1 117 407 2914 I A94 I-B13 HPLCJ 1.08 510 I 2957 A3- -8a HPLCJ) 135 493 2315 A6-M-B13 HPLC. 1 13 505 j 2958 A11-M-S18 ÍHPLC Go 122 421 291S A104Í-B13 HPLC 1 118 471 11 2959 A6- -B1S HPLC 1 1.34 487 2S17 A1M-B14 HPLC 1 123 379 I 2960 A10-M-S18 HPLC 1 1.19 453 2e? S A2-M-B14 HPLC. 1 1.2 387 ¡2961 A7-M-B19 HPLC 1 129 2? ? 919 A7- -B1 HPLC 1 1.16 353 2962 A8-M-S19 jHPLC 1 119 407 2920 ÁS- -B14 HPLC 1 103 337 2963 A114MB19 iHPLC 1 124 421 2S21 A11-M-B14 HPLC 1 1.09 351 -5 2964 A5-M-S19 HPLC 1 134 S01 2922 A5-M-B14 HPLC 11 122 431 2965 A944-819 HPLC 1 1.11 492 2923 A94M-B1 HPLC 1 0.97 i22 i 2966 A6-M-B19 HPLC 1 135 487 2824 AS-M-B14 HPLC 1j 1.24 417 2967 A10-M-B19 HPLC 1 1.2 453 2925 A10-M-B14 HPLC 11 106 383 2968 A1 -M-B20 HPLC 1 142 467 2926 A1 A-T15 HPLC 11 1.22 399 2389 A24 / M320 HPLC 1 139 f 475 2927 A2-M- &15 NPLC 1 1.2 07 2370 A7-M-B20 IHPLC 1 136! 441 2928 A7-M-B15 HPLC 1 1.15 373 2971 AS4? -B20 IHPLC 3 1.25! 425 2929 A3-M-B15 HPLCJ 103 357 2972 A3-M-820 HPLC 1 142 ¡511 2930 A3-M-B15 HPLC 1 1.24 44Z 2373 A4-M-B20 HPLC 1 147 509 2931 A4-M-B1 S jHPLC 1? 1.2.9 4 1 2974 A114W320 IHPLC U 39 Í9 $ 2 A11-M-BÍ5 NPLC 1I 109 371 2975 A5-M.S20 HPLC 1 1.41 §19 2933 A5-M-B15 HPLCJ j 1.22 451 2_ > 7d A9-M-820 HPLC 1 117 510 2934 A9-M-B1S HPLC 1 0.97 442 29177 A &4 -820 HPLC 1 1.42 505 2935 AS-M-B13 HPLC 11 124 437 2978 A1O4.1BP0 HPLC 1 1.27 71 2936 A1P- -B-E5 HPLC (106 403 2979 A1-M-B21 HPLC 1 | - 112 365 [2937 A14? -B16 KPLC 1 126 417 2980 A24? -B21 HPLC 1 1.0S 37 2B3B A2- -18 HPLC 1 1 24 425 2981 A7-M-B21 HPLC 1 104 335- 2939 A11- -B16 HPLC 1 1.14 389 2982 A84.1-S21 HPLC 1 0.91 323-2940 A5-M-B16 | HPLC, 1j 1.26 4-69 2983 A3-M-B21 HPLC 1 1.14 403 > 2941 A9-M-B16 IHPLC 1 101 460 2984 A4-W-B21 HPLC 1j, 21 407 2942 A64 / 1-B16 IKPLC 1 128 45S 2985 A11-M-B21 IHPLC ... 1 (0.97 337 2943 A10? -B16 KPLC 1 111 421 2986 A6-MB21 .HPLC H.Í5 403 2844 A1-M-B17 WPLC 1 1.34 483 2387 A104.16 1 HPLC I 0.95 369 2945 A2-M-B17 iHPLC 13 491? 9B8 A1-4? -B22 HPLC I I 1.Í9 459 294ß [A7-M-B17 HPLC 127 457. 2999 A2-M-B22 HPLÓ I I 1.1 = 7 467 2947 1 A &-M-B17 WPLC 1 1.1? 441 ^ 29SO A6-M «B22 HPLC 1 1.22 1 497 2948 A3-M- &17 KPLC 1.34 S27 2 &91? 10-M-B22 HPLC 1 1.04 463 2949 A4-M-B17 HPLC 1 139 525 29S2 A1-M-B23 iHPLC 1 141 467 2950 AÜ- -B1? HPLC 1 1 21 455 2993 A2 * M «B23 HPLC t 1.36 475 2351! A6- -817 BPLCJI 134 521 2994 A7- -B23 HPLC 1.34 441 2S52 A10-M-B 7 HPLCJ 1 17 487 2995 | AS- -B23 HPLC 1 124 425 m6.Cort Input Compound Extruded, .RC-tOdo t.r. CLAJ5 (rain) Cop? Ous < .to J tHT CLAP (tnin) [M + Hf 2996 A3-M * 823 HPLC 11 14 511 303S j A13-M-B11 HPLC 1 0.99 325 2997 A5-M-B23 HPLC 1 139 519 3 = 040 A13-M-B12 HPLC 1 Í 131 i 401 2998 A9-M-B23 HPLC 1 11B 510 3041 AÍ4-M-B2 IHPLC. , 1j 1.06 389 2999 A6 -823 MPIC 1 141 505 3042 A14-M * B4 HPLC 1 0.81 I 327 3000 A10-M-B23 IHPLC 1 126 471 3043 A14-M-B5 HPLC 1 102 435 3001 A144-B24 HPLC 1 123 417 3044 A14-M-B6 HPLC 1! 102 405 3002 1 A2 - ?? - B24 HPLC. 1 1.2 425 3045 A1 44-87 HPLC 1, 1.25 431 3003 A7-M-B24 HPLCJ US 391 3046 1 A14-W1B8 HPLC 1 1.04 409 3004 A6- -B24 HPLC 1 1.04 375 3047 A1 M-B9 HPLC 1 1.04 411 3005 A3-M-B24 HPLC 1 1.24 461 3043 A14-M - B10 IHPLC 1 1.14 443 [3006 A44? -B24 HPLC 1 13 459 3049 A144? -811 HPLC 1 0.89 341 3007 A11-M-B24 HPLC 1 109 f- 389 3050 A14-M-B12 HPLC 1 122 417 3G0B AS-W5-B24 HPLC 1 123 469 1 3051 A1S-M-B2 HPLC 1 109 371 3009 A9-M-B24 HPLC ll -0.9? 460 3052 A15- -B4 HP1C 1) 0.84 309 3010 f A6-M-B24 HPLC 1 1.24 455 3053 A15-M-B5 HPLC 1 104} 417 3011 104? -824, 'HPLC 1 1.05 421 3054 A15-M-B6 HPLC 1 104 337 3012 A3-M-811 JHPLC l 117 4-09 305S A154Í-B8 HPLC 1 107 391 3013. A4- -11 HPLC 1 1.23 407 3056 A15-M-B9 HPLC 1 1.07 393 3014 A11- -B11 HPLC 1 101 337 i 3057 A15-M-B10 HPLC 1 117 425 301 S A6-M-B1 HPLC 1 1.17 403 3058 A15-M-B11 HPLC 1 0.92 323 3015 A10-M-B1 1 HPLC 0.98 369 3059 A15-M-B12 JHFLC .... 1 j 1 25 399 3017 A1-M-812 HPLC 1 142 441 3060 A17-M.B1 1HPLC 1 112 353- 301 to A2-M -B S2 jHPLCJ. 1.39 449 3061 A17- -B4 ÍHPLC .1 117 -373 3019 A7- -B12 HPLC 1 1.36 415 30-82 A17-M-B5 HPLC 1 13 481 3020, A8- -B12 HPLC .1 126 399 3063 1 A17-M-B8 fHPLC 1 133 3021 I A7- - B22 HPLC I 113 433 3064 A174Í-B9 IHPLC 1 133 457 3022 A8-M-B22 HPLC 1 101 417 30-85 A174? -B10 HPLC 1 142 489 3023 A3- -822 HPLCJ 1.21 503 3066 A17-M-S11 HPLC 1 123 387 302 A114? -B22 HPLC 1 1.07 431 3067 A17-M-B12 HPLC 1 147 463 3D25 A5-M-B22 IHPLC 1 1.2, 511 3068 A12-M-B13 HPLC 1 136) 493 3026 A9-iti-B22 IHPLG 11 0.96 and 502 3068 A12-M-B14 HPLC 1 126 405 3027 A12? -B1, HPLC 1 1.07 363 3070 A12-M-B1S LHPLC 1 1.26 425 3028 A12-M-B4 HPLC 1 112 377 3071 A12-M-B 1 HPLC 1 1.17 391 . «329 A 2 U-B5 HPLC 1 127 485 3072 A1244-824 HPLC 1Í 125 443 3030 AlZ-M-Bß HPLC 1 1.29 and 4S9 3073 A134? -B13 HPLC 1 122 427 3031. A12-M-B9 HPLCJ 1.29 461 3074 A13 A-B14 HPLG 1 109 339 3032 A12-W-B10. HPLC 1 1.37 493 3075 A13-M-B15 HPLC 1 1.08 358 3033 A12-M-B11 HPLC 1 118 391 3073 A13-W-B16 HPLC "1j 114 377 3034 A13-M-B1 HPLCJ 0.84 1 297 3077 A13-M-B17 HPLC 1 122 443 3035 A 134.4-84 HPLC 1 0.9 311 3078 A1 4rlB18 HPLC 1 1.23 409 303B A13-M-BS iHPLCJ 1.1 419 3079 A134Í-B19 HPLC 1 1.24 409 3037 Al34J.-B9JHP.LCJt 113 395 3000 A13-M-B20 HPLC 1 1 3 427 3038! A13- -B1Q jHPLC 11 124 42/3081 Al 41-821 iHPLC 1 | 0.90 325 Eudoda I Composite mstoao i i r. »T.r. CLAP (ín_? Mia y: Input Composed CLAP (mip) W + H7 3082 A134? -B22 HPLC 1 107 419 3125 'A22-W-BS1HPLC 0.96 436 3083 -. 3083 - A1344-B23 HPLG 1 129 427 A22- -B9 JHPLC 1 i 0.96 43d_ 3084 i A13-M-B24 iHPLC 1 1.1 377 A22-M-B10 iHPLC os: 470 3085 A14-M-B13 HPLC 1 1.13 443 Í 3128 A22-M-B11 HPLC 1 (0.S2T 36B 3086 A14-M-B1 IHPLG 1 355 3129 A22-M-B12 HPLC 1 1.13 444 3087 A14-M-B15? PLC I 101 375 3130 A23-M-B2 HPLC 0.98 444 3088 A14-M-B16 HPLC 1 104 393 131 A23-M-B3 HPLC 1 103 464 3089 A 14-M-B1 HPLC 1 1.13 459 3132 A234? -B4 HPLC 1 0.74 382 3090 A14- -B18 HPLC 1 114 425 3133 A234r1-Bfi ÍHPLC 1 0.95 490 3091 14-M-B19 HPLC 1 116 425 3434 A23- -B6 iHPLC 1 0.95 460 3092 A14-M-B2.0 HPLC 1 1.23 443 3135 A23-MB8 HPLC 1 3093 A14- -B21 HSPLC 1 0.88 1 341 3136 A2344-B9 ÍHPLC 1 3094 14- -622 iKPLC 11 0.99 (435 3137 A25- -B10 IHPLC í IOS 498 309S A14-MM323 HPLG 1 121 443 31? 8 A23-M-B11 HPLC 1 (0.82 96_ 3096 A14-M-B24 KPLC 1 1.01 393 3139 A2441B3 HPLC 102 * 478 3097 A15-M-B13 HPLC 1 1.15 425 3140 A244? -B9 IHPLC 0.96 480 3098 A15-M-B14 iHPLG 1 1, 03 337 3141 A25-M-B1 IHPLC 1 0.86 297 3099 A15-M-B1S HPLC 1 1.03 357 3142 A25-? Ü.-B2 HPLC 1 115 373 31 or A1S-M-B16 H'PLC 1.06 375 3143 A25-M-B3 HPLC i 1.21 393 3101 A15-M-B17 HPLG 1.16 441 3144 A2S-M-B4 IHPLC 1 0.91 311 3102 A 154 * 1818 HPLC 1 1.17 407 3145 A2S4? -B5 JHPLC 1.11 419- 3103 A15-M-B19 HPLC 1 119 407 3146 A25-M-B6 thPLC 1 | 1.11 3B9 > 3104 A 15 * 1820 HPLC 1 1,25 425 3147 A25- -B7 JHPLC 1 J 135 415 3105 A15-M-B21 KPLC 1 0.91 323 1 31-48 i A254.1-B6 HPLC 1 I 4. 393 3106 A15-M-B22 JHP.LC .1 1.01 417 3149 j A25- -B9 IHPLC 1 1,147 395 3107 A 154 * 1823 HPLC 1 1.24 425 3150 A25-M-B10 HPLC 1 124 I 427 3108 1S-M-B24 jKPLC 1 1.04 375 3151 A25-M-B11 HPLC 1 0.99 325 3109 A16-M-B15 HPLC 1 1.25 437 3152 A254U-B12 HPLC 1 131 401 3110 A1644-B16 KPLC 1 1.29 455 3153 A214? -B1 HPLC 108 359 3111 A16-M-B23 KPLC 1 142 505 3154 A21-M-B2 HPLC 1 1.32 435 3112 } A17- -B13 KPLC 1 1.39 489 3155 A21M-B3 1HPLC 1 136 455 3113 A _74 i-B14 KPLC 1 13 401 3156 A214? -B4; HPLC 11 1.12 and 373 3114 A17-M-B1 5 JHPLCJ 129 421 I 31S7 A21-M-S5 .'HPLC I 127 481 3115 A17-M-B1 HPLC 1 1.38 SOS 316S A21-M-B8 | HPLC "11 1.2a 451 3116 A17-M-B2Q HPLC 1 144 469 3159 A21- -B7 SHPLC 1 1.47 477 3117 A174? -B21 HPLC 1 121 3S7 31T0 A21-M-B8 IHPLC 1 1.3 455 3113 A174Í-B24 iHPLC 1 129 43§ 3161 A21-M-B9 IHPLC 1 131 45? 3119 AZ2-M-B2 HPLCJ 0.98 41S 3162 A214? -B10? HPLC 1 139 j 439 3120 A22-M-B3 HPLC 1 1.02 436 3163. A21- -B 1 IHPLC 1 11 9 387 3121 A22-W-84 JHPLC 1 0.74 354 31 S4 A21-M-B12 HPLC 1 144 463 3122 A22-M-B5 HPLC 1 0. &4 462 n A19-M-B1 IHPLCJ 11 J J59 3123 A22-M-B6 HPLC 1 O.S4 432 3166 A19-M-B2 IHPLC. 134 í 435 3124 A22-M-B7 HPLC 1 1.17 458 316? A? 9-M.B4 lHPLCjTl J ~ 7? \ F. Compound input method method t.r. CLAP (mJn) [M + f Enter the Compuos? Or CLAP (min). { M * tfp 3168 A194 -B5 iHPLC 1 481 3211 A21- -B22 HPLC 1 12 481 3169 A1944-87 JHPLCJ 15 477 3212 A21-M-B2.3 HPLC 1 139 480 3170 A19- -B8 IHPLC 1 133 455- 3213 A21M-B24 HPLC 1 123 439 3171 A194.1-89 HPLC 1 13 457 3214 A19-M-813 IHPLC: 1 1.34 4S9 3172 A19-M-B10 HPLC ... 1 142 489 3215 A1S-M-BM HPLC 1 1.25 401 3173 AÍ9-MB1 Í iHPLC 1 123 387 3216 A19-M-B15 HPLCJ 1.25 421 3174 A20-M-B1 JHPLC O.S 32? 3217 A18-M-B16 ÍKPLC 1 128 439 3175 A20-IVt-B2 HPLC 1 1.09 403 3218, A19- -B17 HPLC 1 134 505 3176 A20-M-B3 HPLC 1 1.14 423 3219 A184? -B1S IHPLC 1 1.35 471 3177 A20-MB4 HPLC 1 0.85 341 3220 A19-M-B2Q HPLC 1 1.42 489 3178 A2D-M-B5 HPLC 1 104 449 3221 A19-M-B21 HPLC 1 1.17 387 3179 A20- -B6 HPLC 11 i.OS 419 3222 A194? -B22 HPLC 1 123 481 3180 A20-M-B7 HPLC 1f l2? 445 3223 A 944-823 HPLC 1 1.41 I 489 3151 A20- -B8 HPLC 1 1, 07 423 3224 A19-M-B24 HPLC 1 1.26 1 43S 3182 A20-M-B9 HPLC 1 1.07 425 3225 A20-M-B13 JHPLC. ..1I 112 | 457 3183 A20-M-ß10 HPLC 1 1.17 457 3S28 A20- -B HPLC 1 369 3184 A20-M-B1 HPLCJ 0.93 355 3227 A £ 0 ^? - B15 'HPLC 1 38-9 3185 A20- -B12 ÍHPLC 1 1.24 431 3228 A20-M-B16: HPLC 1 104 407 3188 A22-M-B 13 HPLC T 1.01 470 322§ A20-M-B 7 HPLC 1 111 473 3187 A224W-B1 HPLC 1] 0.9 382 3230 I A204r1-B18 iHPLC 1 | U2 433 313S A22-M-B 5 HPLC 1 0.89 402 3231 f A20-M-B1 | HFLC_.1 114 Í39 3189 A22- .B1S HPLC 11 0.93 420 3232 A2O-M-B20 HPLC 1 12. 457 3190 A22-M-B 7 HPLC 1 1.01 486 3233 A20-M-B21 HPLC 1 0-89 355 3191 A22-M-B18 HPLC i 1.03 452 3234 A20-IW-B22 HPLC 1 0.98 449 3192 A22- -B19 HPLC 1 104 452 3235 I A20-M-B23. TITOLL T J, 457 I 3193 A22-M-B20 HPLC 1 1.09 4v70 3236 f A204.1-B24 H CC a, OI 407 3194 A22-iVf-B21 HPLC 1 -0.77 368 3? 37 A24-M-813 HPLC 1 0.94 4S2 A22-iy-B22 HPLC 1 0.¡ 462 3238 A24-M-B17 HPLC 1 323 3196 A22- -B23 HPLC 1 108 70 3239 A24-M-B13 HPLC 1 103 494 3197 A22-M-B24 ÍHPLC 1 0.9 420 3240 A2S4? -B13 HPLC 1 118 ¡427 3198 A23-M-BÍ3 SHPLC 1 101 498 3241 A25-M-B14 HPLC 1 106 33S 3199 A23-M-B1 HPLC 1 0.9 410 3242 A254? -B15 HPLC 1 | 106 359 3200 A23-M-B15 fHPLC 1. 0.89 430 3243 A254 -T16 JHPLC 1 1 377 j 3201 j A23-M-815 jHPLC 0.93 448 3244 A26-M-B17 fHPLC 11 118 443 3202 A23-M-B17 HPLC 1 514 3245 A25-M-B18 IHPLC 1 1.18 409 3203 A234 -B1 S HPLC 1 5.02 480 3246 A25-M-B19 HPLC 1 12 409 3204 A234.4-B19 HPLC 1 1.03 480 3247 A254.-B20 HPLC 1 1.27 427 3205 A23-M-B21 ÍHPLC., 1 0.77 395 3248 I AZ5-M-B21 - HPLC 1 0.95? 2S 3206 A23-M-B22 HPLC 0.89 490 3249 > A2S-M-B22 HPLC 1 1.04 419 3207 A214W-B18 íPLC 1 133 471 3230. .42o4 -S23 HPLC 1 j 1.25 (427 3203 A21-M-B1-9 iHPLC JJJ .33 j 471 32S1 A25-U-B24 HPLC 1 1.06 377 3209 A214.1-B20 HPLC 1 14 i 489 3252 A21-M-B13 HPLC 1 132] 469 I 3210 A21-M-B21 HPLC 1 1.14 j 33.7.)! 3253 A21- -S14 HPLC 1! 1.22. 401 EXAMPLE 7 Loaded with 4-fiorobenzylamine (corresponding to fragment A12 of Table I) on an acid-sensitive methoxybenzaldehyde resin (AMEBA II resin) The reaction is carried out by working as indicated in example 4, in the presence of 4-fluorobenzylamine instead of isoamylamine.

EXAMPLE 8 Preparation of A12-M-B139 Step a: loaded scaffold 7-azaindole (compound of the title of example 3) on the resin of example 7 To the resin of example 7 (7.5 g, 0.77 mmole) in 75 ml of anhydrous DMF are added 3-carboxy-5- nitro-7-azaindole (1794 g, 8.67 mmol), TBTU (2.78 g, 8.67 mmol) and DIPEA (2.24 g, 17.34 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 75 ml of DMF, 75 ml of DCM, 75 ml of DMF, 75 ml of DCM, 75 ml of MeOH, 75 ml of DCM, 75 ml of MeOH, 75 ml of DCM, 75 ml of MeOH. and TBME (75 ml x 2) and dried under vacuum to provide 8.50 g of 7-azaindole bound to resin.

Verification of resin loading The verification of resin loading is carried out to demonstrate the complete loading of the building block on the resin and that no oligomerization has occurred while coupling with TBTU. To the resin (0.035 g, 0.027 mmoles) in 1 ml of DCM, DIPEA (0.035 g, 0.265 mmoles) and benzoyl chloride (0.038 g, 0.265 mmoles) were added. The reaction mixture is stirred for 4 hours and the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1ml of DCM, 1ml of MeOH, and TBME (1ml x 2) and then air-dried. The product is separated from the resin (1 ml of 60% TFA / DCM for 20 minutes) to give a white solid (0.007 g, 64%). LCMS (HPLCJ) (N-benzoylated indole): m / z 419 [M + H] + at t.r.1.56 min (97% by detection of ELS). ? lid b: protection with N-BOC of 7-azaindole in solid phase To the resin obtained in step (a) (8.4 g, 5.7 mmol) in 75 ml of anhydrous DCM are added DMAP (0.07 g, 0.58 mmole) and diterbutyl carbonate (12.60 g, 57.8 mmole). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 75 ml of DMF, 75 ml of DCM, 75 ml of DMF, 75 ml of DCM, 75 ml of MeOH, 75 ml of DCM, 75 ml of MeOH and 75 ml of DCM, 75 ml of MeOH. and TBME (75 ml x 2) and dried under vacuum to provide 9.0 g of protected 7-azaindole bound to resin.

Protection verification of 1-N-azaindole The protection verification of 1-N-azaindole is carried out to demonstrate complete protection with terbutoxycarbonyl (boc) at the nitrogen atom indazole at position 1 and to demonstrate that they are not present free NH groups. To the resin (0.035 g, 0.027 mmoles) in 1 ml of DCM, DIPEA (0.035 g, 0.265 mmoles) and benzoyl chloride (0.038 g, 0.265 mmoles) are added. The reaction mixture is stirred for 4 hours and the resin is isolates by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1 ml of DCM, 1 ml of MeOH and TBME (1 ml x 2) and then air-dried. The product is separated from the resin (1 ml of 60% TFA / DCM for 20 minutes) to give an off white solid (0.008 g, 80%). LCMS (HPLCJ): m / z 315 [M + H] + at t.r. 1.26 min (91% by detection of ELS).

Step c: reduction of the nitro group To the resin of step (b) (9 g, 5.7 mmol) in 100 ml of NMP is added tin (II) chloride dihydrate (13.03 g, 57.75 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 100 ml of DMF, 100 ml of DCM, 100 ml of DMF, 100 ml of DCM, 100 ml of MeOH, 100 ml of water, 100 ml of MeOH, 100 ml of DCM, 100 ml of MeOH. , 100 ml of DCM, 100 ml of MeOH and TBME (100 ml x 2) and dried under vacuum to provide 8.8 g of resin-bound azaindole. 0.01 g of resin (1 ml of 60% TFA / DCM for 20 minutes) are removed to give an off white solid (0.0015 g, 69%). LCMS (HPLCJ): m / z 285 [M + H] + at t.r. 0.91 min (100% by detection of ELS).

Step d: formation of phenyl carbamate (and bisphenyl carbamate) To the resin of step (c) (8.8 g, 5.78 mmol) in 70 ml of DCM are added triethyl amine (11.66 g, 115.5 mmol) and phenyl chloroformate (18.01 g, 115.5 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 100 ml of DMF, 100 ml of DCM, 100 ml of DMF, 100 ml of DCM, 100 ml of MeOH, 100 ml of DCM, 100 ml of MeOH, 100 ml of DCM, 100 ml of MeOH. and TBME (100 ml x 2) and dried under vacuum to provide 9.5 g of resin bound azaindole. 0.01 g of resin (1 ml of 60% TFA / DCM for 20 minutes) are removed to give an off-white solid (0.0025 g, 62%). LCMS (HPLCJ) (only bis-carbamate is observed): m / z 525 [M + H] + at t.r. 1.47 min (97% by detection of ELS).

Step 3: Urea formation To the resin of step (d) (0.11 g, 0.077 mmol) in 1 ml of DCM, 2.6 dimethylpiperazine (corresponding to fragment B139 of Table II, 0.176 g, 1.54 mmol) is added. . The reaction mixture is stirred for 72 hours and then the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1 ml of DCM, 1 ml of MeOH and TBME (1 ml x 2) and then air-dried. The product is separated from the resin (TFA 60% / DCM, 3 x (3 x 0.5 ml)) to give an off white solid (0.031 g, 95%). corresponding to compound A12-M-B139 (see entry 3769 in Table VI below). NMR 1H-method 1 (MeOH d-4): 8.65 (1 H, d, 2.3 Hz), 8.46 (1 H, d, 2.3 Hz), 8.13 (1 H, s), 7.44-7.37 (2H, m) , 7.10-7.03 (2H, m), 4.57 (2H, s), 4.42 (1H, dd, 14.4 Hz, 2.0 Hz), 3.49-3.38 (1H, m), 3.34-3.31 (2H, m), 2.98- 2.89 (2H, m), 1.39 (6H, d, 6.6 Hz), the indole and amide NH are not observed; LCMS (PHPCJ): m / z 425 [M + H] + at t.r. 0.95 min (98% by ELS detection). When working in a manner analogous to that described above and using any suitable initial material and reactive thereof, the following compounds of Table VI (ie the library) are prepared TABLE VI Compound Efitrac? Iltód? I t-rrrtííotto: gfU aífaj C o. «Position tr. f AUMn) [IW + HT CLAP (tnlnj- [M-t-H 3ßes AB-MB109 HPLC 1 0.75 371 Í 3728 A13-M-B132 HPLC 1 0.91 421 3886 I A8-M-B11 S HPLC 1 0.75 318 3728 A29-M-812S HPLC 1 0.92 431 3687 A8-M-B117 HPLC 1 0.74 365 3730 A2S-M-B123 HPLC 1 0.97 451 3689 A84? -B11 B HPLCJ 0.78 371 3731 A29-M-B129 HPLC 1 1.07 503 36d§ A124Í-B1 0 HPLC 1 1.09 382 3732 A2S-M-B130 HPLC 1 0.95 I 452 3SQQ A12- S120 HPLCJ 0.93 439 3733 A29-W-B131 HPLC 1 1.12 426 I 3591 A124? -B121 HPLC 1 1.23 39S 3734 AI29-M-B133 HPLC 1 0.96 459 3692 IA12-M-YES22 HPLC 1 124 398 373S A29-M-B132 HPLCJJ I.06 499 36S3 -A12-M-B123 HPLCJ 0.98 474 3736 A25-M-812S HPLC 1 0.75 353 1 0.S1 408 3737 A25-M-B129.HPLC Jl Q.93 425. ? 6S5 A294? -B119.H.PLC 1 1.07 394 3.738 A55- -B130IHPLC 11 0.79 574 ' 3696 A29-M-B1ZQ HPLC 1 0.96 451 3-739 A25-M-.3131 HPLC 1 Q.97 34? 3697 A29-M-B121 HPLC 11 122 410 3740 A254MB1331HPLC 1 0.81 381 369B A29-M -B122 H LCJ i 123 410 3741 JA25- -B132IHPLC 1 O.92 421 3699 A29.M »B123 | HPLC 1 0.96 486 37421 A2-M-B126 HPLC 1 0.9 401 370O JA254.1-B120.HPLG 1 • 0.81 373 3743 A241-B129 HPLC 1 106 473 3701 JA2544-B121 HPLC 1 107 332 3744 A24? -ai30 IHPLC .1 0.93 422 3702 IA25-M-B1? 2IHPLCJ 109 332 3745 &M-8131 HPLC 1 111 i 396 3703 'A2S-M-B124rH LCJ 1.1 332 3746 I A24I-B132 HPLC 1 | 1.04 469 3704; A254 -B123 HPLC..1 0.B1 4? To 3747 A1S-M-B126 HPLC 1 0.99 415 3705 A2-M-B120 HPLC 1 0.S4 421 3748 A19-M-B127 HPLC 1 138 420 370S A24? -B121 HPLC 1 1.21 380 3749 A19-M-B128 HPLC 1 1 03 435 3707 A -B122 HPLC- 1 122 3S0 3750 A194.VB12SHHPLC 1 1.13 487 3706 A2-M-B124 HPLCJ 122 380 3751: A19 ».B130JHPLC 1j 101 43S 3709 A24W3123 ÍHPLC 1 0.94 45S 3752 A .9-M-B131 jHPLC 1 | 1.19 410 3710 A19-M-B120IHPLC 11 102 435 3753 A194? -B134 HPLC n? . -175 371Í "A19-M-BT2SIHPLC 1 129 406 3754 WMWai33> HPLC 11 -1.02 43 3712 A19-J? -B121 HPLC 1 127 394 3755 IA1F-M-B132 HPLC 1 1 .12 4T3 3713- AÍ9-M-B122 HPLCJ 128 394 3756 IA454W-B129 HPLC 1 0.9 455 3714 IA19- -B 23 HPLC 1 102 470 3757 JA45-M-B131 HPLCJ 0.93 37-S j 3715 A454? -8119 HPLC 1 O.B9 346 3758 A454? -B132 HPLC 1 0.89 451 3716 A454.-8120 HPLC 1 0.79 403 3759 A8-M-B126 HPLC. 11 0.72 351 3717 AS-M-B122 HPLC 11 107 330 3760 J 8-M-B129 HPLC 1 0 9 423 F 3719 AS-M-B123 HPLC 1 0.76 4-06 (3761 AB4W-B 131 HPLC II 0.93 346 3719 AI1241-B126 HPLCJ 0.94 419 3762 A8-M-B134 HPLC 1 0.79 411 3720 ¡A12-M-B127 HPLC 1 134 424 3753 A8-M-B133 HPLC 1 0.7S 379 3721 A1241B128 HPLC 1 0.93 439 3764 A8-M-8132 HPLC 1 0.6 f 419 ; 3722 A12- -B129 iHPLC 1 109 401 3765 A12-M-8135 HPLC J 1.11 [414 3723 A12-M-B130 HPLC 1 0.97 440 375ß A12-M-B13SJH LC 1 132 | 424 5724 A12- -B131 HPLC 1 1.14 414 3757 A12-M-8137 IHPLC 1 412 3725 A1245-B132 HPLC 1 1.08 457 3768 A12-M-813S HPLCJ 0.93 441 3726 A134.1B129 HPLC 1 0.92 425 3769 A124? -S139 HPLC 1 0.95 4 = S 3727 A13-M-B131 HPLC 11 0.95 348 3770 A12-M.ST40 iHPLC 1 11? J EXAMPLE 9 Loaded with piperazine (corresponding to fragment A50 of Table 1) on a PNP Wang resin To a stirred suspension of PNP Wang resin (Wang p-nitrophenyl carbonate resin, 4.7 g, 0.52 mmol / g, 2.5 mmol) in 50 ml of anhydrous DMF at room temperature is added piperazine (0.637 g, 7.41 mmol) and base de Hunig (0.956 g, 7.41 mmoles). The reaction mixture is stirred for 20 hours and isolated by filtration. The resin is washed sequentially with 50 ml of DMF, 50 ml of DCM, 50 ml of DMF, 50 ml of DCM, 50 ml of MeOH, 50 ml of DCM, 50 ml of MeOH, 50 ml of DCM, 50 ml of MeOH. , TBME (50 ml x 2) and dried under vacuum to provide 4.6 g of resin bound diamine. The resin bound carbonate is captured on the next stage without further analysis.

EXAMPLE 10 Preparation of A50-M-B25 Step a: loaded scaffold 7-azaindole (compound of the title of example 3) on the resin of example 9 To the resin (4.6 g, 0.52 mmoles / g, 2.4 mmoles) in 50 ml of anhydrous DMF is added 3-carboxy -5-nitro-7-azaindazole (0.743 g, 3.588 mmol), TBTU (1,152 g, 3,588 mmol) and DIPEA (0.927 g, 7,176 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 50 ml of DMF, 50 ml of DCM, 50 ml of DMF, 50 ml of DCM, 50 ml of MeOH, 50 ml of DCM, 50 ml of MeOH, 50 ml of DCM, 50 ml of MeOH , TBME (50 ml x 2) and dried under vacuum to provide 5.2 g of 7-azaindole bound to resin.

Verification of resin loaded To the resin (0.035 g, 0.0182 mmoles) in 1 ml of DCM add DIPEA (0.024 g)0.182 mmole) and benzoyl chloride (0.025 g, 0.182 mmole). The reaction mixture is stirred for 4 hours and then the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1 ml of DCM, 1 ml of MeOH, TBME (1 ml x 2) and then air-dried. The product is separated from the resin (1 ml of 40% TFA / DCM) to give an off white solid (0.008 g, 80%). LCMS: m / z 380 [M + H] +, m / z 421 [M + MeCN + H] + at t.r. 1.44 min (84% purity at 215 nm).

Step b: reduction of the nitro group To the resin (5 g, 2.3 mmol) in 50 ml of NMP is added tin (II) chloride dihydrate (5.4 g, 23.92 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 50 ml of DMF, 50 ml of DCM, 50 ml of DMF, 50 ml of DCM, 50 ml of MeOH, 50 ml of water, 50 ml of MeOH, 50 ml of DCM, 50 ml of MeOH. , 50 ml of DCM, 50 ml of MeOH, TBME (50 ml x 2) and dried under vacuum to provide 5.0 g of resin bound azaindole. 0.01 g of resin (1 ml of 40% TFA / DCM) is removed to give an off white solid (0.0009 g, 75%). LCMS: m / z 246 [M + Hf to t.r. 0.22 min (94% purity at 215 nm).

Stage c: topped with acid chlorides To the resin (0.11 g, 0.025 mmol) in 1 ml of DCM is added Hunig's base (0.034 g, 0.26 mmol) and benzoyl chloride which corresponds to fragment B25 of Table II, 0.036 g, 0.26 mmole). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1 ml of DCM, 1 ml of MeOH, TBME (1 ml x 2) and then air-dried. The resin is stirred in an acetonitrile / ammonia solution (1 ml, 4: 1) for 4 hours and then isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH , 1 ml of DCM, 1 ml of MeOH, TBME (1 ml x 2) and then air-dried. The product is separated from the resin (TFA 40% / DCM, 3 x 0.5 ml) to provide a whitish solid (0.012 g, 63%) corresponding to compound A50-M-B25 (see entry 3808 of Table VII below). LCMS (HPLCJ): m / z 350 [M + H] + at t.r. 0.83 min (95% by ELS detection). When working as described in Example 10 and using any amino derivative supported on suitable resin and acyl chloride reagent, the following compounds (for example library) are prepared: TABLE VII EXAMPLE 11 Preparation of A50-M-B1 The title compound is prepared by working as described in steps (a) and (b) of Example 10 and by carrying out the finishing reaction of step (c) with sulfonyl chloride, as follows: Step c: topped with sulfonyl chlorides To the resin (0.11 g, 0.052 mmol) which is obtained in step (b) of example 10 in 1 ml of DCM is added pyridine (0.021 g, 0.26 mmol), DMAP (0.001 g, 0.0052 mmol) and methanesulfonyl chloride (corresponding to fragment B1 of Table II, 0.030 g, 0.26 mmol). The reaction mixture is stirred at room temperature for 20 hours and then the resin is isolated by filtration. The resin is washed sequentially with 1 ml of DMF, 1 ml of DCM, 1 ml of DMF, 1 ml of DCM, 1 ml of MeOH, 1 ml of water, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH, 1 ml of DCM, 1 ml of MeOH, TBME (1 ml x 2) and then air-dried. The product is separated from the resin (TFA 40% / DCM 3 x 0.5 ml) to provide a whitish solid (0.018 g, 100%) corresponding to the compound of the title A50-M-B1 (see entry 3858 of table VIII). LCMS (HPLCJ): m / z 324 [M + H] + at t.r. 0.22 min (92% by ELS detection). When working as described in Example 11 and using any amino derivative supported on suitable resin and sulfonyl chloride reagent, the following compounds are prepared: TABLE VIII carriers, metabolites, prodrugs and pharmaceutically acceptable salts thereof. 2. The compound of formula (I) according to claim 1, further characterized in that R is Ra and R-i is -NRcRd. 3. The compound of formula (I) according to claim 1, further characterized in that R is -CORa and R-i is -NRcRd. 4. The compound of formula (I) according to claim 1, further characterized in that R is -CONRaRb and R-i is -NRcRd. 5. The compound of formula (I) according to claim 1, further characterized in that R is -S02Ra and Ri is -NRcRd. 6. The compound of formula (I) according to claim 1, further characterized in that R is -C00R3 and Ri is -NRcRd. 7. The compound of formula (I) according to claim 1, further characterized in that R ^ is -ORc. 8. The compound of formula (I) according to claim 1, further characterized in that Ra, Rb, Rc and Rd are each independently selected as defined in tables I and II. 9. The compound of formula (I) according to claim 1, further characterized in that it additionally comprises Ra, Rb, Rc and Rd which are independently optionally substituted by a portion selected from the group consisting of halogen, nitro , oxo groups (= 0), carboxy, cyano, alkyl, polyfluorinated alkyl,

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A compound of formula (I) wherein R is selected from the group consisting of -Ra, -CORa, -CONRaRb, -S02Ra or -COORa; R-, is a group -NRcRd or -ORc; wherein Ra, Rb, Rc and Rd are identical or different and are each independently hydrogen or an optionally substituted group, which is selected from linear or branched alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 linear or branched carbon atoms, linear or branched alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms or cycloalkylalkyl of 1 to 6 carbon atoms, aryl or arylalkyl of 1 to 6 carbon atoms or heterocycle or heterocycloalkyl of 1 to 6 carbon atoms or, taken together with the nitrogen atom to which they are attached, either Ra and Rb as well as Rc and Rd can form an optionally substituted 4- to 7-membered heterocycle, optionally containing a heteroatom or an additional heteroatomic group which is selected from S, O, N or NH; or isomers, tautomers, alkenyl, alkynyl, cycloalkyl, cycloalkenyl; aril; heterocyclyl, aminoalkylamino, dialkylamino, arylamino, diarylamino, ureido, alkylureido or arylureido; carbonylamino, formylamino, alkylcarbonylamino, alkenylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino; hydroxy, alkoxy, aryloxy, alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy or alkylidenaminoxy; alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl; alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, arisulfinyl, aryisulphonyloxy, aminosulfonyl, alkylaminosulfonyl and dyalkylaminosulfonyl. 10. The compound of formula (I) according to claim 1, further characterized in that it is selected from: A12-M-B25, A12-M-B26, A12-M-B27, A12-M-B28, A12- M-B29, A12-M-B30, A12-M-B31, A12-M-B32, A12-M-B33, A12-M-B34, A12-M-B35, A12-M-B36, A13-M- B25, A13-M-B26, A13-M-B27, A13-M-B28, A13-M-B29, A13-M-B30, A13-M-B31, A13-M-B32, A13-M-B33, A13-M-B34, A13-M-B35, A13-M-B36, A14-M-B25, A14-M-B26, A14-M-B27, A14-M-B28, A14-M-B30, A14- M-B31, A14-M-B32, A14-M-B33, A14-M-B34, A14-M-B35, A14-M-B36, A15-M-B25, A15-M-B26, A15-M- B27, A15-M-B28, A15-M-B29, A16-M-B30, A15-M-B31, A15-M-B32, A15-M-B33, A15-M-B34, A15-M-B35, A15-M-B36, A16-M-B25, A16-M-B28, A16-M-B29, A16-M-B30, A16-M-B31, A16-M-B32, A16-M-B33, A16- M-B34, A17-M-B25, A17-M-B26, A17-M-B27, A17-M-B28, A17-M-B29, A17-M-B30, A17-M-B31, A17-M- B32, A17-M-B33, A17-M-B34, A17-M-B35, A12-M- B37, A12-M-B38, A13-M-B39, A13-M-B40, A13-M-B41, A13-M-B42, A13-M-B43, A13-M-B44, A13-M-B45, A13-M-B46, A13-M-B47, A13-M-B37, A13-M-B38, A14-M-B39, A14-M-B40, A14-M-B41, A14-M-B42, A14- M-B43, A14-M-B44, A14-M-B45, A14-M-B46, A14-M-B47, A14-M-B37, A14-M-B38, A15-M-B39, A15-M- B41, A15-M-42, A15-M-B44, A15-M-B45, A15-M-B46, A15-M-B47, A15-M-B37, A15-M-B38, A16-M-B40, A16-M-B41, A16-M-B42, A16-M-B44, A16-M-B45, A16-M-B46, A16-M-B47, A16-M-B37, A17-M-B39, A17- M-B41, A17-M-B42, A17-M-B43, A17-M-B44, A17-M-B45, A17-M-B46, A17-M-B47, A17-M-B37, A17-M- B38, A18-M-B45, A18-M-B37, A12-M-B48, A12-M-B49, A12-M-B50, A12-M-B51, A12-M-B52, A12-M-B53, A12-M-B54, A12-M-B55, A12-M-B56, A12-M-B57, A12-M-B58, A13-M-B48, A13-M-B49, A13-M-B50, A13- M-B51, A13-M-B52, A13-M-B53, A13-M-B54, A13-M-B55, A13-M-B56, A13-M-B58, A14-M-B48, A14-M- B49, A14-M-B50, A14-M-B51, A14-M-B52, A14-M-B54, A14-M-B55, A14-M-B56, A14-M-B57, A14-M-B58, A15-M-B48, A19-M-B58, A20-M-B48, A20-M-B49, A15-M-B51, A15-M-B5 2, A15-M-B55, A15-M-B56, A15-M-B57, A15-M-B58, A16-M-B52, A16-M-B54, A16-M-B57, A17-M-B50, A17-M-B51, A17-M-B52, A17-M-B54, A17-M-B56, A17-M-B57, A17-M-B58, A12-M-B59, A12-M-B60, A12- M-B61, A13-M-B59, A13-M-B62, A13-M-B63, A13-M-B60, A13-M-B64, A13-M-B65, A13-M-B61, A13-M- B66, A14-M-B59, A14-M-B62, A14-M-B67, A14-M-B60, A14-M-B64, A14-M-B65, A14-M-B61, A14-M-B68, A14-M-B69, A14-M-B66, A14-M-B70, A15-M-B59, A15-M-B62, A15-M-B63, A15-M-B60, A15-M-B61, A15- M-B68, A15-M-B66, A15-M-B70, A17-M-B59, A17-M-B62, A17-M-B60, A17-M-B68, A17-M- B69, A17-M-B36, A18-M-B27, A18-M-B28, A18-M-B29, A18-M-B32, A18-M-B33, A18-M-B34, A18-M-B35, A12-M-B39, A12-M-B40, A12-M-B41, A12-M-B421, A12-M-B43, A12-M-B441, A12-M-B451, A12-M-B461, A12- M-B471, A21-M-B34, A21-M-B35, A19-M-B26, A19-M-B27, A19-M-B28, A17-M-B66, A17-M-B70, A18-M- B62, A18-M-B63, A1B-M-B64, A18-M-B68, A18-M-B66, A12-M-B71, A12-M-B72, A12-M-B73, A12-M-B74, A12-M-B75, A12-M-B76, A12-M-B77, A12-M-B78, A12-M-B79, A12-M-B80, A13-M-B81, A13-M-B71, A13- M-B72, A13-M-B73, A13-M-B74, A13-M-B75, A13-M-B76, A13-M-B77, A13-M-B78, A13-M-B79, A13-M- B80, A14-M-B81, A14-M-B71, A14-M-B72, A14-M-B73, A14-M-B74, A14-M-B75, A14-M-B76, A14-M-B77, A14-M-B78, A14-M-B79, A14-M-B82, A14-M-B80, A15-M-B81, A15-M-B71, A15-M-B72, A15-M-B73, A15- M-B75, A15-M-B76, A15-M-B77, A15-M-B79, A15-M-B80, A16-M-B81, A16-M-B71, A16-M-B72, A16-M- B73, A16-M-B74, A16-M-B78, A16-M-B80, A17-M-B81, A17-M-B71, A17-M-B72, A17-M-B73, A17-M-B74, A17-M-B75, A17-M-B76, A17-M-B77, A17-M-B78, A17-M-B79, A17-M -B80, A18-M-B75, 18-M-B77, A18-M-B79, A18-M-B80, A12-M-B83, A12-M-B84, A12-M-B85, A12-M-B86 , A12-M-B87, A12-M-B88, A12-M-B89, A12-M-B90, A12-M-B91, A12-M-B92, A13-M-B83, A13-M-B84, A13 -M-B85, A13-M-B86, A13-M-B87, A13-M-B89, A19-M-B29, A13-M-B90, A13-M-B93, A13-M-B91, A14-M -B83, A14-M-B84, A14-M-B94, A14-M-B85, A14-M-B86, A14-M-B87, A14-M-B89, A14-M-B93, A14-M-B91 , A14-M-B92, A15-M-B86, A15-M-B89, A15-M-B90, A15-M-B93, A15-M-B91, A16-M-B85, A17-M-B85, A17 -M-B86, A17-M-B87, A17-M-B89, A19-M-B30, A19-M-B31, A19-M-B32, A19-M-B33, A19-M-B34, A19-M-B36, A20-M-B25, A19-M-B48, A19-M-B49, A19-M-B51, A19-M-B52, A19-M-B53, 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A19-M -B40, A19-M-B41, A19-M-B42, A19-M-B43, A19-M-B44, A19-M-B45, A19-M-B46, A19-M-B47, A19-M-B37 , A19-M-B38F, A20-M-B39, A20-M-B40, A20-M-B41, A20-M-B42, A20-M-B43, A20-M-B44, A20-M-B45, A20 -M-B46, A20-M-B47, A20-M-B38, A22-M-B58, A23-M-B48, A23-M-B50, A23-M-B51, A23-M-B55, A25-M -B48, A25-M-B491, A25-M-B501, A25-M-B51, A25-M-B52, A25-M-B531, A25-M-B54, A25-M-B55, A25-M-B56 , A25-M-B57, A25-M-B58, A21-M-B48, A21-M-B49, A21-M-B50, A21-M-B51, A21-M-B52, A21-M-B53, A21-M-B54, A21-M-B55, A21-M-B56, A21-M-B57, A21-M-B58, A20-M-B57, A20- M-B58, A22-M-B59, A22-M-B63, A22-M-B60, A22-M-B64, A22-M-B65, A22-M-B68, A22-M-B70, A23-M- B59, A23-M-B62, A23-M-B67, A23-M-B53, A23-M-B64, A23-M-B65, A23-M-B61, A23-M-B68, A23-M-B69, A23-M-B66, A23-M-B70, A24-M-B59, A24-M-B62, A24-M-B67, A24-M-B63, A24-M-B64, A24-M-B65, A24- M-B68, A24-M-B69, A24-M-B66, A24-M-B70, A25-M-B59, A25-M-B62, A25-M-B67, A25-M-B63, A25-M- B60, A25-M-B64, A25-M-B65, A25-M-B61, A25-M-B68, A25-M-B69, A25-M-B66, A25-M-B70, 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A31-M-B83, A31-M-B54, A31-M-B94, A31-M-B85, A31-M-B86, A31-M -B87, A31-M-B89, A31-M-1390, A31-M-B93, A31-M-B91, A31-M-B92, A32-M-B83, A32-M-B94, A32-M-B85, A32-M-B86, A32-M-B87, A32-M-B88, A32-M-B89, A32-M-B90, A32-M-B93, A322- M-B91, A32-M-B92, A34-M-B25, A34-M-B27, A34-M-B28, A34-M-B29, A34-M-B30, A34-M-B32, A34-M- B33, A34-M-B34, A34-M-B36, A35-M-B25, A35-M-B26, A35-M-B27, A35-M-B28, A35-M-B29, A35-M-B30, A35-M-B31, A35-M-B32, A35-M-B33, A36-M-B26, A36-M-B33, A36-M-B36, A37-M-B25, A37-M-626, A37- M-B27, A37-M-B28, A37-M-B29, A37-M-B30, A37-M-B31, A37-M-B32, A37-M-B33, A37-M-B34, A37-M- B35, A37-M-B36, A38-M-B25, A38-M-B26, A38-M-B27, A38-M-B28, A38-M-B29, A38-M-B30, A38-M-B31, A38-M-B32, A38-M-B33, A38-M-B34, A38-M-B35, A39-M-B26, A39-M-B32, A34-M-B39, A34-M-B42, A34- M-B43, A34-M-B95, A34-M-B44, A34-M-B45, A34-M-B46, A34-M-B47, A34-M-B37, A34-M-B38, A35-M- B39, A35-M-B40, A35-M-B41, A35-M-B42, A35-M-B43, A35-M-B95, A35-M-B44, A35-M-B45, A35-M-B46, A35-M-B47, A35-M-B37, A40-M-B40, A40-M-B44, A40-M-B46, A40-M-B47, A40-M-B37, A41-M-B95, A41- M-B45, A36-M-B43, A36-M-B95, A36-M-B45, A36-M-B46, A36-M-B37, A37-M-B40, A37-M -B41, A37-M-B42, A37-M-B95, A37-M-B44, A37-M-B45, A37-M-B46, A37-M-B47, A37-M-B37, A38-M-B39 , A38-M-B40, A38-M-B41, A38-M-B42, A38-M-B95, A38-M-B44, A38-M-B45, A38-M-B47, A38-M-B37, A39 -M-B43, A39-M-B95, A39-M-B45, A39-M-B46, A39-M-B37, A34-M-B48, A34-M-B49, A34-M-B51, A34-M -B52, A32-M-B38, A26-M-B48, A26-M-B49, A26-M-B50, A26-M-B51, A26-M-B61, A26-M-B68, A26-M-B69 , A26-M-B66, A26-M-B70, A27-M-B59, A27-M-B62, A27-M-B67, A27-M-B63, A27-M-B60, A27-M-B64, A27 -M-B65, A27-M-B61, A27-M-B68, A27-M-B69, A27-M-B66, A27-M-B70, A27-M-B77, A27-M-B78, A27-M-B79, A28-M-B81, A28-M-B71, A28-M-B73, A28-M-B74, A28-M-B75, A28- M-B76, A28-M-B77, A2B-M-B78, A28-M-B79, A28-M-B80, A29-M-B81, A29-M-B71, A29-M-B90, A29-M- B93, A29-M-B91, A29-M-B92, A30-M-B83, A30-M-B84, A30-M-B94, A30-M-B85, A30-M-B86, A30-M-B87, A30-M-B88, A35-M-B34, A35-M-B36, A40-M-B25, A40-M-B28, A40-M-B31, A41-M-B26, A34-M-B53, A34- M-B54, A34-M-B55, A34-M-B57, A34-M-B58, A35-M-B48, A35-M-B49, A35-M-B50, A35-M-B51, A35-M- B52, A35-M-B53, A35-M-B54, A35-M-B55, A35-M-B56, A35-M-B57, A35-M-B58, A40-M-B58, A41-M-B51, A41-M-B52, A41-M-B53, A41-M-B57, A41-M-B58, A36-M-B51, A36-M-B52, A36-M-B53, A36-M-B56, A36- M-B57, A36-M-B58, A37-M-B48, A37-M-B49, A37-M-B50, A37-M-B51, A37-M-B52, A37-M-B54, A37-M- B55, A37-M-B57, A37-M-B58, A38-M-B48, A38-M-B49, A38-M-B50, A38-M-B51, A38-M-B52, A38-M-B53, A38-M-B54, A38-M-B55, A38-M-B56, A38-M-B57, A38-M-B58, A39-M-B51, A39-M-B57, A39-M-B58, A34- M-B59, A34-M-B68, A34-M-B69, A34-M-B70, A35-M-B59, A35-M-B62, A35-M-B64, A35-M-B65, A35-M-B66, A41 -M-B60, A41-M-B70, A36-M-B68, A37-M-B59, A37-M-B62, A37-M-B67, A37-M-B63, A37-M-B60, A37-M -B64, A37-M-B65, A37-M-B61, A37-M-B68, A37-M-B69, A38-M-B59, A38-M-B62, A38-M-B67, A38-M-B63 , A38-M-B60, A38-M-B64, A38-M-B65, A36-M-B61, A38-M-B68, A38-M-B69, A38-M-B66, A38-M-B70, A39 -M-B67, A39-M-B61, A39-M-B70, A34-M-B81, A34-M-B72, A34-M-B78, A34-M-B80, A35-M-B73, A35-M -B78, A35-M-B80, A41-M-B73, A41-M-B75, A41-M-B76, A36-M-B81, A36-M-B71, A36-M-B72, A36-M-B75 , A36-M-B76, A36-M-B78, A36-M-B82, A36-M-B80, A37-M-B81, A37-M-B71, A37-M-B72, A37-M-B73, A37-M-B74, A37-M-B75, A37-M-B76, A37-M-B77, A37- M-B78, A37-M-B50, A38-M-B81, A38-M-B71, A38-M-B72, A38-M-B73, A38-M-674, A38-M-B75, A38-M- B76, A38-M-B77, A38-M-B78, A38-M-B79, A38-M-B82, A39-M-B75, A39-M-B76, A39-M-B78, A39-M-B82, A34-M-B83, A34-M-B87, A34-M-B90, A34-M-B93, A34-M-B92, A35-M-B83, A35-M-B85, A35-M-B87, A35- M-B88, A35-M-B89, A35-M-693, A35-M-B92, A41-M-B89, A36-M-B86, A36-M-B87, A36-M-B89, A37-M- B83, A37-M-B84, A37-M-B85, A37-M-B87, A37-M-B88, A37-M-B89, A37-M-B90, A37-M-B93, A37-M-B91, A37-M-B92, A38-M-B83, A38-M-B84, A38-M-B94, A38-M-B85, A38-M-B87, A38-M-B90, A38-M-B92, A39- M-B86, A39-M-B90, A42-M-B25, A42-M-B26, A42-M-B27, A42-M-B28, A42-M-B29, A42-M-B30, A42-M- B32, A42-M-B33, A42-M-B34, A42-M-B36, A43-M-B25, A43-M-B26, A43-M-B28, A43-M-B29, A43-M-B30, A43-M-B32, A43-M-B33, A43-M-B34, A43-M-B56, A44-M-B25, A44-M-B29, A44-M-B32, A45-M-B25, A45- M-B26, A45-M-B27, A45-M-B29, A45-M-B30, A45-M-B32, A45-M-B33, A45-M-B34, A45-MB 36, A46-M-B25, A46-M-B27, A46-M-B29, A1-M-B26, A1-M-B29, A1-M-B30, A1-M-B33, A1-M-B34, A1-M-B36, A2-M-B25, A2-M-B29; A2-M-B31, A2-M-B32, A2-M-B33, A2-M-B35, A2-M-B36, A42-M-B39, A42-M-B40, A42-M-B41, A42- M-B43, A42-M-B44, A42-M-B45, A42-M-B46, A42-M-B47, A42-M-B37, A42-M-B38, A43-M-B39, A43-M- 640, A43-M-B41, A43-M-B42, A43-M-B43, A43-M-B95, A43-M-B44, A43-M-B45, A43-M-B46, A43-M-B47, A43-M-B37, A43-M-B38, A44-M-B39, A44-M-B46, A45-M-B39, A45-M-B40, A45-M-B41, A45-M-B42, A45- M-B43, A45-M-B95, A45-M-B44, A45-M-B45, A45-M- B46, A45-M-B47, A45-M-B37, A45-M-B38, A46-M-B39, A46-M-B41, A46-M-B46, A1-M-B39, A1-M-E340, A1-M-B41, A1-M-B42, A1-M-B43, A1-M-B95, A1-M-B44, A1-M-B45-, A1-M-B46, A1-M-B47, A2 -M-B39, A2-M-B40, A2-M-B41, A2-M-B43, A2-M-B95, A2-M-B44, A2-M-B45, A2-M-B46, A2-M -B47, A2-M-B37, A2-M-B38, A42-M-B48, A42-M-B49, A42-M-B51, A42-M-B52, A42-M-B54, A42-M-B57 , A42-M-B58, A43-M-B48, A43-M-B49, A43-M-B50, A43-M-B51, A43-M-B52, A43-M-B54, A43-M-B55, A43 -M-B56, A43-M-B57, A43-M-B58, A44-M-B48, A44-M-B51, A44-M-B53, A44-M-B54, A45-M-B48, A45-M - B49, A45-M-B50, A45-M-B51, A45-M-B52, A45-M-B53, A45-M-B54, A45-M-B55, A45-M-B56, A45-M-B57 , A45-M-B58, A46-M-B53, A46-M-B55, A46-M-B57, A46-M-B58, A1-M-B48, A1-M-B49 IH, A1-M-E350 jH , A1-M-B51, A1-M-B52 jH, A1-M-B53, A1-M-B54, A1-M-B55, A1-M-B57, A1-M-B58, A2-M-B49, A2-M-B50, A2-M-B51, A2-M-B52, A2-M-B53, A2-M-B54, A2-M-B55, A2-M-B57, A2-M-B58, A42- M-B59, A42-M-B62, A42-M-B67, A42-M-B63, A42-M-B60, A42-M-B61, A42-M-B69, A42-M-B70, A43-M- B59, A43-M-B6 3, A43-M-B60, A43-M-B64, A43-M-B65, A43-M-B61, A43-M-B68, A43-M-B69, A43-M-B66, A43-M-B70, A44-M-B60, A44-M-B69, A44-M-B70, A45-M-B59, A45-M-B62, A45-M-B67, A45-M-B63, A45-M-B60, A45- M-B64, A45-M-B65, A45-M-B61, A45-M-B68, A45-M-B69, A45-M-B66, A45-M-B70, A46-M-B59, A46-M- B62, A46-M-B67, A46-M-B63, A46-M-B70, A1-M-B59, A1-M-B62, A1-M-B67, A1-M-B63, A1-M-B60, A1-M-B64, A1-M-B65, A1-M-B61, A1-M-B68, A1-M-B66, A1-M-B70, A2-M-B59, A2-M-B62, A2- M-B67, A2-M-B60, A2-M-B64, A2-M-B61, A2-M-B68, A2-M-B69, A2-M-B66, A2-M-B70, A42-M- B81, A42-M-B71, A42-M-B72, A42-M-B73, A42-M-B74, A42-M-B75, A42-M-B76, A42-M-B77, A42-M-B78, A42-M-B79, A42- M-B82, A42-M-B80, A47-M-B77, A43-M-B81, A43-M-B71, A43-M-B73, A43-M-B75, A43-M-B76, A43-M- B77, A43-M-B78, A43-M-B79, A43-M-B80, A44-M-B71, A44-M-B75, A44-M-B78, A45-M-B81, A45-M-B71, A45-M-B72, A45-M-B73, A45-M-B74, A45-M-B75, A45-M-B76, A45-M-B77, A45-M-B78, A45-M-B79, A45- M-B82, A45-M-B80, A46-M-B77, A46-M-B78, A46-M-B82, A1-M-B81, A1-M-B71, A1-M-B72, A1-M- B73, A1-M-B74, A1-M-B76, A1-M-B79, A1-M-B80, A2-M-B81, A2-M-B71, A2-M-B72, A2-M-B74, A2-M-B75, A2-M-B76, A2-M-B77, A2-M-B78, A2-M-B79, A2-M-B82, A2-M-B80, A42-M-B83, A42- M-B94, A42-M-B85, A42-M-B86, A42-M-B87, A42-M-B88, A42-M-B89, A42-M-B90, A42-M-B93, A43-M- B83, A43-M-B84, A43-M-B94, A43-M-B85, A43-M-B86, A43-M-B88, A43-M-B89, A43-M-B90, A43-M-B93, A43-M-B91, A43-M-B92, A44-M-B85, A44-M-B87, A45-M-B83, A45-M-B84, A45-M-B94, A45-M-B85, A45- M-B86, A45-M-B87, A45-M-B88, A45-M-B90, A45-M-B93, A45-M-B91, A45-M-B92, A46-M-B85, A1-M-B85, A1 -M-B86, A1-M-B87, A1-M-B90, A1-M-B93, A2-M-B83, A2-M-B94, A2-M-B85, A2-M-B86, A2-M -B87, A2-M-B88, A7-M-B25, A7-M-B26, A7-M-B27, A7-M-B28, A7-M-B29, A7-M-B30, A7-M-B32 , A7-M-B33, A8-M-B25, A8-M-B26, A8-M-B27, A8-M-B28, A8-M-B29, A8-M-B30, A8-M-B32, A8 -M-B33, A8-M-B34, A8-M-B35, A8-M-B36, A11 -M-B25, A11 -M-B26, A11 -M-B27, A11 -M-B28, A11 -M -B29, A11-M-B30, A11-M-B32, A11-M-B33, A11-M-B34, A11-M-B36, A4-M-B26, A4-M-B27, A4-M-B28 , A4-M-B29, A4-M-B30, A4-M-B33, A4-M-B34, A4-M-B36, A3-M-B25, A3-M-B26, A3-M-B27, A3 -M-B28, A3-M-B29, A5-M-B30, A3-M-B32, A3-M-B33, A3-M-B34, A3-M-B36, A5-M-B25, A5-M-B26, A5-M-B27, A5-M-B29, A5- M-B32, A5-M-B33, A5-M-B35, A9-M-B25, A9-M-B26, A9-M-B27, A9-M-B28, A9-M-B29, A9-M- B30, A9-M-B31, A9-M-B32, A9-M-B33, A9-M-B36, A10-M-B25, A10-M-B27, A10-M-B28, A10-M-B29, A10-M-B30, A10-M-B31, A10-M-B32, A10-M-B33, A10-M-B34, A10-M-B35, A10-M-B36, A7-M-B39, A7- M-B44, A7-M-B46, A7-M-B38, A8-M-B39, A8-M-B40, A8-M-B44, A8-M-B45, A8-M-B46, AB-M- B47, A8-M-B38, A11-M-B44, A11-M-B46, A11-M-B47, A4-M-B40, A4-M-B41, A4-M-B44, A4-M-B45, A4-M-B46, A3-M-B39, A3-M-B41, A3-M-B43, A3-M-B44, A3-M-B45, A3-M-B46, A3-M-B47, A3- M-B37, A5-M-B39, A5-M-B40, A5-M-B45, A5-M-B46, A9-M-B39, A9-M-B44, A9-M-B46, A10-M- B39, A10-M-B42, A10-M-B95, A10-M-B44, A10-M-B46, A10-M-B47, A10-M-B37, A10-M-B38, A7-M-B49, A7-M-B51, A7-M-B52, A7-M-B54, A7-M-B55, A7-M-B57, A8-M-B48, A8-M-B49, A8-M-B50, AB- M-B51, A8-M-B52, AB-M-B54, A8-M-B55, A8-M-B57, A8-M-B58, A11-M-B48, A11-M-B49, A11-M- B50, A11-M-B51, A11-M-B52, A11-M-B54, A11-M-B55, A4-M-B49, A4-M-B50, A4-M-B51, A4-M-B52, A4-M-B53, A4-M-B54, A4-M-B55, A4-M-B56, A4- M-B57, A4-M-B58, A3-M-B48, A3-M-B49, A3-M-B50, A3-M-B51, A3-M-B52 F, A3-M-B54, A3-M -B55, A3-M-B56 F, A3-M-B57, A3-M-B58, A5-M-B51, A5-M-B52, A5-M-B53, A5-M-B54, A5-M- B57, A5-M-B58, A9-M-B49, A9-M-B50, A9-M-B51, A9-M-B52, A9-M-B53, A9-M-B54, A9-M-B55, A9-M-B56, A9-M-B57, A9-M-B58, A10-M-B48, A10-M-B49, A10-M-B50, A10-M-B51, A10-M-B52, A10- M-B53, A10-M-B54, A10-M-B55, A10-M-B56, A10-M-B57, A10-M-B58, A7-M-B59, A7-M-B67, A7-M- B53, A7-M-B60, A7-M-B64, A7-M-B65, A7- M-B69, A7-M-B66, A7-M-B70, A8-M-B59, A8-M-B62, A8-M-B67, A8-M-B63, A8-M-B60, A8-M- B64, A8-M-B65, A8-M-B61, A8-M-B68, A8-M-B69, A8-M-B70, A11-M-B59, A11-M-B62, A4-M-B59, A4-M-B62, A4-M-B64, A4-M-B65, A4-M-B61, A4-M-B68, A4-M-B69, A4-M-B66, A4-M-B70, A3- M-B59, A3-M-B62, A3-M-B67, A3-M-B60, A3-M-B64, A3-M-B65, A3-M-B61, A3-M-B68, A3-M- B69, A3-M-B66, A3-M-B70, A5-M-B59, A5-M-B60, A5-M-B64, A5-M-B68, A5-M-B69, A5-M-B66, A5-M-B70, A9-M-B59, A9-M-B67, A9-M-B60, A9-M-B64, A9-M-B61, A9-M-B68, A9-M-B66, A9- M-B70, A10-M-B59, A10-M-B67, A10-M-B63, A10-M-B60, A10-M-B64, A10-M-B68, A10-M-B69, A10-M- B66, A10-M-B70, A7-M-B81, A7-M-B71, A7-M-B72, A7-M-B76, A7-M-B77, A7-M-B78, A7-M-B79, A7-M-B82, A7-M-B80, A8-M-B81, A8-M-B72, A8-M-B73, A8-M-B74, A8-M-B75, A8-M-B76, A8- M-B77, A8-M-B78, A8-M-B79, A8-M-B82, A8-M-B80, A11-M-B81, A11-M-B72, A11-M-B73, A11-M- B77, A11-M-B78, A11-M-B79, A11-M-B82, A4-M-B81, A4-M-B72, A4-M-B73, A4-M-B74, A4-M-B75, A4-M-B76, A4-M-B77, A4-M-B78, A4-M-B79, A4-M-B80, A3-M-B72, A3-M-B73, A3-M-B76, A3-M-B77, A3-M-B78, A3-M-B79, A3-M-B80, A5-M-B71, A5- M-B74, A5-M-B75, A5-M-B77, A5-M-B78, A5-M-B80, A9-M-B73, A9-M-B78, A9-M-B79, A10-M- B81, A10-M-B72, A10-M-B77, A10-M-B80, A7-M-B83, A7-M-B86, A7-M-B89, A7-M-B90, A8-M-B83, A8-M-B94, A8-M-B55, A8-M-B86, A8-M-B87, A8-M-B58, A8-M-B89, A8-M-B90, A8-M-B93, A11- M-B83, A11-M-B84, A11-M-B85, A11-M-B90, A11-M-B93, A11-M-B91, A4-M-B83, A4-M-B84, A4-M- B94, A4-M-B85, A4-M-B86, A4-M-B57, A4-M-B88, A4-M-B89, A4-M-B90, A3-M-B83, A3-M-B84, A3-M-B94, A3-M-B85, A3-M-B86, A3-M- B87, A3-M-B88, A3-M-B89, A3-M-B90, A3-M-B93, A5-M-B83, A5-M-B84, A5- M-B85, A5-M-B87, A5-M-B89, A5-M-B90, A5-M-B93, A5-M-B91, A5-M-B92, A9-M-B83, A9-M-B84, A9-M-B94, A9- M-B85, A9-M-B86, A9-M-B87, A9-M-B89, A9-M-B90, A9-M-B93, A48-M-B28, A48-M-B33, A16-M- B27, A48-M-B44, A48-M-B45, A48-M-B46, A48-M-B47, A48-M-B37, A15-M-B40, A16-M-B39, A16-M-B43, A17-M-B40, A18-M-B39, A19-M-B40, A18-M-B42, A18-M-B46, A18-M-B47, A48-M-B50, A48-M-B51, A48- M-B52, A48-M-B54, A48-M-B55, A48-M-B57, A14-M-B53, A15-M-B49, A15-M-B50, A16-M-B48, A16-M- B49, A16-M-B50, A16-M-B51, A16-M-B53, A16-M-B55, A16-M-B56, A16-M-B58, A17-M-B48, A17-M-B53, A18-M-B48, A18-M-B50, A18-M-B51, A18-M-B54, A18-M-B55, A18-M-B56, A18-M-B57, A12-M-B62, A12- M-B67, A15-M-B64, A15-M-B65, A16-M-B59, A16-M-B62, A16-M-B60, A16-M-B61, A16-M-B68, A16-M- B70, A18-M-B59, A18-M-B65, A18-M-B69, A48-M-B73, A48-M-B74, A48-M-B76, A15-M-B78, A15-M-B82, A16-M-B75, A16-M-B77, A16-M-B82, A18-M-B72, A18-M-B73, A18-M-B74, A12-M-B93, A13-M-B92, A15 -M-B92, A16-M-B83, A16-M-B87, A16-M-B89, A16-M-B90, A16-M-B91, A17-M-B92, A18-M-B90, A21-M -B36, A20-M-B37, A19-M-B50, A22-M-B67, A21-M-B67, A22-M-B75, A22-M-B77, A21-M-B82, A25-M-B87 , A19-M-B94, A33-M-B28, A27-M-B39, A33-M-B38, A31-M-B38, A28-M-B53, A33-M-B57, A28-M-B63, A29 -M-B67, A27-M-B82, A29-M-B82, A30-M-B82, A33-M-B74, A27-M-B90, A28-M-B90, A28-M-B93, A29-M -B94, A29-M-B86, A34-M-B35, A35-M-B35, A40-M-B30, A40-M-B33, A40-M-B34, A40-M-B35, A40-M-B36 , A34-M-B40, A35-M-B38, A40-M-B42, A40-M-B48, A40-M-B49, A40-M-B51, A40-M-B52, A40-M-B53, A40-M-B57, A36-M-B49, A37-M-B53, A39-M-B55, A34-M-B60, A34-M-B61, A35-M-B60, A35- M-B61, A35-M-B68, A35-M-B69, A40-M-B62, A40-M-B70, A41-M-B59, A36-M-B67, A37-M-B66, A37-M- B70, A39-M-B62, A34-M-B71, A34-M-B75, A34-M-B77, A35-M-B71, A35-M-B72, A35-M-B75, A35-M-B77, A40-M-B74, A40-M-B77, A39-M-B72, A39-M-B73, A39-M-B80, A34-M-B85, A35-M-B84, A35-M-B91, A40- M-B84, A37-M-B94, A38-M-B93, A38-M-B91, A39-M-B87, A43-M-B27, A43-M-B35, A44-M-B26, A44-M- B27, A44-M-B31, A44-M-B33, A44-M-B36, A45-M-B28, A45-M-B35, A46-M-B26, A46-M-B31, A46-M-B32, A46-M-B34, A1-M-B25, A1-M-B27, A1-M-B28, A1-M-B31, A2-M-B26, A42-M-B95, A47-M-B45, A47- M-B47, A44-M-B40, A44-M-B41, A44-M-B42, A44-M-B43, A44-M-B44, A44-M-B45, A44-M-B47, A44-M- B37, A46-M-B42, A46-M-B43, A46-M-B44, A46-M-B45, A46-M-B37, A46-M-B38, A1-M-B38, A2-M-B42, A42-M-B53, A42-M-B55, A47-M-B58, A43-M-B53, A44-M-B49, A44-M-B52, A44-M-B55, A44-M-B57, A44- M-B58, A46-M-B49, A46-M-B50, A46-M-B51, A46-M-B52, A46-M-B54, A46-M-B56, A2-M -B48, A42-M-B65, A42-M-B66, A47-M-B68, A43-M-B62, A43-M-B67, A44-M-B59, A44-M-B64, A44-M-B65 , A44-M-B61, A46-M-B60, A46-M-B64, A46-M-B65, A46-M-B69, A46-M-B66, A1-M-B69, A47-M-B76, A47 -M-B79, A43-M-B74, A43-M-B82, A44-M-B81, A44-M-B73, A44-M-B74, A44-M-B76, A44-M-B77, A44-M -B79, A44-M-B80, A46-M-B81, A46-M-B71, A46-M-B72, A46-M-B74, A46-M-B80, A1-M-B77, A1-M-B78 , A1-M-B82, A42-M-B91, A43-M-B87, A44-M-553, A44-M-B84, A44-M-B89, A44-M-B90, A44-M-B93, A45 -M-B89, A46-M-B83, A46-M-B84, A46-M-B94, A46-M-B86, A46-M-B87, A46-M-B89, A46-M- B90, A46-M-B93, A46-M-B91, A46-M-B92, A1-M-B83, A1-M-B84, A1-M-B94, A1-M-B91, A2-M-B84, A2-M-B89, A2-M-B90, A2-M-B93, A7-M-B31, A7-M-B35, A8-M-B31, A11-M-B35, A4-M-B25, A4- M-B31, A4-M-B32, A4-M-B35, A3-M-B31, A5-M-B28, A5-M-B30, A5-M-B34, A5-M-B36, A10-M- B26, A7-M-B40, A7-M-B42, A7-M-B45, A7-M-B37, A8-M-B41, A8-M-B42, A8-M-B43, A8-M-B37, A11-M-B39, A11-M-B41, A11-M-B42, A11-M-B43, A11-M-B45, A11-M-B37, A11-M-B38, A4-M-B39, A4- M-B42, A4-M-B43, A4-M-B47, A4-M-B38, A3-M-B42, A5-M-B41, A5-M-B42, A5-M-B47, A5-M- B37, A5-M-B38, A9-M-B41, A9-M-B43, A9-M-B95, A9-M-B45, A9-M-B37, A10-M-B41, A10-M-B45, A7-M-B48, A7-M-B50, A7-M-B53, A7-M-B58, A8-M-B53, A8-M-B56, A11-M-B53, A11-M-B56, A11- M-B57, A11-M-B58, A4-M-B48, A3-M-B53, A5-M-B48, A5-M-B49, A5-M-B50, A5-M-B55, A9-M- B48, A7-M-B62, A7-M-B61, A7-M-B68, A8- M-B66, A11-M-B67, A11-M-B63, A11-M-B60, A11-M-B65, A11-M-B61, A11-M-B69, A11-M-B66, A11-M-B70, A4-M-B63, A4-M-B60, A5-M-B62, A5-M-B67, A5- M-B63, A5-M-B61, A9-M-B62, A9-M-B63 , A9-M-B65, A10-M-B62, A10-M-B65, A10-M-B61, A7-M-B75, A11-M-B71, A11-M-B74, A11-M-B75, A11 -M-B80, A4-M-B71, A4-M-B82, A3-M-B81, A3-M-B71, A3-M-B82, A5-M-B81, A5-M-B72, A5-M -B79, A5-M-B82, A9-M-B81, A9-M-B71, A9-M-B75, A9-M-B77, A9-M-B80, A10-M-B74, A10-M-B76 , A10-M-B78, A10-M-B82, A7-M-B84, A7-M-B85, A7-M-B87, A7-M-B93, A7-M-B92, A8-M-B91, A8 -M-B92, A11-M-B94, A11-M-B89, A11-M-B92, A4-M-B93, A4-M-B91, A4-M-B92, A3-M-B91, A5-M -B94, A9-M-B91, A9-M-B92, A10-M-B92, A10-M-B83, A10-M-B84, A10-M-B94, A10-M-B85, A10-M-B86 , A10-M-B87, A10-M-B59, A10-M-B90, A10-M-B93, A10-M-B91, A48-M-B38, A16-M-B38, A15-M-B53, A15-M-B54, A17-M-B49, A17-M-B55, A12-M-B63, A12- M-B64, A12-M-B66, A48-M-B60, A48-M-B61, A48-M-B68, A48-M-B69, A16-M-B64, A16-M-B65, A16-M- B69, A16-M-B66, A17-M-B67, A17-M-B65, A17-M-B61, A18-M-B61, A12-M-B82, A13-M-B82, A15-M-B74, A17-M-B82, A12-M-B94, A48-M-B87, A14-M-B90, A15-M-B83, A15-M-B84, A15-M-B94, A15-M-B87, A16- M-B86, A17-M-B94, A17-M-B90, A18-M-B83, A18-M-B85, A18-M-B91, A27-M-B38, A28-M-938, A29-M- B38, A33-M-B56, A27-M-B80, A28-M-B82, A33-M-B78, A34-M-B26, A34-M-B31, A40-M-B95, A34-M-B50, A40-M-B50, A40-M-B54, A40-M-B55, A40-M-B56, A34-M-B67, A34-M-B63, A34-M-B64, A34-M-B65, A34- M-B66, A35-M-B67, A35-M-B63, A40-M-B59, A40-M-B63, A40-M-B60, A40-M-B64, A40-M-B65, A40-M- B68, A40-M-B69, A40-M-B66, A36-M-B59, A34-M-B76, A34-M-B82, A35-M-B76, A35-M-B82, A40-M-B72, A40-M-B73, A40-M-B78, A40-M-B82, A40-M-B80, A37-M-B82, A39-M-B74, A34-M-B84, A34-M-B86, A34-M-B91, A35-M-B94, A35-M-B56, A35-M-B90, A40-M-B83, A40 -M-B85, A40-M-B87, A40-M-B91, A40-M-B92, A41-M-B87, A42-M-B31, A47-M-B32, A47-M-B35, A43-M -B31, A44-M-B28, A44-M-B30, A44-M-B34, A44-M-B35, A45-M-B31, A46-M-B30, A46-M-B35, A1-M-B32 , A1-M-B35, A2-M-B27, A2-M-B28, A2-M-B34, A42-M-B42, A44-M-B95, A44-M-B38, A47-M-B57, A44 -M-B50, A46-M-B48, A42-M-B64, A42-M-B68, A47-M-B62, A47-M-B63, A47-M-B64, A47-M-B65, A47-M -B61, A44-M-B62, A44-M-B67, A44-M-B63, A44-M-B68, A46-M-B68, A2-M-B63, 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A4-M-B2, A5-M-B2, A9- M-B2, A6-M-B2, A10-M-B2, A1-M-B3, A2-M-B3, A8-M-B3, A4-M-B3, A5-M-B3, A9-M- B3, A10-M-B3, A1-M-B4, A 2-M-B4, A7-M-B4, A8-M-B4, A3-M-B4, A4-M-B4, A9-M-B4, A6-M-B4, A1-M-B5, A2- M-B5, A7-M-B5, A8-M-B5, A3-M-B5, A4-M-B5, A9-M-B5, A6-M-B5, A10-M-B5, A1-M- B6, A2-M-B6, A7-M-B6, A8-M-B6, A3-M-B6, A4-M-B6, A5-M-B6, A9-M-B6, A10-M-B6, A1-M-B7, A2-M-137, A7-M-B7, A3-M-B7, A4-M-B7, A5-M-B7, A9-M-B7, A6-M-B7, A10- M-B7, A1-M-B8, A2-M-B8, A7-M-B8, A8-M-B8, A3-M-B8, A4-M-B8, A6-M-B8, A10-M- B8, A1-M-B9, A2-M-B9, A7-M-B9, A8-M-B9, A3-M-B9, A4-M-B9, A11-M-B9, A5-M-B9, A9-M-B9, A6-M-B9, A10-M-B9, A2-M-B10, A7-M-B10, A8-M-B10, A3-M-B10, A4-M-B10, A11- M-B10, A6-M-B10, A10-M-B10, A1-M-B11, A2-M-B11, A8-M-B11, A3-M-B12, A11-M-B12, A5-M-B12, A9-M-B12, A10-M-B12, A1- M-B13, A2-M-B13, A7-M-B13, A8-M-B13, A3-M-B13, A4-M-B13, A11-M-B13, A9-M-B13, A6-M- B13, A10-M-B13, A1-M-B14, A2-M-B14, A7-M-BI4, A8-M-B14, A11-M-B14, A5-M-B14, A9-M-B14, A6-M-B14, A10-M-B14, A1-M-B15, A2-M-B15, A7-M-B15, A8-M-B15, A3-M-B15, A4-M-B15, A11- M-B15, A5-M-B15, A9-M-B15, A6-M-B15, A10-M-B15, A1-M-B16, A2-M-B16, A11-M-B16, A5-M- B16, A9-M-B16, A6-M-B16, A10-M-B16, A1-M-B17, A2-M-B17, A7-M-B17, A8-M-B17, A3-M-B17, A4-M-B17, A11-M-B17, A6-M-B17, A10-M-B17, A1-M-B18, A2-M-B18, A7-M-B18, A8-M-B18, A3- M-B18, A11-M-B18, A6-M-B18, A10-M-B18, A7-M-B19, A8-M-B19, A11-M-B19, A5-M-B19, A9-M- B19, A6-M-B19, A10-M-B19, A1-M-B20, A2-M-B20, A7-M-B20, A8-M-B20, A3-M-B20, A4-M-B20, A11-M-B20, A5-M-B20, A9-M-B20, A6-M-B20, A10-M-B20, A1-M-B21, A2-M-B21, A7-M-B21, A8- M-B21, A3-M-B21, A4-M-B21, A11-M-B21, A6-M-B21, A10-M-B21, A1-M-B22, A2-M-B22, A6-M- B22, A10-M-B22, A1-M-B23, A2-M-B23, A7-M-B23, A8-M-B23, A3-M-B23, A5-M-B23, A9-M-B23, A6-M-B23, A10-M-B23, A1-M-B24, A2-M-B24, A7- M-B24, A8-M-B24, A3-M-B24, A4-M-B24, A11-M-B24, A5-M-B24, A9-M-B24, A6-M-B24, A10-M- B24, A3-M-B11, A4-M-B11, A11-M-B11, A6-M-B11, A10-M-B11, A1-M-B12, A2-M-B12, A7-M-B12, A8-M-B12, A7-M-B22, A8-M-B22, A3-M-B22, A11-M-B22, A5-M-B22, 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A17-M-B24, A22-M-B2, A22-M-B3, A22-M-B4, A22-M-B5, A22-M-B6, A22-M-B7, A22-M- B8, A22-M-B9, A22-M-B10, A22-M-B11, A22-M-B12, A23-M-B2, A23-M-B3, A23-M-B4, A23-M-B5, A23-M-B6, A23-M-B8, A23-M-B9, A23 -M-B10, A23-M-B11, A24-M-B3, A24-M-B9, A25-M-B1, A25-M-B2, A25-M-B3, A25-M-B4, A25-M -B5, A25-M-B6, A25-M-B7, A25 M-B8, A25-M-B9, A25-M-B10, A25-M-B11, A25-M-B12, A21-M-B1, A21-M-B2, A21-M-B3, A21-M-B4, A21-M-B5, A21-M-B6, A21-M-B7, A21-M-B8, A21-M-B9, A21- M-B10, A21-M-B11, A21-M-B12, A19-M-B1, A19-M-B2, A19-M-B4, A19-M-B5, A19-M-B7, A19-M- B8, A19-M-B9, A19-M-B10, A19-M-B1, A20-M-B1, A20-M-B2, A20-M-B3, A20-M-B4, A20-M-B5, A20-M-B6, A20-M-B7, A20-M-98, A20-M-B9, A20-M-B10, A20-M-B11, A20-M-B12, A22-MB 3, A22-M -B14, A22-M-B15, A22-M-B16, A22-M-B17, A22-M-B18, A22-M-B19, A22-M-B20, A22-M-B21, A22-M- B22, A22-M-B23, A22-M-B24, A23-M-B13, A23-M-B14, A23-M-B15, A23-M-B16, A23-M-B17, A23-M-B18, A23-M-B19, A23-M-B21, A23-M-B22, A21-M-918, A21-M-B19, A21-M-B20, A21-M-B21, A21-M-B22, A21- M-B23, A21-M-B24, A19-M-B13, A19-M-B14, A19-M-B15, A19-M-B16, A19-M-B17, A19-M-B18, A19-M- B20, A19-M-B21, A19-M-B22, A19-M-B23, A19-M-B24, A20-M-B13, A20-M-B14, A20-M-B15, A20-M-B16, A20-M-B17, A20-M-B18, A20-M-B19, A20-M-B20, A20-M-B21, A20-M-B22, A20-M-B23, A20-M-B24, A24- M-B16, A24-M-B17, A24-M-B18, A25-M-B13, A25-M-B14, A25-M-B15, A25-M-B16, A25-M-B17, A25-M- B18, A25-M-B19, A25-M-B20, A25-M-B21, A25-M-B22, A25-M-B23, A25-M-B24, A21-M-B13, A21-M-B14, A21-M-B15, A21-M-B16, A21-M-B17, A26-M-B2, A26-M-B4, A26-M-B5, A26-M-B6, A26-M-B7, A26- M-B8, A26-M-B9, A26-M-B10, A26-M-B11, A26-M-B12, A27-M-B1, A27-M-B4, A27-M-B5, A27-M- B6, A27-M-B8, A27-M-B9, A27-M-B10, A27-M-B11, A28-M-B1, A28-M-B2, A28-M-B4, A28-M-B5, A28-M-B6, A28-M-B8, A28-M-B9, A28-M-B10, A28-M-B11, A29-M-B1, A29-M-B4, A29-M- B5, A29-M-B8, A29-M-B9, A29-M-B10, A29-M-B11, A30-M-B1, A30-M-B2, A30-M-B4, A30-M-B5, A30-M-B6, A30-M-B8, A30-M-B9, A30-M-B11, A33-M-B1, A33-M-B2, A33-M-B4, A33-M-B5, A33- M-B6, A33-M-B7, A33-M-B8, A32-M-B11, A26-M-B13, A26-M-B14, A26-M-B17, A26-M-B18, A26-M- B20, A26-M-B21, A26-M-B22, A26-M-B24, A27-M-B13, A27-M-B14, A27-M-B17, A27-M-B20, A27-M-B21, A27-M-B22, A27-M-B23, A27-M-B24, A28-M-B13, A28-M-B14, A28-M-B16, A28-M-B17, A28-M-B18, A28- M-B24, A29-M-B13, A29-M-B14, A29-M-B17, A29-M-B21, A29-M-B24, A30-M-B13, A30-M-B14, A30-M- B16, A30-M-B17, A30-M-B18, A30-M-B20, A30-M-B22, A30-M-B23, A30-M-B24, A33-M-B13, A33-M-B14, A33-M-B15, A33- M-B16, A33-M-B17, A33-M-B19, A33-M-B20, A33-M-B21, A33-M-B22, A33-M-B23, A33-M-B24, A31-M- B13, A31-M-B14, A31-M-B15, A31-M-B16, A31-M-B17, A31-M-B18, A31-M-B20, A31-M-B21, A31-M-B22, A31-M-B24, A32-M-B13, A32-M-B14, A32-M-B15, A32-M-B16, A32-M-B17, A32-M-B18, A32-M-B19, A32- M-B20, A32-M-B21, A32-M-B22, A32-M-B23, A32-M-B24, A33-M-B9, A33-M-B10, A33-M-B11, A31-M- B1, A31- M-B2, A31-M-B4, A31-M-B5, A31-M-B6, A31-M-B8, A31-M-B9, A31-M-B10, A31-M-B11, A32-M-B1, A32-M-B2, A32-M-B4, A32-M-B5, A32-M-B6, A32-M-B9, A32-M-B10, A34-M-B4, A34- M-B5, A34-M-B8, A34-M-B9, A34-M-B10, A34-M-B11, A35-M-B4, A35-M-B5, A35-M-B8, A35-M- B9, A35-M-B10, A35-M-B11, A37-M-B6, A37-M-B11, A38-M-B2, A38-M-B3, A38-M-B4, A38-M-B5, A38-M-B6, A38-M-B8, A38-M-B9, A38-M-B10, A38-M-B11, A34-M-B13, A34-M-B14, A34-M-B16, A34- M-B17, A34-M-B18, A34-M-B20, A34-M-B21, A34-M-B22, A34-M-B24, A35-M-B13, A35-M-B14, A35-M- B17, A35 -M-921, A40-M-B13, A36-M-B21, A37-M-B14, A37-M-B16, A37-M-B17, A37-M-B21, A37-M-B24, A38-M -B13, A38-M-B14, A38-M-B16, A38-M-B17, A38-M-B18, A38-M-B20, A38-M-B21, A38-M-B23, A38-M-B24 , A42-M-B1, A42-M-B4, A42-M-B5, A42-M-B6, A42-M-B7, A42-M-B8, A42-M-B9, A42-M-B10, A42 -M-B11, A43-M-B1, A43-M-B2, A43-M-B4, A43-M-B5, A43-M-B6, A43-M-B7, A43-M-B8, A43-M -B9, A43-M-B10, A43-M-B11, A43-M-B12, A44-M-B5, A44-M-B6, A44-M-B9, A45-M-B1, A45-M-B2 , A45-M-B3, A45-M-B4, A45-M-B5, A45-M-B6, A45-M-B7, A45-M-B8, A45-M-B9, A45-M-B10, A45 -M-B11, A45-M-B12, A46-M-B9, A46-M-B11, A46-M-B12, A42-M-B13, A42-M-B14, A42-M-B15, A42-M-B16, A42-M-B17, A42-M-B18, A42- M-B20, A42-M-B21, A42-M-B22, A42-M-B24, A43-M-B13, A43-M-B14, A43-M-B15, A43-M-B16, A43-M- B17, A43-M-B18, A43-M-B19, A43-M-B20, A43-M-B21, A43-M-B22, A43-M-B24, A44-M-B13, A44-M-B20, A44-M-B22, A44-M-B24, A45-M-B13, A45-M-B14, A45-M-B15, A45-M-B16, A45-M-B17, A45-M-B18, A45- M-B19, A45-M-B20, A45-M-B21, A45-M-B22, A45-M-B23, A45-M-B24, A6-M-B3, A6-M-B6, A9-M- B5, A9-M-B10, A7-M-B11, A9-M-B11, A4-M-B12, A3-M-B14, A4-M-B14, A7-M-B16, A9-M-B17, A2-M-B19, A4-M-B22, A16-M-B2, A16-M-B9, A16-M-B11, A12-M-B22, A48-M-B16, A16-M-B17, A16- M-B18, A17-M-B18, A17-M-B22, A17-M-B23, A30-M-B10, A28-M-B20, A28-M-B22, A33-M-B18, A34-M- B7, A40-M-B5, A40-M-B6, A40-M-B7, A40-M-B8, A40-M-B9, A40-M-B10, A35-M-B24, A40-M-B17, A40-M-B18, A40-M-B20, A40-M-B24, A36-M-B17, A37-M-B13, A39-M-B17, A44-M-B2, A44-M-B4, A44-M-B7, A44-M-B8, A44-M-B10, A44-M-B11, A46-M-B1, A46-M-B2, A46-M-B4, A46 -M-B5, A46-M-B6, A46-M-B8, A46-M-B10, A43-M-B23, A44-M-B14, A44-M-B16, A44-M-B17, A44-M -B18, A44-M-B21, A46-M-B13, A46-M-B14, A46-M-B15, A46-M-B16, A46-M-B19, A5-M-B5, A5-M-B8 , A1-M-B10, A6-M-B12, A5-M-B13, A4-M-B18, A5-M-B18, A9-M-B18, A12-M-B16, A12-M-B17, A12 -M-B18, A12-M-B20, A27-M-B18, A29-M-B18, A35-M-B18, A40-M-B14, A46-M-B3, A46-M-B7, A46-M -B17, A46-M-B20, A46-M-B21, A46-M-B22, A46-M-B23, A12-M-B98, A12-M-B100, A12-M-B101, A29-M-B98 , A29-M-B100, A29-M-B102, A25-M-B98, A2-M-B98, A2-M-B103, A2-M-B100, A2-M-B102, A19-M-B96, A19 -M-B98, A19-M-B103, A19-M-B100, A19-M-B99, A19-M-B102, A19-M-B101, A8-M-B98, A12-M-B104, A12-M-B105, A12-M-B106, A12-M-B107, A12-M-B108, A29- M-B108, A25-M-B105, A2-M-B104, A2-M-B106, A2-M-B108, A19-M-B104, A19-M-B105, A19-M-B106, A19-M- B107, A19-M-B108, A45-M-B97, A12-M-B109, A12-M-B110, A12-M-B111, A12-M-B112, A12-M-B113, A12-M-B114, A12-M-B115, A12-M-B116, A12-M-B117, A12-M-B118, A29-M-B109, A29-M-B111, A29-M-B112, A29-M-B115, A29- M-B116, A29-M-B117, A29-M-B118, A25-M-B109, A25-M-B112, A25-M-B115, A25-M-B116, A25-M-B117, A25-M- B118, A2-M-B109, A2-M-B111, A2-M-B112, A2-M-B113, A2-M-B114, A2-M-B115, A2-M-B117, A2-M-B118, A19-M-B109, A19-M-B110, A1g-M-B111, A19-M-B112, A19-M-B114, A19-M-B115, A19-M-B117, A19-M-B118, A8- M-B109, A8-M-B115, A8-M-B117, A8-M-B118, A12-M-B119, A12-M-B120, A12-M-B121, A12-M-B122, A12-M- B123, A13-M-B123, A29-M-B119, A29-M-B120, A29-M-B121, A29-M-B122, A29-M-B123, A25-M-B120, A25-M-B121, A25-M-B122, A25-M-B124, A25-M-B123, A2-M-B120, A2-MB 21, A2-M-B122, A2-M-B124, A2-M-B123, A19-M -B120, A19-M-B125 , A19-M-B121, A19-M-B122, A19-M-B123, A45-M-B119, A45-M-B120, A8-M-B122, A8-M-B123, A12-M-B126, A12 -M-B127, A12-M-B128, A12-M-B129, A12-M-B130, A12-M-B131, A12-M-B132, A13-M-B129, A13-M-B131, A13-M -B132, A29-M-B126, A29-M-B128, A29-M-B129, A29-M-B130, A29-M-B131, A29-M-B133, A29-M-B132, A25-M-B126 , A25-M-B129, A25-M-B130, A25-MB 31, A25-M-B133, A25-M-B132, A2-M-B126, A2-M-B129, A2-M-B130, A2- M-B131, A2-M-B132, A19-M-B126, A19-M-B127, A19-M-B128, A19-M-B129, A19-M-B130, A19-M-B131, A19-M- B134, A19-M-B133, A19-M-B132, A45-M-B129, A45-M-B131, A45-M-B132, A8-M-B126, A8-M-B129, A8-M-B131, A8-M-B134, A8-M-B133, A8- M-B132, A12-M-B135, A12-M-B136, A12-M-B137, A12-M-B138, A12-M-B139, A12-M-B140, A12-M-B141, A13-M- B135, A13-M-B142, A13-M-B138, A13-M-B139, A13-M-B141, A29-M-B142, A29-M-B136, A29-M-B143, A29-M-B138, A29-M-B139, A29-M-B141, A25-M-B142, A25-M-B143, A25-M-B138, A25-M-B139, A25-M-B141, A2-M-B142, A2- M-B136, A2-M-B143, A2-M-B138, A2-M-B139, A2-M-B140, A2-M-B141, A19-M-B144, A19-M-B142, A19-M- B136, A19-M-B143, A19-M-B138, A19-M-B139, A19-M-B141, A45-M-B135, A8-M-B141, A45-M-B141, A8-M-B142, A8-M-B138, A8-M-B139, A50-M-B25, A51-M-B25, A52-M-B25, A50-M-B26, A51-M-B26, A53-M-B26, A50- M-B28, A54-M-B28, A51-M-B28, A55-M-B28, A53-M-B28, A52-M-B28, A51-M-B29, A50-M-B30, A54-M- B30, A51-M-B30, A52-M-B30, A54-M-B31, A51-M-B31, A52-M-B31, A50-M-B33, A51-M-B33, A54-M-B39, A51-M-B39, A51-M-B40, A50-M-B48, A51-M-B48, A50-M-B49, A51-M-B49, A53-M-B49, A51-M-B51, A50- M-B52, A51-M-B52, A50-M-B34, A51-M-B34, A50-M-B57, A51-M-B57, A50-M-B54, A51-M-B54, A50-M-B69, A51-M-B69, A50-M-B70, A51-M-B70, A50- M-B73, A51-M-B73, A53-M-B73, A50-M-B75, A51-M-B75, A51-M-B85, A50-M-B86, A50-M-B1, A50-M- B2, A51-M-B2, A51-M-B4, A50-M-B8, A51-M-B5, A50-M-B11, A51-M-B11, A50-M-B12, A51-M-B12, A50-M-B15, A51-M-B15, A50-M-B22, A51-M-B22 or A56-M-B22. 11. The use of a compound as defined in claim 1 or isomers, tautomers, carriers, metabolites, prodrugs and pharmaceutically acceptable salts thereof, for preparing a medicament for treating diseases or conditions caused by and / or associated with an altered protein kinase activity in a mammal. 12. The use claimed in claim 11, wherein the disease caused by and / or associated with an altered protein kinase activity is a prolific cell disorder that is selected from the group consisting of cancer, Alzheimer's disease, infections viral diseases, autoimmune diseases and neurodegenerative disorders. 13. The use claimed in claim 12, wherein the cancer is selected from the group consisting of carcinoma, squamous cell carcinoma, hematopoietic tumors of myeloid or lymphoid line, tumors of mesenchymal origin, tumors of the central nervous system and peripheral, melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, follicular thyroid cancer and Kaposi's sarcoma. 14. The use claimed in claim 12, wherein the cell proliferative disorder is selected from the group consisting of benign prostatic hyperplasia, familial adenomatosis, polyposis, neurofibromatosis, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis and postsurgical stenosis and restenosis. 15. The use of a compound as defined in claim 1 or isomers, tautomers, carriers, metabolites, prodrugs or pharmaceutically acceptable salts thereof, for preparing a drug to inhibit tumor angiogenesis and metastasis in a mammal. 16. The use of a compound as defined in claim 1 or isomers, tautomers, carriers, metabolites, prodrugs or pharmaceutically acceptable salts thereof, for preparing a medicament for treating rejection of organ transplantation or rejection disease inverse in a mammal. 17. The use of a compound as defined in claim 1 or isomers, tautomers, carriers, metabolites, prodrugs or pharmaceutically acceptable salts thereof, for preparing a medicament for treating or preventing alopecia induced by radiotherapy or induced by chemotherapy in a mammal. 18. The use claimed in claim 11, wherein a regimen of radiotherapy or chemotherapy in combination with at least one cytostatic or cytotoxic agent is also administrable. 19. The use claimed in claim 11, wherein the mammal in need thereof is a human. 20. A method for inhibiting protein kinase activity, comprising contacting the kinase with an effective amount of a compound of formula (I) as defined in claim 1 or isomers, tautomers, carriers, metabolites, prodrugs or pharmaceutically acceptable salts thereof. 21. - A library characterized in that it comprises two or more compounds according to claim 1. 22. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) as defined in claim 1 and at least one pharmaceutically acceptable excipient, carrier and / or diluent. 23. The pharmaceutical composition according to claim 22, further characterized in that it additionally comprises one or more chemotherapeutic agents. 24. A kit comprising a compound of formula (I) as defined in claim 1 which is optionally associated with a pharmaceutically acceptable carrier, diluent or excipient and one or more chemotherapeutic agents.