ES2352841T3 - DERIVATIVES OF PIRAZOLOPIRIDINE. - Google Patents

Abstract

A compound of general formula I I where: A represents N or N + O-; R1 represents phenyl or Het optionally substituted by one or more substituents selected from Ra and Rb; R2 represents 4-pyridone or 4-pyrimidine optionally substituted by one or more substituents selected from halogen, -ORc ', -NRc'Rc', SRc 'and -SO2Rc; R3 represents H, Cy optionally substituted by one or more substituents selected from Ra and Rb, or R3 represents C1-6alkyl optionally substituted by one or more substituents selected from Rb and Cy *, where Cy * may be optionally substituted by one or more substituents selected from Rb and Rc; R4 represents H, Ra, halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -NRa'Ra', -NRa 'CORa', -NRa'CONRa'Ra ', -NRa'CO2Ra, -NRa'SO2Ra, -SRa', -SORa, -SO2Ra or -SO2NRa'Ra '; R5 may be located on any of the 2 N of the pyrazolic ring of the formula I and represents H or Rf; each Ra independently represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where C1-6alkyl, C2-6alkenyl or C2-6alkynyl groups may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc; each Ra 'independently represents H or Ra; each Rb independently represents halogen, -ORc ', -OCORc, -OSO2Rc, -OCONRcRc', -NO2, -CN, -CORc ', -CO2Rc', -CONRc'Rc ', -CONRc'NRc'Rc', -NRc 'Rc', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'CO2Rc, -NRc'SO2Rc, -SRc ', -SORc, -SO2Rc, -SO2NRc'Rc', -C (NRc ') NRc'Rc ', -C (NSO2NRc'Rc') NRc'Rc ', -C (NORc') Rc ', -C (NNRc'Rc') Rc ', -NRc'C (NRc') NRc'Rc ' or -NRc'C (NCN) NRc'Rc '; each Rc independently represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where all these groups may be optionally substituted by one or more Rd substituents; each Rc 'independently represents H or Rc; each Rd independently represents halogen, Re, -ORe ', -OCORe, -OSO2Re, -OCONReRe', -NO2, -CN, -CORe ', -CO2Re', -CONRe'Re ', -CONRe'NRe'Re', -NRe'Re ', -NRe'CORe', -NRe'CONRe'Re ', -NRe'CO2Re, -NRe'SO2Re, -SRe', -SORe, -SO2Re, -SO2NRe'Re ', -C (NRe ') NRe'Re', -C (NSO2NRe'Re ') NRe'Re', -C (NORe ') Re', -C (NNRe'Re ') Re', -NRe'C (NRe ') NRe' Re ', -NRe'C (NCN) NRe'Re' or Cy optionally substituted by one or more substituents selected from halogen, Re, -ORe ', -OCORe, -OSO2Re, -OCONReRe', -NO2, -CN, -CORe ', -CO2Re', -CONRe'Re ', -CONRe'NRe'Re', -NRe'Re ', -NRe'CORe', -NRe'CONRe'Re ', -NRe'CO2Re, -NRe' SO2Re, -SRe ', -SORe, -SO2Re, -SO2NRe'Re', -C (NRe ') NRe'Re', -C (NSO2NRe'Re ') NRe'Re', -C (NORe ') Re' , -C (NNRe'Re ') Re', -NRe'C (NRe ') NRe'Re' and -NRe'C (NCN) NRe'Re '; each Re independently represents C1-6alkyl or haloC1-6alkyl; each Re 'independently represents H or Re; Rf represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where C1-6alkyl, C2-6alkenyl or C2-6alkynyl groups may be optionally substituted by one or more substituents selected from Rg and Cy *, and where any of the groups Cy or Cy * may be optionally substituted by one or more substituents selected from Rg and Ra; each Rg independently represents halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -CONRa'NRa'Ra', -NRa 'Ra', -NRa'CORa ', -NRa'CONRa'Ra', -NRa'CO2Ra, -NRa'SO2Ra, -SRa ', -SORa, -SO2Ra, -SO2NRa'Ra', -C (NRa ') NRa'Ra ', -C (NSO2NRa'Ra') NRa'Ra ', -C (NORa') Ra ', -C (NNRa'Ra') Ra ', -NRa'C (NRa') NRa'Ra ' or -NRa'C (NCN) NRa'Ra '; a Het group in the above definitions represents pyridine, pyrazine, pyrimidine, pyridazine, 2 (1H) -pyridone, 2 (1H) -pyrazinone, 2 (1H) -pyrimidinone or 2 (1H) -pyridazinone; a Cy or Cy * group in the above definitions represents a monocyclic carbocyclic group of 3 to 7 members or bicyclic of 8 to 12 partially unsaturated, saturated or aromatic, optionally containing 1 to 4 heteroatoms selected from N, S and O, which may also optionally contain 1 or 2 oxo groups when the ring is saturated or partially unsaturated, and where said ring or rings can be attached to the rest of the molecule through a carbon or nitrogen atom; or a salt thereof.

Description

Sector of the technique to which the invention relates

The present invention relates to a new series of pyrazolopyridine derivatives, as well as to a process for their preparation, to pharmaceutical compositions containing these compounds and to their use in medicine.

State of the art relating to the invention

Kinases are proteins involved in various cellular responses to external signals. In the 1990s a new family of kinases called MAPK (mitogen-activated protein kinases) was discovered. MAPKs activate their substrates by phosphorylation in serine and threonine residues.

MAPKs are activated by other kinases in response to a wide variety of signals including growth factors, proinflammatory cytokines, UV radiation, endotoxin and osmotic stress. Once activated, MAPKs activate by phosphorylation other kinases or proteins, such as the so-called transcription factors, which ultimately cause the increase or decrease of the expression of a particular gene or group of genes.

Within the MAPK family are included p38, ERK (extracellular regulated protein kinase) and JNK (C-Jun N-terminal kinase).

The p38 kinase plays a crucial role in the response of cells to stress and in the activation pathway of the synthesis of numerous cytokines, especially tumor necrosis factor (tumor necrosis factor, TNF-), interleukin-1 (IL- 1), interleukin-6 (IL-6) and interleukin-8 (IL-8).

IL-1 and TNF- are produced by macrophages and monocytes and are involved in the mediation of immunoregulation processes and other pathophysiological conditions. For example, elevated levels of TNF- are related to inflammatory, autoimmune diseases and processes that trigger the degradation of connective and bone tissue such as rheumatoid arthritis, osteoarthritis, diabetes, inflammatory bowel disease and sepsis.

Thus, compounds that inhibit p38 kinase could be useful in the treatment or prevention of cytokine-mediated pathologies such as IL-1 and TNF-, such as those already mentioned.

image 1

On the other hand, it has also been seen that p38 inhibitors inhibit other pro-inflammatory proteins such as IL-6, IL-8, interferon- and GM-CSF (granulocyte-macrophage colony-stimulating factor). Also, in recent studies it has been shown that p38 inhibitors not only block the

5 synthesis of cytokines but also the cascade of signals induced by them, such

as the induction of the enzyme cyclooxygenase-2 (COX-2). Explanation of the invention One aspect of the present invention is the new compounds of

general formula I

I

10 where: A represents N or N + O-;

R1 represents phenyl or Het optionally substituted by one or more substituents selected from Ra and Rb;

R2 represents Het optionally substituted by one or more substituents selected from Ra and Rb;

R3 represents H, Cy optionally substituted by one or more substituents selected from Ra and Rb, or R3 represents C1-6alkyl optionally substituted by one or more substituents selected from Rb and Cy *, where Cy * may be optionally substituted by one or more substituents selected from Rb and Rc;

R4 represents H, Ra, halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -NRa'Ra', - NRa'CORa ', -NRa'CONRa'Ra', -NRa'CO2Ra, -NRa'SO2Ra, -SRa ', -SORa, -SO2Ra or -SO2NRa'Ra'; R5 may be located on any of the 2 N of the pyrazolic ring of the formula I and represents H or Rf;

each Ra independently represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where C1-6alkyl, C2-6alkenyl or C2-6alkynyl groups may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc;

each Ra ’independently represents H or Ra;

each Rb independently represents halogen, -ORc ', -OCORc, -OSO2Rc, -OCONRcRc', -NO2, -CN, -CORc ', -CO2Rc', -CONRc'Rc ', -CONRc'NRc'Rc', -NRc 'Rc', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'CO2Rc, -NRc'SO2Rc, -SRc ', -SORc, -SO2Rc, -SO2NRc'Rc', -C (NRc ') NRc'Rc ', -C (NSO2NRc'Rc') NRc'Rc ', -C (NORc') Rc ', -C (NNRc'Rc') Rc ', -NRc'C (NRc') NRc'Rc ' or -NRc'C (NCN) NRc'Rc ';

each Rc independently represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where all these groups may be optionally substituted by one or more Rd substituents;

each Rc ’independently represents H or Rc;

each Rd independently represents halogen, Re, -ORe ', -OCORe, -OSO2Re, -OCONReRe', -NO2, -CN, -CORe ', -CO2Re', -CONRe'Re ', -CONRe'NRe'Re', -NRe'Re ', -NRe'CORe', -NRe'CONRe'Re ', -NRe'CO2Re, -NRe'SO2Re, -SRe', -SORe, -SO2Re, -SO2NRe'Re ', -C (NRe ') NRe'Re', -C (NSO2NRe'Re ') NRe'Re', -C (NORe ') Re', -C (NNRe'Re ') Re', -NRe'C (NRe ') NRe' Re ', -NRe'C (NCN) NRe'Re' or Cy optionally substituted by one or more substituents selected from halogen, Re, -ORe ', -OCORe, -OSO2Re, -OCONReRe', -NO2, -CN, -CORe ', -CO2Re', -CONRe'Re ', -CONRe'NRe'Re', -NRe'Re ', -NRe'CORe', -NRe'CONRe'Re ', -NRe'CO2Re, -NRe' SO2Re, -SRe ', -SORe, -SO2Re, -SO2NRe'Re', -C (NRe ') NRe'Re', -C (NSO2NRe'Re ') NRe'Re', -C (NORe ') Re' , -C (NNRe'Re ') Re', -NRe'C (NRe ') NRe'Re' and -NRe'C (NCN) NRe'Re ';

each Re independently represents C1-6alkyl or haloC1-6alkyl;

each Re ’independently represents H or Re;

Rf represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where C1-6alkyl, C2-6alkenyl or C2-6alkynyl groups may be optionally substituted by one or more substituents selected from Rg and Cy *, and where any of the groups Cy or Cy * may be optionally substituted by one or more substituents selected from Rg and Ra;

each Rg independently represents halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -CONRa'NRa'Ra', -NRa 'Ra', -NRa'CORa ', -NRa'CONRa'Ra', -NRa'CO2Ra, -NRa'SO2Ra, -SRa ', -SORa, -SO2Ra, -SO2NRa'Ra', -C (NRa ') NRa'Ra ', -C (NSO2NRa'Ra') NRa'Ra ', -C (NORa') Ra ', -C (NNRa'Ra') Ra ', -NRa'C (NRa') NRa'Ra ' or -NRa'C (NCN) NRa'Ra ';

a Het group in the above definitions represents pyridine, pyrazine, pyrimidine, pyridazine, 2 (1H) -pyridone, 2 (1H) -pyrazinone, 2 (1H) -pyrimidinone or 2 (1H) -pyridazinone;

a Cy or Cy * group in the above definitions represents a monocyclic carbocyclic group of 3 to 7 members or bicyclic of 8 to 12 partially unsaturated, saturated or aromatic, optionally containing 1 to 4 heteroatoms selected from N, S and O, which may also optionally contain 1 or 2 oxo groups when the ring is saturated or partially unsaturated, and where said ring or rings can be attached to the rest of the molecule through a carbon or nitrogen atom.

Addition salts of the compounds of the invention as well as their solvates are also included in the present invention.

Some compounds of formula I may have chiral centers, which may give rise to various stereoisomers. The subject of the present invention are each individual stereoisomer as well as mixtures thereof. Also, some of the compounds of the present invention may have cis / trans isomerism. The object of the present invention is each of the geometric isomers as well as their mixtures.

The compounds of formula I are selective inhibitors of p38 kinase.

Therefore, another aspect of the present invention is pharmaceutical compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof and one or more pharmaceutically acceptable excipients.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of diseases mediated by p38.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of cytokine-mediated diseases.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of diseases mediated by TNF-, IL-1, IL-6 and / or IL-8.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of a disease selected from among immune, autoimmune and inflammatory diseases, cardiovascular diseases. , infectious diseases, bone resorption disorders, neurodegenerative diseases, proliferative diseases and processes associated with the induction of cyclooxygenase-2.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the treatment or prevention of diseases mediated by p38.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the treatment or prevention of cytokine-mediated diseases.

Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the treatment or prevention of diseases mediated by TNF-, IL-1, IL-6 and / or IL

8. Another aspect of the present invention is the use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof for the

10 treatment or prevention of a disease selected from among immune, autoimmune and inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases, proliferative diseases and processes associated with the induction of cycloosigenase-2.

Another aspect of the present invention is a process for the preparation of a compound of formula I, comprising:

(a) react a ketone of formula IV

image2

IV

where R1 and R2 have the meaning described above, with an aminopyrazole of

twenty

formula V and an aldehyde of formula VI

R5

H2N

N

R3 CHO

V

R4 SAW

where R3, R4 and R5 have the meaning described above; or

(b) when in a compound of formula I R5 represents H and R3 has the same

meaning that R1, reacting a ketone of formula IV or an enolate of formula VII

image3

image4

R1 image5 R1 image5 OO image5 OR

image5 R1

R2 R2

IV VII

where R1 and R2 have the meaning described above, with an aminopyrazole of formula Va H2N H

Goes

5 where R4 has the meaning described above; or

(c) when in a compound of formula I R4 represents NH2, treat a compound

of formula XIX R1 image5

N image5 Cl

image5 CN R3

R2

XIX

where R1, R2 and R3 have the meaning described above, with a hydrazine 10 of formula VIIIa

NH2 NHR5

VIIIa

where R5 has the meaning described above; or

(d) transforming, in one or several stages, a compound of formula I into another compound of formula I; and 15 (e) if desired, after the above steps, to react a compound of formula I with a base or with an acid to give the corresponding salt.

In the above definitions, the term C1-6alkyl, as a group or part of a group, means a straight or branched chain alkyl group containing 1 to 6 carbon atoms. Examples include among others the methyl, ethyl groups,

Propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl and hexyl.

A haloC1-6alkyl group means a group resulting from the substitution of one or more hydrogen atoms of a C1-6alkyl group by one or more halogen atoms (i.e. fluoro, chloro, bromo or iodo), which may be the same or different . Examples include, among others, trifluoromethyl, fluoromethyl, 1-chloroethyl, 2-chloroethyl, 1-fluoroethyl, 2-fluoroethyl, 2-bromoethyl, 2-iodoethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 3-chloropropyl, 2,2,3,3-tetrafluoropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 4-fluorobutyl, nonafluorobutyl, 5-fluoropentyl and 6-fluorohexyl.

The term C2-6alkenyl, as a group or part of a group, means a linear or branched alkyl chain containing 2 to 6 carbon atoms and also containing one or more double bonds. Examples include, among others, the groups ethenyl, 1-propenyl, 2-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3butenyl, 1,3-butadienyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4- pentenyl, 1hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl and 5-hexenyl.

The term C2-6alkynyl, as a group or part of a group, means a linear or branched alkyl chain containing from 2 to 6 carbon atoms and also containing one or more triple bonds. Examples include the ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 1,3-butadiinyl, 3-butynyl, 1pentinyl, 2-pentinyl, 3-pentinyl, 4-pentinyl, 1-hexinyl groups, 2-hexinyl, 3-hexinyl, 4hexinyl and 5-hexinyl.

An oxo group means a carbonyl group (-CO-).

A halogen radical means fluoro, chloro, bromo or iodo.

A Het group in the definitions of R1 and R2 means pyridine, pyrazine, pyrimidine, pyridazine, 2 (1H) -pyridone, 2 (1H) -pyrazinone, 2 (1H) -pyrimidinone or 2 (1H) -pyridazinone. As indicated above, these groups may be optionally substituted by one or more substituents selected from Ra and Rb, which may be located at any available position of the Het group, and may be attached to the rest of the molecule through any atom. Carbon or nitrogen available.

The term Cy or Cy *, as a group or as part of a group, refers to a monocyclic carbocyclic group of 3 to 7 members or bicyclic of 8 to 12 members that can be partially unsaturated, saturated or aromatic, and optionally containing 1 to 4 heteroatoms selected from N, S and O. When the Cy or Cy * group is saturated or partially unsaturated, it may optionally contain 1 or 2 oxo groups. The Cy or Cy * ring or rings may be optionally substituted as indicated in the definition of the general formula I, said substituents being able to be in any available position, and may be attached to the rest of the molecule through any carbon atom or nitrogen available. Examples of Cy or Cy * groups include, among others, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, aziridine, oxirane, oxetane, imidazolidine, isothiazolidine, isoxazolidine, oxazolidine, pyrazolidine, pyrrolidine, thiazolidine, dioxane, morpholine, piranidine, piranidine tetrahydropyran, azepine, oxazine, oxazoline, pyrroline, thiazoline, pyrazoline, imidazoline, isoxazoline, isothiazoline, phenyl, naphthyl, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-oxadiazole, 1, 3,4-thiadiazole, furan, imidazole, isoxazole, isothiazole, oxazole, pyrazole, pyrrole, thiazole, thiophene, 1,2,3-triazole, 1,2,4-triazole, pyrazine, pyridazine, pyridine, pyrimidine, benzimidazole, benzofuran, benzothiazole, benzothiophene, imidazopyrazine, imidazopyridazine, imidazopyridine, imidazopyrimidine, indazol, indole, isoindol, isoquinoline, tetrahydroisoquinoline, naphthyridine, pyrazolopyrazine, pyrazolopyridine, cyclozoline, cycloquinoline, cycloquinoline, cyclobenzine cyclobenzine cyclobenzine cyclobenzine xanone, cycloheptanone, pyrrolidin-2-one, piperidin-2-one, piperidin-4-one, 2 (1H) -pyridone, 2 (1H) -pyrazinone, 2 (1H) -pyrimidinone, 2 (1H) -pyridazinone and phthalimide

The term "heteroaryl", as a group or as part of a group, refers to a 5- to 6-membered monocyclic or 8 to 12-membered bicyclic aromatic ring containing from 1 to 4 heteroatoms selected from N, S and O, and which may be optionally substituted as indicated each time this term is used, where said substituents may be located at any available position. The heteroaryl group can be attached to the rest of the molecule through any available carbon or nitrogen atom. Examples of heteroaryl groups include, among others, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, furan, imidazole, isoxazole, isothiazole, oxazole, pyrazole , pyrrole, thiazole, thiophene, 1,2,3-triazole, 1,2,4-triazole, pyrazine, pyridazine, pyridine, pyrimidine, benzimidazole, benzofuran, benzothiazole, benzothiophene, imidazopyrazine, imidazopyridazine, imidazopyridine, imidazopyrimidine, indazole, indole , isoindole, isoquinoline, naphthyridine, pyrazolopyrazine, pyrazolopyridine, pyrazolopyrimidine,

purine, quinazoline, quinoline and quinoxaline. In the previous definitions of Het, heteroaryl, Cy and Cy *, the indicated group should be understood as the radical derived from the corresponding cycle. In the previous definitions of heteroaryl, Cy and Cy *, when the examples

5 specified refer to a bicycle in general terms, all possible arrangements of atoms are included. Thus, for example, the term pyrazolopyridine should be understood as including groups such as 1H-pyrazolo [3,4-b] pyridine, pyrazolo [1,5-a] pyridine, 1H-pyrazolo [3,4-c] pyridine, 1H-pyrazolo [4,3-c] pyridine and 1Hpyrazolo [4,3-b] pyridine, the term imidazopyrazine should be understood as

10 may include groups such as 1H-imidazo [4,5-b] pyrazine, imidazo [1,2-a] pyrazine and imidazo [1,5-a] pyrazine and the term pyrazolopyrimidine should be understood as including groups such as 1H -pyrazolo [3,4-d] pyrimidine, 1H-pyrazolo [4,3d] pyrimidine, pyrazolo [1,5-a] pyrimidine and pyrazolo [1,5-c] pyrimidine. The expression "optionally substituted by one or more" means that a

The group may be substituted by one or more, preferably by 1, 2, 3 or 4 substituents, provided that said group has 1, 2, 3 or 4 positions that can be substituted.

In the above definitions, when it is indicated that R5 may be located on any of the 2 N of the pyrazolic ring it means that R5 may be 20 on the N in position 1 of the ring or on the N in position 2. Thus, the

Compounds of formula I include the two types of compounds:

R5

image5 7

7

R image5 1 6 N image5 one

R image5 1 6 N image5 one

N

N

image5 R5

image5

image5 N

N

image5

2 image5 5

5

2

3 R2

3 R4

R2 4

R4 4

R3 R3

An embodiment of the invention are those compounds of formula I where A represents N. Another embodiment of the invention are compounds of formula I where A represents N and R5 may be located on any of the 2 N of the pyrazolic ring of formula I and represents H or Ra.

Another embodiment of the invention are the compounds of formula I in which when R3 and R5 both represent H and R2 represents Het optionally substituted by one or more substituents selected from halogen, -CN, CF3, -OH, -NO2, -OR6 , -NR6R6, -OCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and Cy, where Cy may be optionally substituted by one or more substituents selected from Rb and Rc, and where R6 represents C1-6alkyl, then R4 does not It can represent -NRa'CORa, -NHCONHRa or -NHCO2Ra.

Another embodiment of the invention are the compounds of formula I in which when R3 and R5 both represent H, then R4 cannot represent -NRa'CORa, -NHCONHRa or -NHCO2Ra.

Another embodiment of the invention are the compounds of formula I where A represents N; R4 represents H, Ra, halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -NRa'Ra', -NRa 'SO2Ra, -SRa', -SORa, -SO2Ra or -SO2NRa'Ra '; and R5 may be located on any of the 2 N of the pyrazolic ring of the formula I and represents H or Ra.

Another embodiment of the invention are the compounds of formula I wherein R 1 represents pyridine or phenyl, where all these groups may be optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R 1 represents phenyl optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R 1 represents phenyl optionally substituted by one or more substituents selected from halogen, -ORc ', -NO2, -CN, -CONRc'Rc', -NRc'Rc 'and C1 -6alkyl optionally substituted by one or more substituents selected from halogen, -ORc ', -CORc', -NRc'Rc 'and -NRc'CORc'.

Another embodiment of the invention are the compounds of formula I wherein R 1 represents phenyl optionally substituted by one or more substituents selected from halogen and haloC 1-6 alkyl.

Another embodiment of the invention are the compounds of formula I wherein R2 represents pyridine or pyrimidine, where all these groups may be optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R2 represents 4-pyridine or 4-pyrimidine, where all these groups may be optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R2 represents 4-pyridine or 4-pyrimidine, where all these groups may be optionally substituted by one or more substituents selected from halogen, -ORc ', -NRc'Rc', -SRc 'and -SO2Rc.

Another embodiment of the invention are the compounds of formula I wherein R2 represents 4-pyridine.

Another embodiment of the invention are the compounds of formula I wherein R2 represents 4-pyrimidine substituted by -NRc'Rc ', where in R2: each Rc' independently represents H or Rc; each Rc independently represents C1-6alkyl optionally substituted by one or more substituents selected from Cy and -ORe '; and each Re 'independently represents H or Re.

Another embodiment of the invention are the compounds of formula I wherein R3 represents H or Cy optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R 3 represents H, heteroaryl or phenyl, where all these groups may be optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R 3 represents heteroaryl or phenyl, where all these groups may be optionally substituted by one or more substituents selected from Ra and Rb.

Another embodiment of the invention are the compounds of formula I wherein R3 represents monocyclic heteroaryl or phenyl, where all these groups may be optionally substituted by one or more substituents selected from halogen, -NO2, -ORc ', C1-6alkyl and Cy, where C1-6alkyl may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc.

Another embodiment of the invention are the compounds of formula I wherein R 3 represents monocyclic heteroaryl or phenyl, where all these groups may be optionally substituted by one or more substituents selected from halogen, -NO2, -ORc ', C1-6alkyl, haloC1- 6alkyl and Cy; and where in R3: each Rc 'independently represents H or Rc; each Rc independently represents C1-6alkyl optionally substituted by one or more Rd substituents; and each Rd independently represents Cy.

Another embodiment of the invention are the compounds of formula I wherein R4 represents H, Ra, halogen, -ORa ', -CN, -CONRa'Ra, -NRa'Ra' or -NRa'CORa '.

Another embodiment of the invention are the compounds of formula I wherein R 4 represents H.

Another embodiment of the invention are the compounds of formula I where R5 represents H or R5 represents Rf and is located on the N in position 2 of the pyrazolic ring.

Another embodiment of the invention are the compounds of formula I wherein R5 represents Rf and is located on the N in position 2 of the pyrazolic ring.

Another embodiment of the invention are the compounds of formula I wherein Rf represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups may be optionally substituted by one or more substituents selected from Rg and Cy * , and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rg and Ra.

Another embodiment of the invention are the compounds of formula I wherein Rf represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups may be optionally substituted by one or more substituents selected from Rg and Cy * , and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rg and Ra, where each Rg independently represents halogen, -ORa ', -CORa', -CO2Ra ', -CONRa'Ra ', -NRa'Ra', -NRa'CORa ', -NRa'CONRa'Ra', -NRa'SO2Ra ', -SRa', -SORa 'or -SO2Ra'.

Another embodiment of the invention are the compounds of formula I wherein Rf represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups may be optionally substituted by one or more substituents selected from Rg and Cy * , and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rg and Ra, where in Rf: each Rg independently represents -ORa ', -CORa', -CONRa'Ra ', - NRa'Ra ', -NRa'CORa', -NRa'CONRa'Ra ', -NRa' SO2Ra ', SORa' or -SO2Ra '; each Ra 'independently represents H or Ra; each Ra independently represents Cy or C1-6alkyl, where C1-6alkyl may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and

Rc; each Rb independently represents -ORc ', -NRc'Rc', -CN, -CORc ', -SRc' or -SORc '; each Rc 'independently represents H or Rc,

Each Rc independently represents C1-6alkyl or Cy, where all these groups may be optionally substituted by one or more substituents Rd.

Another embodiment of the invention are the compounds of formula I where R5 is located on the N in position 2 of the pyrazolic ring and represents Rf, where Rf represents C1-6alkyl optionally substituted by one or more substituents selected from -ORa ', -CORa ', -CONRa'Ra', -NRa'Ra ', -NRa'CORa', -NRa'CONRa'Ra 'and Cy * optionally substituted by one or more substituents selected from Ra; where in Rf: each Ra 'independently represents H or Ra; each Ra independently represents Cy or C1-6alkyl, where C1-6alkyl may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and

Rc; each Rb independently represents -ORc ', -NRc'Rc', -CN, -CORc ', -SRc' or

-SORc '; each Rc 'independently represents H or Rc, Each Rc independently represents C1-6alkyl or Cy, where all these groups may be optionally substituted by one or more Rd; Y each Rd independently represents –ORe ’

Another embodiment of the invention are the compounds of formula I where R5 represents H or R5 represents Ra and is located on the N in position 2 of the pyrazolic ring.

Another embodiment of the invention are the compounds of formula I where R 5 represents Ra and is located on the N in position 2 of the pyrazolic ring.

Another embodiment of the invention are the compounds of formula I where Ra in R5 represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc.

Another embodiment of the invention are the compounds of formula I where Ra in R5 represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc, where each Rb in R5 independently represents halogen, -ORc ', -CORc', -CO2Rc ', -CONRc'Rc ', -NRc'Rc', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'SO2Rc ', -SRc', -SORc 'or -SO2Rc'.

Another embodiment of the invention are the compounds of formula I where Ra in R5 represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc, where in R5: each Rb independently represents -ORc ', -CORc', -CONRc'Rc ' , -NRc'Rc ', -NRc'CORc', -NRc'CONRc'Rc ', -NRc' SO2Rc ', SORc' or -SO2Rc '; each Rc 'independently represents H or Rc;

Each Rc independently represents Cy or C1-6alkyl, where all these groups may be optionally substituted by one or more substituents selected from among Rd; each Rd independently represents Re, -ORe ', -NRe'Re', -CN, -CORe ', -SRe', -SORe 'or Cy.

Another embodiment of the invention are the compounds of formula I where R5 is located on the N in position 2 of the pyrazolic ring and represents Ra, where Ra in R5 represents C1-6alkyl optionally substituted by one or more substituents selected from -ORc ', -CORc ', -CONRc'Rc', -NRc'Rc ', -NRc'CORc', -NRc'CONRc'Rc ', -NRc'SO2Rc' and Cy * optionally substituted by one or more substituents selected from Rc; where in R5: each Rc 'independently represents H or Rc; each Rc independently represents Cy or C1-6alkyl, where all these groups may be optionally substituted by one or more substituents selected from among Rd; each Rd independently represents -ORe ', -NRe'Re', -CN, -CORe ', -SRe', -SORe 'or Cy; Each Re 'independently represents H or Re, and each Re independently represents C1-6alkyl.

Likewise, all possible combinations of each of the aforementioned embodiments are also part of the invention.

The compounds of the present invention may contain one or more basic nitrogen and, therefore, may form salts with organic or inorganic acids, which are also part of the present invention. Examples of such salts include: salts with inorganic acids such as hydrochloric acid, hydrobromic acid, iodhydric acid, nitric acid, perchloric acid, sulfuric acid or phosphoric acid; and salts with organic acids, such as methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, ptoluenesulfonic acid, fumaric acid, oxalic acid, acetic acid or maleic acid, among others. The compounds of the present invention may contain one or more acidic protons and, therefore, may form salts with bases, which are also part of the present invention. Examples of such salts include: salts with inorganic cations such as sodium, potassium, calcium, magnesium, lithium, aluminum, zinc, etc; and salts formed with pharmaceutically acceptable amines such as ammonia, alkylamines, hydroxyalkylamines, lysine, arginine, N-methylglucamine, procaine and the like. There is no limitation on the nature of such salts, provided that when used for therapeutic purposes they are pharmaceutically acceptable. The salts can be prepared by treating the compound of formula I with a sufficient amount of the desired acid or base to give the salt in a conventional manner. The compounds of formula I and their salts differ in certain physical properties but are equivalent for the purposes of the invention.

Some compounds of the present invention may exist in solvated form, including hydrated forms. In general, the solvated forms with pharmaceutically acceptable solvents such as water, ethanol and the like are equivalent to the non-solvated form for purposes of the invention.

Some compounds of the present invention could exist in the form of several diastereoisomers and / or several optical isomers. The diastereoisomers can be separated by conventional techniques such as chromatography or fractional crystallization. Optical isomers can be resolved by using conventional optical resolution techniques, to give optically pure isomers. This resolution can be performed on synthesis intermediates that are chiral or on products of general formula I. Optically pure isomers can also be obtained individually using enantiospecific synthesis. The present invention covers both individual isomers and mixtures (for example racemic mixtures) whether they are obtained by synthesis or by physically mixing them.

Also, some of the compounds of the present invention could exhibit cis / trans isomerism. The present invention includes each of the geometric isomers as well as their mixtures.

The compounds of formula I can be obtained following the procedures described below. As will be apparent to one skilled in the art, the precise method used for the preparation of a given compound may vary depending on its chemical structure. Also, in some of the procedures detailed below, it may be necessary or convenient to protect reactive or labile groups by conventional protecting groups. Both the nature of these protecting groups and the

Procedures for their introduction or removal are well known and are part of the state of the art (see for example Greene T.W. and Wuts P.G.M, "Protective Groups in Organic Synthesis", John Wiley & Sons, 3rd edition, 1999). By way of example, tert-butoxycarbonyl (Boc) or benzyl (Bn) groups can be used as protecting groups of an amino function. Carboxyl groups can be protected, for example, in the form of C1-6 alkyl esters or arylalkyl esters, such as benzyl, while hydroxyl groups can be protected, for example, with tetrahydropyranyl groups (THP). Whenever a protective group is present, a subsequent stage of

10 deprotection, which is carried out under the usual conditions in organic synthesis, such as those described in the reference mentioned above.

Compounds of formula I are generally obtained by reacting a compound of formula IV with an aminopyrazole of formula V and an aldehyde of formula VI, as shown in the following scheme:

R5

image5 image5 R1 R5R1 image5 H2N

image5 NO NN

image5 N

N

R3 CHO

R2R2 R4 image5 R4 R3

I

IVV VI where R1, R2, R3, R4 and R5 have the meaning described in the general formula I. This reaction is preferably carried out in the presence of an inorganic acid such as hydrochloric acid, in a suitable polar solvent such as 2-methoxyethanol or ethanol, and heating, preferably at reflux.

The compounds of formula I wherein R5 represents R5 * (that is, the compounds of formula Ia and Ib) are generally obtained by reaction of a compound of formula I where R5 represents H (ie, a compound of formula Ic) with an alkylating agent of formula R5 * -X (II), as shown in the following scheme:

25

R5 *

H

image5

R image5 1 N

image5 image5 R1 N image5

image5 R image5 1 N

N image5 N

image5 N

R5 *

image5 R5 *

image5 N

N

N

X

R2

R2

R2

R4

R4

R4

image5

R3 R3R3

Ic II Ia Ib

where R5 * represents Ra or Rf. R1, R2, R3, R4, Ra and Rf have the meaning described in the general formula I and X represents a leaving group, for example an alkylsulfonate or arylsulfonate such as mesylate or tosylate, or a halogen such as 5 Cl, Br or I This reaction is carried out in the presence of a base, such as KOH, K2CO3 or NaH, in a suitable solvent, such as acetone, toluene, dimethylformamide, 1,2-dimethoxyethane or diglyme, and heating, preferably at reflux. In the case of using apolar solvents such as toluene, this reaction can be carried out in the presence of a cation sequestrant such as ether

Crown 18-C-6 or a phase transfer agent such as a tetraalkylammonium salt. The compounds of formula Ia and Ib wherein Ra represents -CH2OH can be prepared by reacting a compound of formula Ic with formaldehyde in a suitable polar solvent, for example water, and heating, preferably

15 at reflux. The compounds of formula Ia and Ib wherein Ra represents a phenyl group

or optionally substituted heteroaryl can be prepared by reacting a compound of formula Ic with a boronic acid of formula Ra-B (OH) 2 (III) where Ra represents an optionally substituted phenyl or heteroaryl group in

The presence of a base, such as pyridine and / or triethylamine, and in the presence of a catalyst, such as copper acetate II, in a suitable solvent, such as an aprotic solvent such as dichloromethane.

The compounds of formula II and III are commercial, are widely described in the literature or can be prepared by methods analogous to those described, and can be conveniently protected if necessary.

Compounds of formula I wherein R5 represents H and R3 has the same meaning as R1 (i.e., compound Id) can also be prepared by reacting a compound of formula IV with an aminopyrazole of

Va formula, as shown in the following scheme:

R1 image5 H2N image5 image5 H image5 image5 H

OR

N R1N

image5 N

image5

N

image5

N R2 R2

R4

R4 R1

IV Go Id

or alternatively reacting a compound of formula VII with a compound of formula Va

H

image5 H image5 R1NH2N

image5 N

N

R1 image5 OR image5 OR

image5

N

image5 R1 R2 R2 R

R4

R1 where R1, R2 and R4 have the meaning described in the general formula I. This reaction is preferably carried out in the presence of an inorganic acid

as hydrochloric acid, in a suitable polar solvent such as 2-methoxyethanol or 10 ethanol, and heating, preferably at reflux.

The aminopyrazoles of formula V and Va and the aldehydes of formula VI are commercial and may be conveniently protected. Alternatively, the compounds of formula Va can be conveniently prepared by reacting a compound of formula VIII with a compound of formula IX, according to

15 is shown in the following scheme: H2N image5 H

NC N image5 ON

image5

NH2 NH2 R4 image5 R4

IX VIII Go where R4 has the meaning described in the general formula I. This reaction is carried out in a suitable polar solvent such as ethanol and heating, preferably at reflux. The compounds of formula V can also

Obtained by this method, using a compound of formula IX and a compound of formula NH2-NHR5 (VIIIa) as starting products.

The compounds of formula IX are commercial and can be conveniently protected or can be conveniently prepared by reacting a compound of formula X

image6

X

5 with acetonitrile, in the presence of a base such as butyllithium, in a suitable solvent such as tetrahydrofuran and at a suitable temperature, preferably 78C.

Esters of formula X are commercial or can be prepared by methods widely described in the literature and can be conveniently protected.

The enol ethers of formula VII can be conveniently prepared by reacting a ketone of formula IV with a compound of formula R1-COY (XI) where Y represents halogen, preferably Cl, in the presence of a base, such as NaH, in a polar solvent suitable as dimethylformamide.

The compounds of formula XI are commercial or can be prepared by conventional reactions from the corresponding carboxylic acids of formula R1-CO2H (XII).

The compounds of formula XII are commercial or can be prepared by methods widely described in the literature and can be conveniently protected. Compounds of formula IV can be prepared by reacting a compound of formula R1-H (XIII) with a compound of formula XIV

image7

XIV where R1 and R2 have the meaning described in general formula I, in the presence of a Lewis acid, such as AlCl3, in a suitable halogenated solvent such as dichloromethane. The compounds of formula XIV are commercial or can be prepared

suitably from the corresponding carboxylic acid by conventional procedures. Alternatively, the compounds of formula IV may conveniently be prepared by reacting a compound of formula R2-CH3 (XV)

5 with a compound of formula R1-CN (XVI), where R1 and R2 have the meaning described in general formula I, in the presence of a base such as lithium diisopropylamide, generated from butyllithium and N, N'-diisopropylamine, in an aprotic polar solvent, such as tetrahydrofuran and cooling, preferably at -78 ° C.

Alternatively, the compounds of formula IV may conveniently be prepared by reacting a compound of formula R2-CH3 (XV) with a compound of formula R1-CO2R6 (XVII), where R1 and R2 have the meaning described in general formula I and R 6 represents C 1-6 alkyl, in the presence of a base such as sodium bis (trimethylsilyl) amide or sodium hydride, in a

Aprotic polar solvent, such as tetrahydrofuran or dimethylformamide and at a suitable temperature, preferably at room temperature. Compounds XIII, XV, XVI and XVII are commercial or can be prepared by methods widely described in the literature. Alternatively, the compounds of formula IV can be prepared

Conveniently by reacting a compound of formula R2-CH3 (XV) with a compound of formula XVIII under the same conditions described above for the reaction of the compound of formula XV with a compound of formula XVI.

XVIII

The compounds of formula XVIII can be conveniently prepared by reacting a compound of formula XI with N hydrochloride, Odimethylhydroxylamine in the presence of a base, such as triethylamine, in a suitable halogenated solvent, such as dichloromethane and preferably cooling to 0 ° C. Alternatively, the compounds of formula XVIII can be prepared

Conveniently by reacting a compound of formula XII with N, O-dimethylhydroxylamine hydrochloride in the presence of a suitable condensing agent such as for example N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide or dicyclohexylcarbodiimide optionally in the presence of 1-hydroxybenzotriazole, or in the presence of a suitable base, such as pyridine, in a suitable solvent, such as dimethylformamide.

image8

The compounds of formula I can also be obtained from a compound of formula XIX, as shown in the following scheme: R1 image5

image5 R1

N image5 Cl NR5

N NH2 NHR5

N R2

image5 CN R2 R3 R3 NH2

XIX VIIIa Ie

image5

image9

I where R1, R2, R3, R4 and R5 have the meaning described in the general formula I. The

The reaction of XIX with a compound of formula VIIIa gives rise to a compound of formula I where R4 = NH2 (Ie). This reaction is carried out in a suitable solvent, such as ethanol and heating, preferably at reflux. From said compounds of formula I where R4 = NH2, compounds of formula I where R4 is different from NH2 can be generated by interconversion reactions,

15 explained in more detail below. This method is useful for preparing those compounds of formula I where R3 represents H, C1-6 optionally substituted alkyl or a Cy group other than R1.

The compounds of formula VIIIa are commercial and may be conveniently protected. The compounds of formula XIX can be conveniently prepared by reacting a compound of formula XX

R1 image5 N

image5 OH

CN image5 R3 R2

XX where R1, R2 and R3 have the meanings described in the general formula I, with a chlorinating agent such as POCl3 or PCl3 without solvent or in a suitable solvent such as dimethylformamide and heating, preferably at reflux.

Compounds of formula XX are generally obtained by reacting a compound of formula XXI with 2-cyanoacetamide, as shown in the following scheme:

R1 image5

Or H2N image5 Or R1 image5 N

image5 OH

image5

NR6R6

image5 CN

R2

R2

CN R3 image5 R3 10 XXI XX where R1, R2 and R3 have the meanings described in the general formula I and each R6 independently represents C1-6alkyl. This reaction is carried out in the presence of a base such as sodium methoxide, in a suitable solvent such as dimethylformamide and heating, preferably at reflux. The compounds of formula XXI can be conveniently prepared by reacting a compound of formula IV with a compound of formula XXII

R6O

NR6R6 R6O

image5 R3

XXII

where R3 and R6 have the meanings described above, in a suitable solvent such as tetrahydrofuran.

image10

Compounds of formula XXII are commercial or can be prepared by methods described in the literature, for example by reaction of an amide of formula XXIII

NR6R6

XXIII

5 with triethyloxonium tetrafluoroborate in the presence of a base such as sodium ethoxide, in a suitable solvent such as ethanol or a mixture of ethanol-diethyl ether.

Alternatively, the compounds of the present invention can also be obtained by interconversion from another compound of formula I, in one or several stages, using customary reactions in organic chemistry in the

standard conditions already described.

Thus, a group R4 can be transformed into another group R4, generating new compounds of formula I. For example, a group R4 = H can be transformed into a group R4 = Br by reaction with a suitable brominating agent, such as Br2,

15 in a suitable solvent such as chloroform, and at a suitable temperature between room temperature and the boiling temperature of the solvent;

or a group R4 = H can be transformed into a group R4 = Cl by reaction with a suitable chlorinating agent such as N-chlorosuccinimide, in a

20 suitable solvent such as dimethylformamide and at a suitable temperature between room temperature and the boiling temperature of the solvent;

or a group R4 = NH2 can be transformed into a group R4 = halogen by formation of a diazonium salt with NaNO2 and subsequent reaction with

A cuprous halide such as CuBr or CuCl, in the presence of an acid such as HBr or HCl;

or a group R4 = NH2 can be transformed into a group R4 = H by formation of a diazonium salt with NaNO2 and subsequent reaction with H3PO2, in a suitable solvent such as water;

30 or an R4 = halogen group can be transformed into an R4 = CN group by reaction with a cyanide salt such as CuCN, in a suitable solvent such as N-methylpyrrolidone and heating, preferably at reflux.

Other transformations on R4, which can also be applied on R5 as well as on the substituents of groups R1, R2 and R3 to generate other compounds of formula I, include, for example:

the transformation of a CN group into a CONH2 group by hydrolysis with a base such as KOH, in a suitable solvent such as tert-butanol and heating, preferably at reflux;

the transformation of a CN group into a CH2NH2 group by reaction with a reducing agent, such as LiAlH4, in a suitable solvent such as diethyl ether;

the transformation of a carboxylic acid group into an ester or an amide by reaction with an alcohol or an amine respectively, in the presence of an activating agent such as N, N'-dicyclohexylcarbodiimide and 4-dimethylaminopyridine and in a suitable solvent such as diethyl ether;

the transformation of an ester group into a carboxylic acid group by hydrolysis in the presence of a base, such as KOH, in a suitable solvent such as ethanol;

the transformation of an OH, SH or NH2 group into OR, SR and NHR or NRR groups, respectively, by reaction with an alkylating agent RX, where R represents Ra, Rc, Re or Rf and X represents halogen, preferably chlorine or bromine, in the presence of a base such as triethylamine, sodium hydroxide, sodium carbonate, potassium carbonate or sodium hydride in a suitable solvent such as dichloromethane, chloroform, dimethylformamide, ethanol or butanol, and at a temperature between room temperature and boiling temperature of the solvent;

alternatively, NHR can be transformed into NCH3R, where R represents Ra, Rc, Re or Rf, by reaction with formaldehyde in acidic medium, for example in formic acid, and preferably heating under reflux;

the transformation of an amine into an amide group by reaction of a carboxylic acid in the presence of a suitable condensing agent such as for example N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide or dicyclohexylcarbodiimide optionally in the presence of 1-hydroxybenzotriazole, a suitable base, such as pyridine, in a suitable solvent, such as dimethylformamide; or alternatively an amine can be transformed into an amide by reaction with an acid chloride in pyridine or in the presence of a base such as triethylamine in a suitable solvent such as dichloromethane, and cooling, preferably at 0 ° C;

the transformation of an amine into a urea or a carbamate through a two-step sequence that involves reacting the amine with an activating agent such as triphosgene, in the presence of a base such as diisopropylethylamine, triethylamine or N-methylmorpholine, in a solvent suitable as acetonitrile or a halogenated hydrocarbon such as chloroform or dichloromethane, and then reacting the resulting compound with the second amine in the case of a urea or with an alcohol in the case of a carbamate, in a suitable solvent, for example the solvent used In the first stage; or alternatively an amine can be transformed into a urea or a carbamate by reaction with an isocyanate or with a chloroformate, respectively, in a suitable solvent, such as dimethylformamide, at a suitable temperature, preferably room temperature;

the transformation of an amine into a sulfonamide by reaction with a sulfonyl halide, such as sulfonyl chloride, optionally in the presence of a base such as 4-dimethylaminopyridine, in a suitable solvent such as dioxane, chloroform, dichloromethane or pyridine;

the transformation of a hydroxyl group into an ester group by reaction with a carboxylic acid under the standard conditions mentioned above;

the transformation of a sulfanyl group into a sulfinyl or sulfonyl group by reaction with 1 or 2 equivalents, respectively, of a suitable oxidizing agent such as m-chloroperbenzoic acid in a suitable solvent such as dichloromethane;

the transformation of a primary or secondary hydroxyl group into a leaving group, for example an alkylsulfonate or arylsulfonate such as mesylate or tosylate

or a halogen such as Cl, Br or I, by reaction with a sulfonyl halide such as methanesulfonyl chloride, in the presence of a base, such as pyridine or triethylamine, in a suitable solvent such as dichloromethane or chloroform, or with a halogenating agent, such as SOCl2, in a suitable solvent such as tetrahydrofuran;

the substitution of said leaving group by reaction with an alcohol, amine or thiol, optionally in the presence of a base, such as K2CO3, and in a suitable solvent such as dimethylformamide, 1,2-dimethoxyethane or acetonitrile;

the removal of a leaving group attached to an alkyl group to give an alkenyl group by reaction with a base, such as KOH, in a suitable solvent, such as toluene and heating, preferably at reflux;

the transformation of a primary amide into a secondary amide by reaction with an alkylating agent in the presence of a strong base, such as sodium hydride, in a suitable solvent and at a temperature between room temperature and the boiling temperature of the solvent;

the transformation of a CHO group into an amine by reaction with an amine in the presence of a reducing agent such as sodium triacetoxyborohydride, in a suitable solvent, such as 1,2-dichloroethane;

the transformation of an acetal group into an aldehyde by reaction in an acid medium, for example in HCl, at a suitable temperature, preferably at reflux;

the transformation of an ester group into an alcohol group by reaction with a reducing agent, such as LiAlH4, in a suitable solvent, such as tetrahydrofuran;

the transformation of a sulfonyl group attached to an aromatic ring into an amino derivative by reaction with the corresponding amine in a suitable solvent such as THF or using the amine as a solvent, preferably heating at a temperature between room temperature and 100 ° C and preferably performing the reaction at atmospheric pressure in a closed tube;

the transformation of a sulfonyl group attached to an aromatic ring by displacement with an alkoxide to give the corresponding alkoxy derivative, in a suitable solvent such as THF or using the corresponding alcohol as solvent, heating, preferably at a temperature between room temperature and 100  C, and carrying out the reaction at atmospheric pressure in a closed tube;

the transformation of vinyl or aromatic halogen in an NHR, where R represents Ra, Rc, Re or Rf, by reaction with an amine of formula H2NR and preferably heating;

alternatively, a vinyl or aromatic halogen can be transformed into an NHR by reaction with an amine of formula H2NR in the presence of a base, such as Cs2CO3 or sodium tert-butoxide, in the presence of a palladium catalyst, such as palladium acetate (II ), and a phosphine such as 2,2'-bis (diphenylphosphino) -1,1'binafthyl, in a solvent, such as toluene and preferably heating;

the transformation of a vinyl or aromatic halogen group into a phenyl or heteroaryl group by treatment with a phenyl- or heteroarylboronic acid in the presence of a catalyst, such as a palladium catalyst, such as palladium (II) acetate or tetrakis (triphenylphosphine ) palladium (0) and a base such as Na2CO3, K2CO3 or CsF, in a suitable polar solvent, such as 1,2-dimethoxyethane or toluene-water mixtures, and preferably heating;

the transformation of an aromatic halogen into H by halogenolysis, with a reducing agent such as Zn, in a suitable solvent, such as acetic acid and heating, preferably at reflux; Y

the oxidation of the N in position 7 of the pyrazolo ring [3,4-b] pyridine to give the corresponding N-oxide by reaction with an oxidizing agent, such as m-chloroperbenzoic acid, in a suitable solvent such as dichloromethane.

Likewise, any of the aromatic rings of the compounds of the present invention may undergo aromatic electrophilic substitution reactions, widely described in the literature.

Many of these interconversion reactions are explained in more detail in the examples.

As will be apparent to those skilled in the art, these interconversion reactions can also be carried out on synthesis intermediates of the compounds of formula I.

The present invention also includes the salts of the compounds of formula I. Said salts can be prepared by conventional methods by treating a compound of formula I with a suitable amount of an acid such as, for example, hydrochloric acid, sulfuric acid, nitric acid, acid. oxalic

or methanesulfonic acid. In the case of compounds of formula I containing some acidic proton, salts thereof can also be obtained by treatment with a base such as sodium hydroxide, potassium hydroxide, calcium hydroxide or calcium carbonate. The salts of the compounds of formula I can in turn be transformed into other salts of compounds of formula I by ion exchange by means of an ion exchange resin.

As mentioned above, the compounds of the present invention act as p38 kinase inhibitors, inducing the reduction of pro-inflammatory cytokines. Therefore, these compounds could be useful for the treatment or prevention of those diseases in which p38 kinase participates. This includes diseases caused by the overproduction of cytokines such as TNF-, IL-1, IL-6 or IL-8. Such diseases include, but are not limited to, immune, autoimmune and inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases, proliferative diseases and processes associated with the induction of cyclooxygenase-2.

As an example, immune, autoimmune and inflammatory diseases that can be treated or prevented with the compounds of the present invention include rheumatic diseases (eg rheumatoid arthritis, psoriatic arthritis, infectious arthritis, progressive chronic arthritis, deforming arthritis, osteoarthritis, traumatic arthritis , gouty arthritis, Reiter's syndrome, polychondritis, acute synovitis and spondylitis), glomerulonephritis (with or without nephrotic syndrome), autoimmune hematological disorders (eg hemolytic anemia, aplastic anemia, idiopathic thrombocytopenia, and neutropenia), autoimmune gastritis and diseases Autoimmune intestinal inflammations (eg ulcerative colitis and Crohn's disease), graft versus host reaction, allograft rejection, chronic thyroiditis, Graves disease, scleroderma, diabetes (type I and type II), active hepatitis (acute and chronic ), primary biliary cirrhosis, myasthenia gravis, multiple sclerosis, lupus erythematosus systemic, psoriasis, atopic dermatitis, contact dermatitis, eczema, sunburns of the skin, chronic renal failure, Stevens-Johnson syndrome, idiopathic sprue, sarcoidosis, Guillain-Barré syndrome, uveitis, conjunctivitis, keratoconjunctivitis, otitis media, disease periodontal, interstitial pulmonary fibrosis, asthma, bronchitis, rhinitis, sinusitis, pneumoconiosis, pulmonary insufficiency syndrome, pulmonary emphysema, pulmonary fibrosis, silicosis, chronic pulmonary inflammatory disease (e.g. ex. chronic obstructive pulmonary disease) and other inflammatory or obstructive diseases of the airways.

Cardiovascular diseases that can be treated or prevented include, among others, myocardial infarction, cardiac hypertrophy, heart failure, disorders caused by ischemia-reperfusion, thrombosis, platelet aggregation induced by thrombin, acute coronary syndromes, atherosclerosis and strokes.

Infectious diseases that can be treated or prevented include, among other sepsis, septic shock, endotoxic shock, Gram negative sepsis, shiguelosis, meningitis, cerebral malaria, pneumonia, tuberculosis, viral myocarditis, viral hepatitis (hepatitis A, hepatitis B and hepatitis C) , HIV infection, retinitis caused by cytomegalovirus, influenza, herpes, treatment of infections associated with severe burns, myalgias caused by infections, cachexia secondary to infections, as well as veterinary viral infections such as lentivirus, goat arthritic virus, visna-maedi virus, Feline immunodeficiency virus, bovine immunodeficiency virus or canine immunodeficiency virus.

Bone resorption disorders that can be treated or prevented include osteoporosis, osteoarthritis, traumatic arthritis, gouty arthritis and bone disorders related to multiple myeloma, among others.

Neurodegenerative diseases that can be treated or prevented include Alzheimer's disease, Parkinson's disease, cerebral ischemia and traumatic neurodegenerative disease, among others.

Proliferative diseases that can be treated or prevented include endometriosis, solid tumors, acute and chronic myeloid leukemia, Kaposi sarcoma, multiple myeloma, metastatic melanoma, and angiogenic disorders such as ocular neovascularization and childhood hemangioma.

P38 kinase inhibitors also inhibit the expression of pro-inflammatory proteins such as cyclooxygenase-2 (COX-2), the enzyme responsible for the production of prostaglandins. Therefore, the compounds of the present invention can also be used for the treatment or prevention of diseases mediated by COX-2 and in particular for the treatment of processes with inflammation, fever and neuromuscular pain such as headache, pain caused by cancer, Dental pain and arthritic pain.

In accordance with the activity of the products described herein, the present invention also relates to compositions containing a compound of the present invention, together with an excipient or other auxiliary agents if necessary. The compounds of the present invention can be administered in the form of any pharmaceutical formulation, the nature of which, as is well known, will depend on the nature of the active ingredient and its route of administration. In principle, any route of administration can be used, for example oral, parenteral, nasal, ocular, rectal, and topical.

In accordance with the present invention, solid compositions for oral administration include tablets, granules and capsules. In any case, the manufacturing method is based on a simple mixture, dry granulation or wet granulation of the active ingredient with excipients. These excipients may be, for example, diluents such as lactose, microcrystalline cellulose, mannitol or calcium hydrogen phosphate; binding agents such as starch, gelatin or polyvinylpyrrolidone; disintegrants such as sodium carboxymethyl starch or croscarmellose sodium; and lubricating agents such as magnesium stearate, stearic acid or talc. The tablets may also be coated with suitable excipients by known techniques in order to delay their disintegration and absorption in the gastrointestinal tract and thus achieve sustained action for a longer period of time, or simply improve their organoleptic properties or their stability. The active ingredient can also be incorporated by coating on inert pellets using natural or synthetic film-forming polymers. It is also possible to make soft gelatin capsules, in which the active ingredient is mixed with water or oily medium, for example coconut oil, liquid paraffin

or olive oil

Powders and granules can be obtained for the preparation of oral suspensions by the addition of water by mixing the active ingredient with dispersing or wetting agents; suspending and preservative. Other excipients can also be added, for example sweeteners, flavorings and dyes.

Liquid forms for oral administration may include emulsions, solutions, suspensions, syrups and elixirs containing commonly used inert diluents, such as distilled water, ethanol, sorbitol, glycerol, polyethylene glycols (macrogols) and propylene glycol. Such compositions may also contain adjuvants such as wetting, suspending, sweetening, flavoring, preservative and pH regulating agents.

Injectable preparations, according to the present invention, for parenteral administration, comprise sterile solutions, suspensions or emulsions, in an aqueous or non-aqueous solvent such as propylene glycol, polyethylene glycol

or vegetable oils. These compositions may also contain adjuvants, such as humectants, preservatives, emulsifiers and dispersants. They could be sterilized by any of the methods known or prepared as sterile solid compositions that will be dissolved in water or any other sterile injectable medium immediately before use. It is also possible to start from sterile materials and keep them in these conditions during the entire manufacturing process.

For rectal administration, the active ingredient may preferably be formulated as a suppository in an oily base, such as for example vegetable oils or solid semi-synthetic glycerides, or in a hydrophilic base such as polyethylene glycols (macrogols).

The compound can also be formulated for topical application for the treatment of pathologies in areas or organs accessible by this route, such as eyes, skin and intestinal tract. The formulations include creams, lotions, gels, ointments, powders, solutions and patches in which the compound is dispersed or dissolved in suitable excipients.

The compounds of the present invention can also be formulated in solid form, dissolved or dispersed in a suitable vehicle, for administration by inhalation in multi-dose or single-dose container. Preparations intended to be administered in aerosol form (dispersion of solid or liquid particles in a gas) employ a device suitable for administration which may be a nebulizer, a pressurized inhaler with a metering valve or a dry powder inhaler. Accordingly, the compound will be formulated with excipients such as propellant agents that generate the pressure necessary to ensure the projection of the formulation after opening the valve, solubilizers, emulsifiers, viscosisants, preservatives, stabilizers and lubricants that prevent valve blockage. .

The administration and frequency of the dose will depend on the nature and severity of the disease to be treated, the age, the general condition and the weight of the patient, as well as the particular compound administered and the route of administration, among other factors. A representative example of an adequate administration range is from about 0.01 mg / kg to about 100 mg / kg per day, which can be administered as a single dose or divided doses. However, administration of the dose is generally at the discretion of the physician.

The activity of the compounds of the present invention can be determined using the following tests:

Test 1: Inhibition of LPS-induced TNF-liberación release in human histiocytic lymphoma cells, U-937 Maintenance and differentiation of U-937 cells: U-937 cells (ATCC No. CRL-159.2) are grown in medium RPMI 1640 supplemented with 10% inactivated fetal bovine serum (Gibco). 0.5x106 cells are incubated in the presence of 20 ng / mL of PMA (phorbol 12-myristate 13-acetate) for 24 h until complete monocytic differentiation is achieved. All incubations are carried out at 37 ° C and in an atmosphere with 5% CO2. The cells are centrifuged (200 x g for 5 min) and resuspended in RPMI 1640 medium supplemented with 2% inactivated fetal bovine serum at a density of 2x106 cells / mL. Inhibition of TNF-liberación release: 100 µL of U-937 cells (2x106 cells / mL) are incubated with 100 µL of the product to be tested (final concentration, 0.001-10 µM) for 30 min in 96-well plates. The stock solutions of the products (10 mM in DMSO) are diluted in culture medium until reaching a final concentration of DMSO equal to or less than 0.1%. 20 µL of LPS is added

(E. coli 055B5, Sigma) at a final concentration of 100 ng / mL and after 4 hours of incubation the amount of TNF- released in the supernatant is quantified by a commercial ELISA kit (Biosource International).

Test 2: Inhibition of the release of TNF- induced by LPS in human peripheral blood mononuclear cells Obtaining mononuclear cells: Heparinized venous blood, obtained from healthy volunteers, is diluted with equal volume of phosphate buffered saline without calcium and magnesium. 30 mL aliquots of this mixture are transferred to 50 mL centrifuge tubes containing 15 mL of Ficoll-Hypaque (1,077 g / mL). The tubes are centrifuged at 1200 x g for 20 min at room temperature without brake. Approximately two thirds of the platelet band located above the mononuclear cells is removed with the help of a pipette. The mononuclear cells are carefully transferred to a 50 mL tube, washed twice with phosphate buffered saline, centrifuged at 300 xg for 10 min at room temperature and resuspended in RPMI supplemented with 1% inactivated fetal bovine serum at a cell density of 2x106 cells / mL. Inhibition of TNF-liberación release: 100 µL of mononuclear cells (2x106 cells / mL) are incubated in 96-well plates with 50 L of the product to be tested (final concentration, 0.001-10 M) and 50 L of LPS (E. coli 055B5, Sigma) at a final concentration of 400 ng / mL for 19 h at 37 ° C in a 5% CO2 atmosphere. The amount of TNF- released in the supernatant is quantified by a commercial ELISA kit (Biosource International).

Test 3: Inhibition of p38- kinase: In a final volume of 25 L, 5 L of the product to be tested is incubated (final concentration, 0.001-10 M), 5-10 mU of p38- with 0.33 mg / mL of myelin basic protein, Mg2 + acetate (10 mM) and [33P-ATP] (100 M, specific activity 500 cpm / pmol) in 25 mM Tris buffer pH7.5, EGTA 0.02 mM. The reaction is initiated by the addition of Mg2 + [ 33P-ATP]. After 40 min incubation at room temperature, the reaction is stopped by adding 5 µL of a 3% phosphoric acid solution. The reaction mixture (10 L) is passed through a filter (P30) and washed three times for 5 min with a 75 mM phosphoric acid solution and once with methanol before drying and counting, by liquid scintillation.

The following table shows the results obtained with representative compounds of the invention in test 2:

No. Example

% Inhibition at 0.1 M

one

57.5

4

68.4

6

81.4

8

66.3

18

82.6

22

56.5

30

83.6

36

92.0

39

51.1

41

90.6

43

61.2

56

58.7

59

60.0

63

53.2

68

50.0

72

52.7

78

73.3

80

69.3

82

59.9

90

86.3

102

67.9

106

69.3

121

52.1

128

82.0

136

67.0

137

61.4

183

66.7

184

71.2

188

73.2

196

70.2

208

67.7

209

84.2

210

57.3

211

70.6

212

67.5

213

68.1

214

71.1

217

53.8

232

67.9

237

53.4

240

58.4

248

53.2

250

67.0

268

69.1

272

65.6

279

100.0

282

65.2

283

52.4

287

71.2

289

51.3

290

65.8

The following examples illustrate, but do not limit, the scope of the present invention.

The following abbreviations have been used in the examples: AcOH: acetic acid AcOEt: ethyl acetate AcONH4: Ammonium Acetate BuLi: Butyllithium

tBuOH: tert-butanol conc .: concentrated DMAP: 4- (N, N-dimethylamino) pyridine DMF: dimethylformamide EtOH: ethanol MeOH: methanol THF: tetrahydrofuran tR: retention time LC-MS: liquid chromatography-mass spectrometry

For the realization of the LC-MS spectra the following methods have been used chromatographic: Method 1: Tracer Excel 120 column, ODSB 5 m (10 mm x 0.21 mm), temperature: 30 ° C, flow: 0.35 mL / min, eluent: A = acetonitrile, B = 0.1% HCOOH, gradient: 0 min 10% A - 10 min 90% A. Method 2: Column X-Terra MS C18 5 m (150 mm x 2.1 mm), temperature: 30 ºC, flow: 0.40 mL / min, eluent: A = acetonitrile, B = 10 mM AcONH4 (pH = 6.80), gradient: 0 min 25% A -6 min 80% A -7.5 min 25% A.

REFERENCE EXAMPLE 1 1- (4-Fluorophenyl) -2- (4-pyridyl) ethanone a) 4-Fluoro-N-methyl-N-methoxybenzamide

Under a stream of argon, N, Odimethylhydroxylamine hydrochloride (25.54 g, 261.8 mmol) and CH2Cl2 (443 mL) are introduced at 0 ° C. 4-Fluorobenzoyl chloride (34.59 g, 218.2 mmol) is added and then triethylamine (48.13 g, 475.6 mmol) is added slowly. The reaction is stirred for 30 min at 5 ° C and allowed to reach room temperature. It is washed with a 5% aqueous solution of citric acid (180 mL) and with a 5% aqueous solution of NaHCO3 (180 mL). The aqueous phase is extracted with CH2Cl2. The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 20.23 g of the desired compound (rto: 88%).

b) Title compound

To a solution of diisopropylamine (23.4 mL, 165.7 mmol) in THF (250 mL), cooled to –78 C, under Argon BuLi (103.5 mL of a 1.6 M solution in hexane, 165.7 mmol) is added dropwise . After 5 min a solution of 4-methylpyridine (10.28 g, 110.4 mmol) in THF (85 mL) is added over a period of 20 min. The mixture is stirred at 0 ° C for 15 min and a solution of 4-fluoro-N-methyl-N-methoxybenzamide (obtained in section a) in THF (85 mL) is added over a period of 30 min. The reaction is allowed to reach room temperature. Water (100 mL) and AcOEt (100 mL) are added and the mixture is stirred for 30 min. The organic phase is separated, dried over Na2SO4 and concentrated to dryness, obtaining 24.32 g of the desired compound (rto: 100%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.29 (s, 2 H), 7.14 - 7.23 (complex signal, 4 H), 8.05 (m, 2 H), 8.59 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

REFERENCE EXAMPLE 2 2- (4-Pyridyl) -1- [3- (trifluoromethyl) phenyl] ethanone a) N-Methyl-N-methoxy-3- (trifluoromethyl) benzamide

Following a procedure analogous to that described in reference example 1 section a, but using 3- (trifluoromethyl) benzoyl chloride instead of 4-fluorobenzoyl chloride, the desired compound is obtained (rto: 86%).

b) Title compound

Following a procedure analogous to that described in reference example 1 section b, but using N-methyl-N-methoxy-3- (trifluoromethyl) benzamide (obtained in section a of this example) instead of 4-fluoro-N- methyl-Nmethoxybenzamide, the title compound is obtained (rto: 22%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.31 (s, 2 H), 7.20 (d, J = 5.8 Hz, 2 H), 7.63 (t, J = 7.8 Hz, 1 H), 7.84 (d , J = 7.8 Hz, 1 H), 8.16 (d, J = 7.9 Hz, 1 H), 8.24 (s, 1 H), 8.56 (d, J = 5.8 Hz, 2 H).

REFERENCE EXAMPLE 3 1-Phenyl-2- (4-pyridyl) ethanone

A solution of diisopropylamine (22 mL, 15.03 mmol) in THF (200 mL) under an argon atmosphere is cooled to –78 C. BuLi (96 mL of a 1.6 M solution in hexane, 153.0 mmol) is added dropwise. After 1 h, a solution of 4-methylpyridine (15.00 g, 161.1 mmol) in THF (75 mL) is added and the temperature is allowed to reach 0 ° C. Stir at this temperature for 30 min. It is cooled to –78 C and benzonitrile (18.27 g, 177.2 mmol) in THF (75 mL) is added and stirred at –78 duranteC for 2 h. It is stirred at room temperature overnight. Water (225 mL) is added, cooled with an ice-water bath and adjusted to pH 1 with 48% HBr. The organic phase is separated. The aqueous phase is heated at reflux for 2 h, allowed to cool and extracted with diethyl ether. The aqueous phase is brought to neutral pH with 1N NaOH and extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 28.53 g of the title compound (rto: 90%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.29 (s, 2 H), 7.20 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 7.49 (m, 2 H), 7.58 (m , 1 H), 8.00 (d, J = 8.2 Hz, 2 H), 8.56 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

REFERENCE EXAMPLE 4 1- (4-fluorophenyl) -2- (4-pyridyl) vinyl 4-fluorobenzoate

To a suspension of NaH (0.81 g, 18.6 mmol) in DMF (30 mL) under an argon atmosphere and cooled to 0 ° C, a solution of 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone ( 2.00 g, 9.3 mmol, obtained in reference example 1) in DMF (15 mL) and stirred at room temperature for 30 min. Subsequently, it is cooled to 0 ° C and a solution of 4-fluorobenzoyl chloride (2.95 g, 1.9 mmol) in DMF (10 mL) is added. It is stirred at room temperature overnight. Water is added and the solvent is evaporated. The residue is dissolved in a mixture of CHCl3 and water and the phases are separated. The aqueous phase is extracted with CHCl3 (x3). The organic phase is washed with water (x2), dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 0.98 g of the desired compound as a yellow solid (rto: 31%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 6.68 (s, 1 H), 7.11 (t, J = 8.6 Hz, 2 H), 7.29 (t, J = 8.6 Hz, 2 H), 7.39 (d , J = 6.0 Hz, 2 H), 7.60 (dd, Jo = 5.2 Hz, Jm = 8.8 Hz, 2 H),

8.27 (dd, Jo = 5.4 Hz, Jm = 8.8 Hz, 2 H), 8.58 (d, J = 6.0 Hz, 2 H)

REFERENCE EXAMPLE 5 1-Phenyl-2- (4-pyridyl) vinyl benzoate

Following a procedure analogous to that described in reference example 4, but using 1-phenyl-2- (4-pyridyl) ethanone (obtained in reference example 3) instead of 1- (4-fluorophenyl) -2- ( 4-pyridyl) ethanone and benzoyl chloride instead of 4-fluorobenzoyl chloride, the title compound is obtained (rto: 62%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 6.72 (s, 1 H), 7.38 - 7.42 (complex signal, 5 H), 7.60 –7.63 (complex signal, 4 H), 7.71 (t, J = 7.4 , 1 H), 8.23 (d, J = 7.1 Hz, 2 H), 8.51 (dd, Jo = 1.5 Hz, Jm = 4.6 Hz, 2 H).

REFERENCE EXAMPLE 6 2- [2- (Methylsulfanyl) pyrimidin-4-yl] -1- [3- (trifluoromethyl) phenyl] ethanone a) 4-Methyl-2- (methylsulfanyl) pyrimidine

To a solution of NaOH (7.46 g, 186.4 mmol) in water (120 mL), 4-methylpyrimidine-2-thiol hydrochloride (13.78 g, 84.7 mmol) is added and subsequently added dropwise and under a stream of argon iodomethane (13.23 g, 93.2 mmol). Stir at room temperature for 2 h. It is extracted with CH2Cl2 (x2). The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 10.26 g of the desired compound (rto: 86%).

b) Title compound

Following a procedure analogous to that described in reference example 1 section b, but using N-methyl-N-methoxy-3- (trifluoromethyl) benzamide (obtained in section a of reference example 2) instead of 4-fluoro- N-methyl-Nmethoxybenzamide and 4-methyl-2- (methylsulfanyl) pyrimidine (obtained in section a of this example) instead of 4-methylpyridine, the title compound is obtained in the form of a crude that is used directly in the following reactions (rto: quantitative).

REFERENCE EXAMPLE 7 3- (Dimethylamino) -1- (4-fluorophenyl) - 2- (4-pyridyl) prop-2-en-1-one

To a solution of 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone (0.30 g, 1.4 mmol, obtained in reference example 1) in anhydrous THF (5 mL), dimethyl acetal dimethylformamide is added (0.27 g, 3.2 mmol) under argon atmosphere. It is stirred at room temperature overnight. The solvent is evaporated to obtain 0.39 g of the title compound (rto: quantitative).

1 H NMR (300 MHz, CDCl 3)  (TMS): 2.79 (s, 6 H), 6.97 (t, J = 8.7 Hz, 2 H), 7.05 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H ), 7.38 (s, 1 H), 7.45 (m, 2 H), 8.48 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

REFERENCE EXAMPLE 8 3- (Dimethylamino) -2- [2- (methylsulfanyl) pyrimidin-4-yl] -1- [3 (trifluoromethyl) phenyl] prop-2-en-1-one

Following a procedure analogous to that described in reference example 7, but using 2- [2- (methylsulfanyl) pyrimidin-4-yl] -1- [3- (trifluoromethyl) phenyl] ethanone (obtained in reference example 6) instead of 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone, the desired compound is obtained in the form of a crude that is used directly in the following reactions.

REFERENCE EXAMPLE 9 1- (6-Chloropyridin-3-yl) -2- (4-pyridyl) ethanone a) 6-Chloronicotinoyl chloride hydrochloride

A solution of 6-chloronicotinic acid (10.00 g, 63.5 mmol) in SOCl2 (37 mL) is heated at reflux for 2 h. The SOCl2 is evaporated to dryness, obtaining

12.56 g of the desired compound (rto: 93%).

b) 6-Chloro-N-methyl-N-methoxynicotinamide

Following a procedure analogous to that described in reference example 1 section a, but using 6-chloronicotinoyl chloride hydrochloride (obtained in section a of this example) instead of 4-fluorobenzoyl chloride, the desired compound is obtained (rto : 71%).

c) Title compound

Following a procedure analogous to that described in reference example 1 section b, but using 6-chloro-N-methyl-N-methoxynicotinamide (obtained in section b of this example) instead of 4-fluoro-N-methyl-N -methoxybenzamide, the title compound (rto: quantitative) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.27 (s, 2 H), 7.18 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.45 (dd, Jo = 0.6 Hz, Jm = 8.4 Hz, 1 H), 8.20 (dd, Jo = 2.5 Hz, Jm = 8.3 Hz, 2 H s, 1 H), 8.56 (18 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 8.98 (d, J = 2.4 Hz, 1 H).

REFERENCE EXAMPLE 10 2- (4-Fluorophenyl) -6-hydroxy-3,4'-bipyridin-5-carbonitrile

To a solution of 3- (dimethylamino) -1- (4-fluorophenyl) -2- (4-pyridyl) prop-2-en-1-one

(12.77 g, 47.2 mmol, obtained in reference example 7) in DMF (175 mL), is added under a stream of argon 2-cyanoacetamide (4.41 g, 52.0 mmol). Subsequently, sodium methoxide (5.35 g, 99.2 mmol) is added and heated to reflux for 1 h. Allow to cool, concentrate and dilute with water. It fits pH at 4 with 1N HCl. A precipitate is obtained which is filtered and dried to give

6.57 g of the desired compound as a solid (rto: 48%). 1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 4.20 (s, OH + NH + CD3OD), 6.96 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H), 7.05 (t, J = 8.7 Hz, 2 H), 7.23 (m, 2 H), 7.96 (s, 1 H), 8.39 (dd, Jo = 1.4 Hz, Jm = 4.6 Hz, 2 H).

REFERENCE EXAMPLE 11 2-Hydroxy-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] pyridine-3carbonitrile

Following a procedure analogous to that described in reference example 10, but using 3- (dimethylamino) -2- [2- (methylsulfanyl) pyrimidin-4-yl] -1- [3 (trifluoromethyl) phenyl] prop-2-en-1-one (obtained in reference example 8) in instead of 3- (dimethylamino) -1- (4-fluorophenyl) -2- (4-pyridyl) prop-2-en-1-one, you get the title compound (rto: 20%). 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 3.28 (s, 3 H), 3.84 (s, OH + CD3OD), 6.38 (d, J = 5.4 Hz, 1 H), 7.42 (d, J = 7.8 Hz, 1 H), 7.53 (t, J = 7.8 Hz, 1 H), 7.61 (s, 1 H), 7.73 (d, J = 7.8 Hz, 1 H), 8.18 (d, J = 5.1 Hz, 1 H), 8.35 (s, 1 H).

REFERENCE EXAMPLE 12 6-Chloro-2- (4-fluorophenyl) -3,4'-bipyridin-5-carbonitrile

A mixture of 2- (4-fluorophenyl) -6-hydroxy-3,4'-bipyridin-5-carbonitrile (6.57 g, 22.5 mmol, obtained in reference example 10), POCl3 (26.3 mL, 287.5 mmol) and DMF (0.37 mL) under argon atmosphere is heated at reflux for 2 h. It is cooled by an ice bath and basified by the addition of a 30% aqueous solution of NH3. The precipitate obtained is filtered and washed with water. The product is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 3.86 g of the desired compound as a yellow solid (rto: 55%).

1 H NMR (300 MHz, CDCl 3)  (TMS): 7.00 (t, J = 8.6 Hz, 2 H), 7.11 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 7.37 (m, 2 H ), 7.98 (s, 1 H), 8.62 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

REFERENCE EXAMPLE 13 1- (6-Methylpyridin-3-yl) -2- (4-pyridyl) ethanone a) 6, N-Dimethyl-N-methoxynicotinamide

To a solution of 6-methylnicotinic acid (5.00 g, 36.5 mmol) in DMF (150 mL), argon 1-hydroxybenzotriazole (4.92 g, 36.5 mmol), N- (3-dimethylaminopropyl) -N hydrochloride are added -ethylcarbodiimide (8.38 g, 45.7 mmol) and 4 methylmorpholine (16.0 mL, 145.8 mmol). Stir at room temperature for 30 min and subsequently add N, O-dimethylhydroxylamine hydrochloride (3.55 g,

36.5 mmol). The mixture is stirred at room temperature overnight. The solvent is evaporated. The residue is dissolved in a mixture of CHCl3 and a 0.2 N aqueous solution of NaHCO3. The phases are separated and the aqueous phase is extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness. The product is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 1.11 g of the desired compound (rto: 29%).

b) Title compound

Following a procedure analogous to that described in reference example 1 section b, but using 6, N-dimethyl-N-methoxynicotinamide (obtained in section a of this example) instead of 4-fluoro-N-methyl-N-methoxybenzamide , the title compound is obtained (rto: 87%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.64 (s, 3 H), 4.28 (s, 2 H), 7.20 (dd, Jo = 1.4 Hz, Jm = 4.6 Hz, 2 H), 7.28 (d , J = 8.1 Hz, 1 H), 8.15 (dd, Jo = 2.4 Hz, Jm = 8.1 Hz, 1 H), 8.57 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 9.10 (d, J = 2.4 Hz, 1 H).

REFERENCE EXAMPLE 14 2-Chloro-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] pyridine-3carbonitrile

Following a procedure analogous to that described in reference example 12, but using 2-hydroxy-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3 (trifluoromethyl) phenyl] pyridin-3-carbonitrile (obtained in reference example 11)

instead of 2- (4-fluorophenyl) -6-hydroxy-3,4'-bipyridin-5-carbonitrile, the titular compound (rto: 44%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.48 (s, 3 H), 6.62 (d, J = 5.1 Hz, 1 H), 7.51 (m, 2 H), 7.71 (d, J = 7.2 Hz, 1 H), 7.82 (s, 1 H), 8.39 (d, J = 5.1 Hz, 1 H), 8.42 (s, 1 H), 8.42 (s, 1 H).

REFERENCE EXAMPLE 15 Methyl 3-Amino-5- (1-benzylpiperidin-4-yl) -2H-pyrazole a) 1-Benzylpiperidin-4-carboxylate

To a solution of methyl piperidine-4-carboxylate (10.00 g, 6.4 mmol) and triethylamine (10.32 g, 10.2 mmol) in CHCl3 (100 mL), argon is added under argon benzyl bromide (14.69 g, 8.6 mmol ) cooling with a water and ice bath. The mixture is stirred at room temperature overnight. CHCl3 and water are added and the two phases are separated. The aqueous phase is extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness, yielding 13.80 g of the desired compound as an orange solid (rto: 88%).

b) 3- (1-Benzylpiperidin-4-yl) -3-oxopropiononitrile

On a solution of BuLi (12.4 mL of a 1.6 M solution in hexane, 19.8 mmol) in THF (25 mL) cooled to –78 C, acetonitrile (1 mL) is added dropwise under argon. After stirring the resulting suspension for 5 min at -78 ° C, a solution of methyl 1-benzylpiperidine-4-carboxylate (2.0 g, 8.1 mmol, obtained in the previous section) in THF (5 mL) is added dropwise. Stir for 30 min at - 78 C. It is allowed to reach room temperature and stirred at that temperature overnight. 1N HCl is added until the pH is adjusted to 7 and the aqueous phase is extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 1.92 g of the desired compound as an orange solid (rto: 98%).

c) Title compound

To a solution of 3- (1-benzylpiperidin-4-yl) -3-oxopropiononitrile (1.85 g, 7.6 mmol, obtained in the previous section) in EtOH (77 mL) is added under a stream of argon hydrazine monohydrate (0.74 mL, 15.3 mmol). It is heated at reflux overnight. The solvent is evaporated and the residue is dissolved in a mixture of water-CHCl3. The aqueous phase is extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 0.46 g of the desired compound (rto: 23%) 1 H NMR (300 MHz, CD3OD)  (TMS): 1.72 (m , 2 H), 1.90 (m, 2 H), 2.15 (m, 2 H),

2.56 (m, 1 H), 2.97 (m, 2 H), 3.57 (s, 2 H), 4.89 (wide s, NH + NH2 + H2O), 5.43 (s, 1 H), 7.27 - 7.34 (complex signal , 5 H).

REFERENCE EXAMPLE 16 3- (Dimethylamino) -1- (4-fluorophenyl) -2- (4-pyridyl) but-2-en-1-one

Following a procedure similar to that described in reference example 7, but using dimethyl acetal of dimethylacetamide instead of dimethyl acetal of dimethylformamide, the desired compound is obtained in the form of a crude which is Use directly in the following reactions. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.15 (s, 3 H), 3.00 (s, 6 H), 6.80 (m, 4 H),

7.45 (m, 2 H), 8.30 (d, J = 8.0 Hz, 2 H).

REFERENCE EXAMPLE 17 2- (4-Fluorophenyl) -6-hydroxy-4-methyl-3,4'-bipyridin-5-carbonitrile

Following a procedure analogous to that described in reference example 10, but using 3- (dimethylamino) -1- (4-fluorophenyl) -2- (4-pyridyl) but-2-en-1-one (obtained in the example reference 16) instead of 3-dimethylamino-1- (4-fluorophenyl) -2- (4-pyridyl) prop-2-en-1-one, the title compound (rto: 21%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.55 (wide s, OH + H2O), 2.30 (s, 3 H),

6.97 (m, 4 H), 7.25 (m, 2 H), 8.52 (m, 2 H).

REFERENCE EXAMPLE 18 6-Chloro-2- (4-fluorophenyl) -4-methyl-3,4'-bipyridin-5-carbonitrile

Following a procedure analogous to that described in reference example 12, but using 2- (4-fluorophenyl) -6-hydroxy-4-methyl-3,4'-bipyridin-5-carbonitrile (obtained in reference example 17) instead of 2- (4-fluorophenyl) -6-hydroxy3,4'-bipyridin-5-carbonitrile, the title compound is obtained (rto: 52%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.41 (s, 3 H), 6.90 (m, 2 H), 7.09 (d, J = 9.0 Hz, 2 H), 7.25 (m, 2 H), 8.62 (m, J = 4.0 Hz, 2 H).

REFERENCE EXAMPLE 19 1- (4-Fluorophenyl) -2- [2- (methylsulfanyl) pyrimidin-4-yl] ethanone

To a solution of 4-methyl-2- (methylsulfanyl) pyrimidine (21.00 g, 150.0 mmol, obtained in reference example 6, section a) and ethyl 4-fluorobenzoate

(25.14 g, 150.0 mmol) in THF (300 mL) under argon, a solution of sodium bis (trimethylsilyl) amide (150 mL 2M solution in THF, 300 mmol) in THF (150 mL) is added dropwise ) while cooling with an ice bath. Stir at room temperature for 2 h. Saturated NH4Cl solution is added and the solvent is evaporated. The residue is dissolved in a mixture of AcOEt and water and the phases are separated. The aqueous phase is reextracted with AcOEt. The combined organic phases are washed with saturated NaCl solution, dried over Na2SO4 and concentrated to dryness, obtaining 36.36 g of the title compound (rto: 93%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.52 (ketone: s, 3 H), 2.61 (enol: s, 3 H), 4.35 (ketone: s, 2 H), 5.92 (enol: s, 1 H), 6.64 (enol: d, J = 5.7 Hz, 1 H), 6.95 (ketone: d, J = 5.1 Hz, 1 H), 7.08 -7.19 (ketone: m, 2H; enol: m, 2 H) , 7.83 (enol: m, 2 H),

8.07 (ketone: m, 2 H), 8.31 (enol: d, J = 5.7 Hz, 1 H), 8.56 (ketone: d, J = 5.1 Hz, 1 H).

REFERENCE EXAMPLE 20 3- (Dimethylamino) -1- (4-fluorophenyl) -2- [2- (methylsulfanyl) pyrimidin-4-yl] prop-2-en1-one

Following a procedure similar to that described in reference example 7, but using 1- (4-fluorophenyl) -2- [2- (methylsulfanyl) pyrimidin-4-yl] ethanone (obtained in reference example 19) instead of 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone, Get the title compound. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.50 (s, 3 H), 2.96 (s, 6 H), 6.20 -8.20 (signal complex, 7 H).

REFERENCE EXAMPLE 21 6- (4-Fluorophenyl) -2- (hydroxy) -5- (2-methylsulfanylpyrimidin-4-yl) pyridine-3carbonitrile

Following a procedure analogous to that described in reference example 10, but using 3- (dimethylamino) -1- (4-fluorophenyl) -2- [2- (methylsulfanyl) pyrimidin-4il] prop-2-en-1-one (obtained in reference example 20) instead of 3 (dimethylamino) 1- (4-fluorophenyl) -2- (4-pyridyl) prop-2-en-1-one, the title compound is obtained (rto: 91 %).

LC-MS (method 1): t R = 7.09 min; m / z = 338.9 [M + H] +

REFERENCE EXAMPLE 22 2-Chloro-6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyridin-3-carbonitrile

A mixture of 6- (4-fluorophenyl) -2- (hydroxy) -5- (2-methylsulfanylpyrimidin-4-yl) pyridin-3carbonitrile (48.84 g, 144.6 mmol, obtained in reference example 21), POCl3 (166 mL, 1.8 mol) and DMF (2.2 mL) is heated at 100 ° C for 2 h. Allow to cool to room temperature and concentrate. It is cooled by acetone-carbonic snow bath and subsequently AcOEt and ice is added. The organic phase is decanted, washed with saturated NaHCO3 solution, dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 31.00 g of the title compound (rto: 60%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.54 (s, 3 H), 6.60 (d, J = 5.1 Hz, 1 H), 7.08 (t, J = 8.5 Hz, 2 H), 7.44 (m , 2 H), 8.37 (d, J = 5.1 Hz, 1 H), 8.39 (s, 1 H).

REFERENCE EXAMPLE 23 2- (2-Chloropyridin-4-yl) -1- (4-fluorophenyl) ethanone

Following a procedure similar to that described in reference example 19, but using as starting compounds 2-chloro-4-methylpyridine and ethyl 4-fluorobenzoate, the title compound is obtained. LC-MS (method 1): t R = 7.96 min; m / z = 250.0, 252.0 [M + H] +

REFERENCE EXAMPLE 24 1-Phenyl-2- [2- (methylsulfanyl) pyrimidin-4-yl] ethanone

Following a procedure similar to that described in reference example 19, but using 4-methyl-2- (methylsulfanyl) pyrimidine as starting compounds (obtained in reference example 6, section a) and ethyl benzoate, Get the title compound. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.52 (ketone: s, 3 H), 2.62 (enol: s, 3 H), 4.39 (ketone: s, 2 H), 5.99 (enol: s, 1 H), 6.65 (enol: d, J = 5.7 Hz, 1 H), 6.98 (ketone: d, J = 5.1 Hz, 1 H), 7.40 -7.51 (m, 3 H), 7.85 (enol: m, 2 H), 8.03 (ketone: m, 2 H),

8.32 (enol: d, J = 5.7 Hz, 1 H), 8.46 (ketone: d, J = 5.1 Hz, 1 H).

REFERENCE EXAMPLE 25 3- (Dimethylamino) -1-phenyl-2- [2- (methylsulfanyl) pyrimidin-4-yl] prop-2-en-1-one

Following a procedure analogous to that described in reference example 7, but using as starting compound 1-phenyl-2- [2- (methylsulfanyl) pyrimidin-4-yl] ethanone (obtained in reference example 24), the compound is obtained headline.

5 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.50 (s, 3 H), 2.90 (s, 6 H), 6.20 -8.00 (complex signal, 8 H).

REFERENCE EXAMPLE 26 6-Phenyl-2-hydroxy-5- (2-methylsulfanylpyrimidin-4-yl) pyridin-3-carbonitrile

Following a procedure analogous to that described in reference example 10,

10 but using 3- (dimethylamino) -1-phenyl-2- [2- (methylsulfanyl) pyrimidin-4-yl] prop-2-en-1one (obtained in reference example 25) instead of 3-dimethylamino- 1- (4fluorophenyl) -2- (4-pyridyl) prop-2-en-1-one, the title compound is obtained. LC-MS (method 1): t R = 6.90 min; m / z = 320.9 [M + H] +

REFERENCE EXAMPLE 27 15 1- [6- (4-Fluorophenyl) -2-hydroxy-5- (2-methylsulfanylpyrimidin-4-yl) pyridin-3yl] ethanone

Following a procedure analogous to that described in reference example 10, but using as starting compounds 3- (dimethylamino) -1- (4-fluorophenyl) -2 [2- (methylsulfanyl) pyrimidin-4-yl] prop-2- en-1-one (obtained in the example of

20 reference 20) and 3-oxobutyramide, the title compound is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.43 (s, 3 H), 2.66 (enol: s, 3 H), 6.53 (d, J =

5.1 Hz, 1 H), 7.12 (t, J = 8.4 Hz, 2 H), 7.42 (m, 2 H), 8.29 (d, J = 5.1 Hz, 1 H),

8.63 (s, 1 H).

REFERENCE EXAMPLES 28-29

25 Following a procedure analogous to that described in reference example 12, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Reference Example

Example Name Starting compounds LC-MS

Method

tR (min) m / z [M + H] +

28

2-Chloro-6-phenyl-5- (2-methylsulfanylpyrimidin-4-yl) pyridin-3-carbonitrile Reference Example 26 one 10.18 338.9

29

4- [6-Chloro-5- (1-chlorovinyl) -2 (4-fluorophenyl) pyridin-3-yl] -2-methylsulfanylpyrimidine Reference Example 27 one 11.62 391.9 393.9 395.9

REFERENCE EXAMPLE 30 1- (4-Fluorophenyl) -2-pyrimidin-4-iletanone

To a suspension of NaH (2.26 g 50%, 47.7 mmol) in DMF (92 mL) under argon

5 cooled to 0 ° C, 4-methylpyrimidine (3.00 g, 31.9 mmol) is added little by little. Subsequently, ethyl 4-fluorobenzoate (6.40 g, 38.2 mmol) is added and stirred at room temperature overnight. Water is added and the solvent is evaporated. The residue is dissolved in a mixture of AcOEt and saturated NaCl solution. The phases are separated and the aqueous phase is reextracted with AcOEt. Phases

10 combined organics are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 3.30 g of the desired compound (rto: 48%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.11 (ketone: s, 2 H), 5.94 (enol: s, 1 H), 6.94

15 (enol: d, J = 5.4 Hz, 1 H), 7.08 -7.16 (m, 2 H), 7.37 (ketone: d, J = 5.1 Hz, 1 H),

7.89 (enol: m, 2 H), 8.08 (ketone: m, 2 H), 8.42 (enol: d, J = 5.4 Hz, 1 H), 8.69 (ketone: d, J = 5.1 Hz, 1 H), 8.81 (enol: s, 1 H), 9.17 (ketone: s, 1 H).

EXAMPLE 1 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

METHOD A 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone (23.56 g, 109.4 mmol, obtained in reference example 1) and 2-methoxyethanol (150 mL) are introduced into a flask. A solution of 3-amino-2H-pyrazole (10.00 g, is added under argon current.

120.3 mmol) in 2-methoxyethanol (170 mL) and 37% HCl (3.23 g, 32.8 mmol). Be

25 heated to reflux for 3 days. It is allowed to cool and concentrated. The solid obtained is dissolved in CHCl3 (400 mL) and MeOH (50 mL). Wash with 0.1N HCl (300 mL) and 1N NaOH (300 mL). The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 9.93 g of the desired compound as a cream solid (rto: 47%)

30 METHOD B

On a solution of 3-amino-2H-pyrazole (60 mg, 71.8 mmol) in EtOH (2 mL) and 1 drop of 37% HCl, 1- (4-fluorophenyl) -2 (argon 4-fluorobenzoate) ( 4-pyridyl) vinyl (0.22 g, 65.0 mmol, obtained in reference example 4). It is heated at reflux for 3 days. The mixture is diluted with CHCl3 and MeOH. It is washed with a saturated solution of NaHCO3. The aqueous phase is extracted with CHCl3 (x2). The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 58 mg of the desired compound as a white solid (rto: 23%). 1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 4.08 (s, NH + CD3OD), 6.80 -7.01 (complex signal, 6 H), 7.21 (m, 2 H), 7.28 (m, 2 H) , 7.95 (s, 1 H), 8.27 (dd, Jo = 1.4 Hz, Jm = 4.6 Hz, 2 H).

EXAMPLE 2 4,6-Diphenyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in Example 1, method B, but using 1-phenyl-2- (4-pyridyl) vinyl benzoate (obtained in reference example 5) instead of 1- (4-) 4-fluorobenzoate fluorophenyl) -2- (4-pyridyl) vinyl, the title compound is obtained as a white solid (rto: 37%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.08 (s, NH + H2O), 6.85 (d, J = 6.0 Hz, 2 H),

7.12 - 7.31 (complex signal, 10 H), 7.98 (s, 1 H), 8.29 (d, J = 5.8 Hz, 2 H).

EXAMPLE 3 5- (4-Pyridyl) -4,6-bis [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 1 method A, but using 2- (4-pyridyl) -1- [3- (trifluoromethyl) phenyl] ethanone (obtained in reference example 2) instead of 1- (4 -fluorophenyl) -2- (4-pyridyl) ethanone, the title compound is obtained (rto: 10%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (s, NH + H2O), 6.86 (wide s, 2 H), 7.30

- 7.60 (complex signal, 8 H), 7.99 (s, 1 H), 8.35 (wide s, 2 H).

EXAMPLE 4 4,6-Bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in Example 1, method B, but using 3-amino-5-methyl-2H-pyrazole instead of 3-amino-2H-pyrazole, the title compound is obtained as a white solid (rto: 19%)

1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 2.03 (wide s, 3 H), 4.08 (s, NH + CD3OD), 6.81 (m, 2 H), 6.96 (m, 2 H), 7.01 (m, 2 H), 7.04 (m, 2 H), 7.29 (m, 2 H),

8.23 (m, 2 H).

EXAMPLE 5 4,6-Diphenyl-3-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in Example 1, method B, but using 3-amino-5-methyl-2H-pyrazole instead of 3-amino-2H-pyrazole and 1-phenyl-2- (4-pyridyl) benzoate vinyl (obtained in reference example 5) instead of 1- (4-fluorophenyl) -2- (4-pyridyl) vinyl 4-fluorobenzoate, the title compound is obtained as a white solid (rto: 16%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.02 (s, 3 H), 2.02 (s, NH + H2O), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.13 ( m, 2 H), 7.23 - 7.33 (complex signal, 6 H),

8.25 (83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 6 2-Ethyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 7 1-Ethyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine A suspension of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

(0.39 g, 0.8 mmol, obtained in example 1), KOH (0.05 g, 0.8 mmol) and crown ether 18-C-6 (0.01 g, 0.03 mmol) in toluene (3 mL) is heated at 100 ° C for 2 h. A solution of iodoethane (0.18 g, 1.2 mmol) in toluene (1 mL) is added and stirred at 100 ° C for 2 days. It is allowed to cool, water and AcOEt are added and the phases are separated. The aqueous phase is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 0.20 g of the compound 2-ethyl-4,6-bis (4fluorophenyl) -5- (4-pyridyl) pyrazolo [3 , 4-b] pyridine (rto: 61%) and 28 mg of 1-ethyl-4,6-bis (4fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (rto: 9% ). Example 6: 1H NMR (300 MHz, CDCl3)  (TMS): 1.68 (t, J = 7.4 Hz, 3 H), 4.51 (c, J = 7.2 Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz , Jm = 4.4 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H),

7.00 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.30 (m, 2 H), 7.78 (s, 1H), 8.31 (dd, Jo =

1.6 Hz, Jm = 4.5 Hz, 2 H).

Example 7: 1H NMR (300 MHz, CDCl3)  (TMS): 1.61 (t, J = 7.4 Hz, 3 H), 4.67 (c, J = 7.2 Hz, 2 H), 6.81 (dd, Jo = 1.6 Hz , Jm = 4.4 Hz, 2 H), 6.96 (t, J = 8.7 Hz, 2 H),

7.01 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.29 (m, 2 H), 7.86 (s, 1H), 8.32 (dd, Jo =

1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 8 4,6-Bis (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 9 4,6-Bis (4-fluorophenyl) -1-methyl- 5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using iodomethane instead of iodoethane, the title compounds are obtained. Example 8: rto: 52%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.25 (s, 3 H), 6.81 (d, J = 5.3 Hz, 2 H), 6.95 (t, J = 8.6 Hz, 2 H), 6.98 (t , J = 8.5 Hz, 2 H), 7.12 (m, 2 H),

7.28 (m, 2 H), 7.77 (s, 1H), 8.29 (d, J = 5.2 Hz, 2 H). Example 9: rto: 5%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.20 (s, 3 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 6.98 (t, J = 8.6 Hz, 2 H), 7.12 (m, 2 H), 7.26 (m, 2 H), 7.84 (s, 1H), 8.29 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 10

4,6-Bis (4-fluorophenyl) -2,3-dimethyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

EXAMPLE 11

4,6-Bis (4-fluorophenyl) -1,3-dimethyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Following a procedure analogous to that described in examples 6 and 7, but using 4, 6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (obtained in example 4) instead of 4,6-bis (4- fluorophenyl) -5- (4-pyridyl) -1 Hpyrazolo [3,4-b] pyridine and iodomethane instead of iodoethane, the title compounds are obtained. Example 10: rto: 53%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.03 (s, 3 H), 4.13 (s, 3 H), 6.79 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.88 (t , J = 8.8 Hz, 2 H), 6.98 - 7.11 (complex signal, 4 H), 7.30 (m, 2 H), 8.26 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 11: rto: 30%; 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 2.01 (wide s, 3 H), 4.15 (wide s, 3 H), 6.81 (m, 2 H), 6.93 (m, 2 H), 7.00 (m, 2 H), 7.07 (m, 2 H), 7.30 (m, 2 H), 8.23 (m, 2 H).

EXAMPLE 12 2- [2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4

pyridyl) pyrazolo [3,4-b] pyridine

EXAMPLE 13

1- [2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4

pyridyl) pyrazolo [3,4-b] pyridine a) 2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] ethanol To a solution of 2- (4-piperidyl) ethanol (9.63 g, 74.5 mmol) in DMF (100 mL) at 0 ° C is slowly added di-tert-butyl dicarbonate (16.26 g, 74.5 mol). The mixture is stirred at room temperature overnight. The solvent is concentrated and the residue is dissolved in a mixture of AcOEt and water. The phases are separated. The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 15.09 g of the desired compound (rto: 88%). b) 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] ethyl methanesulfonate To a solution of 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] ethanol (7.50 g, 32.7 mmol, obtained in section a) in CHCl3 (180 mL), triethylamine (4.6 mL) is added under argon and cooled to 0 ° C. Subsequently, methanesulfonyl chloride (2.6 mL, 32.7 mmol) is added dropwise. The mixture is stirred at room temperature overnight. Water is added and the phases are separated. The aqueous phase is extracted with CHCl3 (x3). The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 11.18 g of the desired compound (rto: quantitative). c) Titular compounds Following a procedure analogous to that described in examples 6 and 7, but using 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] ethyl methanesulfonate (obtained in section b) instead of iodoethane, the title compounds are obtained. Example 12: rto: 14%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.00 -1.40 (complex signal, 3 H), 1.45 (s, 9 H), 1.70 (m, 2 H), 2.66 (m, 2 H), 2.05 ( m, 2 H), 4.09 (m, 2 H), 4.90 (t, J = 7.4 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.90 (t, J =

8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.28 (m, 2 H), 7.77 (s, 1 H),

8.31 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 13: rto: 29%; 1H NMR (300 MHz, CDCl3)  (TMS):): 1.00 -1.40 (signal complex, 3 H), 1.46 (s, 9 H), 1.82 (m, 2 H), 1.98 (m, 2 H), 2.67 (m, 2 H), 4.08 (m, 2 H), 4.65 (t, J = 7.0 Hz Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t, J

= 8.7 Hz, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 7.25 (m, 2 H), 7.28 (m, 2 H), 7.86 (s, 1 H),

8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 14

2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -3-methyl-5- (4

pyridyl) pyrazolo [3,4-b] pyridine

EXAMPLE 15

1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -3-methyl-5- (4

pyridyl) pyrazolo [3,4-b] pyridine a) 1- (tert-butoxycarbonyl) piperidin-4-yl methanesulfonate Following a procedure analogous to that described in examples 12 and 13 section b, but using (1-tert-butoxycarbonyl) ) piperidin-4-ol instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] ethanol, the desired compound is obtained (rto: 97%). b) Titular compounds Following a procedure analogous to that described in examples 6 and 7, but using 4,6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4- b] pyridine (obtained in example 4) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1Hpyrazolo [3,4-b] pyridine and 1- (tert-butoxycarbonyl methanesulfonate) ) piperidin-4-yl (obtained in section a) instead of iodoethane, the title compounds are obtained. Example 14: rto: 13%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.51 (s, 9 H), 1.97 (m, 2 H), 2.06 (s, 3 H), 2.45 (m, 2 H), 2.94 (m, 2 H), 4.35 (m, 3 H), 6.78 (d, J = 6.0 Hz, 2 H), 6.87 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.10 (m, 2 H), 7.33 (m, 2 H), 8.26 (d, J = 6.0 Hz, 2 H). Example 15: rto: 52%; 1H NMR (300 MHz, CDCl3)  (TMS): 1.54 (s, 9H), 2.00 (s, 3 H), 2.00 (m, 2 H), 2.31 (m, 2 H), 2.99 (m, 2 H ), 4.33 (m, 2 H), 5.10 (m, 1 H), 6.78 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.92 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.08 (m, 2 H), 7.30 (m, 2 H), 8.27 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 16 2- (3-Chloropropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 17 1- (3-Chloropropyl) -4.6 -bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 1-bromo-3-chloropropane instead of iodoethane, the title compounds are obtained. Example 16: rto: 28%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.54 (m, 2 H), 3.52 (t, J = 6.0 Hz, 2 H), 4.61 (t, J = 6.0 Hz, 2 H), 6.81 (dd , Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H),

6.86

(t, J = 8.8 Hz, 2 H), 6.98 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.28 (m, 2 H),

7.83

(s, 1 H), 8.29 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 17: rto: 19%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.51 (m, 2 H), 3.61 (t, J = 6.3 Hz, 2 H), 4.78 (t, J = 6.4 Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H),

6.92

(t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.26 (m, 2 H),

7.86

(s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 18

3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol METHOD A a) 4, 6-Bis ( 4-fluorophenyl) -5- (4-pyridyl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine

A suspension of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

(0.30 g, 0.8 mmol, obtained in example 1), KOH (0.05 g, 0.8 mmol) and crown ether 18-C-6 (0.01 g, 0.03 mmol) in toluene (10 mL) is heated at 100 ° C for 1 hour. 2- (3-Bromopropoxy) tetrahydropyran (0.17 g, 0.8 mmol) is added and stirred at 100 ° C for 24 h. It is allowed to cool, water and AcOEt are added and the phases are separated. The aqueous phase is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 0.22 g of the desired compound (rto: 54%). LC-MS (method 1): t R = 7.60 min; m / z = 527.2 [M + H] +.

b) Title compound

A solution of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine (0.22 g, 0.42 mmol, obtained in section a) in a 4: 2: 1 mixture of AcOH: THF: H2O (9 mL) is heated at 55 ° C for 3 h. It is allowed to cool and concentrated. To the residue is added saturated aqueous NaHCO3 and 1N NaOH solution and extracted with AcOEt. The organic phase is dried over

Na2SO4 and concentrated to dryness, obtaining 0.15 g of the title compound (rto: 83%). LC-MS (method 1): t R = 5.37 min; m / z = 443.1 [M + H] +.

EXAMPLE 18 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol EXAMPLE 19 3- [4,6 -Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propan-1-ol

METHOD B

Following a procedure analogous to that described in examples 6 and 7, but using 3-iodopropanol instead of iodoethane, the compounds are obtained Headlines. Example 18: rto: 33%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.58 (s, OH + H2O),

2.17 (m, 2 H), 3.71 (m, 2 H), 4.63 (t, J = 6.4 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm =

4.4 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.29 (m, 2 H), 7.82 (s, 1 H), 8.33 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 19: rto: 21%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (s, OH + H2O),

2.17 (m, J = 5.9 Hz, 2 H), 3.58 (m, 2 H), 4.78 (t, J = 6.0 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.94 (t, J = 8.7 Hz, 2 H), 7.02 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.27 (m, 2 H), 7.90 (s, 1 H), 8.34 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 20 2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 21 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 1- (tert-butoxycarbonyl) piperidin-4-yl methanesulfonate (obtained in example 14 section a) instead of iodoethane, the title compounds are obtained. Example 20: rto: 30%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.48 (s, 9 H), 2.00-2.20 (m, 4 H), 2.87 (m, 2 H), 4.21 (m, 2 H), 4.50 (m , 1 H), 6.73 (dd, Jo = 1.5 Hz, Jm =

4.5 Hz, 2 H), 6.81 (t, J = 8.7 Hz, 2 H), 6.92 (t, J = 8.7 Hz, 2 H), 7.03 (m, 2 H), 7.20 (m, 2 H), 7.73 (s, 1 H), 8.23 (dd, Jo = 1.4 Hz, Jm = 4.4 Hz, 2 H).

Example 21: rto: 28%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.46 (s, 9 H), 2.10 -

2.30 (complex signal, 4 H), 2.96 (m, 2 H), 4.30 (m, 2 H), 4.60 (m, 1 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H) , 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.31 (m, 2 H), 7.82 (s, 1 H) , 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 22

4,6-Diphenyl-2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

EXAMPLE 23

4,6-Diphenyl-1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine To a suspension of 4,6-diphenyl-5- (4-pyridyl) -1H-pyrazolo [3, 4-b] pyridine (0.10 g, 0.3 mmol, obtained in example 2) in acetone (1 mL), is added under a stream of argon KOH (21 mg, 0.4 mmol). Subsequently, a solution of iodomethane (47 mg, 0.3 mmol) in acetone (0.1 mL) is added and stirred overnight at room temperature. Water is added and extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 47 mg of the compound 4,6-diphenyl-2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (rto: 47%) and 38 mg of 4,6-diphenyl-1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (rto: 38%). Example 22: 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.24 (s, 3 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.16 - 7.21 (complex signal, 4 H), 7.26 - 7.31 (complex signal, 6 H), 7.77 (s, 1H), 8.24 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 23: 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.23 (s, 3 H), 6.81 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 7.17 (m, 2 H), 7.22 - 7.32 (complex signal, 8 H), 7.89 (s, 1H), 8.26 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 24 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -2- [2- (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 2- (2-bromoethoxy) tetrahydropyran instead of iodoethane, the title compound (rto: 50%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.48 - 1.63 (complex signal, 6 H), 3.47 (m, 1 H), 3.67 (m, 1 H), 4.02 (m, 1 H), 4.22 ( m, 1 H), 4.57 (m, 1 H), 4.65 (m, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.31 (m, 2 H), 7.92 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 25 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] ethanol

Following a procedure analogous to that described in examples 22 and 23, but using 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (obtained in the example 1) instead of 4,6-diphenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine and 2-bromoethanol instead of iodomethane, the title compound is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.19 (m, 2 H), 4.32 (m, OH), 4.77 (t, J = 4.7 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.95 (t, J = 8.7 Hz, 2 H), 7.02 (t, J = 8.6 Hz, 2 H), 7.15 (m, 2 H), 7.26 (m, 2 H) , 7.89 (s, 1 H), 8.34 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 26

4,6-Bis (4-fluorophenyl) -2- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3,4

b] pyridine

EXAMPLE 27

4,6-Bis (4-fluorophenyl) -1- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3,4

b] pyridine a) 1-Chloromethyl-4- (methylsulfanyl) benzene A solution of thionyl chloride (0.2 mL, 3.2 mmol) in THF (9 mL) is slowly added over 4- (methylsulfanylphenyl) methanol (0.346g, 2.2 mmol ) under argon current. Stir at room temperature for 2 days. A saturated aqueous solution of NaCl (9 mL) is added and the phases are separated. The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 0.37 g of the desired compound (rto: 95%). b) Titular compounds In a flask, 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (0.30 g, 78.0 mmol, obtained under argon) in example 1) and DMF (3.5 mL). KOH (0.06 g, 1.1 mmol) and subsequently a solution of 1-chloromethyl-4- (methylsulfanyl) benzene (0.15 g, 0.9 mmol, obtained in section a) in DMF (0.4 mL) are added. It is heated at 60 duranteC overnight. It is allowed to cool and concentrated. The residue is dissolved in a mixture of water and AcOEt. The phases are separated. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 0.10 g of the compound 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylbenzyl) 5- (4- pyridyl) pyrazolo [3,4-b] pyridine (rto: 25%) and 0.19 g of the compound 4,6-bis (4fluorophenyl) -1- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3, 4-b] pyridine (rto: 47%). Example 26: 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.50 (s, 3 H), 5.60 (s, 2 H), 6.84 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.92 (t, J = 8.8 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.05 (m, 2 H), 7.24 - 7.37 (complex signal, 6 H), 7.76 (s, 1 H), 8.34 (dd, Jo =

1.5 Hz, Jm = 4.5 Hz, 2 H). Example 27: 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.49 (s, 3 H), 5.77 (s, 2 H), 6.85 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.97 (t, J = 8.8 Hz, 2 H), 7.03 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.24 - 7.33 (complex signal, 4 H), 7.42 (d, J = 8.1 Hz, 2 H), 7.89 (s, 1 H), 8.36 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 28

2- [1- (tert-Butoxycarbonyl) piperidin-4-ylmethyl] -4,6-bis (4-fluorophenyl) -5- (4

pyridyl) pyrazolo [3,4-b] pyridine

EXAMPLE 29

1- [1- (tert-Butoxycarbonyl) piperidin-4-ylmethyl] -4,6-bis (4-fluorophenyl) -5- (4

pyridyl) pyrazolo [3,4-b] pyridine a) (4-Piperidyl) methanol To a suspension of LiAlH4 (10.10 g, 0.266 mol) in THF (150 mL) at 0 ° C, a solution of piperidine- is slowly added Ethyl 4-carboxylate (18.13 g,

0.120 mol) in THF (300 mL). It is stirred at room temperature overnight. It is cooled with an ice bath and a mixture of water (14 mL) and THF (28 mL) is added slowly. Subsequently a mixture of a 15% aqueous NaOH solution (14 mL) and water (37 mL) is added and stirred at room temperature for 30 min. The precipitate obtained is filtered and the filtrate is concentrated, obtaining 17.88 g of the desired compound (rto: quantitative).

b) [1- (tert-Butoxycarbonyl) piperidin-4-yl] methanol

Following a procedure analogous to that described in example 12 section a, but using (4-piperidyl) methanol (obtained in section a of this example), instead of 2- (4-piperidyl) ethanol, the title compound (rto) is obtained : 77%).

c) [1- (tert-butoxycarbonyl) piperidin-4-yl] methyl methanesulfonate

Following a procedure analogous to that described in example 12 section b, but using [1- (tert-butoxycarbonyl) piperidin-4-yl] methanol (obtained in section b of this example) instead of 2- [1- (tert -butoxycarbonyl) piperidin-4-yl] ethanol, the title compound is obtained (rto: 71%).

d) Headlines

Following a procedure analogous to that described in examples 26 and 27, but using [1- (tert-butoxycarbonyl) piperidin-4-yl] methyl methanesulfonate (obtained in section c) instead of 1-chloromethyl-4- (methylsulfanyl) ) benzene, the title compounds are obtained. Example 28: rto: 22%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.47 (s, 9 H), 1.63 (m, 2 H), 2.43 (m, 1 H), 2.72 (m, 2 H), 4.15 (m, 2 H), 4.33 (d, J = 7.2 Hz, 2 H), 6.86 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t, J = 8.7 Hz, 2 H), 7.04 (t , J = 8.7 Hz, 2 H), 7.17 (m, 2 H), 7.33 (m, 2 H), 7.77 (s, 1 H), 8.35 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H ). Example 29: rto: 71%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.20 - 1.8 (complex signal, 5 H), 1.49 (s, 9 H), 2.35 (m, 1 H), 2.74 (m, 2 H), 4.15 ( m, 2 H), 4.54 (d, J = 7.2 Hz, 2 H), 6.86 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.97 (t, J = 8.7 Hz, 2 H),

7.04 (t, J = 8.7 Hz, 2 H), 7.18 (m, 2 H), 7.28 (m, 2 H), 7.90 (s, 1 H), 8.36 (dd, Jo =

1.6 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 30 4,6-Bis (4-fluorophenyl) -2- [2- (morpholin-4-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 31 4,6- Bis (4-fluorophenyl) -1- [2- (morpholin-4-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 26 and 27, but using 4- (2-chloroethyl) morpholine hydrochloride instead of 1-chloromethyl-4 (methylsulfanyl) benzene and 2 equivalents of KOH, the title compounds are obtained. Example 30: rto: 10%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.55 (m, 4 H), 3.06 (t, J = 6.4 Hz, 2 H), 3.70 (m, 4 H), 4.58 (t, J = 6.4 Hz , 2 H), 6.86 (dd, Jo = 1.6 Hz, Jm =

4.4 Hz, 2 H), 6.93 (t, J = 8.9 Hz, 2 H), 7.04 (t, J = 8.7 Hz, 2 H), 7.16 (m, 2 H), 7.31 (m, 2 H), 7.88 (s, 1 H), 8.35 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 31: rto: 24%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.63 (m, 4 H), 3.04 (t, J = 6.9 Hz, 2 H), 3.69 (m, 4 H), 4.77 (t, J = 6.8 Hz, 2 H), 6.86 (dd, Jo = 1.5 Hz, Jm =

4.5 Hz, 2 H), 6.96 (t, J = 8.7 Hz, 2 H), 7.05 (t, J = 8.7 Hz, 2 H), 7.18 (m, 2 H), 7.28 (m, 2 H), 7.90 (s, 1 H), 8.36 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 32 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl acetate EXAMPLE 33 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] ethyl acetate

Following a procedure analogous to that described in examples 26 and 27, but using ethyl bromoacetate instead of 1-chloromethyl-4- (methylsulfanyl) benzene, the title compounds are obtained. Example 32: rto: 6%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.32 (t, J = 7.2 Hz, 3 H),

4.32 (c, J = 7.2 Hz, 2 H), 5.27 (s, 2 H), 6.86 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H),

6.93

(t, J = 8.7 Hz, 2 H), 7.03 (t, J = 8.6 Hz, 2 H), 7.18 (m, 2 H), 7.32 (m, 2 H),

7.93

(s, 1 H), 8.35 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 33: rto: 21%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.32 (t, J = 7 Hz, 3 H),

4.31 (c, J = 6.9 Hz, 2 H), 5.42 (s, 2 H), 6.84 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H),

6.95

(t, J = 8.7 Hz, 2 H), 7.05 (t, J = 8.7 Hz, 2 H), 7.19 (m, 2 H), 7.28 (m, 2 H),

7.98

(s, 1 H), 8.36 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 34 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propionate ethyl EXAMPLE 35 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propionate ethyl

Following a procedure analogous to that described in examples 26 and 27, but using ethyl 3-bromopropionate instead of 1-chloromethyl-4 (methylsulfanyl) benzene, the title compounds are obtained. Example 34: rto: 5%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.26 (t, J = 7.2 Hz, 3 H),

3.20 (t, J = 6.3 Hz, 2 H), 4.31 (c, J = 7.2 Hz, 2 H), 4.76 (t, J = 6.3 Hz, 2 H), 6.85 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.93 (t, J = 8.8 Hz, 2 H), 7.03 (t, J = 8.5 Hz, 2 H), 7.16 (m, 2 H), 7.32 (m, 2 H), 7.92 (s, 1 H), 8.34 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 35: rto: 3%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.25 (t, J = 7.2 Hz, 3 H),

3.10 (t, J = 7.2 Hz, 2 H), 4.17 (c, J = 7.1 Hz, 2 H), 4.94 (t, J = 7.0 Hz, 2 H), 6.85

(dd, Jo = 1.6 Hz, Jm = 4.6 Hz, 2 H), 6.96 (t, J = 8.6 Hz, 2 H), 7.04 (t, J = 8.6 Hz, 2 H), 7.18 (m, 2 H) , 7.31 (m, 2 H), 7.89 (s, 1 H), 8.36 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 36 4,6-Bis (4-fluorophenyl) -2- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

To a solution of 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (0.62 g, 1.1 mmol, obtained in example 20) in CH2Cl2 (19 mL) under argon and cooled to 0 ° C, trifluoroacetic acid (1.8 mL) is added. Stir at room temperature for 2.5 h. The solvent is evaporated. The residue is dissolved in CHCl3 and washed with a 1N saturated aqueous NaOH solution and a saturated NaCl solution. The organic phase is dried over Na2SO4 and concentrated to dryness, obtaining 319 mg of the title compound (rto: 62%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.71 (broad s, NH + H2O), 2.21 (m, 2 H),

2.34 (m, 2 H), 2.88 (m, 2 H), 3.35 (m, 2 H), 4.54 (m, 1 H), 6.87 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.95 (t, J = 8.7 Hz, 2 H), 7.06 (t, J = 8.6 Hz, 2 H), 7.18 (m, 2 H),

7.34 (m, 2 H), 7.88 (s, 1 H), 8.36 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 37 4,6-Bis (4-fluorophenyl) -1- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (obtained in example 21) in 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 29%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.62 (broad s, NH + H2O), 2.13 (m, 2 H),

2.32 (m, 2 H), 2.92 (m, 2 H), 3.33 (m, 2 H), 4.52 (m, 1 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.94 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H),

7.27 (m, 2 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.4 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 38 4,6-Bis (4-fluorophenyl) -2- (4-piperidylmethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [1- (tert-butoxycarbonyl) piperidin-4-ylmethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3, 4-b] pyridine (obtained in example 28) instead of 2- [1- (tert

butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 13%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.30 -1.80 (complex signal, 4 H), 1.63 (s width, NH + H2O), 2.38 (m, 1 H), 2.64 (m, 2 H), 3.14 (m, 2 H), 4.32 (d, J = 7.2 H),

6.86 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.93 (t, J = 8.8 Hz, 2 H), 7.04 (t, J = 8.6 Hz, 2 H), 7.18 (m, 2 H ), 7.33 (m, 2 H), 7.78 (s, 1 H), 8.35 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 39 4,6-Bis (4-fluorophenyl) -1- (4-piperidylmethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 1- [1- (tert-butoxycarbonyl) piperidin-4-ylmethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3, 4-b] pyridine (obtained in example 29) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [ 3,4-b] pyridine, the title compound is obtained (rto: 12%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.80 - 2.10 (complex signal, 4 H), 2.47 (m, 1 H), 3.0 (m, 3 H), 3.50 (m, 2 H), 4.63 ( d, J = 6.6, 2 H), 7.04 (t, J = 8.4 Hz, 2 H), 7.12

- 7.16 (complex signal, 4 H), 7.22 (m, 2 H), 7.31 (m, 2 H), 7.95 (s, 1 H), 8.58 (d, J = 6.6, 2 H).

EXAMPLE 40 4,6-Bis (6-chloropyridin-3-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 1 method A, but using 1- (6-chloropyridin-3-yl) -2- (4-pyridyl) ethanone (obtained in reference example 9) instead of 1- ( 4-fluorophenyl) -2- (4-pyridyl) ethanone, the title compound is obtained (rto: 17%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 6.90 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.21 (d, J = 8.4 Hz, 1 H), 7.30 (d, J = 8.4 Hz, 1 H), 7.38 (dd, Jo = 2.5 Hz, Jm = 8.3 Hz, 1 H), 7.49 (dd, Jo = 2.4 Hz, Jm = 8.4 Hz, 1 H), 8.00 (s, 1 H) , 8.36 (d, J = 2.4 Hz, 1 H),

8.46 - 8.48 (complex signal, 3 H), 11.34 (wide s, 1 H).

EXAMPLE 41 4,6-Bis (4-fluorophenyl) -3-methyl-2- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 14) instead of 2- [1- (tert

butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 73%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.55 (broad s, NH + H2O), (s, 3 H), 2.35 (m, 2 H), 3.34 (m, 2 H), 3.85 (m, 2 H), 4.73 (m, 2 H), 4.75 (m, 1 H), 6.78 (d, J = 6.3 Hz, 2 H), 6.89 (t, J = 8.6 Hz, 2 H), 7.03 - 7.19 (complex signal, 4 H), 7.29 (m, 2 H),

8.27 (d, J = 6.0 Hz, 2 H).

EXAMPLE 42 4,6-Bis (4-fluorophenyl) -3-methyl-1- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 1- [1- (tert-butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 15) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4- pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 59%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.55 (wide s, NH + H2O), 2.01 (s, 3 H), 2.07 (m, 2 H), 2.29 (m, 2 H), 2.90 (m , 2 H), 3.32 (m, 2 H), 4.75 (m, 1 H), 6.78 (dd, Jo =

1.6 Hz, Jm = 4.4 Hz, 2 H), 6.93 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.08 (m, 2 H), 7.30 (m, 2 H), 8.27 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 43 4,6-Bis (4-fluorophenyl) -2- [2- (4-piperidyl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in Example 12) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 88%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.00 - 1.60 (complex signal, 3 H), 1.66 (s, NH + H2O), 1.74 (m, 2 H), 2.03 (m, 2 H), 2.60 (m, 2 H), 3.10 (m, 2 H), 4.85 (t, J =

7.2 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H) , 7.13 (m, 2 H), 7.30 (m, 2 H), 7.76 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 44 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid

To a solution of ethyl 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetate (0.09 g, 0.2 mmol, obtained in the example 32) in EtOH (4.2 mL) a solution of KOH (0.09 g, 2.5 mmol) in water (0.5 mL) is added. It is heated at reflux for 1 h. It is allowed to cool and concentrated. The residue is dissolved in a mixture of AcOEt and water. The phases are separated. The aqueous phase is acidified and extracted with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness, obtaining 57 mg of the title compound (rto: 66%). 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 4.00 (wide s, 1H + CD3OD), 5.28 (wide s, 2 H), 6.92 - 7.05 (complex signal, 6 H), 7.15 -7.30 (signal complex, 4 H), 8.02 (wide s, 1 H), 8.26 (m, 2 H).

EXAMPLE 45 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetic acid

Following a procedure analogous to that described in Example 44, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetate ethyl (obtained in example 33) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl acetate, is obtained the title compound (rto: 96%). 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 3.88 (wide s, 1H + CD3OD), 5.32 (s, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H) , 6.88 (t, J = 8.7 Hz, 2 H), 6.98 (t, J = 8.6 Hz, 2 H), 7.11 (m, 2 H), 7.20 (m, 2 H), 7.90 (s, 1 H) , 8.21 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 46 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propionic acid

Following a procedure analogous to that described in Example 44, but using 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propionate ethyl (obtained in example 34) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl acetate, the titular compound (rto: 69%). 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 3.08 (t, J = 6.3 Hz, 2 H), 4.50 (wide s, 1H + CD3OD), 4.72 (t, J = 6.3 Hz, 2 H) , 6.88 (dd, Jo = 1.6 Hz, Jm = 4.6 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.23 (m, 2 H), 8.03 (s, 1 H), 8.21 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 47 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1yl] propionic acid

Following a procedure analogous to that described in Example 44, but using 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propionate ethyl (obtained in example 35) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl acetate, is obtained the title compound (rto: 88%). 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 3.02 (t, J = 7.2 Hz, 2 H), 4.50 (wide s, 1H + CD3OD), 4.86 (t, J = 7.3 Hz, 2 H) , 6.87 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.12 (m, 2 H), 7.24 (m, 2 H), 7.84 (s, 1 H), 8.21 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 48 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -1- (morpholin-4-yl) ethanone

To a solution of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid (0.05 g, 0.1 mmol, obtained in the example 44) in DMF (1 mL) are added under argon N, N'-dicyclohexylcarbodiimide (0.02 g, 0.1 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.1 mmol). The mixture is stirred for 15 min and morpholine (0.01 g, 0.1 mmol) is added. Stir at room temperature for 2 days. AcOEt is added and filtered. The filtrate is washed with a saturated aqueous solution of NaHCO3. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures AcOEt-MeOH of increasing polarity, obtaining 18 mg of the title compound (rto: 35%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.66 - 3.76 (complex signal, 8 H), 5.30 (s, 2 H), 6.82 (d, J = 5.7 Hz, 2 H), 6.91 (t, J = 8.8 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H),

7.14 (m, 2 H), 7.28 (m, 2 H), 7.99 (s, 1 H), 8.32 (d, J = 6.0 Hz, 2 H).

EXAMPLE 49 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetamide

Following a procedure analogous to that described in Example 48, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetic acid (obtained in example 45) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4

pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid, and aqueous NH3 instead of morpholine, se Obtain the title compound (rto: 36%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.35 (s, 2 H), 5.56 (wide s, 1 H), 6.15 (s width, 1 H), 6.85 (d, J = 5.4 Hz, 2 H), 6.96 (t, J = 8.6 Hz, 2 H), 7.06 (t, J = 8.6 Hz, 2 H), 7.17 (m, 2 H), 7.29 (m, 2 H), 8.01 (s, 1 H), 8.38 (d, J = 5.4 Hz, 2 H).

EXAMPLE 50 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -1- (morpholin-4-yl) ethanone

Following a procedure analogous to that described in Example 48, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetic acid (obtained in example 45) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid, the compound is obtained holder (rto: 60%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.67 - 3.70 (complex signal, 4 H), 3.75 -

3.81 (complex signal, 4 H), 5.50 (s, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H),

6.95

 (t, J = 8.7 Hz, 2 H), 7.04 (t, J = 8.7 Hz, 2 H), 7.17 (m, 2 H), 7.27 (m, 2 H),

7.99

(s, 1 H), 8.35 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H)

EXAMPLE 51 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -1- (morpholin-4-yl) propan-1-one

Following a procedure analogous to that described in Example 48, but using 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propionic acid (obtained in example 46) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid, the compound is obtained holder (rto: 64%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.20 (t, J = 6.0 Hz, 2 H), 3.45 (m, 2 H), 3.55 -

3.63 (complex signal, 6 H), 4.79 (t, J = 6.1 Hz, 2 H), 6.81 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.30 (m, 2 H), 7.94 (s, 1 H), 8.31 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H)

EXAMPLE 52 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -N-Propylpropionamide

Following a procedure analogous to that described in example 48, but using 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propionic acid (obtained in example 47) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4

pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid, and propylamine instead of morpholine, se Obtain the title compound (rto: 76%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 0.84 (t, J = 7.3 Hz, 3 H), 1.42 (m, 2 H), 2.98 (t, J = 6.7 Hz, 2 H), 3.18 (m, 2 H), 4.95 (t, J = 6.7 Hz, 2 H), 6.05 (m, NH), 6.84 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.96 (t, J = 8.7 Hz, 2 H), 7.04 (t, J = 8.7 Hz, 2 H),

7.16 (m, 2 H), 7.32 (m, 2 H), 7.89 (s, 1 H), 8.36 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 53 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -1- (morpholin-4il) propan-1-one

Following a procedure analogous to that described in example 48, but using 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propionic acid (obtained in Example 47) instead of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid, the compound is obtained holder (rto: 72%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.13 (t, J = 7.3 Hz, 2 H), 3.49 (m, 2 H), 3.63 -

3.67 (complex signal, 6 H), 4.99 (t, J = 7.3 Hz, 2 H), 6.84 (dd, Jo = 1.4 Hz, Jm = 4.4 Hz, 2 H), 6.96 (t, J = 8.7 Hz, 2 H), 7.04 (t, J = 8.7 Hz, 2 H), 7.16 (m, 2 H), 7.30 (m, 2 H), 7.89 (s, 1 H), 8.36 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H)

EXAMPLE 54 4,6-Bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 55 4,6-Bis (4-fluorophenyl) - 1- (4-Methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Under a stream of argon, 4 Å molecular sieve (1 g, previously dried for 3 h at 200 C and vacuum), 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo are introduced into a flask [3,4-b] pyridine (0.30 g, 0.8 mmol, obtained in example 1), (4-methylsulfanylphenyl) boronic acid (0.26 g, 1.6 mmol), copper acetate II (0.28 g,

1.6 mmol), pyridine (0.12 g, 1.6 mmol), triethylamine (0.16 g, 1.6 mmol) and CH2Cl2 (22 mL). Stir at room temperature for 2 days. It is filtered on celite and concentrated. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 40 mg of the compound 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5 (4- pyridyl) pyrazolo [3,4-b] pyridine (rto: 10%) and 90 mg of 4,6-bis (4-fluorophenyl) -1- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4 -b] pyridine (rto: 23%).

Example 54: 1H NMR (300 MHz, CDCl3)  (TMS): 2.46 (s, 3 H), 6.76 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.83 (t, J = 8.7 Hz , 2 H), 6.95 (t, J = 8.6 Hz, 2 H), 7.11 (m, 2 H), 7.26 (m, 2 H), 7.29 (d, J = 8.7 Hz, 2 H), 7.83 (d , J = 8.7 Hz, 2 H), 8.16 (s, 1 H),

8.26 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 55: 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.46 (s, 3 H), 6.76 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.86 (t, J = 8.7 Hz, 2 H), 6.96 (t, J = 8.7 Hz, 2 H), 7.08 (m, 2 H), 7.22 (m, 2 H), 7.34 (d, J = 9.0 Hz, 2 H), 7.94 (s, 1 H), 8.23 (d, J = 8.7 Hz, 2 H),

8.26 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 56 4,6-Bis (4-fluorophenyl) -2- (4-methylsulfinylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 57 4,6-Bis (4-fluorophenyl) - 2- (4-Methylsulfonylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

To a solution of 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (0.09 g, 0.2 mmol, obtained in example 54) in CH2Cl2 (3.5 mL) 3-chloroperbenzoic acid is added under a stream of argon

(0.04 g, 0.2 mmol) and stir for 2 h at room temperature. CHCl3 is added and washed with a saturated aqueous solution of NaHCO3. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 15 mg of the compound 4,6-bis (4fluorophenyl) -2- (4-methylsulfinylphenyl) -5- (4-pyridyl ) pyrazolo [3,4-b] pyridine (rto: 16%) and 10 mg of the compound 4,6-bis (4-fluorophenyl) -2- (4-methylsulfonylphenyl) -5- (4-pyridyl) pyrazolo [3,4 -b] pyridine (rto: 11%) Example 56: 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.83 (s, 3 H), 6.90 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H ), 6.96 (t, J = 8.7 Hz, 2 H), 7.08 (t, J = 8.7 Hz, 2 H), 7.24 (m, 2 H), 7.36 (m, 2 H), 7.75 (HA of a system AB, J = 8.9 Hz, 2 H), 8.32 (HB of an AB system, J = 8.9 Hz, 2 H), 8.38 (s, 1 H), 8.39 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 57: 1H NMR (300 MHz, CDCl3)  (TMS): 3.16 (s, 3 H), 6.89 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.97 (t, J = 8.7 Hz , 2 H), 7.09 (t, J = 8.7 Hz, 2 H), 7.24 (m, 2 H), 7.36 (m, 2 H), 8.05 (HA of an AB system, J = 9.0 Hz, 2 H) , 8.38 (HB of an AB system, J = 9.0 Hz, 2 H), 8.39 (dd, Jo = 1.6 Hz, Jm = 4.6 Hz, 2 H), 8.41 (s, 1 H).

EXAMPLE 58

4,6-Bis (4-fluorophenyl) -1- (4-methylsulfinylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine Following a procedure analogous to that described in example 56, but using 4, 6-bis (4-fluorophenyl) -1- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 55) instead of 4,6-bis (4 -fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound (rto: 70%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.82 (s, 3 H), 6.90 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H ), 7.09 (t, J = 8.6 Hz, 2 H), 7.20 (m, 2 H), 7.35 (m, 2 H), 7.86 (dd, Jo = 2.1 Hz, Jm = 6.9 Hz, 2 H), 8.10 (s, 1 H), 8.41 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 8.69 (dd, Jo = 1.8 Hz, Jm = 6.9 Hz, 2 H).

EXAMPLE 59 4,6-Bis (4-fluorophenyl) -2- (4-methylsulfinylbenzyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine EXAMPLE 60 4,6-Bis (4-fluorophenyl) -2- (4-methylsulfonylbenzyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 56, but using 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 26) instead of 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compounds are obtained. Example 59: rto: 48%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.74 (s, 3 H), 5.70 (s, 2 H), 6.85 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t , J = 8.8 Hz, 2 H), 7.02 (t, J =

8.7 Hz, 2 H), 7.16 (m, 2 H), 7.32 (m, 2 H), 7.59 (HA of an AB system, J = 8.2 Hz, 2 H), 7.68 (HB of an AB system, J = 8.2 Hz, 2 H), 7.87 (s, 1 H), 8.39 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 60: rto: 16%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.07 (s, 3 H), 5.73 (s, 2 H), 6.85 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.93 (t, J = 8.7 Hz, 2 H), 7.03 (t, J =

8.8 Hz, 2 H), 7.16 (m, 2 H), 7.32 (m, 2 H), 7.61 (HA of an AB system, J = 8.7 Hz, 2 H), 7.89 (s, 1 H), 7.97 (HB of an AB system, J = 8.7 Hz, 2 H), 8.36 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 61

4,6-Bis (4-fluorophenyl) -1- (4-methylsulfinylbenzyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine EXAMPLE 62 4,6-Bis (4-fluorophenyl) -1- (4-methylsulfonylbenzyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in Example 56, but using 4,6-bis (4-fluorophenyl) -1- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 27) instead of 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compounds are obtained. Example 61: rto: 69%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.71 (s, 3 H), 5.84 (s, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.94 (t , J = 8.7 Hz, 2 H), 7.01 (t, J =

8.6 Hz, 2 H), 7.13 (m, 2 H), 7.25 (m, 2 H), 7.61 (HA of an AB system, J = 8.4 Hz, 2 H), 7.92 (HB of an AB system, J = 8.4 Hz, 2 H), 7.91 (s, 1 H), 8.34 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 62: rto: 4%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.03 (s, 3 H), 5.87 (s, 2 H), 6.83 (d, J = 6.0 Hz, 2 H), 6.94 (t, J = 8.8 Hz, 2 H), 7.02 (t, J = 8.7 Hz, 2 H),

7.14 (m, 2 H), 7.26 (m, 2 H), 7.60 (HA of an AB system, J = 8.2 Hz, 2 H), 7.91 (s, 1H), 7.93 (HB of an AB system, J = 8.2 Hz, 2 H), 8.34 (d, J = 6.3 Hz, 2 H).

EXAMPLE 63 3-Chloro-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

To a solution of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine (0.20 g, 0.5 mmol, obtained in example 1) in DMF ( 5 mL) is added under a stream of argon N-chlorosuccinimide (0.10 g, 0.8 mmol) and the mixture is heated at 60 ° C for 5 h. It is washed with 1N NaOH and extracted with CHCl3 and AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 171 mg of the title compound (rto: 79%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.61 (wide s, NH + H2O), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.98 (t, J = 8.7 Hz, 2 H), 7.03 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.29 (m, 2 H), 8.35 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H) .

EXAMPLE 64 3-Bromo-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

To a suspension of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

(1.00 g, 2.6 mmol, obtained in example 1) in CHCl3 (10 mL), a solution of Br2 (0.69 g, 4.3 mmol) in CHCl3 (3 mL) is added under argon current. Acetonitrile (4 mL) is added and allowed to stir at room temperature for 2 days. It is concentrated and the residue is dissolved in CHCl3 and washed with 1N NaOH. A precipitate forms, which is filtered and dissolved with MeOH. The solution is concentrated and washed with a 1 N aqueous solution of NaOH. It is extracted with AcOEt, dried over Na2SO4 and concentrated. It is treated with diethyl ether, the solvent is decanted and the product obtained is dried, obtaining 1.16 g of the title compound (rto: 97%) 1 H NMR (300 MHz, CD3OD)  (TMS): 4.78 (broad s, NH + CD3OD ), 6.89 (t, J =

8.8 Hz, 2 H), 6.93 - 6.99 (complex signal, 4 H), 7.14 (m, 2 H), 7.27 (m, 2 H), 8.12 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H ).

EXAMPLE 65 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine-3-carbonitrile

In a flask, 3-bromo-4,6-bis (4-fluorophenyl) 5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (0.20 g, 0.4 mmol, obtained) in example 64), copper cyanide I (0.05 g, 0.6 mmol) and anhydrous 1-methyl-2-pyrrolidone (1 mL) and heated at reflux for 2 h. It is poured onto a 10% aqueous solution of ethylenediamine (4 mL) and extracted with CHCl3. A saturated aqueous solution of NaCl is added to the aqueous phase and extracted with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining the title compound in solid form (rto: quantitative). 1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 4.00 (wide s, NH + CD3OD), 6.80

- 7.40 (complex signal, 12 H), 8.25 (m, 2 H).

EXAMPLE 66 3-Bromo-4,6-bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 64, but using 4,6-bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in

example 9) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 15%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.21 (s, 3 H), 6.78 (d, J = 6.0 Hz, 2 H), 6.93 -

7.02 (complex signal, 4 H), 7.08 (m, 2 H), 7.27 (m, 2 H), 8.29 (d, J = 6.0 Hz, 2 H).

EXAMPLE 67 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine-3-carboxamide

A solution of KOH (0.07 g, 1.3 mmol) in tBuOH (2.5 mL) is added under a stream of argon over 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4 -b] pyridine-carbonitrile (0.05 g, 0.1 mmol, obtained in example 65) and is heated at reflux overnight. Water and AcOEt are added and the phases are separated. The aqueous phase is extracted with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 15 mg of the title compound in solid form (rto: 28%) 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (wide s, NH2 + H2O), 6.80 (d, J = 4.5 Hz, 2 H), 6.90 - 7.10 (complex signal, 6 H), 7.30 (m, 2 H), 8.30 (d, J = 4.5 Hz , 2 H).

EXAMPLE 68 3-Aminomethyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

In a flask, LiAlH4 (0.06 g, 1.5 mmol) and anhydrous diethyl ether (2 mL) are introduced. It is cooled with an ice bath and a solution of 4,6-bis (4fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine-3-carbonitrile (0.15) is added dropwise g, 0.4 mmol, obtained in example 65) in diethyl ether (1 mL). THF (2 mL) is added and the mixture is stirred at room temperature overnight. It is cooled with an ice bath and water (0.1 mL), THF (0.2 mL), a 15% aqueous solution of NaOH (0.1 mL) and water (0.3 mL) are succesively added. The precipitate obtained is filtered and washed with THF. The solvent of the filtrate is evaporated. The residue obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, yielding 71 mg of the title compound in solid form (rto: 47%).

1H NMR (300 MHz, CDCl3)  (TMS): 2.10 (wide s, NH2 + H2O) 3.62 (s, 2 H),

6.80 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t, J = 8.7 Hz, 2 H), 7.03 (t, J = 8.6 Hz, 2 H), 7.11 (m, 2 H ), 7.25 (m, 2 H), 8.30 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 69 4,6-Bis (4-fluoro-3-nitrophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

To a solution of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine (0.20 g, 0.5 mmol, obtained in example 1) in conc. H2SO4 . (3 mL) is added under a stream of argon HNO3 65% (0.1 mL, 0.2 mmol). It is heated at 90 duranteC for 30 min. It is cooled with an ice bath and brought to pH = 8 with 1N NaOH. It is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 69 mg of the title compound in solid form (rto: 28%) 1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS ): 4.28 (s, NH + CD3OD), 7.03 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.22 (dd, Jo = 2.7 Hz, Jm = 10.5 Hz, 1 H), 7.36 (dd , Jo = 2.6 Hz, Jm = 10.4 Hz, 1 H), 7.53 (m, 2 H), 7.99 -8.01 (complex signal, 2 H), 8.13 (m, 1 H), 8.41 (dd, Jo = 1.5 Hz , Jm = 4.5 Hz, 2 H).

EXAMPLE 70 3-Amino-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in reference example 15 section c, but using 6-chloro-2- (4-fluorophenyl) -3,4'-bipyridin-5-carbonitrile (obtained in reference example 12) instead of 3- (1-benzylpiperidin-4-yl) -3-oxopropiononitrile, the title compound (rto: 41%) is obtained. 1 H NMR (300 MHz, CD3OD)  (TMS): 4.38 (s, NH2 + CD3OD), 7.05 (t, J = 8.8 Hz, 2 H), 7.26 (dd, Jo = 1.6 Hz, Jm = 4.6 Hz, 2 H), 7.39 (m, 2 H), 8.27 (s, 1 H), 8.42 (dd, Jo = 1.4 Hz, Jm = 4.6 Hz, 2 H).

EXAMPLE 71 3-Amino-6- (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in reference example 15 section c, but using 6-chloro-2- (4-fluorophenyl) -3,4'-bipyridin-5-carbonitrile (obtained in reference example 12) instead from 3- (1-benzylpiperidin-4-yl) -3oxypropiononitrile and methylhydrazine instead of hydrazine monohydrate, the title compound (rto: 70%) is obtained.

1 H NMR (300 MHz, CDCl 3)  (TMS): 4.00 (s, 3 H), 4.17 (wide s, 2 H), 6.98 (t, J =

8.7 Hz, 2 H), 7.09 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.37 (m, 2 H), 7.90 (s, 1 H),

8.50 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 72 4- [6- (4-Fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridin-4-yl] phenol

A solution of 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone (0.30 g, 1.4 mmol, obtained in reference example 1) in 2-methoxyethanol (2 mL), is added under a stream of Argon 3-amino-2H-pyrazole (0.13 g, 1.5 mmol), 4-hydroxybenzaldehyde

(0.17 g, 1.4 mmol), 2-methoxyethanol (2 mL) and 37% HCl (0.04 g, 0.4 mmol). It is heated at reflux overnight. It is allowed to cool and concentrated. The solid obtained is dissolved in CHCl3 and a few drops of MeOH. Saturated NaHCO3 solution is added and the aqueous phase is extracted 3 times with CHCl3. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 0.22 g of the desired compound (rto: 41%). LC-MS (method 1): t R = 5.56 min; m / z = 383.0 [M + H] +.

EXAMPLE 73 2- (2,2-Diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 74 1- (2,2-Diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Under a stream of argon, 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (0.20 g, 0.5 mmol, obtained in example 1) is introduced , KOH (0.03 g, 0.5 mmol), 2-bromo-1,1-diethoxyethane (0.10 g, 0.5 mmol) and 1-methoxy2- (2-methoxyethoxy) ethane (2 mL). It is heated to 100 yC and stirred at that temperature overnight. It is allowed to cool and a mixture of H2O-AcOEt is added. The phases are separated and the aqueous phase is extracted with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 139 mg of the compound 2- (2,2-diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (rto: 53%) and 60 mg of the compound 1- (2,2-diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) ) pyrazolo [3,4-b] pyridine (rto: 24%).

Example 73: 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.15 (t, J = 7.0 Hz, 6 H), 3.50 (m, 2 H), 3.73 (m, 2 H), 4.49 (d, J = 5.4 Hz, 2 H), 5.06 (t, J = 5.4 Hz, 1 H), 6.83 (dd, Jo = 1.4 Hz, Jm = 4.4 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H ), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 74: 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.21 (t, J = 6.9 Hz, 6 H), 3.58 (m, 2 H), 3.82 (m, 2 H), 4.74 (d, J = 5.7 Hz, 2 H), 5.19 (t, J = 5.7 Hz, 1 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.92 (t, J = 8.7 Hz, 2 H ), 7.01 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.25 (m, 2 H), 7.87 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 75 4,6-Bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-3-carbonitrile

Following a procedure analogous to that described in example 65, but using 3-bromo-4,6-bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 66) instead of 3-bromo-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1Hpyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 48 %). 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.32 (s, 3 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.96 (t, J = 8.4 Hz, 2 H ), 7.05 (t, J = 8.4 Hz, 2 H), 7.13 (m, 2 H), 7.29 (m, 2 H), 8.35 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 76 3-Bromo-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

To a solution of 3-amino-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

(0.20 g, 0.7 mmol, obtained in example 70) in 48% HBr (1 mL) at 0 ° C, a solution of NaNO2 (0.05 g, 0.7 mmol) in water (0.1 mL) is added dropwise during a period of 15 min maintaining the temperature between 0-5 C. The mixture is stirred 15 min at this temperature. Subsequently, a solution of CuBr (0.24 g, 1.7 mmol) in 48% HBr (1 mL) is added slowly at 0 ° C. The resulting solution is stirred for 3 h at 0 ° C. Allow to reach room temperature, neutralize to pH = 7 with a saturated aqueous solution of sodium bicarbonate and a 30% aqueous solution of NH3. Filter and the solid is washed with a mixture of CH2Cl2 and water. The organic phase is washed with a solution of 1N NaOH and the aqueous phase is extracted with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent

CHCl3-MeOH mixtures of increasing polarity, obtaining 50 mg of the compound holder (rto: 21%) 1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 4.24 (s, NH + CD3OD), 6.92 (m, 2 H), 7.15 (m, 2 H), 7.29 (m, 2 H), 7.95 (s, 1 H), 8.39 (d, J = 6.0 Hz, 2 H).

EXAMPLE 77 6-Fluorophenyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

3-Amino-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (0.20 g,

0.7 mmol, obtained in example 70) and a solution of H3PO2 (0.2 mL, 2.0 mmol) in water (2 mL) and cooled to 5 C. A solution of NaNO2 (0.10 g, 1.4 mmol) in water (0.4 mL) is added dropwise. It is stirred for 30 min at 5 ° C, allowed to reach room temperature and stirred at room temperature for 4 h. It is neutralized by 1N NaOH and extracted with CHCl3. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 63 mg of the title compound (rto: 33%) 1 H NMR (300 MHz, MeOH + CDCl 3)  (TMS): 3.46 (s, NH + CD3OD), 6.92 (t, J =

8.6 Hz, 2 H), 7.07 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 7.26 (m, 2 H), 8.08 (s, 1 H),

8.09 (s, 1 H), 8.37 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 78 N-Methyl- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propyl] amine

To a solution of 2- (3-chloropropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (0.07 g, 0.1 mmol, obtained in example 16) in acetonitrile (0.3 mL), argon methylamine (1.8 mL of a 33% solution in EtOH, 14.6 mmol) is added. Heat at 60 ° C for 3 days, adding methylamine (0.9 mL and

3.6 mL of a 33% solution in EtOH) at 24 and 48 h respectively. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent Mixtures AcOEt-MeOH of increasing polarity, obtaining 24 mg of the title compound in solid form (rto: 29%) 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.00 (wide s, NH + H2O), 2.53 (m, 2 H),

2.61 (s, 3 H), 2.99 (t, J = 6.7 Hz, 2 H), 4.67 (t, J = 6.4 Hz, 2 H), 6.82 (dd, Jo = 1.5

Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.13 (m, 2 H), 7.27 (m, 2 H), 7.90 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 79 [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] methanol

A suspension of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

(0.20 g, 0.5 mmol, obtained in example 1) in a 30-40% aqueous solution of formaldehyde (0.9 mL) is stirred at 130 ° C under an argon atmosphere for 4h. The solvent is concentrated and the residue is dissolved in a mixture of CHCl3 and water and the phases are separated. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 140 mg of the title compound in solid form (rto: 65%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.5 (t, 1 H, OH), 6.11 (d, J = 7.8 Hz, 2 H),

6.85 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.97 (t, J = 8.7 Hz, 1 H), 7.08 (t, J = 8.7 Hz, 1 H), 7.16 (m, 2 H ), 7.31 (m, 2 H), 7.97 (s, 1 H), 8.37 (dd, Jo = 1.6 Hz, Jm =

4.3 Hz, 2 H).

EXAMPLE 80 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -N, N-dimethylacetamide EXAMPLE 81 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -N, N-dimethylacetamide

Following a procedure analogous to that described in examples 73 and 74, but using 2-chloro-N, N-dimethylacetamide instead of 2-bromo-1,1-diethoxyethane, it they obtain the title compounds. Example 80: rto: 10% Example 81: rto 32%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.01 (s, 3 H), 3.18 (s, 3 H), 5.47 (s, 2 H), 6.79 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 1 H),

7.01 (t, J = 8.6 Hz, 1 H), 7.15 (m, 2 H), 7.23 (m, 2 H), 7.95 (s, 1 H), 8.31 (dd, Jo =

1.6 Hz, Jm = 4.3 Hz, 2 H).

EXAMPLE 82 4,6-Bis (4-fluorophenyl) -2- [2- (2-methoxyethoxy) ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine EXAMPLE 83 4,6-Bis (4- fluorophenyl) -1- [2- (2-methoxyethoxy) ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 1-bromo-2- (2-methoxyethoxy) ethane instead of iodoethane, the titular compounds. Example 82: rto: 27%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.28 (s, 3 H), 3.45 (m, 2 H), 3.57 (m, 2 H), 4.05 (t, J = 5.1 Hz, 2 H), 4.63 (t, J = 5.1 Hz, 2 H), 6.82 (dd, Jo =

1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.93 (s, 1 H), 8.31 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 83: rto: 19%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.32 (s, 3 H), 3.50 (m, 2 H), 3.68 (m, 2 H), 4.08 (t, J = 6.0 Hz, 2 H), 4.81 (t, J = 6.0 Hz, 2 H), 6.81 (dd, Jo =

1.4 Hz, Jm = 4.4 Hz, 2 H), 6.92 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.13 (m, 2 H), 7.26 (m, 2 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 84

4,6-Bis (4-fluorophenyl) -2- [3- (morpholin-4-yl) propyl] -5- (4-pyridyl) pyrazolo [3,4

b] pyridine a) 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] propyl methanesulfonate Following a procedure analogous to that described in the example 12 section b, but using 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol (obtained in Example 18) instead of 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] ethanol, the desired compound (rto: quantitative) is obtained. b) Title compound In a flask, 3- [4,6bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] methanesulfonate are introduced under argon current propyl (0.10 g, 0.2 mmol, obtained in section a), NaI (0.003 g, 0.02 mmol), morpholine (0.03 g, 0.4 mmol) and 1,2-dimethoxyethane (2 mL). It is heated to 90 ° C and stirred at that temperature overnight. A mixture of water and AcOEt is added. The phases are separated. The aqueous phase is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures AcOEt-MeOH of increasing polarity, obtaining 37 mg of the title compound (rto: 36%).

1 H NMR (300 MHz, CDCl 3)  (TMS): 2.27 (m, 2 H), 2.30 - 2.43 (complex signal, 6 H), 3.69 (m, 4 H), 4.53 (t, J = 6.6 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H),

6.89

(t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.31 (m, 2 H),

7.81

(s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 85 4,6-Bis (6-chloropyridin-3-yl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 86 4,6-Bis (6-chloropyridin-3 -il) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 73 and 74, but using 4,6-bis (6-chloropyridin-3-yl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine ( obtained in example 40) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1Hpyrazolo [3,4-b] pyridine and iodomethane instead of 2-bromo-1,1- diethoxyethane, the title compounds are obtained. Example 85: rto: 26%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (s, NH + H2O),

4.32 (s, 3 H), 6.88 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 1 H),

7.31 (m, 2 H), 7.58 (dd, Jo = 2.4 Hz, Jm = 8.4 Hz, 1 H), 7.84 (s, 1 H), 8.37 (dd, Jo =

2.4 Hz, Jm = 6.9 Hz, 2 H), 8.43 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 86: rto: 27%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (s, NH + H2O),

4.26 (s, 3 H), 6.88 (dd, J o = 1.8 Hz, Jm = 4.5 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 1 H),

7.29 (d, J = 8.1 Hz, 1 H), 7.35 (dd, J o = 2.4 Hz, Jm = 8.1 Hz, 1 H), 7.50 (dd, J o =

2.6 Hz, Jm = 8.2 Hz, 1 H), 7.91 (s, 1 H), 8.34 (d, J = 2.1 Hz, 1 H), 8.43 - 8.45 (complex signal, 3 H)

EXAMPLE 87 4,6-Bis (6-chloropyridin-3-yl) -3-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 1 method A, but using 1- (6-chloropyridin-3-yl) -2- (4-pyridyl) ethanone (obtained in the example of reference 9) instead of 1- (4-fluorophenyl) -2- (4-pyridyl) ethanone and 3-amino-5-methyl2H-pyrazole instead of 3-amino-2H-pyrazole, the title compound (rto : 9%) 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 2.09 (s, 3 H), 3.51 (s, NH + H2O),

6.92 (m, 2 H), 7.23 (d, J = 8.4 Hz, 1 H), 7.32 (m, 1 H), 7.51 (m, 1 H), 7.54 (dd, Jo =

2.4 Hz, Jm = 8.4 Hz, 1 H), 8.26 (wide s, 1 H), 8.35 - 8.38 (complex signal, 3 H).

EXAMPLE 88 4,6-Bis (6-methylpyridin-3-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in Example 1 method A, but using 1- (6-methylpyridin-3-yl) -2- (4-pyridyl) ethanone (obtained in reference example 13) instead of 1- ( 4-fluorophenyl) -2- (4-pyridyl) ethanone, the title compound is obtained (rto: 23%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.59 (s, NH + H2O), 2.59 (s, 6 H), 6.90 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.99 ( d, J = 8.1 Hz, 1 H), 7.09 (d, J = 7.8 Hz, 1 H),

7.33 (m, 2 H), 7.99 (s, 1 H), 8.39 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 8.47 (d, J =

2.1 Hz, 1 H), 8.80 (wide s, 1 H).

EXAMPLE 89 4,6-Bis (4-fluorophenyl) -2- (2-phthalimidoethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using N- (2-bromoethyl) phthalimide instead of iodoethane, the title compound (rto: 29%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 4.32 (t, J = 6.1 Hz, 2 H), 4.76 (t, J = 6.0 Hz, 2 H), 6.81 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.88 (t, J = 8.7 Hz, 2 H), 6.95 (t, J =

8.6 Hz, 2 H), 7.07 (m, 2 H), 7.25 (m, 2 H), 7.50 (m, 2 H), 7.61 (s, 1 H), 7.71 (m, 2 H), 8.32 (dd , Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 90 2- (2-Aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

To a solution of 4,6-bis (4-fluorophenyl) -2- (2-phthalimidoethyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (0.09 g, 0.2 mmol, obtained in example 89) in EtOH (2 mL) hydrazine monohydrate (0.02 g, 0.3 mmol) is added and heated at reflux for 3 h. A mixture of water and AcOEt is added. The phases are separated. The aqueous phase is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures CHCl3-MeOH of increasing polarity, obtaining 57 mg of the title compound (rto: 83%). 1H NMR (300 MHz, CDCl3)  (TMS): 1.57 (s, NH2 + H2O), 3.38 (t, J = 5.7 Hz, 2 H),

4.49 (t, J = 5.5 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.8 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.31 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.6 Hz, 2 H).

EXAMPLE 91

2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol A solution of 4,6-bis (4-fluorophenyl) - 5- (4-pyridyl) -2- [2- (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4-b] pyridine (1.08 g, 2.09 mmol, obtained in example 24) in a 4: 2: 1 mixture of AcOH: THF: H2O (42 mL) is heated at 55 ° C overnight. It is allowed to cool and is basified with a saturated aqueous solution of NaHCO3 and extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 0.78 g of the title compound (rto: 87%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.61 (wide s, OH + H2O), 4.21 (t, J = 4.7 Hz, 2 H), 4.58 (t, J = 4.7 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.91 (t, J =

8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.27 (m, 2 H), 7.87 (s, 1 H),

8.33 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 92 6- (4-Fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 6-fluorophenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine (obtained in example 77) instead of 4, 6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine and iodomethane instead of iodoethane, the title compound (rto: 35%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (broad s, NH + H2O), 4.31 (s, 3 H), 6.95 (t, J = 8.7 Hz, 2 H), 7.11 (d, J = 6.0 Hz, 2 H), 7.41 (m, 2 H), 8.01 (s, 1 H), 8.06 (s, 1 H), 8.51 (d, J = 6.0 Hz, 2 H).

EXAMPLE 93 4,6-Bis (4-fluorophenyl) -2- (3-phthalimidopropyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using N- (3-bromopropyl) phthalimide instead of iodoethane, the title compound (rto: 31%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.54 (q, J = 6.4 Hz, 2 H), 3.79 (t, J = 6.2 Hz, 2 H), 4.50 (t, J = 6.6 Hz, 2 H ), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J =

8.7 Hz, 2 H), 7.02 (t, J = 8.7 Hz, 2 H), 7.17 (m, 2 H), 7.28 (m, 2 H), 7.71 (m, 2 H),

7.83 (m, 2 H), 7.93 (s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 94 2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetaldehyde

2- (2,2-Diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (0.31 g, 0.6 mmol, obtained in the flask) example 73) and HCl 1N (2.6 mL). It is heated at 100 duranteC for 1 h. Allow to cool and bring to pH = 7. It is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 166 mg of the title compound (rto: 65%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.26 (s, 2 H), 6.83 (dd, Jo = 1.4 Hz, Jm = 4.4 Hz, 2 H), 6.91 (t, J = 8.5 Hz, 2 H), 7.00 (t, J = 8.8 Hz, 2 H), 7.15 (m, 2 H), 7.30 (m, 2 H), 7.88 (s, 1 H), 8.31 (m, 2 H), 9.85 (s, 1 H).

EXAMPLE 95 2- (3-Aminopropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 90, but using 4,6-bis (4-fluorophenyl) -2- (3-phthalimidopropyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 93) instead of 4,6-bis (4-fluorophenyl) -2- (2-phthalimidoethyl) -5 (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound (rto) is obtained : 49%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.54 (s, NH2 + H2O), 2.19 (m, 2 H), 2.76 (t, J = 6.7 Hz, 2 H), 4.57 (t, J = 6.7 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H),

6.90

(t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.30 (m, 2 H),

7.81

(s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 96 N- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridin-3-ylmethyl] -1- (tertbutoxycarbonyl) piperidin-4- carboxamide

Following a procedure analogous to that described in Example 48, but using 1- (tert-butoxycarbonyl) piperidin-4-carboxylic acid instead of 2- [4,6-bis (4fluorophenyl) -5- (4-pyridyl) pyrazolo acid [3,4-b] pyridin-2-yl] acetic acid and 3-aminomethyl-4,6-bis (4fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (obtained in Example 68) instead of morpholine, the title compound is obtained (rto: 26%).

EXAMPLE 97 N- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-methyl] piperidine-4-carboxamide

Following a procedure analogous to that described in Example 36, but using N- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-ylmethyl ] -1- (tert

butoxycarbonyl) piperidine-4-carboxamide (obtained in example 96) instead of 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine, the title compound (rto) is obtained : 63%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.40 - 1.90 (complex signal, 3 H + H2O), 2.18 (m, 2 H), 2.63 (m, 2 H), 3.13 (m, 2 H), 4.15 (d, J = 5.1 Hz, 2 H), 5.20 (wide s, 1H, NH), 6.20 (wide s, 1 H, NH), 6.78 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.94 (t, J =

8.7 Hz, 2 H), 7.03 (t, J = 8.7 Hz, 2 H), 7.08 - 7.14 (complex signal, 4 H), 8.30 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 98 2- (3-Benzyloxypropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 99 1- (3-Benzyloxypropyl) -4.6 -bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using the benzyl ether of 3-bromopropanol instead of iodoethane, the title compounds are obtained. Example 98: rto: 43%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.38 (m, 2 H), 3.48 (t, J = 5.6 Hz, 2 H), 4.44 (s, 2 H), 4.57 (t, J = 6.7 Hz , 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm =

4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.10 (m, 2 H), 7.26

- 7.32 (complex signal, 7 H), 7.73 (s, 1 H), 8.32 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H). Example 99: rto: 20%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.19 (m, 2 H), 3.58 (t, J = 6.1 Hz, 2 H), 4.48 (s, 2 H), 4.75 (t, J = 6.9 Hz, 2 H), 6.81 (dd, Jo = 1.5 Hz, Jm =

4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.12 (m, 2 H), 7.24 –7.33 (complex signal, 7 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 100 N, N-Diethyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine EXAMPLE 101 N, N-Diethyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1yl] ethyl] amine

Following a procedure analogous to that described in examples 6 and 7, but using N- (2-chloroethyl) diethylamine hydrochloride instead of iodoethane and 2 equivalents of KOH, the title compounds are obtained.

Example 100: rto: 5%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 0.99 (t, J = 7.2 Hz, 6 H), 2.56 (c, J = 7.1 Hz, 4 H), 3.08 (t, J = 6.5 Hz, 2 H ), 4.48 (t, J = 6.5 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.8 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H) . Example 101: rto: 73%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.05 (t, J = 7.2 Hz, 6 H), 2.66 (c, J = 7.2 Hz, 4 H), 3.09 (t, J = 7.2 Hz, 2 H ), 4.69 (t, J = 7.2 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.92 (t, J = 8.7 Hz, 2 H), 6.98 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.26 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H) .

EXAMPLE 102 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -2- (3-pyridylmethyl) pyrazolo [3,4-b] pyridine EXAMPLE 103 4,6-Bis (4-fluorophenyl) - 5- (4-pyridyl) -1- (3-pyridylmethyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 3-chloromethylpyridine hydrochloride instead of iodoethane, the title compounds are obtained. Example 102: rto: 16%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.63 (s, 2 H), 6.81 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.8 Hz, 2 H ), 6.99 (t, J = 8.7 Hz, 2 H), 7.10 (m, 2 H), 7.31 (m, 2 H), 7.82 (m, 2 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 8.61 (dd, Jo = 1.5 Hz, Jm = 4.8 Hz, 2 H), 8.68 (s, 1 H). Example 103: rto: 22%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.80 (s, 2 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.94 (t, J = 8.6 Hz, 2 H ), 7.01 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H), 7.27 (m, 2 H), 7.79 (m, 1 H), 7.88 (s, 1 H), 8.32 (dd , Jo = 1.4 Hz, Jm = 4.4 Hz, 2 H), 8.56 (d, J = 5.0 Hz, 2 H), 8.75 (s, 1 H).

EXAMPLE 104 N, N-Dimethyl- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propyl] amine EXAMPLE 105 N, N-Dimethyl- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1yl] propyl] amine

Following a procedure analogous to that described in examples 6 and 7, but using N- (3-chloropropyl) dimethylamine hydrochloride instead of iodoethane, the title compounds are obtained. Example 104: 22%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.21 - 2.29 (complex signal, 10 H), 4.51 (t, J = 6.6 Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz , 2 H),

6.89

(t, J = 8.8 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.30 (m, 2 H),

7.81

(s, 1 H), 8.31 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 105: rto: 19%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.18 - 2.27 (complex signal, 8 H), 2.43 (t, J = 7.2 Hz, 2 H), 4.65 (t, J = 7.1 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t, J = 8.8 Hz, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H ), 7.27 (m, 2 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 106 1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin4-ol

Under a stream of argon, 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetaldehyde (0.08 g, 0.2) are introduced into a flask mmol, obtained in example 94), sodium triacetoxyborohydride (0.08 g, 0.4 mmol), 4-hydroxypiperidine

(0.02 g, 0.2 mmol) and 1,2-dichloroethane (3 mL). The mixture is stirred at room temperature overnight. It is concentrated and a mixture of water and AcOEt is added. The phases are separated. The aqueous phase is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures of AcOEt-MeOH of increasing polarity, obtaining 19 mg of the title compound (rto: 20%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (s wide 1 H + OH + H2O), 1.85 (m, 2 H), 2.05 (m, 2 H), 2.30 (m, 2 H), 2.80 (m, 2 H), 3.01 (m, 2 H), 4.54 (m, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.6 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.34 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 107 3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -2hydroxypropan-1-ol EXAMPLE 108

3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -2hydroxypropan-1-ol

Following a procedure analogous to that described in examples 6 and 7, but using 3-bromopropane-1,2-diol instead of iodoethane, the title compounds are obtained. Example 107: rto: 17%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.49 (s, 1 H, OH), 3.72 (m, 2 H), 4.32 (m, 1 H), 4.60 (m, 2 H), 5.30 (s, 1H, OH), 6.83 (dd, Jo = 1.6 Hz, Jm =

4.4 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.28 (m, 2 H), 7.88 (s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 108: rto: 26%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 3.65 (m, 2 H), 4.26 (m, 1 H), 4.78 (m, 2 H), 5.30 (s, 2 H, OH), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H),

6.94

(t, J = 8.6 Hz, 2 H), 7.03 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.28 (m, 2 H),

7.91

(s, 1 H), 8.34 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 109 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -2- (4-pyridylmethyl) pyrazolo [3,4-b] pyridine EXAMPLE 110 4,6-Bis (4-fluorophenyl) - 5- (4-pyridyl) -1- (4-pyridylmethyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 4-chloromethylpyridine hydrochloride instead of iodoethane, the title compounds are obtained. Example 109: rto: 29%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.63 (s, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H ), 6.99 (t, J = 8.7 Hz, 2 H), 7.12 (m, 2 H), 7.23 - 7.33 (complex signal, 4 H), 7.84 (s, 1 H), 8.32 (dd, Jo =

1.5 Hz, Jm = 4.5 Hz, 2 H), 8.61 (dd, Jo = 1.5 Hz, Jm = 4.8 Hz, 2 H). Example 110: rto: 15%; 5.80 (s, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H ), 7.14 (m, 2 H), 7.20 - 7.26 (complex signal, 4 H), 7.93 (s, 1 H), 8.34 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 8.61 (dd , Jo = 1.5 Hz, Jm = 4.8 Hz, 2 H).

EXAMPLE 111 N- (tert-Butoxycarbonyl) - [1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] propyl] piperidin -4-il] amina

To a solution of 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate (0.15 g, 0.3 mmol, obtained in the Example 84 section a) in acetonitrile (2 mL) under argon, N- (tertbutoxycarbonyl) -N- (4-piperidyl) amine (0.12 g, 0.6 mmol) is added and heated at 60 ° C overnight . A mixture of CHCl3 and saturated aqueous NaHCO3 solution is added. The phases are separated. The aqueous phase is extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures AcOEt-MeOH of increasing polarity, obtaining 40 mg of the title compound (rto: 22%). 1H NMR (300 MHz, CDCl3)  (TMS): 1.44 (wide s, 2 H + NH2 + H2O), 1.95 (m, 2 H), 2.06 (m, 2 H), 2.25 (m, 2 H), 2.35 (m, 2 H), 3.46 (m, 2 H), 4.40 (m, 1 H), 4.51 (t, 2 H), 6.83 (d, J = 6.0 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H),

7.14 (m, 2 H), 7.29 (m, 2 H), 7.80 (s, 1 H), 8.32 (d, J = 6.0 Hz, 2 H).

EXAMPLE 112 2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 113 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 6-fluorophenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine (obtained in example 77) instead of 4, 6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine and 1- (tert-butoxycarbonyl) piperidine-4-yl methanesulfonate (obtained in example 14 section a) instead of iodoethane, the title compounds are obtained. Example 112: rto: 26%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.50 (s, 9 H), 2.17 -

2.32 (complex signal, 2 H), 2.99 (m, 2 H), 4.33 (m, 2 H), 4.60 (m, 1 H), 6.95 (t, J =

8.7 Hz, 2 H), 7.11 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.41 (m, 2 H), 8.06 (s, 1 H),

8.07 (s, 1 H), 8.52 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H). Example 113: rto: 55%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.50 (s, 9 H), 2.04 (m, 2 H), 2.30 (m, 2 H), 3.00 (m, 2 H), 4.42 (m, 2 H), 5.10 (m, 1 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.10 (dd, Jo = 1.6 Hz, Jm = 4.5 Hz, 2 H), 7.37 (m, 2 H), 8.07 (s, 1 H), 8.10 (s, 1 H), 8.52 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 114 3-Methyl-4,6-bis (6-methylpyridin-3-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in Example 1 method A, but using 1- (6-methylpyridin-3-yl) -2- (4-pyridyl) ethanone (obtained in reference example 13) instead of 1- ( 4-fluorophenyl) -2- (4-pyridyl) ethanone and 3-amino-5-methyl2H-pyrazole instead of 3-amino-2H-pyrazole, the title compound (rto: 24%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.07 (s, 3 H), 2.54 (s, 3 H), 2.57 (s, 3 H), 6.85 (m, 2 H), 6.99 (d, J = 8.1 Hz, 1 H), 7.08 (d, J = 8.1 Hz, 1 H), 7.30 (m, 1 H), 8.10 (dd, Jo = 2.4 Hz, Jm = 8.1 Hz, 1 H), 8.32 (dd , Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 8.38 (s, 1 H), 8.57 (s, 1 H), 10.74 (wide s, NH).

EXAMPLE 115 1- [3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-one

Under a stream of argon, 3- [4,6bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methane sulfonate are introduced into a flask , 0.3 mmol, obtained in example 84 section a), NaI (0.008 g, 0.06 mmol), 4piperidone hydrochloride monohydrate (0.04 g, 0.3 mmol), K2CO3 (0.07 g, 0.5 mmol) and DMF (2 mL). The mixture is heated at 60 ° C for 24 h. Allow to cool and add a mixture of water and AcOEt. The phases are separated. The aqueous phase is extracted with AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent Mixtures AcOEt-MeOH of increasing polarity, obtaining 16 mg of the title compound (rto: 10%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (wide s, 4 H + H2O), 2.30 (m, 2 H),

2.42 (m, 2 H), 2.48 (m, 2 H), 2.73 (t, 2 H), 4.55 (t, 2 H), 6.83 (d, J = 6.0 Hz, 2 H),

6.90

 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.18 (m, 2 H), 7.27 (m, 2 H),

7.82

(s, 1 H), 8.32 (d, J = 6.0 Hz, 2 H).

EXAMPLE 116

N- (tert-Butoxycarbonyl) - [1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4

b] pyridin-2-yl] ethyl] piperidin-4-yl] amine a) 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin- methanesulfonate 2-yl] ethyl Following a procedure analogous to that described in example 12 section b, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine -2-yl] ethanol (obtained in example 91) instead of 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] ethanol, the desired compound (rto: quantitative) is obtained.

b) Title compound

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl methanesulfonate (obtained in section a) instead of 3- methanesulfonate [4,6-bis (4fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl, the compound is obtained desired (rto: 66%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.44 (s, 9 H), 1.57 (wide s, 1 H + NH + H2O), 1.90 (m, 2 H), 2.22 (m, 2 H), 2.82 (m, 2 H), 3.01 (t, J = 6.6 Hz, 2 H), 3.45 (m, 1 H), 4.40 (m, 1 H), 4.52 (t, J = 6.5 Hz, 2 H), 6.82 (d, J = 5.7 Hz, 2 H), 6.89 (t, J =

8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.82 (s, 1 H),

8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 117 N- [1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-yl] methylamine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and N -methyl-N (piperidin-4-yl) amine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound (rto: 50%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.61 (wide s, 1 H + NH + H2O), 2.28 (s, 3 H), 2.41 (m, 4 H), 2.57 (m, 4 H), 3.03 (t, J = 6.5 Hz, 2 H), 4.55 (t, J = 6.5 Hz, 2 H),

6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H ), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 118 [1- [3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-yl] amine

Following a procedure analogous to that described in example 36, but using N- (tert-butoxycarbonyl) - [1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3, 4-b] pyridin2-yl] propyl] piperidin-4-yl] amine (obtained in example 111) instead of 2- [1- (tert

butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 89%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.35 (m, 2 H), 1.62 (s wide NH2 + H2O),

1.85 (m, 2 H), 2.03 (m, 2 H), 2.25 (m, 2 H), 2.36 (m, 2 H), 2.70 (m, 1 H), 2.82 (m, 2 H), 4.52 ( d, J = 6.6 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J =

8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.13 (m, 2 H), 7.29 (m, 2 H), 7.81 (s, 1 H),

8.31 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 119 2- [1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-yl] ethanol

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 2 - (4-piperidyl) ethanol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound (rto: 50%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.48 - 1.53 (complex signal, 5 H), 2.11 (m, 2 H), 2.88 (m, 2 H), 2.99 (m, 2 H), 3.70 ( t, J = 6.5 Hz, 2 H), 4.55 (t, J = 6.5 Hz, 2 H),

6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H ), 7.29 (m, 2 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 120 [1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin4-yl] amine

Following a procedure analogous to that described in example 36, but using N- (tert-butoxycarbonyl) - [1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin2-yl] ethyl] piperidin-4 -il] amine (obtained in example 116) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3 , 4-b] pyridine, the title compound is obtained (rto: 77%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.38 (m, 2 H), 1.78 (wide s, 2 H + NH2 + H2O), 2.18 (m, 2 H), 2.75 (m, 1 H), 2.84 (m, 2 H), 3.02 (t, J = 6.3 Hz, 2 H), 4.54 (t, J = 6.5 Hz, 2 H), 6.82 (d, J = 5.7 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.84 (s, 1 H), 8.31 (d, J = 6.0 Hz, 2 H).

EXAMPLE 121 6- (4-Fluorophenyl) -2- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (obtained in example 112) instead of 2 - [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 77%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.89 (m, NH + H2O), 2.25 (m, 2 H), 2.30 (m, 2 H), 2.89 (m, 2 H), 3.34 (m, 2 H), 4.60 (m, 1 H), 6.95 (t, J = 8.7 Hz, 2 H), 7.11 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.40 (m, 2 H), 8.07 (s, 1 H), 8.08 (s, 1 H), 8.51 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 122 6- (4-Fluorophenyl) -1- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 36, but using 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (obtained in Example 113) instead of 2 - [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: quantitative). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.60 (m, NH + H2O), 2.42 (m, 2 H), 2.67 (m 2 H), 3.28 (m, 2 H), 3.72 (m, 2 H), 5.28 (m, 1 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.11 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.37 (m, 2 H), 8.10 (s, 1 H), 8.12 (s, 1 H), 8.54 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 123 3-Amino-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1 Hpirazolo [3,4-b] pyridine

Following a procedure analogous to that described in reference example 15 section c, but using 2-chloro-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3 (trifluoromethyl) phenyl] pyridin-3-carbonitrile (obtained in reference example 14) instead of 3- (1-benzylpiperidin-4-yl) -3-oxopropiononitrile, the title compound (rto: 78%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.44 (s, 3 H), 4.32 (wide s, NH2), 6.61 (d, J = 5.1 Hz, 1 H), 7.44 - 7.84 (complex signal, 2 H), 7.65 (d, J = 7.2 Hz, 1 H), 7.84 (s, 1 H), 8.30 (d, J = 5.1 Hz, 1 H), 8.40 (s, 1 H), 9.55 (wide s, NH).

EXAMPLE 124 2- [3- [1- (tert-Butoxycarbonyl) piperazin-4-yl] propyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 84 section b, but using 1- (tert-butoxycarbonyl) piperazine instead of morpholine and adding triethylamine (1.5 equivalents), the desired compound (rto: 14%) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.66 (m, 2 H), 2.98 (m, 4 H), 3.10 (m, 2 H),

3.66 - 3.74 (complex signal, 4 H), 4.66 (m, 2 H), 6.85 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.28 (m, 2 H), 7.98 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz , 2 H).

EXAMPLE 125 4,6-Bis (4-fluorophenyl) -2- [3- (piperazin-4-yl) propyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [3- [1- (tert-butoxycarbonyl) piperazin-4-yl] propyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) ) pyrazolo [3,4-b] pyridine (obtained in example 124) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4 -pyridyl) pyrazolo [3,4-b] pyridine, the title compound (rto: quantitative) is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.78 (wide s, 2 H + NH + H2O), 2.26 (m, 2 H), 2.40 - 2.59 (complex signal, 6 H), 3.04 (m, 2 H), 4.52 (m, 2 H), 6.83 (dd, Jo =

1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.80 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 126 5- [2- (Methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 77, but using 3-amino-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4b ] pyridine (obtained in example 123) instead of 3-amino-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine, the title compound (rto: 3. 4%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.55 (wide s, NH + H2O), 6.70 (d, J = 5.1 Hz, 1 H), 7.50 (m, 2 H), 7.72 (m, 1 H ), 7.86 (s, 1 H), 8.24 (s, 1 H), 8.35 (d, J = 5.1 Hz, 1 H), 8.54 (s, 1 H).

EXAMPLE 127 5- [2- (Methylsulfonyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 56, but using 5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4-b] pyridine (obtained in example 126) instead of 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine and 2 equivalents of mloroperbenzoic acid, the title compound is obtained (rto: quantitative). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (wide s, NH + H2O), 3.22 (s, 3 H), 7.21 (d, J = 5.1 Hz, 1 H), 7.49 (d, J = 4.8 Hz, 2 H), 7.71 (m, 1 H), 7.84 (s, 1 H), 8.30 (s, 1 H), 8.71 (m, 2 H).

EXAMPLE 128 (1S) -N- (1-Phenylethyl) - [4- [6- [3- (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine

A mixture of 5- [2- (methylsulfonyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1 Hpyrazolo [3,4-b] pyridine (0.55 g, 0.13 mmol, obtained in Example 127 ) and (1S) -1phenylethylamine (0.16 g, 1.3 mmol) is heated at 100 C for 1 h. It is allowed to cool and the crude obtained is purified by chromatography on silica gel using as eluent mixtures of AcOEt-hexane of increasing polarity, obtaining 10 mg of the title compound (rto: 16%). 1H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 1.50 (d, 3 H), 3.80 (wide s, 2 NH

+ H2O), 6.30 (d, 1 H), 7.20 - 7.40 (complex signal, 6 H), 7.50 (d, 1 H), 7.68 (d, 1 H), 7.76 (d, 1 H), 7.83 (s , 1 H), 8.08 (d, 1 H), 8.15 (s, 1 H), 8.24 (wide s, 1 H).

EXAMPLE 129 1- [3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-ol

Following a procedure analogous to that described in example 111, but using piperidin-4-ol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound (rto: 39%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (m, 2 H), 1.88 -2.50 (complex signal, 5 H + OH + H2O), 2.75 (m, 2 H), 3.44 - 3.51 (complex signal, 4 H), 4.52 (t, J = 6.6 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.34 (m, 2 H), 7.82 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 130 2- [1- [3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-yl] ethanol

Following a procedure analogous to that described in example 111, but using 2- (4-piperidyl) ethanol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 44 %). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.20-2.00 (wide s, 8 H + OH + H2O), 2.50 (m, 1 H), 2.85 (m, 1 H), 3.50 (m, 1 H ), 3.70 (m, 4 H), 4.59 (m, 2 H), 6.83 (d, J = 6.0 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.30 (m, 2 H), 7.89 (s, 1 H), 8.32 (d, J = 6.0 Hz, 2 H).

EXAMPLE 131

4,6-Bis (4-fluorophenyl) -3- (4-piperidyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine a) 3- (1-Benzylpiperidin-4-yl ) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridine Following a procedure analogous to that described in example 1 method A, but using 3-amino-5 - (1-Benzylpiperidin-4-yl) -2H-pyrazole (obtained in reference example 15) instead of 3-amino-2H-pyrazole, the title compound (rto: 6%) is obtained. b) Titular compound A solution of 3- (1-benzylpiperidin-4-yl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1Hpyrazolo [3,4-b] pyridine (23 mg, 0.04 mmol, obtained in the previous section) in MeOH (1 mL) under argon, Pd / C and a solution of HCOONH4 (0.01 g, 0.2 mmol) in water (0.06 mL) are added. It is heated at reflux for 5

h. It is filtered on celite and concentrated. The residue is dissolved in CHCl3 and washed with a saturated aqueous solution of NaHCO3, obtaining 2 mg of titular compound (rto: 10%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.10 - 1.90 (wide s, 7 H), 2.23 (m, 2 H),

2.99 (m, 2 H), 6.80 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.92 (t, J = 8.7 Hz, 2 H),

7.02 (t, J = 8.7 Hz, 2 H), 7.12 (m, 2 H), 7.28 (m, 2 H), 8.28 (dd, Jo = 1.5 Hz, Jm =

4.5 Hz, 2 H).

EXAMPLE 132 6- (4-Fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridin-3-carbonitrile

Following a procedure analogous to that described in example 65, but using 3-bromo-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (obtained in example 76 ) instead of 3-bromo-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4b] pyridine, the title compound (rto: 38%) is obtained.

EXAMPLE 133 2- [2 - [[1- (tert-Butoxycarbonyl) piperidin-4-yl] amino] ethyl] -4,6-bis (4-fluorophenyl) -5 (4-pyridyl) pyrazolo [3,4- b] pyridine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and [ N- (tertbutoxycarbonyl) piperidin-4-yl] amine instead of N- (tert-butoxycarbonyl) -N- (4piperidyl) amine, the desired compound is obtained (rto: 40%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.20 (m, 2 H), 1.45 (s, 9 H), 1.55 (NH wide s

+ H2O), 1.83 (m, 2 H), 2.65 (m, 1 H), 2.77 (m, 2 H), 3.31 (t, 2 H), 4.02 (m, 2 H),

4.53 (t, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.8 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H ), 7.13 (m, 2 H), 7.28 (m, 2 H), 7.84 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 134 4,6-Bis (4-fluorophenyl) -2- [2 - [(4-piperidyl) amino] ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [2 - [[1- (tert-butoxycarbonyl) piperidin-4-yl] amino] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 133) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b ] pyridine, the title compound is obtained (rto: 97%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.30 (m, 2 H), 1.70 (wide s, 2 NH + H2O),

1.85 (m, 2 H), 2.61 (m, 3 H), 3.09 (m, 2 H), 3.31 (t, J = 5.7 Hz, 2 H), 4.53 (t, J = 5.7 Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.90 (t, J = 8.8 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H ), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H).

EXAMPLE 135 N- (2-Methoxyethyl) - [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl] amine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 2-methoxyethylamine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 63%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.57 (wide s, NH + H2O), 2.81 (t, J = 5.1 Hz, 2 H), 3.30 (t, J = 5.8 Hz, 2 H), 3.31 (s, 3 H), 3.45 (t, J = 5.1 Hz, 2 H), 4.55 (t, J =

5.7 Hz, 2 H), 6.82 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H) , 7.14 (m, 2 H), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 136 1- [4- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperazin-1-yl] ethanone

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 1 - (piperazin-1il) ethanone instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 50%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.07 (s, 3 H), 2.50 (m, 4 H), 3.07 (t, J = 6.3 Hz, 2 H), 3.41 (t, J = 4.9 Hz , 2 H), 3.57 (t, J = 4.9 Hz, 2 H), 4.55 (t, J = 6.3 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J =

8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.82 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm =

4.5 Hz, 2 H).

EXAMPLE 137 3- [4,6-Diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol EXAMPLE 138 3- [4,6-Diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propan-1-ol

Following a procedure analogous to that described in examples 6 and 7, but using 4,6-diphenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine (obtained in example 2) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine and 3-iodopropanol instead of iodoethane, the title compounds are obtained. Example 137: rto: 44%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (s, OH + H2O),

2.25 (m, 2 H), 3.70 (m, 2 H), 4.62 (t, J = 6.3 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm =

4.6 Hz, 2 H), 7.17 - 7.34 (complex signal, 10 H), 7.84 (s, 1 H), 8.26 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 138: rto: 27%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.58 (s, OH + H2O),

2.15 (m, 2 H), 3.59 (m, 2 H), 4.79 (t, J = 6.0 Hz, 2 H), 6.83 (dd, Jo = 1.6 Hz, Jm =

4.4 Hz, 2 H), 7.17 (m, 2 H), 7.21 - 7.33 (complex signal, 8 H), 7.91 (s, 1 H), 8.27 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H ).

EXAMPLE 139

2-Ethyl-4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

EXAMPLE 140

1-Ethyl-4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Following a procedure analogous to that described in examples 6 and 7, but using 4,6-diphenyl-5- ( 4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (obtained in example 2) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3 , 4-b] pyridine, the title compounds are obtained. Example 139: rto: 12%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.67 (t, J = 7.3 Hz, 3 H), 4.50 (c, J = 7.3 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.15 - 7.34 (complex signal, 10 H), 7.80 (s, 1H), 8.25 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 140: rto: 21%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.61 (t, J = 7.2 Hz, 3 H), 4.68 (c, J = 7.2 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.17 (m, 2 H),

7.23 - 7.32 (complex signal, 8 H), 7.88 (s, 1H), 8.26 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 141 4,6-Diphenyl-2- (2-phthalimidoethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using 4,6-diphenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine (obtained in example 2) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine and N- (2-bromoethyl) phthalimide instead of iodoethane, the title compound (rto: 31%)

1 H NMR (300 MHz, CDCl 3)  (TMS): 4.32 (t, J = 6.1 Hz, 2 H), 4.75 (t, J = 6.1 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.11 (m, 2 H), 7.18 - 7.32 (complex signal, 7 H), 7.73 (m, 2 H), 7.80 (s, 1 H), 7.83 (m, 2 H), 8.25 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 142 2- (2-Aminoethyl) -4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 90, but using 4,6-diphenyl-2- (2-phthalimidoethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 141) instead of 2- (2-phthalimidoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound (rto: 51%) is obtained. 1H NMR (300 MHz, CDCl3)  (TMS): 1.50 (s, NH2 + H2O), 3.37 (t, J = 5.5 Hz, 2 H),

4.48 (t, J = 5.4 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.17 - 7.34 (complex signal, 10 H), 7.86 (s, 1 H), 8.25 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 143 2-Allyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine EXAMPLE 144 1-Alyl-4,6-bis (4-fluorophenyl) - 5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in examples 6 and 7, but using allyl bromide instead of iodoethane, the title compounds are obtained. Example 143: rto: 33%; 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.08 (d, J = 6.3 Hz, 2 H), 5.40 (m, 2 H), 6.16 (m, 1 H), 6.82 (dd, Jo = 1.5 Hz , Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.13 (m, 2 H), 7.30 (m, 2 H ), 7.78 (s, 1 H),

8.34 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H). Example 144: rto: 10%; 1H NMR (300 MHz, CDCl3)  (TMS): 5.22 - 5.34 (signal complex, 4 H), 6.14 (m, 1 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.93 (t, J =

8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.87 (s, 1 H),

8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 145 1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin4-one

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and hydrochloride 4-Piperidone monohydrate instead of N- (tert-butoxycarbonyl) -N- (4piperidyl) amine and by adding triethylamine (3 equivalents), the desired compound is obtained (rto: 18%).

1 H NMR (300 MHz, CDCl 3)  (TMS): 2.41 (t, J = 6.0 Hz, 4 H), 2.84 (t, J = 6.0 Hz, 4 H), 3.20 (t, J = 6.4 Hz, 2 H ), 4.58 (t, J = 6.4 Hz, 2 H), 6.83 (d, J = 6.0 Hz, 2 H),

6.90

 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.30 (m, 2 H),

7.85

(s, 1 H), 8.32 (d, J = 6.0 Hz, 2 H).

EXAMPLE 146 3-Aminomethyl-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 68, but using 6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridin-3-carbonitrile (obtained in example 132) instead of 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridin-3-carbonitrile, the title compound is obtained (rto: 22%) . 1 H NMR (300 MHz, CDCl3 + CD3OD)  (TMS): 4.24 (s, 2 H), 4.25 (wide s, NH + NH2 + CD3OD), 6.95 (m, 2 H), 7.16 (m, 2 H), 7.29 (m, 2 H), 8.25 (wide s, 1 H),

8.38 (wide s, 2 H).

EXAMPLE 147 3-Amino-6- (4-fluorophenyl) -4-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in reference example 15 section c, but using 6-chloro-2- (4-fluorophenyl) -4-methyl-3,4'-bipyridine-5carbonitrile (obtained in reference example 18) instead of 3- (1-benzylpiperidin-4-yl) -3-oxopropiononitrile, the title compound is obtained (rto: 27%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (wide s, NH + NH2 + H2O), 2.51 (s, 3 H), 6.80 - 7.20 (complex signal, 4 H), 7.22 (m, 2 H ), 8.55 (d, J = 8.0 Hz, 2 H).

EXAMPLE 148 3- [N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amino] propan-1-ol

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 3 -amino-1propanol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 57%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.50 - 1.80 (complex signal, 2 H + NH + OH

+ H2O), 2.91 (t, J = 5.7 Hz, 2 H), 3.31 (t, J = 5.4 Hz, 2 H), 3.77 (t, J = 5.4 Hz, 2 H),

4.54 (t, J = 5.4 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.15 (m, 2 H), 7.29 (m, 2 H), 7.82 (s, 1 H), 8.31 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 149 N-Ethyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and ethylamine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 58%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.09 (t, J = 7.0 Hz, 3 H), 1.71 (wide s, NH + H2O), 2.70 (c, J = 7.1 Hz, 2 H), 3.29 (t, J = 5.7 Hz, 2 H), 4.56 (t, J = 5.7 Hz, 2 H),

6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H ), 7.29 (m, 2 H), 7.84 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 150 2- [N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amino] ethanol

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 2 -aminoethanol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 54%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.70 (broad s, NH + OH + H2O), 2.82 (t, J =

5.3 Hz, 2 H), 3.32 (t, J = 5.6 Hz, 2 H), 3.62 (t, J = 5.3 Hz, 2 H), 4.55 (t, J = 5.6 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J =

8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.83 (s, 1 H), 8.31 (dd, Jo = 1.8 Hz, Jm =

4.5 Hz, 2 H).

EXAMPLE 151 N - [(2-Pyridyl) methyl] - [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and ( 2-pyridyl) methylamine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 52%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.62 (wide s, NH + H2O), 3.33 (t, J = 5.7 Hz, 2 H), 3.92 (s, 2 H), 4.58 (t, J = 5.7 Hz, 2 H), 6.83 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.6 Hz, 2 H) , 7.14 (m, 4 H), 7.29 (m, 2 H),

7.60 (m, 1 H), 7.86 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 8.51 (m, 1 H).

EXAMPLE 152 N - [(2-Thienyl) methyl] - [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl] amine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and ( 2-thienyl) methylamine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 25%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.55 (wide s, NH + H2O) 3.32 (t, J = 5.6 Hz, 2 H), 4.00 (s, 2 H), 4.54 (t, J = 5.6 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 6.91 (m, 1 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.16 (m, 3 H),

7.29 (m, 3 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 153 1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidine-4-carboxamide

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and piperidin -4carboxamide instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 75%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.61 - 1.76 (complex signal, 5 H), 1.84 (m, 2 H), 2.91 (m, 2 H), 3.01 (t, J = 6.3 Hz, 2 H), 4.52 (t, J = 6.3 Hz, 2 H), 5.27 (wide s, NH), 5.41 (wide s, NH), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.02 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.30 (m, 2 H), 7.83 (s, 1 H), 8.32 (dd, Jo = 1.4 Hz, Jm = 4.6 Hz, 2 H).

EXAMPLE 154 4,6-Bis (4-fluorophenyl) -2- [2- (pyrrolidin-1-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and pyrrolidine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 75%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.77 (m, 4 H), 2.55 (m, 4 H), 3.17 (t, J = 6.6 Hz, 2 H), 4.58 (t, J = 6.6 Hz , 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.84 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 155 (3R) -1- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] pyrrolidin-3-ol

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and ( 3R) -3-pyrrolidinol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 52%). 1H NMR (300 MHz, CDCl3)  (TMS): 1.69 (wide s, 1H + OH + H2O), 2.14 (m, 1 H), 2.40 (m, 1 H), 2.58 (m, 1 H), 2.69 (m, 1 H), 2.94 (m, 1 H), 3.20 (t, J = 6.4 Hz, 2 H), 4.32 (m, 1 H), 4.57 (t, J = 6.4 Hz, 2 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H),

6.89

(t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.29 (m, 2 H),

7.82

(s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 156 2- [N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -N-methylamino] ethanol

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 2 (methylamino) ethanol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 71%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (wide s, OH + H2O), 2.34 (s, 3 H), 2.60 (t, J = 5.2Hz, 2H), 3.14 (t, J = 6.0 Hz, 2H), 3.53 (t, J = 5.2Hz, 2H), 4.53 (t, J =

6.0 Hz, 2 H), 6.83 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H) , 7.14 (m, 2 H), 7.29 (m, 2 H), 7.81 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 157 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -2- [2- (1,2,3,4-tetrahydroisoquinolin-2yl) ethyl] pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 1 , 2,3,4-tetrahydroisoquinoline instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 57%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.78 - 2.85 (complex signal, 4 H), 3.20 (t, J =

6.3 Hz, 2 H), 3.72 (s, 2 H), 4.63 (t, J = 6.3 Hz, 2 H), 6.81 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.86-7.17 ( complex signal, 10 H), 7.30 (m, 2 H), 7.86 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 158 4,6-Bis (4-fluorophenyl) -2- [2- (4-phenylpiperazin-1-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 1-phenylpiperazine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 71%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.69 (m, 4 H), 3.10 (t, J = 6.4 Hz, 2 H), 3.16 (m, 4 H), 4.59 (t, J = 6.4 Hz , 2 H), 6.82 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H), 6.86 -

7.02 (complex signal, 9 H), 7.14 (m, 2 H), 7.29 (m, 2 H), 7.86 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H) .

EXAMPLE 159 4,6-Bis (4-fluorophenyl) -2- [2- [4- (1-piperidyl) piperidin-1-yl] ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 4piperidinopiperidine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 51%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.40 - 1.60 (complex signal, 8 H), 1.78 (m, 2 H), 2.04 - 2.22 (complex signal, 3 H), 2.48 (m, 4 H) , 2.96 (m, 4 H), 4.52 (t, J = 6.4 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.13 (m, 2 H), 7.29 (m, 2 H), 7.85 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 160 3- [N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -Nmethylamino] propiononitrile

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 3 (methylamino) propiononitrile instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound (rto: 50%) is obtained.

1H NMR (300 MHz, CDCl3)  (TMS): 2.35 (complex signal, 5 H), 2.71 (t, J = 6.4 Hz, 4H), 3.13 (t, J = 5.9Hz, 2H), 4.50 (t, J = 5.9Hz, 2H), 6.83 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H ), 7.17 (m, 2 H),

7.31 (m, 2 H), 7.87 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 161 N-Methyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl] amine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and methylamine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 51%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.61 (broad s, NH + H2O), 3.25 (t, J = 5.6 Hz, 2 H), 4.57 (t, J = 5.6 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H) , 7.29 (m, 2 H), 7.84 (s, 1 H), 8.31 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 162 2- [2- [4- (tert-Butoxycarbonyl) piperazin-1-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 1 - (tertbutoxycarbonyl) piperazine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 63%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.45 (s, 9 H), 2.46 (m, 4 H), 3.05 (t, J = 6.4 Hz, 2 H), 3.40 (m, 4 H), 4.54 (t, J = 6.4 Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.15 (m, 2 H), 7.30 (m, 2 H), 7.86 (s, 1 H), 8.33 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 163 4,6-Bis (4-fluorophenyl) -2- [2- (piperazin-1-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in example 36, but using 2- [2- [4- (tert-butoxycarbonyl) piperazin-1-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in Example 162) instead of 2- [1- (tertbutoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine, the title compound is obtained (rto: 62%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.56 (broad s, NH + H2O), 2.45 (m, 4 H),

2.85 (m, 4 H), 3.00 (t, J = 6.4 Hz, 2 H), 4.55 (t, J = 6.4 Hz, 2 H), 6.82 (dd, Jo = 1.6 Hz, Jm = 4.4 Hz, 2 H ), 6.89 (t, J = 8.7 Hz, 2 H), 7.03 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H), 7.30 (m, 2 H), 7.86 (s, 1 H ), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 164 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -2-vinylpyrazolo [3,4-b] pyridine

A solution of 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate (0.15 g, 0.3 mmol, obtained in the example 116 section a) and KOH (0.02 g, 0.3 mmol) in toluene (4 mL) is heated at 100 ° C overnight. Water and AcOEt are added and the phases are separated. The aqueous phase is saturated with NaCl (solid) and extracted with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 110 mg of the title compound (rto: 90%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 5.27 (dd, Jgem = 1.8 Hz, Jvec = 8.7 Hz, 1 H),

6.22 (dd, Jgem = 1.4 Hz, Jvec = 15.4 Hz, 1 H), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.15 (m, 2 H), 7.17 - 7.34 (complex signal, 3 H), 7.90 (s, 1 H), 8.33 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 165 2- [N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -N- (2-hydroxyethyl) ) amino] ethanol

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of methanesulfonate of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl and 2 - (2-hydroxyethylamino) ethanol instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 51%).

1 H NMR (300 MHz, CDCl 3)  (TMS): 1.50 (wide s, 2 OH + H2O), 2.73 (t, J = 5.0 Hz, 4H), 3.21 (t, J = 5.6 Hz, 2 H), 3.52 (t, J = 5.0 Hz, 4 H), 4.54 (t, J = 5.4 Hz, 2 H),

6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.89 (t, J = 8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.13 (m, 2 H ), 7.29 (m, 2 H), 7.89 (s, 1 H), 8.32 (dd, Jo = 1.8 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 166 N-Cyclopropyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine

Following a procedure analogous to that described in example 111, but using 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate ( obtained in example 116 section a) instead of 3 [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl methanesulfonate and cyclopropylamine instead of N- (tert-butoxycarbonyl) -N- (4-piperidyl) amine, the desired compound is obtained (rto: 47%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 0.30 (m, 2 H), 0.45 (m, 2 H), 1.60 (wide s, NH + H2O), 2.20 (m, 1 H), 3.36 (t , J = 5.7 Hz, 2 H), 4.55 (t, J = 5.7 Hz, 2 H), 6.82 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.90 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.30 (m, 2 H), 7.82 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 167 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] acetamide Following a procedure analogous to that described in Reference example 1 section a, but using acetyl chloride instead of 4fluorobenzoyl chloride and 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3, 4b] pyridine (obtained in example 90) instead of N, O-dimethylhydroxylamine, the desired compound is obtained (rto: 48%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.98 (s, 3 H), 3.95 (m, 2 H), 4.58 (t, J = 5.4 Hz, 2 H), 6.47 (m, NH), 6.83 (d, J = 9.0 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.6 Hz, 2 H), 7.14 (m, 2 H), 7.28 (m, 2 H), 7.82 (s, 1 H), 8.33 (d, J = 9.0 Hz, 2 H).

EXAMPLE 168 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -N'isopropylurea

To a solution of 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (0.06 g, 0.15 mmol, obtained in example 90) in DMF (1 mL), argon isopropylisocyanate (0.02 g, 0.18 mmol) is added under a stream of argon. Let it stir at room temperature for 2 days. The solvent is concentrated again and diethyl ether is added to the residue obtained. The solvent is concentrated, obtaining 38 mg of the title compound as a solid (rto: 50%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.05 (d, J = 6.3 Hz, 6 H), 3.84 (m, 3 H), 4.22 (m, NH), 4.58 (t, J = 5.4 Hz, 2 H), 5.30 (m, NH), 6.82 (dd, Jo = 1.4 Hz, Jm = 4.6 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.00 (t, J = 8.6 Hz , 2 H), 7.13 (m, 2 H), 7.28 (m, 2 H), 7.84 (s, 1 H), 8.32 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLE 169 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] methanesulfonamide

To a solution of 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine (0.06 g, 0.15 mmol, obtained in example 90) and DMAP (0.001 g, 0.0058 mmol) in pyridine (0.6 mL) is added under argon and cooling with an ice bath methanesulfonyl chloride (0.017 mL, 0.22 mmol). Let it stir at room temperature overnight. The solvent is concentrated. The residue is dissolved in CHCl3 and saturated aqueous NaHCO3 solution is added. The phases are separated. The organic phase is dried over Na2SO4 and concentrated. The crude obtained is purified by chromatography on silica gel using AcOEt as solvent, obtaining 70 mg of the title compound (rto: 95%). 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.99 (s, 3 H), 3.86 (m, 2 H), 4.64 (t, J = 5.3 Hz, 2 H), 5.33 (m, NH), 6.83 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 6.91 (t, J = 8.7 Hz, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 7.14 (m, 2 H) , 7.29 (m, 2 H), 7.88 (s, 1 H), 8.33 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

EXAMPLES 170-178 Following a procedure analogous to that described in example 72, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

image11

Method

tR (min) m / z [M + H] +

170

6- (4-Fluorophenyl) -4- (4piperidyl) -5- (4-pyridyl) -1Hpyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 1 (tert-butoxycarbonyl) piperidin-4-carbaldehyde one 3.34 374.1

6- (4-Fluorophenyl) -4- (2-fury)

Reference Example 1,

171

5- (4-pyridyl) -1H 3-amino-2H-pyrazole and one 5.72 357.1

pyrazolo [3,4-b] pyridine

furan-2-carbaldehyde

6- (4-Fluorophenyl) -4- (1H

Reference Example 1,

172

imidazol-4-yl) -5- (4-pyridyl) 3-amino-2H-pyrazole and 2H one 3.25 357.1

1H-pyrazolo [3,4-b] pyridine

pyrazole-3-carbaldehyde

173

4- (5-Bromothien-2-yl) -6- (4fluorophenyl) -5- (4-pyridyl) -1 Hpyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 5-bromothiophene-2-carbaldehyde one 7.46 450.9 452.9

174

4,6-Bis (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) 1H-pyrazolo [3,4-b] pyridine Reference example 19, 3-amino-2H-pyrazole and 4-fluorobenzaldehyde one 9.11 432.2

175

5- (2-Chloropyridin-4-yl) -4,6bis (4-fluorophenyl) -1 Hpirazolo [3,4-b] pyridine Reference example 23, 3-amino-2H-pyrazole and 4-fluorobenzaldehyde one 8.99 419.0 421.0

176

4- (2-Phenylethyl) -6- (4fluorophenyl) -5- (4-pyridyl) -1Hpyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 3-phenylpropionaldehyde one 6.52 395.0

177

4- (6-Chloropyridin-3-yl) -6- (4fluorophenyl) -5- (4-pyridyl) -1 Hpyrazolo [3,4-b] pyridine Reference example 1, 6-chloropyridin-3carbaldehyde and amino2H-pyrazole one 5.50 402.0 404.0

178

4- (3,4-Dichlorophenyl) -1-ethyl-6 (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine Reference example 1, 3,4-dichlorobenzaldehyde and 3-amino-2-ethylpyrazole one 10.56 462.9 464.9

EXAMPLE 179

6- (4-Fluorophenyl) -4- (1-methylpiperidin-4-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridine

To a suspension of 6- (4-fluorophenyl) -4- (4-piperidyl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridine (0.24 g, 0.6 mmol, obtained in example 170) in formic acid (0.64 mL) 35-40% aqueous formaldehyde (0.96 mL) is added. It is heated at 70-80 ° C for 24 h. It is allowed to cool and 1N NaOH is added. It is extracted with CHCl3 and the combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures of CHCl3-MeOH-NH3 of increasing polarity, obtaining 47 mg of the desired compound (rto: 19%). LC-MS (method 1): t R = 3.28 min; m / z = 388.1 [M + H] +.

EXAMPLE 180 3-Amino-6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4b] pyridine

Following a procedure analogous to that described in reference example 15 section c, but using 2-chloro-6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4yl) pyridine-3-carbonitrile (obtained in the reference example 22) instead of 3- (1-benzylpiperidin-4-yl) -3-oxopropanonitrile, the title compound is obtained. LC-MS (method 1): t R = 6.70 min; m / z = 353.0 [M + H] +.

EXAMPLE 181 6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1H-pyrazolo [3,4-b] pyridine

To a solution of 3-amino-6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 Hpyrazolo [3,4-b] pyridine (10.00 g, 28.4 mmol, obtained in example 180) in AcOH (52 mL), water (22 mL) and conc. HCl. (5.7 mL), cooled to 0 ° C, a solution of NaNO2 (2.30 g, 33.4 mmol) in water (7.5 mL) is added dropwise. Stir for 30 min at 0 ° C and slowly add H3PO2 (50% aqueous solution, 56.8 mL). Stir at 0 ° C for 6 h. Allow to reach room temperature, basify at 0 ° C by slow addition of 6N NaOH until pH = 8 and extract with AcOEt. The combined organic phases are dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 4.00 g of the title compound (rto: 42%) LC-MS (method 1): t R = 7.80 min; m / z = 338.0 [M + H] +.

EXAMPLES 182-193

Following a procedure analogous to that described in Examples 6 and 7, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compounds LC-MS

Method

tR (min) m / z [M + H] +

182

4,6-Diphenyl-5- (4-pyridyl) -2- [2 (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4-b] pyridine Example 2 and 2- (2-Bromoethoxy) tetrahydropyran one 6.70 477.1

183

6- (4-Fluorophenyl) -4- (2-furyl) -2methyl-5- (4-pyridyl) pyrazolo [3,4b] pyridine Example 171 and iodomethane one 5.32 371.1

184

6- (4-Fluorophenyl) -2-methyl-4- (1methyl-1H-imidazol-4-yl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 172 and iodomethane (2 equivalents) one 3.66 385.2

185

6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2- [2 (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4-b] pyridine Example 181 and 2 (2-bromoethoxy) tetrahydropyran one 8.79 466.1

186

6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2- [3 (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine Example 181 and 2 (3-bromopropoxy) tetrahydropyran one 9.11 480.2

187

4,6-Bis (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2- [3 (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine Example 174 and 2 (3-bromopropoxy) tetrahydropyran one 10.26 574.2

188

4- (5-Bromothien-2-yl) -6- (4fluorophenyl) -2-methyl-5- (4-pyridyl) 1H-pyrazolo [3,4-b] pyridine Example 173 and iodomethane one 6.94 464.9 466.9

189

6- (4-Fluorophenyl) -2-methyl-5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridine Example 181 and iodomethane one 7.29 352.0

190

5- (2-Chloropyridin-4-yl) -4,6-bis (4fluorophenyl) -2-methylpyrazolo [3,4b] pyridine Example 175 and Iodomethane one 8.55 433.0 435.0

191

4- (2-Phenylethyl) -6- (4-fluorophenyl) - 5 (4-pyridyl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine Example 176 and 2 (3-bromopropoxy) tetrahydropyran one 7.74 537.0

192

4- (6-Chloropyridin-3-yl) -6- (4fluorophenyl) -5- (4-pyridyl) -2- [3 (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine Example 177 and 2 (3-bromopropoxy) tetrahydropyran one 9.05 544.2 546.2

193

4- (6-Chloropyridin-3-yl) -6- (4fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 177 and iodomethane one 5.34 416.1 418.1

EXAMPLE 194 5- (2-Methylsulfanylpyrimidin-4-yl) -2- [3- (tetrahydropyran-2-yloxy) propyl] -6- (3

5 trifluoromethylphenyl) pyrazolo [3,4-b] pyridine Following a procedure analogous to that described in examples 6 and 7, but using as starting compounds 5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3 (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4-b] pyridine (obtained in example 126) and 2- (3-bromopropoxy) tetrahydropyran, the title compound is obtained.

10 1 H NMR (300 MHz, CDCl 3)  (TMS): 1.50 - 1.90 (m, 4 H), 2.40 (complex signal, 5 H), 3.37 -3.50 (m, 4 H), 3.85 (m, 2 H) , 4.53 (m, 1 H), 4.65 (m, 2 H), 6.68 (d, J =

5.1 Hz, 1 H), 7.40 (t, J = 7.8 Hz, 1 H), 7.52 (d, J = 7.6 Hz, 1 H), 7.61 (d, J = 7.5 Hz, 1 H), 7.93 (s, 1 H), 8.13 (s, 1 H), 8.32 (d, J = 5.1 Hz, 1 H), 8.49 (s, 1 H).

EXAMPLE 195 15 6- (4-Fluorophenyl) -2-methyl-5- (4-pyridyl) -4- [5- (3-pyridyl) thien-2-yl] pyrazolo [3,4b] pyridine

A suspension of 4- (5-bromothien-2-yl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) -1 Hpyrazolo [3,4-b] pyridine (0.10 g, 0.2 mmol , obtained in example 188), 3-pyridylboronic acid (0.04 g, 0.3 mmol), K2CO3 (0.06 g, 0.4 mmol), Pd (PPh3) 4 (0.017 g,

20 0.01 mmol), 1,2-dimethoxyethane (1.31 mL) and water (0.04 mL) is heated at 80 ° C under argon overnight. Allow to cool and dilute with CHCl3 and water. The combined organic phases are dried over Na2SO4 and concentrated to

dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 35 mg of the desired compound (rto: 50%). LC-MS (method 1): t R = 5.42 min; m / z = 464.0 [M + H] +.

EXAMPLES 196-202

Following a procedure analogous to that described in example 91 but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

196

2- [4,6-Diphenyl-5- (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] ethanol Example 182 one 4.67 393.0

197

3- [5- (2-Methylsulfanylpyrimidin-4-yl) -6- (3trifluoromethylphenyl) pyrazolo [3,4-b] pyridin2-yl] propan-1-ol Example 194 one 7.67 446.0

198

2- [6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2yl] ethanol Example 185 one 6.58 382.0

199

3- [6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2il] propan-1-ol Example 186 one 6.79 396.1

200

3- [4,6-Bis (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 187 one 8.10 490.2

201

3- [4- (2-Phenylethyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol Example 191 one 5.80 453.2

202

3- [4- (6-Chloropyridin-3-yl) -6- (4fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 192 one 5.88 460.2 462.2

EXAMPLES 203-207

Following a procedure analogous to that described in example 56 but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compounds LC-MS

Method

tR (min) m / z [M + H] +

203

6- (4-Fluorophenyl) -2-methyl-5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4b] pyridine Example 189 one 5.76 384.0

204

3- [5- (2-Methylsulfonylpyrimidin-4-yl) -6- (3trifluoromethylphenyl) pyrazolo [3,4-b] pyridin2-yl] propan-1-ol Example 197 one 6.39 478.0

205

2- [6- (4-Fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4b] pyridin-2-yl] ethanol Example 198 one 5.28 414.0

206

3- [6- (4-Fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 199 one 5.46 428.0

207

3- [4,6-Bis (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 200 one 6.76 522.2

EXAMPLE 208 N-Cyclopropylmethyl- [4- [6- [3- (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4-b] pyridin-510 yl] pyrimidin-2-yl] amine A solution of 5- [2 - (methylsulfonyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1 Hpyrazolo [3,4-b] pyridine (90 mg, 0.2 mmol, obtained in example 127) and (cyclopropylmethyl) amine (75 mg, 1.0 mmol) in THF (2 mL) is heated in a closed tube at 60 ° C overnight. It is allowed to cool and concentrated. The crude obtained is purified by chromatography on silica gel using as eluent

hexane-AcOEt mixtures of increasing polarity, obtaining 57 mg of desired compound (rto: 67%). LC-MS (method 1): t R = 8.12 min; m / z = 411.0 [M + H] +.

Following a procedure analogous to that described in Example 208 but using in each case the suitable starting compounds, the products are obtained indicated in the following table:

Example

Example Name Starting compounds LC-MS

Method

tR (min) m / z [M + H] +

209

(1S) -3- [5- [2- (1-Phenylethylamino) pyrimidin-4-yl] -6- (3-trifluoromethylphenyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol Example 204 and (1S) -1phenylethylamine one 9.11 519.1

210

N-Cyclopropylmethyl- [4- [6- (4fluorophenyl) -2-methylpyrazolo [3,4b] pyridin-5-yl] pyrimidin-2-yl] amine Example 203 and (cyclopropylmethyl) amine one 6.43 375.1

211

2- [5- [2 - [(Cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol Example 205 and (cyclopropylmethyl) amine one 5.85 405.1

212

3- [5- [2 - [(Cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol Example 206 and (cyclopropylmethyl) amine one 6.06 419.1

213

3- [5- [2 - [(Cyclopropylmethyl) amino] pyrimidin-4-yl] -4,6-bis (4-fluorophenyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol Example 207 and (cyclopropylmethyl) amine one 7.63 513.3

EXAMPLE 214 10 4- [4- [4,6-Bis (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyridin-2 -lamino] benzenesulfonamide

A mixture of 5- (2-chloropyridin-4-yl) -4,6-bis (4-fluorophenyl) -2-methylpyrazolo [3,4b] pyridine (100 mg, 0.23 mmol, obtained in example 190) and 4-aminobenzenesulfonamide (46 mg, 0.27 mmol) is heated at 190 ° C overnight. It is allowed to cool and the crude obtained is purified by chromatography on

silica gel using as eluent AcOEt, obtaining 23 mg of the compound desired (rto: 17%). LC-MS (method 1): t R = 6.91 min; m / z = 569.0 [M + H] +.

EXAMPLES 215-230

Following a procedure analogous to that described in example 72, but using the appropriate starting compounds in each case, the products indicated in the following tables are obtained:

Example

Example Name Starting compounds LC-MS

Method

tR (min) m / z [M + H] +

215

4,6-Bis (4-fluorophenyl) -5 (4-pyridyl) pyrazolo- [3,4b] pyridin-3-ol Reference example 1, 5-amino-1H-pyrazol-3-ol and 4-fluorobenzaldehyde one 5.02 401.1

216

6- (4-Fluorophenyl) -4- (3Himidazol-4-yl) -5- (4-pyridyl) 1H-pyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 3Himidazol-4-carbaldehyde one 3.23 357.1

217

6- (4-Fluorophenyl) -4- (1Hpirazol-3-yl) -5- (4-pyridyl) 1H-pyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 2-pyrazol-3-carbaldehyde one 4.24 357.1

218

3- [6- (4-Fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridin-4-yl] phenol Reference example 1, 3-amino-2H-pyrazole and 3-hydroxybenzaldehyde one 4.99 383.1

219

4-Cyclopropyl-6- (4fluorophenyl) -5- (4-pyridyl) 1H-pyrazolo [3,4-b] pyridine Reference Example 1,3-amino-2H-pyrazole and cyclopropancarbaldehyde one 4.99 331.1

220

6- (4-Fluorophenyl) -4- (5methylfuran-2-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridine Reference example 1, 3-amino-2H-pyrazole and 5-methylfuran-2-carbaldehyde one 8.45 445

221

4- (5-Bromofuran-2-yl) -6 (4-fluorophenyl) -5- (4-pyridyl) 1H-pyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 5-methylfuran-2-carbaldehyde one 7.02 435.0 437.0

222

4- (4-Benzyloxyphenyl) -6- (4fluorophenyl) -2-methyl-5pyrimidin-4-yl-1H Reference example 30, 3-amino-2H-pyrazole and 4-benzyloxybenzaldehyde one 9.05 474.1

pyrazolo [3,4-b] pyridine

223

4- (4-Benzyloxyphenyl) -6- (4fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) 1H-pyrazolo [3,4-b] pyridine Reference example 19, 3-amino-2H-pyrazole and 4-benzyloxybenzaldehyde one 10.52 520.1

224

6- (4-Fluorophenyl) -4-propyl-5- (4-pyridyl) -1 Hpirazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and butyraldehyde one 5.42 333.0

225

4- (3-Benzyloxyphenyl) -6- (4fluorophenyl) -5- (4-pyridyl) 1H-pyrazolo [3,4-b] pyridine Reference example 1, 3-amino-2H-pyrazole and 3-benzyloxybenzaldehyde one 8.00 473.2

226

5- (2-Chloropyridin-4-yl) -6 (4-fluorophenyl) -1 Hpirazolo [3,4-b] pyridine Reference example 23, 3-amino-2H-pyrazole and paraformaldehyde one 7.73 325.2 327.2

227

4- [6- (4-Fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4b] pyridin-4-yl] butan-1-ol Reference example 1, 3-amino-2H-pyrazole and 5-hydroxypentanal one 4.23 363.2

228

4-Benzyl-6- (4-fluorophenyl) 5- (4-pyridyl) -1 Hpirazolo [3,4-b] pyridine Reference example 1,3-amino-2H-pyrazole and phenylacetaldehyde one 6.37 381.2

Example

Example Name Starting compounds 1H NMR (300 MHz, CDCl3)  (TMS)

5.06 (s, 2 H), 6.85 (dd, Jo = 1.5 Hz,

4- (4-Benzyloxyphenyl) -6

Reference Example Jm = 4.5 Hz, 2 H), 6.91 (m, 4 H),

(4-fluorophenyl) -2-methyl

1,3-amino-2H-pyrazole 6.95 (m, 2 H), 7.23 - 7.40 (m, 7 H),

229

5- (4-pyridyl) -1H

and 4-benzyloxy 8.01 (s, 1 H), 8.35 (dd, Jo = 1.5 Hz,

pyrazolo [3,4-b] pyridine

benzaldehyde Jm = 4.5 Hz, 2 H), 10.62 (wide s, 1 H, NH).

Reference Example

6.92 -7.08 (complex signal, 5 H),

4,6-Bis (4-fluorophenyl)

30, 3-amino-2H 7.23 (m, 2 H), 7.32 (m, 2 H), 7.99

230

5-pyrimidin-4-yl-1H pyrazole and 4 (s, 1 H), 8.45 (d, J = 5.1 Hz, 1 H),

pyrazolo [3,4-b] pyridine

fluorobenzaldehyde 9.03 (s, 1 H), 11.40 (wide s, 1 H, NH).

EXAMPLE 231

[(2S) -2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2

il] ethyl] pyrrolidin-2-carboxamide a) [(2S) -2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl ] ethyl] -1 (benzyloxycarbonyl) pyrrolidin-2-carboxamide

Following a procedure analogous to that described in example 48, but using as starting compounds 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 90) and (2S) -1 (benzyloxycarbonyl) pyrrolidin-2-carboxylic acid, the desired compound is obtained. LC-MS (method 1): t R = 7.13 min; m / z = 659.3 [M + H] +.

b) Title compound

Following a procedure analogous to that described in example 269, but using as a starting compound [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl ] ethyl] -1- (benzyloxycarbonyl) pyrrolidin-2-carboxamide (obtained in section a), the title compound is obtained. LC-MS (method 1): t R = 4.35 min; m / z = 525.2 [M + H] +.

EXAMPLE 232 2- [2- (4,6-Diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl) ethylamino] ethanol a) 2- [4,6-Diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate

Following a procedure analogous to that described in example 12 section b, but using as starting compound 2- [4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] ethanol (obtained in example 196), the desired compound is obtained. 1 H NMR (300 MHz, CDCl 3)  (TMS): 2.94 (s, 3 H), 4.76 (m, 2 H), 4.85 (m, 2 H),

6.88 (d, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H), 7.15 -7.90 (complex signal, 10 H), 8.27 (s, 1H), 8.28 (dd, Jo = 1.5 Hz, Jm = 4.5 Hz, 2 H).

b) Title compound

Following a procedure analogous to that described in example 111, but using 2- [4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl methanesulfonate as starting compounds (obtained in section a) and 2-amino-1ethanol, the desired compound is obtained. LC-MS (method 1): t R = 3.89 min; m / z = 436.1 [M + H] +.

EXAMPLE 233 6- (4-Fluorophenyl) -2-methyl-4- (3-pyridyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

To a solution of 4- (6-chloropyridin-3-yl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (74 mg, 0.2 mmol, obtained in Example 193) in AcOH (1 mL) Zn (72 mg, 1.1 mmol) is added under argon and the mixture is heated at reflux overnight. It is allowed to cool and concentrated.

5 The residue is treated with a saturated NaHCO3 solution and extracted with CHCl3. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt-MeOH of increasing polarity, obtaining 2.4 mg of the title compound (rto: 4%)

10 LC-MS (method 1): t R = 4.02 min; m / z = 382.2 [M + H] +.

EXAMPLES 234-235

Following a procedure analogous to that described in reference example 15 section c, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compounds LC-MS

Method

tR (min) m / z [M + H] +

2. 3. 4

6- (4-Fluorophenyl) -3-methyl-5- (2-methylsulfanylpyrimidin-4-yl) -1 Hpyrazolo [3,4-b] pyridine Reference Example 29 and Hydrazine Monohydrate one 8.57 352.0

235

3-Amino-6-phenyl-5- (2-methylsulfanylpyrimidin-4-yl) -1 Hpyrazolo [3,4-b] pyridine Reference Example 28 and Hydrazine Monohydrate one 6.55 335.0

EXAMPLES 236-237

Following a procedure analogous to that described in example 77, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

236

6-Phenyl-5- (2-methylsulfanylpyrimidin-4il) -1H-pyrazolo [3,4-b] pyridine Example 235 one 7.54 320.0

237

6- (4-Fluorophenyl) -4-methyl-5- (2 Example 147 one 4.42 305.0

Methylsulfanylpyrimidin-4-yl) -1 Hpirazolo [3,4-b] pyridine

EXAMPLE 238 5- (2-Methoxypyrimidin-4-yl) -6- (3-trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridine

To a solution of 5- [2- (methylsulfonyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1H

5 pyrazolo [3,4-b] pyridine (90 mg, 0.2 mmol, obtained in example 127) in MeOH (5 mL) in a closed tube is added sodium methoxide (11 mg, 0.2 mmol) and heated to 60 ºC for 24 h. Sodium methoxide (11 mg, 0.2 mmol) is added and stirred at 60 ° C for a further 2 h. It is allowed to cool and concentrated. AcOEt and buffer solution of pH = 5.3 are added. The phases are separated and the organic phase is washed

10 with water, dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using 50% hexane-AcOEt mixtures as eluent, obtaining 38 mg of the title compound (rto: 47%) LC-MS (method 1): t R = 7.71 min; m / z = 372.0 [M + H] +. EXAMPLES 239-242

15 Following a procedure analogous to that described in reference example 1 section a, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

239

N- [2- [4,6- (Diphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] acetamide Example 142 and acetyl chloride one 5.34 434.1

240

N- [3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propyl] acetamide Example 95 and acetyl chloride one 5.31 484.1

241

N- [2- (4,6-Diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl) ethyl] -N- (2-hydroxyethyl) acetamide Example 232 and acetyl chloride one 5.27 478.1

242

N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] propionamide Example 90 and propionyl chloride one 5.39 484.1

EXAMPLE 243 N- [3- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propyl] methanesulfonamide

Following a procedure analogous to that described in example 169, but using as starting compound 2- (3-aminopropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 95), the desired compound is obtained. LC-MS (method 1): t R = 5.79 min; m / z = 520.1 [M + H] +.

EXAMPLE 244 5- (2-Aminopyrimidin-4-yl) -6- (3-trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridine

A solution of THF (20 mL) saturated with NH3 (g) at -20 ° C is added over 5- [2 (methylsulfonyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1H-pyrazolo [ 3,4-b] pyridine (90 mg, 0.2 mmol, obtained in example 127) in a closed tube. It is stirred at room temperature for 2 days and concentrated. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt of increasing polarity, obtaining 7 mg of the title compound (rto: 9%) LC-MS (method 1): t R = 6.01 min; m / z = 357.0 [M + H] +.

EXAMPLE 245 N- [5- (2-Methylsulfanylpyrimidin-4-yl) -6- (3-trifluoromethylphenyl) -1 H -pyrazolo [3,4b] pyridin-3-yl] acetamide

A solution of 3-amino-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] 1 H -pyrazolo [3,4-b] pyridine (200 mg, 0.5 mmol, obtained in example 123) and acetyl chloride (39 mg, 0.5 mmol) in pyridine (10 mL) is stirred at room temperature for 3 h. It is concentrated and a mixture of AcOEt and 1N NaOH is added to the residue. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt mixtures of increasing polarity as eluent, obtaining 78 mg of the title compound (rto: 37%) LC-MS (method 1): t R = 8.55 min; m / z = 445.0 [M + H] +.

EXAMPLE 246 N-Cyclopropylmethyl- [4- [3-benzyloxycarbonylamino-6- (3-trifluoromethylphenyl) -1 Hpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine

a) N-Benzyloxycarbonyl- [5- (2-methylsulfanylpyrimidin-4-yl) -6- (3trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridin-3-yl] amine

Following a procedure analogous to that described in example 245, but using as starting compounds 3-amino-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3 (trifluoromethyl) phenyl] -1H-pyrazolo [ 3,4-b] pyridine (obtained in example 123) and benzyl chloroformate, the desired compound is obtained. LC-MS (method 1): t R = 10.00 min; m / z = 537.1 [M + H] +.

b) N-Benzyloxycarbonyl- [5- (2-methylsulfonylpyrimidin-4-yl) -6- (3trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridin-3-yl] amine

Following a procedure analogous to that described in Example 56, but using as starting compound N-benzyloxycarbonyl- [5- (2-methylsulfanylpyrimidin-4-yl) -6 (3-trifluoromethylphenyl) -1H-pyrazolo [3,4-b ] pyridin-3-yl] amine (obtained in section a), the desired compound is obtained. LC-MS (method 1): t R = 8.47 min; m / z = 567.1 [M + H] +.

c) Title compound

Following a procedure analogous to that described in Example 208, but using as starting compounds N-benzyloxycarbonyl- [5- (2-methylsulfonylpyrimidin-4-yl) -6 (3-trifluoromethylphenyl) -1H-pyrazolo [3,4-b ] pyridin-3-yl] amine (obtained in section b) and (cyclopropylmethyl) amine, the desired compound is obtained. LC-MS (method 1): t R = 9.44 min; m / z = 560.3 [M + H] +.

EXAMPLE 247 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2-hydroxyacetamide

Following a procedure analogous to that described in example 48, but using as starting compounds 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 90) and hydroxyacetic acid, the title compound is obtained. LC-MS (method 1): t R = 4.84 min; m / z = 486.1 [M + H] +.

EXAMPLE 248 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin

4-carboxamide a) N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -1- (tertbutoxycarbonyl) ) piperidin-4-carboxamide

Following a procedure analogous to that described in example 48, but using as starting compounds 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (obtained in example 90) and 1- (tertbutoxycarbonyl) -piperidin-4-carboxylic acid, the desired compound is obtained.

b) Title compound

Following a procedure analogous to that described in example 36, but using as the starting compound N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2 -il] ethyl] -1- (tert-butoxycarbonyl) piperidin-4-carboxamide (obtained in section a), the title compound is obtained. LC-MS (method 1): t R = 4.29 min; m / z = 539.2 [M + H] +.

EXAMPLE 249 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2

(methylamino) acetamide a) N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2chloroacetamide

Following a procedure analogous to that described in reference example 1 section a, but using as starting compounds 2- (2-aminoethyl) -4,6-bis (4fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4 -b] pyridine (obtained in example 90) and chloroacetyl chloride, the title compound is obtained. LC-MS (method 1): t R = 5.72 min; m / z = 504.1, 506.1 [M + H] +.

b) Title compound

Following a procedure analogous to that described in example 78, but using as starting compounds N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2 -il] ethyl] -2-chloroacetamide (obtained in section a) and methylamine, the title compound is obtained. LC-MS (method 1): t R = 4.28 min; m / z = 499.2 [M + H] +.

EXAMPLE 250 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2- (2-hydroxyethylamino) acetamide

Following a procedure analogous to that described in example 78, but using as starting compounds N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridin-2 -il] ethyl] -2-chloroacetamide (obtained in example 249 section a) and 2-amino ethanol, the title compound is obtained.

LC-MS (method 1): t R = 4.29 min; m / z = 529.2 [M + H] +.

EXAMPLE 251 N- [2- [4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] nicotinamide

5 a) Nicotinoyl chloride hydrochloride A solution of nicotinic acid (0.50 g, 4.0 mmol) and POCl3 (5 mL) is heated at reflux for 1.5 h and concentrated. The product obtained is used directly in the next stage.

b) Title compound

10 Following a procedure analogous to that described in example 245, but using 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] as starting compounds pyridine (obtained in example 90) and nicotinoyl chloride hydrochloride (obtained in section a), the title compound is obtained. LC-MS (method 1): t R = 5.25 min; m / z = 533.1 [M + H] +.

EXAMPLES 252-265 Following a procedure analogous to that described in Examples 6 and 7, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

252

4- (4-Benzyloxyphenyl) -6- (4fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 229 and iodomethane one 7.53 487.1

253

6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2-methylpyrazolo [3,4-b] pyridine Example 181 and iodomethane one 7.13 352.1

254

6- (4-Fluorophenyl) -2,4-dimethyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 237 and iodomethane one 4.11 319.00

255

4- (4-Benzyloxyphenyl) -6- (4fluorophenyl) -2-methyl-5- (2-methylsulfanylpyrimidin-4yl) pyrazolo [3,4-b] pyridine Example 223 and iodomethane one 10.16 534.2

256

2- (1-Benzylpyrrolidin-2-ylmethyl) -4.6 Example 1 and 1 one 6.10 558.2

bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine

benzyl-2-chloromethylpyrrolidine

257

4- (4-Benzyloxyphenyl) -6- (4fluorophenyl) -2-methyl-5-pyrimidin-4-pyrazolo [3,4-b] pyridine Example 222 and iodomethane one 8.72 488.2

258

6- (4-Fluorophenyl) -2-methyl-4- (5methylfuran-2-yl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 220 and iodomethane one 5.85 385.0

259

4- (5-Bromofuran-2-yl) -6- (4fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 221 and iodomethane one 6.48 449.1 451.1

260

6- (4-Fluorophenyl) -2-methyl-4-propyl5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 224 and iodomethane one 4.88 347.0

261

4- (3-Benzyloxyphenyl) -6- (4fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 225 and iodomethane one 7.79 487.0

262

4- (2-Phenylethyl) -6- (4-fluorophenyl) -2methyl-5- (4-pyridyl) pyrazolo [3,4b] pyridine Example 176 and iodomethane one 5.94 409.0

263

5- (2-Chloropyridin-4-yl) -6- (4fluorophenyl) -2-methylpyrazolo [3,4b] pyridine Example 226 and iodomethane one 7.30 339.2 341.2

264

4-Benzyl-6- (4-fluorophenyl) -2-methyl5- (4-pyridyl) pyrazolo [3,4-b] pyridine Example 228 and iodomethane one 5.95 395.2

265

4- [6- (4-Fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4il] butan-1-ol Example 227 and iodomethane one 3.69 377.2

EXAMPLE 266 4- [6- (4-Fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol

To a solution of 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine (112 mg, 0.2 mmol, obtained in example 252 ) in EtOH (13 mL), 10% Pd / C (20 mg) is added and hydrogenated at atmospheric pressure and at room temperature for 2 days. Filter on celite, wash with EtOH and concentrate. The crude obtained is purified by chromatography on silica gel using hexane-AcOEt-MeOH mixtures of increasing polarity as eluent, obtaining 61 mg of the title compound (rto: 67%) LC-MS (method 1): t R = 4.65 min; m / z = 397.1 [M + H] +.

EXAMPLE 267 N- [6- (4-Fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridin-3-yl] acetamide

Following a procedure analogous to that described in Example 245, but using as starting compounds 3-amino-6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridine (obtained in example 180) and acetyl chloride, the title compound is obtained. LC-MS (method 1): t R = 7.01 min; m / z = 395.1 [M + H] +.

EXAMPLE 268 N- [5- [2 - [(Cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) -1H

pyrazolo [3,4-b] pyridin-3-yl] acetamide a) N- [6- (4-Fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -1H-pyrazolo [3,4b] pyridin- 3-yl] acetamide and N- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridin-3-yl] acetamide oxide

Following a procedure analogous to that described in Example 56, but using as the starting compound N- [6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 Hpirazolo [3,4-b] pyridin- 3-yl] acetamide (obtained in example 267) and using 2 equivalents of m-chloroperbenzoic acid, the title compounds are obtained. N- [6- (4-Fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridin-3yl] acetamide: LC-MS (method 1): tR = 5.64 min; m / z = 427.1 [M + H] +. N- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -1 H -pyrazolo [3,4b] pyridin-3-yl] acetamide oxide: LC-MS (method 1) : t R = 4.44 min; m / z = 443.0 [M + H] +.

b) Title compound

Following a procedure analogous to that described in Example 208, but using as starting compounds N- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) 1H-pyrazolo [3,4-b] pyridin -3-yl] acetamide (obtained in section a) and (cyclopropylmethyl) amine, the title compound is obtained. LC-MS (method 1): t R = 6.19 min; m / z = 418.1 [M + H] +.

EXAMPLE 269 3- [6- (4-Fluorophenyl) -4- (2-furyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol a) 6 - (4-Fluorophenyl) -4- (2-furyl) -5- (4-pyridyl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in Examples 6 and 7, but using as starting compounds 6- (4-fluorophenyl) -4- (2-furyl) -5- (4-pyridyl) -1H

5 pyrazolo [3,4-b] pyridine (obtained in example 171) and 2- (3-bromopropoxy) tetrahydropyran, the desired compound is obtained. LC-MS (method 1): t R = 7.19 min; m / z = 499.2 [M + H] +.

b) Title compound

Following a procedure analogous to that described in example 91, but using

10 as the starting compound 6- (4-fluorophenyl) -4- (2-furyl) -5- (4-pyridyl) -2- [3 (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine (obtained in section a), the title compound is obtained. LC-MS (method 1): t R = 5.05 min; m / z = 415.1 [M + H] +.

15 Following a procedure analogous to that described in example 269, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

270

2- [4- (4-Benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol Example 229 and 2- (2-Bromoethoxy) tetrahydropyran one 6.76 517.2

271

3- [4- (4-Benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol Example 229 and 2- (3-bromopropoxy) tetrahydropyran one 6.91 531.2

272

3- [6- (4-Fluorophenyl) -4- (5methylfuran-2-yl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2il] propan-1-ol Example 220 and 2- (3-bromopropoxy) tetrahydropyran one 5.42 429.1

273

3- [4-Cyclopropyl-6- (4fluorophenyl) -5- (4-pyridyl) Example 219 and 2- (3-bromopropoxy) tetra one 4.40 389.1

pyrazolo [3,4-b] pyridin-2il] propan-1-ol

hydropyrene

274

3- [4- (5-Bromotien-2-yl) -6- (4fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2il] propan-1-ol Example 173 and 2- (3-bromopropoxy) tetrahydropyran one 6.25 508.9 510.9

275

3- [6- (4-Fluorophenyl) -4-propyl-5 (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 224 and 2- (3-bromopropoxy) tetrahydropyran one 4.90 391.2

276

3- [4,6-Bis (4-fluorophenyl) -5-pyrimidin-4-ylpyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 230 and 2- (3-bromopropoxy) tetrahydropyran one 6.56 444.2

277

3- [4- (3-Benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol Example 225 and 2- (3-bromopropoxy) tetrahydropyran one 7.03 531.3

278

3- [4-Benzyl-6- (4-fluorophenyl) -5 (4-pyridyl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol Example 228 and 2- (3-bromopropoxy) tetrahydropyran one 5.27 439.2

EXAMPLES 279-285

Following a procedure analogous to that described in example 268, but using the appropriate starting compound and amine in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound Amine LC-MS

Method

tR (min) m / z [M + H] +

279

(1S) -N- (1-Phenylethyl) - [4- [6- (4fluorophenyl) -3-methyl-1 Hpyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-yl] amine Example 234 (1S) -1Phenylethylamine one 9.32 425.1

N-Cyclopropylmethyl-4- [6- (4

(Cycle

280

fluorophenyl) -3-methyl-1 Hpyrazolo [3,4-b] pyridin-5 Example 234 propylmethyl) 2 5.54 373.2

il] pyrimidin-2-yl] amine

amine

281

1- [4- [6- (4-Fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-ylamino] propan2-ol Example 253 1-Aminopropan2-ol one 4.73 379.2

282

N-Cyclopropylmethyl-4- [6- [phenyl1H-pyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-yl] amine Example 236 (Cyclopropylmethyl) amine one 7.53 343.1

283

2- [4- [6- (4-Fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-ylamino] propan1-ol Example 253 2-Aminopropan1-ol one 4.74 379.1

284

4- [4- [6- (4-Fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-ylamino] butan1-ol Example 253 4-Aminobutan-1ol one 4.61 393.2

285

(1S) -N- (1-Phenylethyl) - [4- [6-phenyl-1 H -pyrazolo [3,4b] pyridin-5-yl] pyrimidin-2-yl] amine Example 236 (1S) -1Phenylethylamine one 8.10 393.1

EXAMPLES 286-290

Following a procedure analogous to that described in Example 208, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

286

N- (3-Methoxypropyl) - [4- [6- (3-trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridin5-yl] pyrimidin-2-yl] amine Example 127 and 3-methoxypropylamine one 7.14 429.1

287

3- [4- [6- (3-Trifluoromethylphenyl) -1 Hpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-lamino] propan-1-ol Example 127 and 3-aminopropan-1-ol one 5.91 415.1

288

3- [4- [6- (4-Fluorophenyl) -2- (3-hydroxypropyl) pyrazolo [3,4-b] pyridin-5 Example 206 and 3-amino one 4.55 423.1

il] pyrimidin-2-ylamino] propan-1-ol

propan-1-ol

289

N-Ethyl- [4- [6- (3-trifluoromethylphenyl) -1 Hpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine Example 127 and ethylamine one 7.21 385.0

290

N-Benzyl- [4- [6- (3-trifluoromethylphenyl) 1H-pyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-yl] amine Example 127 and benzylamine one 8.86 447.1

EXAMPLE 291 4- [5- [2 - [(Cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-4-yl] phenol

5 a) 4- (4-Benzyloxyphenyl) -6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -2-methylpyrazolo [3,4-b] pyridine

Following a procedure analogous to that described in example 56, but using as starting compound 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3, 4-b] pyridine (obtained in example 255), is

10 obtains the desired compound. LC-MS (method 1): t R = 8.77 min; m / z = 566.2 [M + H] +.

b) 4- [6- (4-Fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -2-methylpyrazolo [3,4b] pyridin-4-yl] phenol

Following a procedure analogous to that described in example 266, but using

15 as starting compound 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4-b] pyridine (obtained in part a) , the desired compound is obtained. LC-MS (method 1): t R = 6.17 min; m / z = 476.1 [M + H] +.

c) Title compound

20 Following a procedure analogous to that described in Example 128, but using as starting compounds 4- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -2-methylpyrazolo [3,4-b] pyridine -4-yl] phenol (obtained in section b) and (cyclopropylmethyl) amine, the title compound is obtained. LC-MS (method 1): t R = 6.62 min; m / z = 467.2 [M + H] +.

25 EXAMPLES 292-295

Following a procedure analogous to that described in example 266, but using the appropriate starting compounds in each case, the products indicated in the following table are obtained:

Example

Example Name Starting compound LC-MS

Method

tR (min) m / z [M + H] +

292

4- [6- (4-Fluorophenyl) -2- (3-hydroxypropyl) -5 (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol Example 271 one 4.41 441.1

293

4- [6- (4-Fluorophenyl) -2-methyl-5-pyrimidin4-yl) pyrazolo [3,4-b] pyridin-4-yl] phenol Example 257 one 5.71 398.1

294

3- [6- (4-Fluorophenyl) -2- (3-hydroxypropyl) -5 (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol Example 277 one 4.54 441.2

295

3- [6- (4-Fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol Example 261 one 4.74 397.0

5

EXAMPLE 296 4,6-Bis (4-fluorophenyl) -5- (4-pyridyl) -2- (pyrrolidin-2-ylmethyl) pyrazolo [3,4-b] pyridine

To a solution of 2- (1-benzylpyrrolidin-2-ylmethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine (83 mg, 0.1 mmol, obtained in example 259) in

10 EtOH (6.9 mL) is added 10% Pd / C (8 mg) and formic acid (0.34 mL) and heated at reflux for 2 h. Allow to cool and filter on celite, wash with EtOH and concentrate. The crude obtained is purified by chromatography on silica gel using as eluent mixtures hexane-AcOEt-MeOH-NH3 of increasing polarity, obtaining 40 mg of the title compound (rto: 57%)

LC-MS (method 1): t R = 4.98 min; m / z = 468.1 [M + H] +. EXAMPLE 297 4- [4- [6- (4-Fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyridin-2 -lamino] benzenesulfonamide Following a procedure analogous to that described in example 214, but using

As starting compounds 5- (2-chloropyridin-4-yl) -6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridine (obtained in example 263) and 4-aminobenzenesulfonamide, the title compound is obtained.

LC-MS (method 1): t R = 5.36 min; m / z = 475.3 [M + H] +.

EXAMPLE 298 7- N- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) 1 H -pyrazolo [3,4-b] pyridin-3-yl] acetamide

Following a procedure analogous to that described in Example 208, but using as starting compounds 7-N- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) -1H-pyrazolo [3,4- b] pyridin-3-yl] acetamide (obtained in example 268 section a) and (cyclopropylmethyl) amine, the title compound is obtained. LC-MS (method 1): t R = 5.45 min; m / z = 434.2 [M + H] +.

EXAMPLE 299 N- [6- (4-Fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridin-3-yl] isonicotinamide a) Isonicotinoyl chloride hydrochloride

A solution of isonicotinic acid (0.10 g, 0.8 mmol) and thionyl chloride (1 mL) is heated at reflux for 2 h and concentrated. The product obtained is used directly in the next stage.

b) Title compound

In a flask, 3-amino-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine (0.20 g, 0.7 mmol, obtained in Example 70) are introduced under argon stream ), isonicotinoyl chloride hydrochloride (0.12 g, 0.7 mmol, obtained in section a) and pyridine (1 mL). Stir at room temperature for 2 days. It is concentrated and the residue is dissolved in a mixture of CHCl3 and 1N HCl. The phases are separated and the aqueous phase is extracted with CHCl3 (x2). The aqueous phase is basified by slow addition of 1N NaOH. A saturated aqueous solution of NaCl is added and extracted with CHCl3 and AcOEt. The organic phase is dried over Na2SO4 and concentrated to dryness. The crude obtained is purified by chromatography on silica gel using as eluent mixtures CHCl3-MeOH of increasing polarity, obtaining 98 mg of the title compound (rto: 68%). LC-MS (method 1): t R = 4.21 min; m / z = 411.1 [M + H] +.

SUMMARY

New compounds of formula I and their salts, solvates and prodrugs, where
meanings of the different substituents are as indicated in the descriptive part 5. Such compounds are useful as p38 kinase inhibitors.

I

10

image9

Claims (4)

image 1 1.-A compound of general formula I I 5 where: A represents N or N + O-; R1 represents phenyl or Het optionally substituted by one or more substituents selected from Ra and Rb; R 2 represents 4-pyridone or 4-pyrimidine optionally substituted by one or more substituents selected from halogen, -ORc ’, -NRc’Rc’, SRc ’and –SO2Rc; R3 represents H, Cy optionally substituted by one or more substituents 15 selected from Ra and Rb, or R3 represents C1-6alkyl optionally substituted by one or more substituents selected from Rb and Cy *, where Cy * may be optionally substituted by one or more substituents selected from Rb and Rc; R4 represents H, Ra, halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -NRa'Ra', - NRa'CORa ', -NRa'CONRa'Ra', -NRa'CO2Ra, -NRa'SO2Ra, -SRa ', -SORa, -SO2Ra or -SO2NRa'Ra'; R5 may be located on any of the 2 N of the pyrazolic ring of formula I and represents H or Rf; each Ra independently represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where C1-6alkyl, C2-6alkenyl or C2-6alkynyl groups may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc; each Ra ’independently represents H or Ra; each Rb independently represents halogen, -ORc ', -OCORc, -OSO2Rc, -OCONRcRc', -NO2, -CN, -CORc ', -CO2Rc', -CONRc'Rc ', -CONRc'NRc'Rc', -NRc 'Rc', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'CO2Rc, -NRc'SO2Rc, -SRc ', -SORc, -SO2Rc, -SO2NRc'Rc', -C (NRc ') NRc'Rc ', -C (NSO2NRc'Rc') NRc'Rc ', -C (NORc') Rc ', -C (NNRc'Rc') Rc ', -NRc'C (NRc') NRc'Rc ' or -NRc'C (NCN) NRc'Rc '; each Rc independently represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where all these groups may be optionally substituted by one or more Rd substituents; each Rc ’independently represents H or Rc; each Rd independently represents halogen, Re, -ORe ', -OCORe, -OSO2Re, -OCONReRe', -NO2, -CN, -CORe ', -CO2Re', -CONRe'Re ', -CONRe'NRe'Re', -NRe'Re ', -NRe'CORe', -NRe'CONRe'Re ', -NRe'CO2Re, -NRe'SO2Re, -SRe', -SORe, -SO2Re, -SO2NRe'Re ', -C (NRe ') NRe'Re', -C (NSO2NRe'Re ') NRe'Re', -C (NORe ') Re', -C (NNRe'Re ') Re', -NRe'C (NRe ') NRe' Re ', -NRe'C (NCN) NRe'Re' or Cy optionally substituted by one or more substituents selected from halogen, Re, -ORe ', -OCORe, -OSO2Re, -OCONReRe', -NO2, -CN, -CORe ', -CO2Re', -CONRe'Re ', -CONRe'NRe'Re', -NRe'Re ', -NRe'CORe', -NRe'CONRe'Re ', -NRe'CO2Re, -NRe' SO2Re, -SRe ', -SORe, -SO2Re, -SO2NRe'Re', -C (NRe ') NRe'Re', -C (NSO2NRe'Re ') NRe'Re', -C (NORe ') Re' , -C (NNRe'Re ') Re', -NRe'C (NRe ') NRe'Re' and -NRe'C (NCN) NRe'Re '; each Re independently represents C1-6alkyl or haloC1-6alkyl; each Re ’independently represents H or Re; Rf represents C1-6alkyl, C2-6alkenyl, C2-6alkynyl or Cy, where C1-6alkyl, C2-6alkenyl or C2-6alkynyl groups may be optionally substituted by one or more substituents selected from Rg and Cy *, and where any of the groups Cy or Cy * may be optionally substituted by one or more substituents selected from Rg and Ra; each Rg independently represents halogen, -ORa ', -OCORa, -OSO2Ra, -OCONRaRa', -NO2, -CN, -CORa ', -CO2Ra', -CONRa'Ra ', -CONRa'NRa'Ra', -NRa 'Ra', -NRa'CORa ', -NRa'CONRa'Ra', -NRa'CO2Ra, -NRa'SO2Ra, -SRa ', -SORa, -SO2Ra, -SO2NRa'Ra', -C (NRa ') NRa'Ra ', -C (NSO2NRa'Ra') NRa'Ra ', -C (NORa') Ra ', -C (NNRa'Ra') Ra ', -NRa'C (NRa') NRa'Ra ' or -NRa'C (NCN) NRa'Ra '; a Het group in the above definitions represents pyridine, pyrazine, pyrimidine, pyridazine, 2 (1H) -pyridone, 2 (1H) -pyrazinone, 2 (1H) -pyrimidinone or 2 (1H) -pyridazinone; a Cy or Cy * group in the above definitions represents a monocyclic carbocyclic group of 3 to 7 members or bicyclic of 8 to 12 partially unsaturated, saturated or aromatic, optionally containing 1 to 4 heteroatoms selected from N, S and O, which may also optionally contain 1 or 2 oxo groups when the ring is saturated or partially unsaturated, and where said ring or rings can be attached to the rest of the molecule through a carbon or nitrogen atom; or a salt thereof. 2. A compound according to claim 1 wherein A represents N. 3. A compound according to claim 2 wherein R5 may be located on any of the 2 N of the pyrazolic ring of the formula I and represents H or Ra. 4. A compound according to any of claims 1 to 4 wherein R1 represents pyridine or phenyl, where all these groups can be optionally substituted by one or more substituents selected from Ra and Rb. 5. A compound according to claim 5 wherein R1 represents phenyl optionally substituted by one or more substituents selected from Ra and Rb . 6. A compound according to claim 6 wherein R1 represents phenyl optionally substituted by one or more substituents selected from halogen, -ORc ', -NO2, -CN, -CONRc'Rc', -NRc'Rc 'and C1-6alkyl optionally substituted by one or more substituents selected from halogen, -ORc ', -CORc', -NRc'Rc 'and -NRc'CORc'. 7. A compound according to claim 6 wherein R1 represents phenyl optionally substituted by one or more substituents selected from halogen and haloC1-6alkyl. 8. A compound according to claim 1 wherein R2 represents 4-pyridine. 9. A compound according to claim 1 wherein R2 represents 4-pyrimidine substituted by -NRc'Rc ', wherein in R2: each Rc' independently represents H or Rc; each Rc independently represents C1-6alkyl optionally substituted by one or more substituents selected from Cy and -ORe '; and each Re 'independently represents H or Re. 10.-A compound according to any of claims 1 to 9 wherein R3 represents represents H or Cy optionally substituted by one or more substituents selected from Ra and Rb. 11. A compound according to claim 10 wherein R3 represents H, heteroaryl

or phenyl, where all these groups may be optionally substituted by one or more substituents selected from Ra and Rb, and where heteroaryl represents a 5- to 6-membered monocyclic or 8 to 12-membered bicyclic aromatic ring, containing from 1 to 4 heteroatoms selected from N, S and O, and which can be attached to the rest of the molecule through a carbon or nitrogen atom. 12. A compound according to claim 11 wherein R3 represents heteroaryl or phenyl, where all these groups may be optionally substituted by one

or more substituents selected from Ra and Rb. 13. A compound according to claim 12 wherein R3 represents monocyclic heteroaryl or phenyl, where all these groups may optionally be

substituted by one or more substituents selected from halogen, -NO2, -ORc ', C1-6alkyl and Cy, where C1-6alkyl may be optionally substituted by one or more substituents selected from Rb and Cy *, and any of the Cy or Cy * groups may be optionally substituted by one or more substituents selected from Rb and Rc. 14. A compound according to claim 13 wherein R3 represents heteroaryl monocyclic or phenyl, where all these groups may optionally be substituted by one or more substituents selected from halogen, -NO2, -ORc ', C1-6alkyl, haloC1-6alkyl and Cy, and where in R3: each Rc 'independently represents H or Rc; Each Rc independently represents C1-6alkyl optionally substituted by one or more substituents Rd; Y each Rd independently represents Cy. 15. A compound according to any of claims 1 to 14 wherein R4 represents H, Ra, halogen, -ORa ', -CN, -CONRa'Ra, -NRa'Ra' or -NRa'CORa '. 16. A compound according to claim 15 wherein R4 represents H. 17.-A compound according to any of claims 1 to 16 wherein R5 represents H or R5 represents Ra and is located on the N in position 2 of the ring of pyrazol. 18. A compound according to claim 17 wherein R5 represents Ra. 19. A compound according to claim 17 or 18 wherein Ra in R5 represents C1-6alkyl, C2-6alkenyl or Cy, where C1-6alkyl or C2-6alkenyl groups they may be optionally substituted by one or more substituents selected from Rb and Cy *, and where any of the Cy or Cy * groups it may be optionally substituted by one or more selected substituents between Rb and Rc. 20. A compound according to claim 19 wherein each Rb in R5 represents independently halogen, -ORc ', -CORc', -CO2Rc ', -CONRc'Rc', -NRc'Rc ', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'SO2Rc ', -SRc', -SORc 'or -SO2Rc'. 21. A compound according to claim 20 wherein in R5: each Rb independently represents -ORc ', -CORc', -CONRc'Rc ', -NRc'Rc', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'SO2Rc ', SORc' or -SO2Rc '; each Rc 'independently represents H or Rc; Each Rc independently represents Cy or C1-6alkyl, where all these groups may be optionally substituted by one or more substituents selected from among Rd; each Rd independently represents Re, -ORe ', -NRe'Re', -CN, -CORe ', -SRe', -SORe 'or Cy. 22.-A compound according to claim 18 wherein Ra in R5 represents C1-6alkyl optionally substituted by one or more selected substituents from -ORc ', -CORc', -CONRc'Rc ', -NRc'Rc', -NRc'CORc ', -NRc'CONRc'Rc', -NRc'SO2Rc 'and Cy * optionally substituted by one or more substituents selected from Rc; where in R5: each Rc 'independently represents H or Rc; Each Rc independently represents Cy or C1-6alkyl, where all these groups may be optionally substituted by one or more substituents selected from among Rd; each Rd independently represents -ORe ', -NRe'Re', -CN, -CORe ', -SRe', -SORe 'or Cy; each Re 'independently represents H or Re; Y Each Re independently represents C1-6alkyl. 23.-A compound according to claim 1 selected from: 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-diphenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 5- (4-pyridyl) -4,6-bis [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 4,6-diphenyl-3-methyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 2-ethyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1-ethyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2,3-dimethyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1,3-dimethyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- [2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- [2- [1- (tert-Butoxycarbonyl) piperidin-4-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -3-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- (3-chloropropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- (3-chloropropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propan-1-ol; 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 4,6-diphenyl-2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-diphenyl-1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2- [2- (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4b] pyridine; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] ethanol; 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-methylsulfanylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- [1- (tert-butoxycarbonyl) piperidin-4-ylmethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- [1- (tert-Butoxycarbonyl) piperidin-4-ylmethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- [2- (morpholin-4-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- [2- (morpholin-4-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; Ethyl 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetate; Ethyl 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetate; Ethyl 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propionate; Ethyl 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propionate; 4,6-bis (4-fluorophenyl) -2- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (4-piperidylmethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-piperidylmethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (6-chloropyridin-3-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -3-methyl-2- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -3-methyl-1- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- [2- (4-piperidyl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetic acid; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetic acid; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propionic acid; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propionic acid; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -1- (morpholin-4yl) ethanone; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] acetamide; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -1- (morpholin-4-yl) ethanone; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -1- (morpholin-4-yl) propan-1-one; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -N-propylpropionamide; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -1- (morpholin-4yl) propan-1-one; 4,6-bis (4-fluorophenyl) -2- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-methylsulfanylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (4-methylsulfinylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (4-methylsulfonylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-methylsulfinylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (4-methylsulfinylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (4-methylsulfonylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-methylsulfinylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- (4-methylsulfonylbenzyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 3-Chloro-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 3-Bromo-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-carbonitrile; 3-Bromo-4,6-bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine-3-carboxamide; 3-aminomethyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluoro-3-nitrophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 3-amino-6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 3-amino-6- (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4- [6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-4-yl] phenol; 2- (2,2-diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- (2,2-diethoxyethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-3-carbonitrile; 3-Bromo-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 6-fluorophenyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; N-methyl- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] amine; [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] methanol; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -N, N-dimethylacetamide; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -N, N-dimethylacetamide; 4,6-bis (4-fluorophenyl) -2- [2- (2-methoxyethoxy) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -1- [2- (2-methoxyethoxy) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- [3- (morpholin-4-yl) propyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (6-chloropyridin-3-yl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (6-chloropyridin-3-yl) -1-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (6-chloropyridin-3-yl) -3-methyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-bis (6-methylpyridin-3-yl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (2-phthalimidoethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- (2-aminoethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol; 6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- (3-phthalimidopropyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] acetaldehyde; 2- (3-aminopropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; N- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-ylmethyl] -1- (tertbutoxycarbonyl) piperidine-4-carboxamide; N- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-ylmethyl] -1 H -piperidine-4-carboxamide; 2- (3-benzyloxypropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- (3-benzyloxypropyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; N, N-diethyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine; N, N-diethyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] ethyl] amine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2- (3-pyridylmethyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1-pyridin-3-ylmethylpyrazolo [3,4-b] pyridine; N, N-dimethyl- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propyl] amine; N, N-dimethyl- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1yl] propyl] amine; 1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-ol; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -2-hydroxypropan-1-ol; 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] -2-hydroxypropan-1-ol; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2- (4-pyridylmethyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -1- (4-pyridylmethyl) pyrazolo [3,4-b] pyridine; N- (tert-butoxycarbonyl) - [1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin2-yl] propyl] piperidin-4 -il] amine; 2- [1- (tert-butoxycarbonyl) piperidin-4-yl] -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 3-methyl-4,6-bis (6-methylpyridin-3-yl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -propyl] piperidin-4one; N- (tert-butoxycarbonyl) - [1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin2-yl] ethyl] piperidin-4 -il] amine; N-methyl- [1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-yl] amine ; [1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-yl] amine; 2- [1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-yl] ethanol; [1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-yl] amine; 6- (4-fluorophenyl) -2- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -1- (4-piperidyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 3-amino-5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4b] pyridine; 2- [3- [1- (1-tert-Butoxycarbonyl) piperazin-4-yl] propyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- [3- (piperazin-1-yl) propyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 5- [2- (methylsulfanyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4-b] pyridine; 5- [2- (methylsulfonyl) pyrimidin-4-yl] -6- [3- (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4-b] pyridine; (1S) -N- (1-phenylethyl) - [4- [6- [3- (trifluoromethyl) phenyl] -1 H -pyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-yl] amine; 1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-ol; 2- [1- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] piperidin-4-yl] ethanol; 4,6-bis (4-fluorophenyl) -3- (4-piperidyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-carbonitrile; 2- [2 - [[1- (tert-butoxycarbonyl) piperidin-4-yl] amino] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine ; 4,6-bis (4-fluorophenyl) -2- [2 - [(4-piperidyl) amino] ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; N- (2-methoxyethyl) - [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl] amine; 1- [4- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperazin-1-yl] ethanone; 3- [4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-1-yl] propan-1-ol; 2-ethyl-4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1-ethyl-4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-diphenyl-2- (2-phthalimidoethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2- (2-aminoethyl) -4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 2-allyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1-allyl-4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-one; 3-aminomethyl-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 3-amino-6- (4-fluorophenyl) -4-methyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 3- [N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl] amino] propan-1-ol; N-ethyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine; 2- [N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amino] ethanol; N - [(2-pyridyl) methyl] - [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine; N - [(2-thienyl) methyl] - [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine; 1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidine-4-carboxamide; 4,6-bis (4-fluorophenyl) -2- [2- (pyrrolidin-1-yl) ethyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; (3R) -1- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] pyrrolidin-3ol; 2- [N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -N-methylamino] ethanol; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2- [2- (1,2,3,4-tetrahydroisoquinolin-2-yl) ethyl] pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- [2- (4-phenylpiperazin-1-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 4,6-bis (4-fluorophenyl) -2- [2- [4- (1-piperidyl) piperidin-1-yl] ethyl] -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 3- [N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -N-methylamino] propiononitrile; N-methyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] amine; 2- [2- [4- (tert-butoxycarbonyl) piperazin-1-yl] ethyl] -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -2- [2- (piperazin-1-yl) ethyl] -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2-vinylpyrazolo [3,4-b] pyridine; 2- [N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -N- (2-hydroxyethyl) amino ]ethanol; N-cyclopropyl- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] ethyl] amine; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] acetamide; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -n'-isopropylurea; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] methanesulfonamide; 6- (4-fluorophenyl) -4- (4-piperidyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4- (2-furyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4- (1 H -imidazol-4-yl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4- (5-bromothien-2-yl) -6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridine; 5- (2-Chloropyridin-4-yl) -4,6-bis (4-fluorophenyl) -1H-pyrazolo [3,4-b] pyridine; 4- (2-phenylethyl) -6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4- (6-Chloropyridin-3-yl) -6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 4- (3,4-dichlorophenyl) -1-ethyl-6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4- (1-methylpiperidin-4-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 3-amino-6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-diphenyl-5- (4-pyridyl) -2- [2- (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4- (2-furyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -2-methyl-4- (1-methyl-1H-imidazol-4-yl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2- [2- (tetrahydropyran-2-yloxy) ethyl] pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine; 4- (5-bromothien-2-yl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -2-methyl-5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridine; 5- (2-Chloropyridin-4-yl) -4,6-bis (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridine; 4- (2-phenylethyl) -6- (4-fluorophenyl) -5- (4-pyridyl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine; 4- (6-Chloropyridin-3-yl) -6- (4-fluorophenyl) -5- (4-pyridyl) -2- [3- (tetrahydropyran-2-yloxy) propyl] pyrazolo [3,4-b] pyridine; 4- (6-Chloropyridin-3-yl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 5- (2-Methylsulfanylpyrimidin-4-yl) -2- [3- (tetrahydropyran-2-yloxy) propyl] -6- (3-trifluoromethylphenyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) -4- [5- (3-pyridyl) thien-2-yl] pyrazolo [3,4-b] pyridine; 2- [4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol; 3- [5- (2-Methylsulfanylpyrimidin-4-yl) -6- (3-trifluoromethylphenyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 2- [6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2-yl] ethanol; 3- [6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2-yl] propan1-ol; 3- [4,6-bis (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4- (2-Phenylethyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4- (6-Chloropyridin-3-yl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 6- (4-fluorophenyl) -2-methyl-5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4-b] pyridine; 3- [5- (2-Methylsulfonylpyrimidin-4-yl) -6- (3-trifluoromethylphenyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 2- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2-yl] ethanol; 3- [6- (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2-yl] propan1-ol; 3- [4,6-bis (4-fluorophenyl) -5- (2-methylsulfonylpyrimidin-4-yl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; N-cyclopropylmethyl- [4- [6- [3- (trifluoromethyl) phenyl] -1H-pyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-yl] amine; (1S) -3- [5- [2- (1-Phenylethylamino) pyrimidin-4-yl] -6- (3-trifluoromethylphenyl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol; N-cyclopropylmethyl- [4- [6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine; 2- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) pyrazolo [3,4-b] pyridin2-yl] ethanol; 3- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) pyrazolo [3,4-b] pyridin2-yl] propan-1-ol; 3- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -4,6-bis (4-fluorophenyl) pyrazolo [3,4b] pyridin-2-yl] propan-1-ol; 4- [4- [4,6-bis (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyridin-2 -lamino] benzenesulfonamide; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-3-ol; 6- (4-fluorophenyl) -4- (3H-imidazol-4-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4- (1 H -pyrazol-3-yl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 3- [6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-4-yl] phenol; 4-cyclopropyl-6- (4-fluorophenyl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4- (5-methylfuran-2-yl) -5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 4- (5-bromofuran-2-yl) -6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -5-pyrimidin-4-yl-1 H -pyrazolo [3,4-b] pyridine; 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4b] pyridine; 6- (4-fluorophenyl) -4-propyl-5- (4-pyridyl) -1H-pyrazolo [3,4-b] pyridine; 4- (3-benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 5- (2-Chloropyridin-4-yl) -6- (4-fluorophenyl) -1H-pyrazolo [3,4-b] pyridine; 4- [6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-4-yl] butan-1-ol; 4-benzyl-6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridine; 4,6-bis (4-fluorophenyl) -5-pyrimidin-4-yl-1 H -pyrazolo [3,4-b] pyridine; [(2S) -2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] pyrrolidine-2-carboxamide; 2- [2- (4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl) ethylamino] ethanol; 6- (4-fluorophenyl) -2-methyl-4- (3-pyridyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -3-methyl-5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridine; 3-amino-6-phenyl-5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridine; 6-phenyl-5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -4-methyl-5- (2-methylsulfanylpyrimidin-4-yl) -1H-pyrazolo [3,4-b] pyridine; 5- (2-Methoxypyrimidin-4-yl) -6- (3-trifluoromethylphenyl) -1 H -pyrazolo [3,4-b] pyridine; N- [2- [4,6- (diphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] acetamide; N- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propyl] acetamide; N- [2- (4,6-diphenyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl) ethyl] -N- (2-hydroxyethyl) acetamide; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] propionamide; N- [3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2yl] propyl] methanesulfonamide; 5- (2-aminopyrimidin-4-yl) -6- (3-trifluoromethylphenyl) -1 H -pyrazolo [3,4-b] pyridine; N- [5- (2-Methylsulfanylpyrimidin-4-yl) -6- (3-trifluoromethylphenyl) -1 H -pyrazolo [3,4-b] pyridin-3-yl] acetamide; N-cyclopropylmethyl- [4- [3-benzyloxycarbonylamino-6- (3-trifluoromethylphenyl) -1Hpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2-hydroxyacetamide; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidine-4-carboxamide; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2 (methylamino) acetamide; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] -2- (2-hydroxyethylamino) acetamide; N- [2- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] nicotinamide; 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -2-methylpyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -2,4-dimethyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5- (2-methylsulfanylpyrimidin-4yl) pyrazolo [3,4-b] pyridine; 2- (1-Benzylpyrrolidin-2-ylmethyl) -4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4b] pyridine; 4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5-pyrimidin-4-ylpyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -2-methyl-4- (5-methylfuran-2-yl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4- (5-bromofuran-2-yl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 6- (4-fluorophenyl) -2-methyl-4-propyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4- (3-benzyloxyphenyl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4- (2-phenylethyl) -6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 5- (2-Chloropyridin-4-yl) -6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridine; 4-benzyl-6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridine; 4- [6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] butan-1-ol; 4- [6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol; N- [6- (4-fluorophenyl) -5- (2-methylsulfanylpyrimidin-4-yl) -1 H -pyrazolo [3,4-b] pyridin-3-yl] acetamide; N- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) -1 H -pyrazolo [3,4b] pyridin-3-yl] acetamide; 3- [6- (4-fluorophenyl) -4- (2-furyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 2- [4- (4-Benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol; 3- [4- (4-benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan1-ol; 3- [6- (4-fluorophenyl) -4- (5-methylfuran-2-yl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan1-ol; 3- [4-cyclopropyl-6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4- (5-bromothien-2-yl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan1-ol; 3- [6- (4-fluorophenyl) -4-propyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4,6-bis (4-fluorophenyl) -5-pyrimidin-4-ylpyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; 3- [4- (3-Benzyloxyphenyl) -6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan1-ol; 3- [4-benzyl-6- (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol; (1S) -N- (1-phenylethyl) - [4- [6- (4-fluorophenyl) -3-methyl-1 H -pyrazolo [3,4-b] pyridin-5yl] pyrimidin-2-yl] amine; N-cyclopropylmethyl-4- [6- (4-fluorophenyl) -3-methyl-1H-pyrazolo [3,4-b] pyridin-5-yl] pyrimidin2-yl] amine; 1- [4- [6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-ylamino] propan-2ol; N-cyclopropylmethyl-4- [6- [phenyl-1H-pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine; 2- [4- [6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-ylamino] propan-1ol; 4- [4- [6- (4-fluorophenyl) -2-methyl-pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-ylamino] butan-1ol; (1S) -N- (1-phenylethyl) - [4- [6-phenyl-1 H -pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine; N- (3-methoxypropyl) - [4- [6- (3-trifluoromethylphenyl) -1 H -pyrazolo [3,4-b] pyridin-5-yl] pyrimidin2-yl] amine; 3- [4- [6- (3-Trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2 5-ylamino] propan-1-ol; 3- [4- [6- (4-fluorophenyl) -2- (3-hydroxypropyl) pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2 -lamino] propan-1-ol; N-ethyl- [4- [6- (3-trifluoromethylphenyl) -1 H -pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2-yl] amine; N-benzyl- [4- [6- (3-trifluoromethylphenyl) -1H-pyrazolo [3,4-b] pyridin-5-yl] pyrimidin-2 10 il] amine; 4- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) -2-methylpyrazolo [3,4b] pyridin-4-yl] phenol; 4- [6- (4-fluorophenyl) -2- (3-hydroxypropyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol; 4- [6- (4-fluorophenyl) -2-methyl-5-pyrimidin-4-yl) pyrazolo [3,4-b] pyridin-4-yl] phenol; 3- [6- (4-fluorophenyl) -2- (3-hydroxypropyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol; 3- [6- (4-fluorophenyl) -2-methyl-5- (4-pyridyl) pyrazolo [3,4-b] pyridin-4-yl] phenol; 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2- (pyrrolidin-2-ylmethyl) pyrazolo [3,4-b] pyridine; 4- [4- [6- (4-fluorophenyl) -2-methylpyrazolo [3,4-b] pyridin-5-yl] pyridin-2 -lamino] benzenesulfonamide; N- [5- [2 - [(cyclopropylmethyl) amino] pyrimidin-4-yl] -6- (4-fluorophenyl) -1-Hirozolo [3,4-b] pyridin-3-yl] acetamide oxide; and N- [6- (4-fluorophenyl) -5- (4-pyridyl) -1 H -pyrazolo [3,4-b] pyridin-3-yl] isonicotinamide; or a salt, solvate or prodrug thereof. 24. Process for the preparation of a compound of formula I according to claim 1, comprising: (a) react a ketone of formula IV image2 IV wherein R1 and R2 have the meaning described in claim 1, with an aminopyrazole of formula V and an aldehyde of formula VI R5 H2N N R3 CHO R4 V VI wherein R3, R4 and R5 have the meaning described in claim 1; or (b) when in a compound of formula I R5 represents H and R3 has the same meaning as R1, reacting a ketone of formula IV or an enolate of 5 formula VII R1 image3 R1 image3 OO image3 OR image3 R1 R2 R2 VII IV wherein R1 and R2 have the meaning described in claim 1, with an aminopyrazole of formula Va H2N H Goes Wherein R4 has the meaning described in claim 1; or (c) when in a compound of formula I R4 represents NH2, treat a compound of formula XIX XIX where R1, R2 and R3 have the meaning described in claim 1, with a hydrazine of formula VIIIa image4 image5 image6 NH2 NHR5 VIIIa wherein R5 has the meaning described in claim 1; or (d) transforming, in one or several stages, a compound of formula I into another compound of formula I; Y 5 (e) if desired, after the above steps, to react a compound of formula I with a base or with an acid to give the corresponding salt. 25. A pharmaceutical composition comprising an effective amount of a compound of formula I according to any one of claims 1 to 23 or a salt or pharmaceutically acceptable solvate thereof and one or more excipients 10 pharmaceutically acceptable. 26. Use of a compound of formula I according to any one of claims 1 to 23 or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of diseases mediated by p38. 27. Use of a compound of formula I according to any one of claims 1 to 23 or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of cytokine-mediated diseases. 28. Use of a compound of formula I according to any one of claims 1 20 to 23 or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of diseases mediated by TNF-, IL-1, IL-6 and / or IL-8. 29. Use of a compound of formula I according to any one of claims 1 to 23 or a pharmaceutically acceptable salt or solvate thereof for the 25 manufacture of a medicament for the treatment or prevention of a disease selected from among immune, autoimmune and inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases, proliferative diseases and processes associated with the induction of 30 cyclooxygenase-2. 30. A compound according to claim 1 which is 2-ethyl-4,6-bis (4-fluorophenyl) -5 (4-pyridyl) pyrazolo [3,4-b] pyridine. 31. A compound according to claim 1 which is 4,6-bis (4-fluorophenyl) -2-methyl5- (4-pyridyl) pyrazolo [3,4-b] pyridine. 32. A compound according to claim 1 which is 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] propan-1-ol. A compound according to claim 1 which is 4,6-bis (4-fluorophenyl) -2- (4-methylsulfinylphenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridine. 34. A compound according to claim 1 which is N-methyl- [3- [4,6-bis (4fluorophenyl) -5- (4-pyridyl) -pyrazolo [3,4-b] pyridin-2-yl] propil] amine. 35. A compound according to claim 1 which is 2- [4,6-bis (4-fluorophenyl) -5- (4 Pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethanol. 36. A compound according to claim 1 which is 1- [2- [4,6-bis (4-fluorophenyl) -5 (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-ol. 37. A compound according to claim 1 which is 3- [4,6-bis (4-fluorophenyl) -5- (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] -2-hydroxypropan-1 -ol. A compound according to claim 1 which is [1- [2- [4,6-bis (4-fluorophenyl) -5 (4-pyridyl) pyrazolo [3,4-b] pyridin-2-yl] ethyl] piperidin-4-yl] amine. 38. A compound according to claim 1 which is 4,6-bis (4-fluorophenyl) -5- (4-pyridyl) -2-vinylpyrazolo [3,4-b] pyridine.