Title of Invention	"PYRAZOLO[1,5-A]PYRIMIDINE COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF"
Abstract	The present invention provides a pyrazolo [1,5-a] pyrimidine compound of formula I or their salts which exhibit excellent kinase inhibiting activity, wherein the drugs comprising the compound or its salts are effective ingredients and are useful as therapeutic ro prophylactic agents for protein kinase mediated disorders.

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DESCRIPTION p /rasolo[l,5-a]pyrimidine derivatives Field of the Invention The present invention relates to novel compounds, their use in the inhibition of protein kinases, their use in medicine and particularly in the prevention and/or treatment of a wide variety of diseases including inflammatory disorders, cancer, angiogenesis, diabetes and neurological disorders. The invention also provides processes for the manufacture of said compounds, compositions containing them and processes for manufacturing such compositions. Background Art Protein kinases are a family of enzymes that catalyse the phosphorylation of hydroxyl groups in proteins. Approximately 2% of the genes encoded by the human genome are predicted to encode protein kinases. The phosphorylation of specific tyrosine, serine, or threonine residues on a target protein can dramatically alter its function in several ways including activating or inhibiting enzymatic activity, creating or blocking binding sites for other proteins, altering subcellular localisation or controlling protein stability. Consequently, protein kinases are pivotal in the regulation of a wide variety of cellular processes, including metabolism, proliferation, differentiation and survival (Hunter, T. Cell, 1995, SO, 224-236). Of the many different cellular functions known to require the actions of protein kinases, some represent targets for therapeutic intervention for certain disease (Cohen, P. Nature Rev. Drug Disc., 2002, 1, 309-315). It is known that several diseases arise from, or involve, aberrant protein kinase activity. In humans, protein tyrosine Idnasec are known to have a significant role in the development of many diseases including diabetes, cancer and have also been linked to a wide variety of congenital syndromes (Robertson. S. C. Trends Genet. 2000, 16, 265-271). Seririe/threonine kinases also represent a class of ensymes, inhibitors of which are likely to have relevance to the treatment of cancer, diabetes and a variety of inflammatory disorders (Adams, J. L. et al. Prog. Med. Chem. 2001, 38,1-60). One of the principal mechanisms by which cellular regulation is affected is through the transduction of extracellular signals across the membrane that in turn modulate biochemical pathways within the cell. Protein phosphorylation represents one course by which intracellular signals are propagated from molecule to molecule resulting finally in cellular responses. These signal transduction cascades are regulated and often overlapping as evidenced by the existence of many protein kinases as well as phosphatases. It is currently believed that a number of disease and/or disorders are a result of either aberrant activation or inhibition in the molecular components of kinase cascades. Three potential mechanisms for inhibition of protein kinases have been identified thus far. These include a pseudo-substrate mechanism, an adenine mimetic mechanism and the locking of the enzyme into an inactive conformation by using surfaces other than the active site (Taylor, S. S. Curr. Opin. Chem. Biol. 1997, 1, 219-226). The majority of inhibitors identified/designed to date act at the ATP-binding site. Such /OTP-competilive inhibitors have demonstrated selectivity by virtue of their ability to target the more poorly conserved areas of the ATP-binding site (Wang, Z. et al. Structure 1998, 6, 1117-1128). There exists a need for the provision of further compounds that are inhibitors of protein kinases. IVIAPKAF-K2 (mitogen-activated protein kinase-activated protein kinase 2) .b a serine/threonine kinase that operates immediately downstream of the p38 kinase in the stress-induced MAPK pathway (Figure 1). The p38 kinase pathway is involved in transducing the effects of a variety of stress-related extracellular stimuli such as heat shock, UV light, bacterial lipopolysaccharide, and pro-inflammatory cytokines. Activation of this pathway results in the phosphorylation of transcription and initiation factors, and affects cell division, apoptosis, invasiveness of cultured cells and the inflammatory response (Martin-Bianco, Bioessays 22, 637-645 (2000)). p3S kinase itself activates a number of protein kinases other than the MAPKAP kinases such as Mnkl/2, PRAK and MSK1 (Figure 1). The specific and/or overlapping functions of the majority of these targets have yet to be resolved. This pathway has been of particular interest for the discovery of new anti-inflammatory agents. Previous strategies to intervene this pathway have involved the development of selective inhibitors of p38 kinase. Such inhibitors are effective both for inhibiting pro-inflammatory cytokine production in cell-based models and animal models of chronic inflammations (Lee et al., Immunopharmacology 47,185-201 (2000)). p38 kinase knockout mouse is embryonic lethal. And cells derived from such embryos have demonstrated a number of abnormalities in fundamental cell responses. These observations indicate that caution should be paid to the long-term therapy with p38 kinase inhibitors. An alternative strategy for the development of anti-inflammatory agents could be the inhibition of this pathway at the level of MAPKAP-K2. Human MAPKAP-K2 Iws two proline-rich domains at its f T-terminu3 follov/ed by the fcinase domain ao.d l:he C-terminal regulatory domain. This kinase has low homology with other serine/threonine kinases except MAPKAP-K3 and -K4. The C-terminal regulatory domain contains a bipartite nuclear localisation signal and a nuclear export signal. The crystal structure of inactive MAPKAP-K2 has been resolved (Meng, W. et. al. J. Biol. Chem. 277, 37401-37405 (2002)). Activation of MAPKAP-K2 by p3S kinase occurs via selective phosphorylation of threonine residues 222 and 334 (Stokoe et al., EMBO J. 11, 3985-3994 (1992)). MAPKAP-K2 has an amphiphilic A-helix motif located within its C-terminal region that is likely to block the binding of substrates. The dual phosphorylation by p3S kinase has been proposed to reposition this motif resulting in enhanced catalytic activity (You-Li et al., J. Biol. Chem. 270, 202-206 (1995)). MAPKAP-K2 is present in the nucleus of unstimulated cells, and translocates to the cytoplasm upon cell stimulation. This kinase is known to phosphorylate a number of nuclear transcription factors as well as cytosolic proteins such as heat shock proteins and 5-lipoxygenase (Stokoe et al., FEES Lett. 313, 307-313 (1992), Werz, et al., Proc. Natl. Acad. Sci. USA 97, 5261-5266 (2000), Heidenreich, et al., J. Biol. Chem. 274, 14434-14443 (1999), Tan, et al., EMBO J. 15,4629-4642 (1996), Neufeld, J. Biol. Chem. 275,20239-20242 (2000)). All such substrates contain a unique ammo acid motif (XX-Hyd-XRXXSXX, where Hyd is a bulky hydrophobic residue) that is required for efficient phosphorylation by MAPKAP-K2 (Stokoe et al.. Biochem. J.296, 843-849 (1993)). Currently MAPKAP-K2 is the only p3S kinase substrate for which a specific function has been identified. A specific role for MAPKAP-K2 in mediating the inflammatory response has been strongly indicated by the phenotype of the lvlAFKj^4I2-deficient mouse (MAPKAF-K2"'") (Kotlyarov, et al.f Mature Cell Biol. 1, 94-97 (1999)). This mouse is viable and normal e::cept for a significantly reduced inflammatory response. Recently it has also been shown thai MAPJLAJ'-K2 deficiency results in a marked neuroprotection from ischaemic brain injury (Wang et al., J. 13iol Chem. 277, 43968-43972 (2002)). MAPKAP-K2 is believed to regulate the translation and/or stability of important pro-inflammatory cytokine mRNAs. It is thought to function via phosphorylation of proteins that bind to the AU-rich elements found within untranslated regions of these cytokines. The identity of these proteins is currently under investigation. MAPKAP-K2 therefore represents an intervention point in the stress-induced kinase cascade for perturbation of the inflammatory response. Disclosure of the Invention As a result of much diligent research directed toward achieving the object stated above, the present inventors have completed the present invention upon discovering that the novel Pyrazolo[l,5-a]pyrimidine derivatives represented by formula I below and their pharmaceutically acceptable salts exhibit excellent kinase inhibiting activit5'. In other words, the present invention provides as follows: (i) A compound of formula I: (Formula Removed) wherein R1 is hydrogen, C1-C8 optionally substituted alkyl. C2-CS optionally substituted alkenyl, C2-CS optionally substituted alkynyl, C3-CS optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl; R2 is hydrogen, halogen, -CN, -NO2. -CHO, -G-R7 [G is a bond, -C(=O)- or -O-C(=O)-: and R7 is Cl-CS optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-CS optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, -OR8 (R8 is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), -NR9R10 (R9 is as defined for Rs; R10 is hydrogen, C1-C8 optionally substituted alkyl. C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl or -OCH3), -R11 (R11 is an optionally substituted saturated heterocyclyl with 5 to 7 members containing one to four heteroatoms selected from N, O and S), C6-C14 optionally substituted aryl or optionally substituted heteroaryl; provided that when. R7 is C6-C14 optionally substituted aryl or optionally substituted heteroaryl. then G is not. a bond], -rlR9C(=C).r12 (R9 is as defined for R3; R12 is hydrogen, Cl-Co optionally substituted alkyl, C2-C8 optionally substituted alkenyl., C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl), -NR9C(=X)OR13 (R9 and R13, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH), -NR9C(=X)NR13R14 (R9, R13 and R14, which may be the same or different, are as defined for R ; X is O, S, N-CN or NH), -NR9SO2R13 (R9 and R13, which may be the same or different, are as defined for R8), -SR9 (R9 is as defined for Rs) or -S(0) mR9 (R9 is as defined for R8; m is 1 or 2); R3 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 unsubstituted aryl, C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CN, -NOa, -CHO, -G-R15 {G is a bond, -C(=O)- or -O-C(=0)-; R15 is Cl-CS optionally substituted alkyl, C2-CS optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-CS optionally substituted cycloalkyl, C6-C14 optionally substituted aryl. optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, -OR16 (R16 is as defined for R8) or -NR17R18 (R17 and R18, which may be the same or different, are as defined for R8)}, -NR17C(=O)R19 (R17 is as defined for Rs ; P.19 is k defined for R12), -I ^17C(=Z)OR1S (F.17 and R1S, which may be the same or different, are as defined for Rs; X is O, 3, N-QT or NH), -NR17C(=yC)r rP12R20 (R17, R18 and R20, which may be the same or different, are as defined for R8; X is O, S, N-CH or NH), -MR17S02R13 (R17 and R18, which may be the same or different, are as defined for R8), -S(0)nlR17 (R17 is as defined for R8; m is 0, 1 or 2) and -SO2NR21R~ (R21 and R22, which may be the same or different, are as defined for R8 ; R21 and R22 together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, -CHO, -G-R23 {G is a bond, -C(=O)- or -0-C(=O)-; R23 is as defined for R15}, -NR^C^C^R25 (R24 is as defined for R8 ; R25 is as defined for R12), -NR24C(=X)OR26 (R24 and R26, which may be the same or different, are as defined for R8; X is 0, S, N-CN or NH), -NR24C(=X)NR26R27 (R24, R26 and R27, which may be the same or different, are as defined for R8; X is 0, S, N-CN or NH), -NR24SO2R26 (wherein R24 and R26, which may be the same or different, are as defined for R8), -S(COmR24 (R24 is as defined for Rs; m is 0, 1 or 2) and -S02NR2SR29 (R28 and R29, which may be the same or different, are as defined for R8 ; R20 and R2? together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, 0 and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl., optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl; R4 is hydrogen, halogen, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyctylalkynyl, -OR30 (R30 is as defined for R8), -SR30 (R30 is as defined for R8), -NR30R31 (R30 and R31, which may be the same or different, are as defined for R8), -NR30C(=O)R32 (R30 is as defined for R8 ; and R32 is as defined for R12), -NR30C(=X)OR31 (R30 and R31, which may be the same or different, are as defined R8; X is 0, S, N-CN or NH), -NR30C(=X)NR31R33 (R30, R31 and R33, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH) or -NR30S02R31 (R30 and R31, which may be the same or different, are as defined for R8); R5 is C1-C8 substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-CS substituted cycloalkyl [As substituents of C3-C8 cycloalkyl may be mentioned one or more selected from the group consisting of halogen, -CM, -MO2, -CHO, -G-R34 {G is a bond, -C(=O)- or -0-C(=O)-; R34 is as defined for R15}, -NR35C(=0)R36 (R35 is as defined for R8; R36 is as defined for R12), -NR35C(=X)OR37 (R35 and R37, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH ), -NR35C(=X)MR37R3S (R35, R37 and R3S, which may be the same or different, are as defined, for Rs; Z is O, 5,1 T-Ci I or ITH) and -1-TR35SO2R37 (R35 and R37, which may be the same or different, are aa defined for R8)], unsubstituted heterocyclyl,' substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CM, -NOa, -CHO, -G-R39 {G is a bond, -C(=0)- or,-O-C(=O>; R39 is as defined for R15}, -NR40C(=O)R41 (R40 is as defined for R8; R41 is as defined for R12), -NR40C(=X)OR42 (R40 and R42, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH), -NR40C(=X)NR42R43 (R40, R42 and R43, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH) and -NR40SO2R42 (R40 and R42, which may be the same or different, are as defined for R8)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl or -NR44R45 (R44 and R45, which may be the same or different, are C1-C8 optionally substituted alkyl ; R44 and R45 together may be taken together with the nitrogen to which they are attached to form a mono heterocycle with 5-7 members and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said mono heterocycle may optionally be substituted with one or more substituents); R6 is hydrogen, Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl; xvith the provisos: that R1, R2 and R4 are not all H; that R4 is not pentafluorophenyl; that R5 is not a group represented as the following (a): (a) C1-C6 alky! or C3-C6 cycloalkyl, in which an alkyl group or a cycloalkyl group optionally may be substituted by phenyl or by one or more fluoro substituents; and phamiaceutically acceptable salts, and other pharmaceutically acceptable biohydrol3'zable derivatives thereof, including esters, amides, carbamates, carbonates, ureides, solvates, hydrates, affinity reagents or prodrugs. (2) A compound of formula I-b: (Figure Removed) wherein Rlb is hydrogen, C1-C6 optionally substituted alkyl, C2-C6 optionally substituted alkenyl, C2-C6 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, optionally substituted arylalkynyl or optionally substituted heteroarylalkynyl; R2b is hydrogen, halogen, -CM, -NO2, -CHO or -G-R52 {G is a bond, -C(=O)- or -0-C(=O)-; and R52 is C1-C6 optionally substituted alkyl, C2-C6 optionally substituted alkenyl. C2-C6 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkyny.l. -OR"*3 (F.53 is hydrogen, C1-C6 optionally substituted alkyl, C2-C6 optionally substituted alkenyl, C2-C6 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, optionally substituted, aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, optionally substituted arylalkynyl or optionally substituted heteroarylalkynyl), -NR54R55, -NR54C(=O)R55, -SR54, optionally substituted aryl or optionally substituted heteroaryl; provided that when R is optionally substituted aryl or optionally substituted heteroaryl then G is not a bond; wherein R54 and R55, which may be the same or different, are as defined for R53; or wherein R54 and R55 together form an optionally substituted ring that optionally contains one or more heteroatoms selected from N, 0 and S}; R3b is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-CS optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, optionally substituted arylalkynyl or optionally substituted heteroar}'lalkynyl; R4b is hydrogen, halogen, C1-C6 optionally substituted alkyl, C2-C6 optionally substituted, alkenyl, C2-C6 optionally substituted alkynyl, C3-CS optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkynyl, -OR56, -SR56, -KR56R57 or -NR56C(=0)R57; wherein R5"' and. RJ/, which may be the same or different, are as defined for P.53; or wherein R5° and R^7 together form an optionally substituted ring which optionally contains one or more heteroatoms: R5b is C1-C6 substituted alkyl, C2-C6 optionally substituted alkenyl. C2-C6 optionally substituted alkyriyl, C3-C8 substituted cycloalkyl, optionally substituted heterocyclyl or optionally substituted heterocyclylalkyl; R6b is hydrogen, C1-C6 optionally substituted alkyl, C2-C6 optionally substituted alkenyl, C2-C6 optionally substituted alkynyl or C3-C8 optionally substituted cycloalkyl; with the provisos: that Rlb, R2b and R4b are not all H; that R4b is not pentafluorophenyl; that R5b is not a group represented as the following (a): (a) C1-C6 alkyl or C3-C6 cycloalkyl, in which an alkyl group optionally may be substituted by phenyl or by one or more fluoro substituents; • and pharmaceutically acceptable salts, and other pharmaceutically acceptable biohydrolyzable derivatives thereof, including esters, amides, carbamates, carbonates, ureides, solvates, hydrates, affinity reagents or prodrugs. The compound as (1) wherein R.1 is hydrogen or Cl-CS optionally substituted alkyl. The compound as (1) wherein R1 is hydrogen. The compound as any one of (1), (3) or (4) wherein R2is -NO2, -OC(=0)R7, -CO2R8 or -COrlH9R10; wherein R7, R3, R9 and R10 are as defined in claim 1. The compound as any one of (1), (3) or (4) v/herein R2 is -NR9C(=O)R12, -HR9C(=X)OR13, -i'>m9C(=X)NR13R14, -NR9SO2R13, -SR9 or -S(O)raR9; wherein R9, R12, R13, R14 and X are as defined in claim 1; m is 1 or 2. The compound as any one of (1), (3) or (4) wherein R2 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl or optionally substituted arylalkyl. The compound as any one of (1), (3) or (4) wherein R2 is hydrogen, halogen, -CN or -SCH3. The compound as any one of (1), (3) or (4) wherein R2 is halogen. The compound as any one of (1), (3) or (4) wherein R2 is F. The compound as any one of (1), (3) or (4) wherein R2 is hydrogen. The compound as any one of (1), (3) to (11) v/herein R3 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C'2-CS optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 unsubstituted aryl, C6-C14 substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl. The compound as any one of (1). (3) to (11) wherein R3 is C6-C14 substituted aryl. The compound as any one of (1), (3) to (11) wherein R3 is C6-C14 substituted aryl {As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, -G-R15, -NR17C(=O)R19 and -S(O)mR17; wherein R15, R17, R19 or G are as defined in claim 1; m is 0,1 or 2.}. The compound as any one of (1), (3) to (11) wherein R3 is C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, -G-R15 {G is a bond or -C(=O)-; R15 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, -OR16 or -NR17R18}, -NR17C(=O)R19 and S(O)mR17; wherein R16, R17, R18 or R19 are as defined in claim 1; m is 0,1 or 2.]. The compound as any one of (1), (3) to (11) wherein R3 is C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CM, -NOc, -G-R15 {G is a bond; R13 is C6-C14 optionally substituted aryl. optionally substituted heteroc'/ctyl, optionally substituted heterocyclylalkyl, -OR16 or -NR17R18}, -NR17C(=0)R19 and S(O)mR17; wherein R16, R17, R18 or R19 are as defined in claim 1; m is 0,1 or 2.]. (17") The compound as any one of 11), (3) to (ID v/herein R3 is C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CM, -W02, -G-R15 {G is a bond or -C(=O)-; R15 is C1-C8 optionally substituted alk}'!, C3-CS optionally substituted cycloalkyl, -OR16 or -NR17R18}, -NR17C(=O)R19 and S(0)mR17; wherein R16, R17, R18 or R19 are as defined in claim 1; m is 0,1 or 2.]. The compound as any one of (1), (3) to (11) wherein R3 is C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CN, -N02, -G-R15 {G is a bond or -C(=O)-; R15 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, -OR16 or -NR17R18}, -NR17C(=0)R19 and S(O)mR17; wherein R16, R17, R18 or R19, which may be the same or different, are hydrogen, C1-C8 optionally substituted alkyl, C3-CS optionally substituted cycloalkyl; m is 0,1 or 2.]. The compound as any one of (1), (3) to (11) wherein R3 is C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CN, -N02 and -G-R15 {G is -C(=0)-; R15 is C1-C8 optionally substituted alkyl, C3-C3 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocydyl, -OR16 or -MPv17R13}; wherein R16, R1' or R10 are as defined in claim 1.]. (20) The compound as any one of (1), (3) to (11) wherein R3 is unsubstituted heterocyclyl. The compound as any one of (1), (3) to (11) wherein R3 is substituted heterocyclyl. The compound as any one of (1), (3) to (11) wherein R3 is substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, -G-R23, -NR24C(=O)R25 and -S(O)mR24; wherein R23, R24, R25 or G are as defined in claim 1; m is 0,1 or 2.]. The compound as any one of (1), (3) to (11) wherein R3 is unsubstituted bicyclic heteroaryl. The compound as any one of (1), (3) to (11) wherein R3 is substituted bicyclic heteroaryl [As substituents of bicyclic heteroaryl may be mentioned one or more selected from the group consisting of halogen, -CN, -N02, -G-R23, -NR24C(=0)R25 and -S(O)mR24; wherein R23, R24, R25 or G are as defined in claim 1; m is 0,1 or 2.]. The compound as any one of (1), (3) to (24) wherein R4 is halogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, -OR30; wherein R30 is as defined in claim 1. The compound as any one of (1), (3) to (24) wherein R4 is C1-C8 optionally substituted alkyl. The compound as any one of (1). (3) to (24) wherein R4 is methyl. The compound as any one of (1), (3) to (24) wherein R4 is hydrogen. The compound as any one of (1), (3) to (28) wherein R5 is C3-C8 substituted cycloalkyl, unsubstituted heterocyclyl or substituted heterocyclyl. The compound as any one of (1), (3) to (28) wherein R5 is C3-C8 substituted cycloalkyl [As substituents of cycloalkyl may be mentioned one or more selected from the group consisting of halogen, -CN, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C3-CS optionally substituted cycloalkyl and -NR17R18; wherein R17 or R18 is as defined in claim 1]. The compound as any one of (1), (3) to (28) wherein R5 is substituted cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, -CN, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C3-C8 optionally substituted cycloalkyl and -NR17R1S; wherein R17or Rl0 is as defined in claim 1]. The compound as any one of (1), (3) to (28) wherein R5 is 4-amino-cyclohe-xyl. The compound as any one of (1), (3) to (28) wherein R5 is unsubc-tituted heterocyclyl or substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CM, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C3-C8 optionally substituted cycloalkyl and -NR17R18; wherein R17or R18 is as defined in claim 1] The compound as any one of (1), (3) to (28) wherein R5 is unsubstituted piperidin-3-yl, unsubstituted piperidin-4-yl or unsubstituted pyrrolidin-3-yl. The compound as any one of (1), (3) to (28) wherein R5 is substituted piperidin-3-yl, substituted piperidin-4-yl or substituted pyrrolidin-3-yl. The compound as any one of (1), (3) to (28) wherein R5 is substituted piperidin-3-yl, substituted piperidin-4-yl or substituted pyrrolidin-3-yl [As their substituents may be mentioned one or more selected from the group consisting of halogen, -CN, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl and C3-C8 optionally substituted cycloalkyl] The compound as any one of (1), (3) to (36) wherein R6 is hydrogen. (38) The compound as any one of (1), (3) to (36) wherein R6 is C1-C8 optionally substituted alkyl or optionally substituted arylalkyl. (39) A compound of the formula 11-26: (Figure Removed) wherein R1 - R6 are as defined in claim 1; R58 is C1-C8 optionally substituted alkyl or optionally substituted arylalkyl; with the provisos: that R1, R2 and R4 are not all H. (40) A compound of the formula 111-01: (Figure Removed) wherein R1 - R4 are as defined in claim 1; R58 is Cl-CS optionally substituted alkyl or optionally substituted arylalkyl; with liic provisos: that R1, R2 and R4 are not all H. (41) A compound of the formula IV: (Figure Removed) wherein R1 - R4 are as defined in claim 1; with the provisos: that R1, R2 and R4 are not all H; that R4 is not optionally substituted aryl or optionally substituted heteroaryl. (42) The compound as any one of (39), (40) or (41) wherein R1 is hydrogen; (43) The compound as any one of (39), (40) or (41) wherein R2 is hydrogen, halogen, -CM, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, -OF5 (JT is hydrogen, or C1-C3 opiionally substituted alkyl), -Nr/L10 (R9 and R10, which may be the same or different, hydrogen or C1-C3 optionally substituted alkyl), -C(=0)NR9R10 (R9 and R10:, which may be the same or different, are hydrogen, C1-C8 optionally substituted alkyl, C3-C3 opiionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9C(=O)R12 (R9 is hydrogen or Cl-CS optionally substituted alkyl; R12 is C1-C8 optionally substituted alkyl, C3-CS optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9C(=O)OR13 (R9 is hydrogen or C1-C8 optionally substituted alkyl; R13 is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9C(=O)NR13R14 (R9 and R13, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl; R14 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9SO2R13 (R9 is hydrogen or C1-C8 optionally substituted alkyl; R13 is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -SR9 (R9 is hydrogen, Cl-CS optionally substituted alk)4, C3-CS optionally substituted cycloalkyl,, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) or -S02F.9 (R9 is Cl-CS optionally substituted alkyl, C3-C3 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl). (44) The compound as any one of (39), (40) or (41) wherein R" is substituted phenyl [As substituenls of phenyl may be mentioned one or more selected from the group consisting of halogen, -CM, -NO2;, Cl-CS optionally substituted alkyl, C2-CS optionally substituted alkynyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, Cl-CS optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl) and -C(=0)NR17R18 (R17 and R18, which may be the same or different, are hydrogen, Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalk)7!, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)], unsubstituted bicyclic heteroaryl, substituted bicyclic heteroaryl [As substituents of bicyclic heteroaryl may be mentioned one or more selected from the group consisting of halogen, -CN, -N02, Cl-CS optionally substituted alkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, Cl-CS optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or Cl-CS optionally substituted alkyl), -NHC(=O)R19 (P.19 is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) and -SR17 (R17 is Cl-CS optionally substituted alkyl)]. The compound as any one of (39), (40) or (41) wherein R4 is hydrogen, methyl or ethyl. The compound as (39) wherein R3 is preferably selected from cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, Cl-CS optionally substituted alkyl, -OH and -NHsL unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NH2]. The compound as (39) wherein R6 is hydrogen. The compound as any one of (39), (40) or (41) wherein R58 is tert-butyl or benzyl. The compound as (39) wherein R1 is hydrogen; R2 is hydrogen, -CN, -SCH3, -NH2, -COOH or COCF3; R3 is substituted phenyl (As substituents of phenyl may be mentioned one or more selected from the group consisting of halogen, -CN, -OH, -OCH3, -OEt, -COOH); R4 is hydrogen or -CH3; R5 is 4-amino-cyclohexyl or piperidin-3-yl; R6 is hydrogen; R5S is tert -butyl; with the provisos that P.1, R2 and R4 are not all H. The compound as (40) wherein R1 is hydrogen; R2 is hydrogen, -CN, ~SCH3, -NH2, -COOH or COCF3; R3 is substituted phenyl (As substituents of phenyl may be mentioned one or more selected, from the group consisting of halogen, -CN, -OH, -OCH3, -OEt, -COOH); r" is hydrogen or -CH3; R55 is ten -butyl; with the provisos that R1, R2 and R4 are not all H The compound as (41) wherein R1 is hydrogen; R2 is hydrogen, -CN, -SCH3, -NH2, -COOH or COCF3; R3 is substituted phenyl (As substituents of phenyl may be mentioned one or more selected from the group consisting of halogen, -CN, -OH, -OCH3> -OEt, -COOH); R4 is hydrogen or -CH3; with the provisos that R1, R2 and R4 are not all H. (52) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein removal of Boc protecting group from compound II. (Figure Removed) (53) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound III (Figure Removed) is reacted with a compound of the formula R5R°NH. (54) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound IV (Figure Removed) is reacted with a compound of the formula R5R6NH. (55) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound IV (Figure Removed) is reacted, v/ith di-^c/v'-but)7! dicarbonate. (56) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound V (Figure Removed) is reacted with a compound of the formula R3NH2 or R3NH(COCH3). (57) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound VI (Figure Removed) is reacted with phosphorus oxychloride or phenyl phosphonic dichloride. (58) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound VII (Figure Removed) (VII) is reacted with a compound of the formula R^CH(CO2Me)2 or R^CHXCC^ECh. (59) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound V-01 (Figure Removed) (Y-01) is reacted v/ith a halogenating, thiocyanating or acylating agent. (60) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound IV-01 (Figure Removed) is reacted with a Grignard reagent. (61) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-01 (Figure Removed) is reacted with a halogenating agent. (62) A process for the manufacture of a compound as defined in any one of (1), (3) lo (38) wherein compound 11-01 (Figure Removed) is reacted with a compound of the formula (CF3CO)2O. (63) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-03 (Figure Removed) is reacted with hydroxide for a hydrolysis of ester group; R67 is methj'l or ethyl. (64) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-04 (Figure Removed) is reacted with a compound of the formula R9R10NH in the presence of a peptide coupling agent. (65) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-06 (Figure Removed) is rearranged via isocyanate intermediate under Hofmann rearrangement conditions, followed by removal of carbonate. (66) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-08 (Figure Removed) is reacted with a compound of the formula R12COC1, R12COOH, R10SO2C1, R10NCO or R10NCS. (67) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-13 R2 (11-13) (Figure Removed) is condensed with an alcohol derivative under Mitsunobu conditions; Ar1 represents C6-C14 optionally substituted aryl or optionally substituted heteroaryl. (68) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-15 (Figure Removed) is reacted with a boronic acid derivative in the presence of metal catalysis under Suzuki-Miyaura coupling conditions; As1 represents C6-C14 optionally substituted aryl or optionally substituted heteroarj'l. (69) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-15 (Figure Removed) is reacted with a 1-alkyne in the presence of metal catalyst under Sonogashira coupling conditions; Ar1 represents C6-C14 optionally substituted aryl or optionally substituted heteroaryl. (70) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-18 (Figure Removed) is reacted with a compound of the formula R16R17NH in the presence of a peptide coupling agent; Ar1 represents C6-C14 optionally substituted aryl or optionally substituted heteroaryl. (71) A process for the manufacture of a compound as defined in any one of (1), (3) to (33) '.'/herein compound 11-20 (Figure Removed) . is reacted with an alkyl lithium reagent. (72) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-22 (Figure Removed) is reacted with alkyl halide, followed by removal of trifluoroacetyl group. (73) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-08 (Figure Removed) is reacted with an aldehyde in the presence of reducing agent. (74) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 11-24 (Figure Removed) R (II-24) H is reacted with alkyl halide in the presence of sodium hydride (75) A process for the manufacture of a compound as defined in any one of (1), (3) to (38) wherein compound 1-26 (Figure Removed) is reacted with hydrogen in the presence of Palladium on activated carbon or with chloroformate followed by methanol; R60 is benzyl orp-MeO-benzyl; n is 1,2 or 3. (76) A process for the manufacture of a compound as defined in any one of (1), (3) to (33) v/herein compound V-04 (Figure Removed) is reacted with reducing agent or diol derivative for formation of acetal. A composition comprising a compound as defined in any one of (1), (3) to (38) in combination with a pharmaceutically acceptable carrier, diluent or excipient. The composition as (77) further comprising one or more active agents. A process for the manufacture of a composition as defined in (77) or (78) comprising combining a compound as defined in any one of (1), (3) to (38) with the pharmaceutically acceptable carrier or diluent, optionally with an additional active agent. A compound as defined in any one of (1), (3) to (38), or a composition as defined in any one of (77) or (78), for use in medicine. A compound as defined in any one of (1), (3) to (38), or a composition as defined in any one of (77) or (78), for inhibiting protein kinase. A compound as defined in any one of (1). (3) to (38), or a composition as defined in any one of (77) or (78), for selectively inhibiting MAPKAP-K2. A compound as defined in any one of (1), (3) to (38), or a composition as defined in any one of (77) or (73), for selectively inhibiting CDK. A compound as defined in any one of (1), (3) to (38), or a composition as defined in any one of (77) or (78), for use in the prevention or treatment of a protein kinase-mediated disorder. The compound or composition as (84), wherein the disorder is a neurodegenerative/neurological disorder (including dementia), inflammatory disease, a disorder linked to apoptosis, particularly neuronal apoptosis, stroke, sepsis, autoimmune disease, destructive bone disorder, proliferative disorder, diabetes, cancer, tumour growth, infectious disease, allergy, ischemia reperfusion injury, heart attack, angiogenic disorder, organ hypoxia, vascular hyperplasia, cardiac hypertrophy and/or thrombin induced platelet aggregation. The compound or composition as (84), wherein the disorder is inflammatory disease and/or autoimmune disease. The compound or composition as (84), wherein the disorder is autoimmune disease. (88) The compound or composition as (87), wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus, glomemlonephritis, scleroderma, Sjogren's syndrome, juvenile rheumatoid arthritis, psoriatic arthritis, chronic thyroiditis, Graves's disease, autoimmune gastritis, diabetes, autoimmune haemoty'tis anaemia, autoimmune neutropaenia, thrombocytopenia, aiopic dermatitis, chronic active hepatitis, myastlienia gravis, multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis or graft rs host disease. The compound or composition as (87), wherein the autoimmune disease is rheumatoid arthritis, psoriasis, ankylosing spondylitis, juvenile rheumatoid artliritis, psoriatic arthritis or Crohn's disease. A method of treating or preventing a protein kinase-mediated disorder in an individual, which method comprises administering to said individual a compound as claimed in any one of (1), (3) to (38) or a composition as defined in (77) or (78). The method as (90) wherein the individual is in need of the treatment or prevention of the disorder. The method as (90) or (91) wherein the disorder is a neurodegenerative/neurological disorder (including dementia), inflammatory disease, a disorder linked to apoptosis, particularly neuronal apoptosis, stroke, sepsis, autoimmune disease, destructive bone disorder, proliferative disorder, diabetes, cancer, tumour growth, infectious disease, allergy, ischemia reperfusion injury, heart attack, angiogenic disorder, organ hypoxia, vascular hyperplasia, cardiac hypertrophy and/or thrombin induced platelet aggregation. The method as (90) or (91) wherein the disorder is autoimmune disease. The method as (93) wherein the autoimmune disease is rheumatoid arthritis, psoriasis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis or Crohn's disease. The method as (90) to (94) wherein one or more active agent is administered to the individual simultaneously, subsequently or sequentially to administering the compound. (96) Use of a compound as defined in any one of (1), (3) to (38) in the manufacture of a medicament for the prevention or treatment of a protein kinase-mediated disorder. Use as (96) wherein the disorder is a neurodegenerative/neurological disorder (including dementia), inflammatory disease, a disorder linked to apoptosis, particularly neuronal apoptosis, stroke, sepsis, autoimmune disease, destructive bone disorder, proliferative disorder, diabetes, cancer, tumour growth, infectious disease, allergy, ischemia reperfusion injury, heart attack, angiogenic disorder, organ hypoxia, vascular hyperplasia, cardiac hypertrophy and/or thrombin induced platelet aggregation. Use as (96) wherein the disorder is autoimmune disease. Use as (98) wherein the autoimmune disease is rheumatoid arthritis, psoriasis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis or Crohn's disease. (100) Use as (96) or (97) wherein one or more active agent is administered i;o the individual simultaneously, subsequently or sequentially to administering the compound. An assay for determining the activity of the compounds as defined in any one of (1). (3) to (38), comprising providing a system for assaying the activity and assaying the activity of a compound as defined in any one of (1), (3) to (38). The assay as (101) wherein the assay is for the protein kinase inhibiting activity of the compound. A method of inhibiting the activity or function of a protein kinase, which method comprises exposing a protein kinase to a compound as defined in any one of (1), (3) to (38) or a composition as defined in (77) or (78). The method as (103) which is performed in a research model, in vitro, in silico or in vivo such as in an animal model. brief description of the drawings Figure 1 shows the p38 MAFK cascade. Figures 2 - 8 show general reaction schemes for the preparation of compounds of Formula I. Best Mode for Carrying Out the Invention In a first aspect the invention provides a compound of formula I: (Figure Removed) wherein R1 is hydrogen, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyi, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl; R2 is hydrogen, halogen, -CN, -NO2.-CHO, -G-R7 [G is a bond, -C(=O)- or -O-C(=0)-; and R7 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, . C3-C8 optionally substituted cycloalkyl, optionally substituted arylalkyi, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, -OR8 (Rs is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyi or optionally substituted heterocyclylalkyl), -NR9R10 (R9 is as defined for R8 : Ft10 is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyL C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyi, optionally substituted heterocyclylalkyl or -OCH3), -R11 (Rn is an optionally substituted saturated heterocyclyl with 5 to 7 members containing one to four heteroatoms selected from N, 0 and S), C6-C14 optionally substituted aryl or optionally substituted, heteroaryl; provided that v/hc-n T.' k C6-C14 optionally substituted aryl or optionally substituted heteroaryl, then G b not a bond], -NR9C(=0)R12 (R9 is as defined for R8; R12 is hydrogen, C1-C8 optionally substituted alkyl, C2-CS optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl), -NR9C(=X)OR13 (R9 and R13, which may be the same or different, are. as defined for R8; X is 0, S, N-CN or NH), -NR9C(=X)NR13R14 (R9, R13 and R14, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH), -NR9SO2R13 (R9 and R13, which may be the same or different, are as defined for R8), -SR9 (R9 is as defined for R8) or -S(0) mR9 (R9 is as defined for R8; m is 1 or 2); R3 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 unsubstituted aryl, C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CN, -NOa, -CHO, -G-R15 {G is a bond, -C(=O)- or -O-C(=0)-; R15 is Cl-CS optionally substituted alkyl, C2-CS optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-CS optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocydylalkynyl, -OR16 (R16 is as defined for R8) or -NR17R18 (R17 and R18, which may be the same or different, are as defined for F.°)}, -1 IF.17C(=0)R19 (R17 ic as defined for R8 ; R19 is as defined for R12), •MRI7C(=lr.)ORlc (R17 arid R18, which may be the same or different, are as defined for R": X is O, S, N-CN or NH), -NR17C(=X)NR1SR20 (R1 , R18 and R20, which may be the same or different, are as defined for Rs; X is O, S, N-CN or NH), -NR17S02R18 (R17 and R18, which may be the same or different, are as defined for R8), -S(0)mR17 (R17 is as defined for Rs; m is 0, 1 or 2) and -S02NR21R22 (R21 and R22, which may be the same or different, are as defined for Rs ; R21 and R22 together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CN, -N02, -CHO, -G-R23 {G is a bond, -C(=O)- or -O-q=O)-; R23 is as defined for R15}, -NR24G(=O)R25 (R24 is as defined for Rs ; R25 is as defined for R12), -NR24C(=X)OR26 (R24 and R26, which may be the same or different, are as defined for R8; X is 0, S, N-CN or NH), -NR24C(=X)NR26R27 (R24, R26 and R27, which may be the same or different, are as defined for Rs; X is 0, S, N-CN or NH), -NR24SO2R2t) (wherein R24 and R2°, which may be the same or different, are as defined for Rs), -S(O)mP.24 (R24 is as defined for Rs; m is 0, 1 or 2) and -SO^NR^R29 (R28 and 1O R"', which may be the same or different, are as defined for R ; R"" and R"' together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatorns selected from IT, O and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted a^lalkynyl or optionally substituted heterocyclylalkynyl; R4 is hydrogen, halogen, C1-C8 optionally substituted alkyl, C2-C8 optionally 'substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, -OR30 (R30 is as defined for R8), -SR30 (R30 is as defined for R8), -NR30R31 (R30 and R31, which may be the same or different, are as defined for R8), -NR30C(=0)R32 (R30 is as defined for R8 ; and R32 is as defined for R12), -NR^C^X^R31 (R30 and R31, which may be the same or different, are as defined R8; X is 0, S, N-CN or NH), -NR30C(=X)NR31R33 (R30, R31 and R33, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH) or -NR30SO2R31 (R30 and R31, which may be the same or different, are as defined for R8); R5 is C1-C8 substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 substituted cycloalkyl [As substituents of C3-C8 cycloalkyl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, -CHO, -G-R311 {G is a bond, -C(=0)- or -O-C(=O)-; R34 is as defined for R15}, -NR35C(=0)R36 (R35 is as defined for R8; R36 is as defined for R12), -NR35C(=X)OR37 (R35 and R3/, which may be the same or different, are as defined for Rs; X is 0, S, iT-CH or ITH )., -1 rP?5C(=/:):IR37R3S (F.35, R37 and. R3S, which may be the same or different, are ac defined for R3; X is Q, 3, H-C1-T or MH) and -WR35SO2R37 (R33 and R37, which may be the same or different, are as defined for R8)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, -CHO, -G-R39 {G is a bond, -C(=0)- or -O-C(=0)-; R39 is as defined for R15}, -NR40C(=O)R41 (R40 is as defined for Rs; R41 is as defined for R12), -NR40C(=X)OR42 (R40 and R42, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH), -NR40C(=X)NR42R43 (R40, R42 and R43, which may be the same or different, are as defined for R8; X is 0, S, N-CN or NH) and -NR40SO2R42 (R40 and R42, which may be the same or different, are as defined n for R)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterbcyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl or -NR44R45 (R44 and R45, which may be the same or different, are C1-C8 optionally substituted alkyl ; R44 and R45 together may be taken together with the nitrogen to which they are attached to form a mono heterocycle with 5-7 members and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said mono heterocycle may optionally be substituted with one or more substituents); R° is hydrogen, Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl; with the provisos: that R1, R2 and R4 are not all H; that R4 is not pentafluorophenyl; that P.5 is not a group represented as the following (a): (a) CI-Cu alkyl or C3-C6 cycloalkyl, in v/hich an alkyl group or a cycloalkyl group optionally may be substituted by phenyl or by one or more fluoro substituents; and pharmaceutically acceptable salts, and other pharmaceutically acceptable biohydrolyzable derivatives thereof, including esters, amides, carbamates, carbonates, ureides, solvates, hydrates, affinity reagents or prodrugs thereof. For the purposes of this invention, alkyl relates to both straight chain or branched alkyl radicals of 1 to 8 carbon atoms including, but not limited to, methyl, ethyl, w-propyl, isopropyl, ;i-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, terf-pentyl, 2-methylpentyl, 4-methylpentyl, 1-ethylbutyl, n-hexyl, n-heptyl, 2-methylhexyl, 5-methylhexyl, 1,1-dimethylpentyl, 6-methylheptyl and n-octyl. The term "cycloalkyl" means a cycloalkyl radical of 3 to 8 carbon atoms including but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. The term "alkenyl" means a straight chain, branched or ring structured alkenyl radical of 2 to 8 carbon atoms and containing one or more carbon-carbon double bonds and includes, but is not limited to, vinyl, allyl, isopropenyl, 1-propenyi, 2-butenyl, 1-butenyl, 2-methyl-l-propenyl, 2-methyl-3-penten3'l, 1-pentenyl, 2-pentenyl, 4-methyl-l-pentenyl, 1-hexenyl, 2-hexenyl, 2-cyclopentenyl, 2-cyclohexenyl, 2-heptenyl, 2-octenyl, 3-cyclopentenyl, 1,3-butadienyl and 1,5-henadienyl. When they have cis and trans geometrical isomers, both isomers are included. The term "alkynyl" means a straight chain or branched alkynyl radical of 2 to 8 carbon atoms and containing one or more carbon-carbon triple bonds and includes, but is not limited to, ethynyl, 2-propynyl, 1-propynyl, 1-butynyl, 2-butynyl, 3-hexynyl, 3-methyl-l-bulynyl, 3,3-dimethyl-1-butynyl., 3-pentynyl, 2-pentynyl, Z-henyrr/l, 3-he?:ynyl, 4-hezynyl, l-methyl-3-pentynyl, l-methyl-3-hexynyl, 2-heptynyl and 2-octynyl. "Ar}'!" means an aromatic 6-10 membered hydrocarbon containing one ring or being fused to one or more saturated or unsaturated rings including, but not limited to, phenyl, naphthyl, anthracenyl, 5-indanyl and 5,6,7,S-tetrahydro-2-naphthyl. "Heteroaryl" means an aromatic 5-10 membered heterocyclic ring containing 1 to 4 heteroatoms selected from N, O or S and containing one ring or being fused to one or more saturated or unsaturated rings. Examples of heteroaryl include, but are not limited to, monovalent group including furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, imidazole, pyrazole, triazole, thiadiazole, oxadiazole, tetrazole, pyridine, pyrazine, pyrimidine, pyridazine, benzofuran, dibenzofuran, benzothiophene, indole, benzimidazole, benzothiazole, benzoxazole, quinoline, isoquinoline, quinazoline, quinoxaline, purine, pteridine, phenoxazine and phenozine. "Saturated heterocyclyl" means a 3-10 membered saturated ring containing 1 to 4 heteroatoms selected from N, O or S and containing one ring or being fused to one or more saturated rings; the saturated heterocyclyl is fully saturated. Examples of saturated heterocyclyl include, but are not limited to, monovalent group including piperidine, piperazine, morpholine, pyrrolidine, imidazolidine, pyrazolidine and quinuclidine. "Heterocyclyl" means a 3-10 membered ring system containing 1 to 4 heteroatoms selected from N. 0 or S. The heterocyclyl system can contain one ring or may be fused to one or more saturated or unsaturated rings; the heterocyclyl can be fully saturated, partially saturated or unsaturated and includes, but is not limited to, heteroaryl and saturated heterocyclyl; the heterocyclyl can contain one or two -(C=O)- or -(C=S)-groups. Examples of heterocyclyl include, but are not Limited to, monovaient group including furan, thiopliene, pyrrole, pyrroline, pyrrolidine, oxazole, o-azolidme, isoiiazolidine, thiazole, thiazolidine, isothiazole, isothiazolidine, imidazole, imidazolme, imidazolidine, pyrazole, pyrazoline, pyrazolidine, triazole, thiadiazole, osadiazole, tetrazole, pyran, tetrahydropyran, thiopyran, tetrahydrothiopyran, pyridine, pyrazine, pyrimidine, pyridazine, benzofuran, dibenzofuran, benzothiophene, indole, benzimidazole, benzothiazole, benzoxazole, chromane, isochromane, quinoline, decahydroquinoline, isoquinoline, quinazoline, quinoxaline, purine, pteridine, azetidine, morpholine, thiomorpholine, piperidine, homopiperidine, piperazine, homopiperazine, indoline, isoindoline, phenoxazine, phenazine, phenothiazine, quinuclidine, acridine, carbazole, cinnoline, dioxane, dioxolane, dithiane, dithiazine, dithiazole, dithiolane, indolizine, indazole, isoindole, isoxazole, napthyridine, oxathiazole, oxathiazolidine, oxazine, oxadiazine, phthalazine, quinolizine, tetrahydrofuran, tetrazine, thiadiazine, thiatriazole, thiazine, thianaphthalene, triazine, 1,3-dioxane, 2,5-dihydrofuran, oxazoline, trithiane, piperidin-2-one, 3H-isobenzofuran-l-one, ep^/'/o/i-caprolactam, 2-furanone, 2-pyrrolidone, tetrahydro-3H-pyrazol-3-one, piperazin-2-one, coumarin, tetrahydro-2-pyrimidinone, glutarimide and morpholine-3,5-dione. "Arylalkyl" used herein is a group comprising a combination of the aryl and the alkyl. Examples thereof include, but are not limited to, benzyl, phenethyl, (2-naphthyl)-methyl, 3-phenylpropyl, 4-phenylbutyl and 5-(l-naphthyl) pentyl. "Heterocyclylalkyl" is a group comprising a combination of the heterocyclyl and the alkyl. Examples thereof include, but are not limited to, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 3-furilmethyl, 2-(3-indolyl)ethyl, 2-morpholinoethyl, 2-piperidinoethyl, 2-(4-pyridyl)-ethyl, 3-(l-piperadinyl)-propyl, 3-(2-thienyl)-propyl, and 2-(l-imidazole)sthyl. "Arylalkenyl" is ?. group comprising a combination of the aryl and. the alkenyl. Examples thereof include, but are not limited to, styryl, cinnamyl and 4-pheriyl-2-butenyl. When they have cis and trans geometrical isomers, both isomers are included. "Heterocyclylalkenyl" used herein is a group comprising a combination of the heterocyclyl and the alkenyl. Examples thereof include, but are not limited to, (3-pyridyl)vinyl, 3-(3-thienyl)propene-2-yl, 3-(4-morpholinyl)-l-propenyl and 4-(l-piperidyl)-2-butenyl. When they have cis and trans geometrical isomers, both isomers are included. "Arylalkynyl" used herein is a group comprising a combination of the aryl and the alkynyl. Examples thereof include, but are not limited to, phenylethynyl and 4-phenyl-2-butynyl. "Heterocyclylalkynyl" used herein is a group comprising a combination of the heterocyclyl and the alkynyl. Examples thereof include, but are not limited to, 4-(4-pyridyl)-2-butynyl and 5-(l-piperazinyl)-2-pentynyl. Halogen means F, Cl, Br or I. Suitable substituents include F, Cl, Br, I, -CN, -N02, -CHO, -G-R46 {G is a bond, -C(=O)-, or -0-C(=0)-; R4l) is optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl optionally substituted C2-C3 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C1.4 aryl, optionally substituted heterocyclyl. -OR47 or -NR47R4S}, -NR47C(=O)R4S, -NR47C(=0)OR4S, -NR47SO2R48, -S(0)mR47, -NR47S02R48 or -SO2NR47R4S; wherein optionally substituted C1-C8 alkyl means C1-C8 alkyl which may be optionally substituted with one or more F, Cl Br, I, -CM, -H02, -CHO, heterocyclyl, -OR47, -MR47R4S, -ITR47C(=0)r4G, -COOR47, -CONR47R43 and -S(0)mR47; wherein optionally substituted C2-C8 alkenyl means C2-C8 alkenyl which may be optionally substituted with one or more F, Cl, Br, I, -CN, -N02, -CHO, heterocyclyl, -OR50, -NR50R51, -NR50C(=0)R51, -COOR50, -CONR50R51 and -S(0)mR50; wherein optionally substituted C2-C8 alkynyl means C2-C8 alkynyl which may be optionally substituted with one or more F, Cl, Br, I, -CN, -NO2, -CHO, heterocyclyl, -OR50, -NR50R51, -NR50C(=0)R51, -COOR50, -CONR50R51 and -S(O)raR50; wherein optionally substituted C3-C8 cycloalkyl means C3-C8 cycloalkyl which may be optionally substituted with one or more F, Cl, Br, I, -CN, -NO2, -CHO, heterocyclyl, -OR50, -NR50R51, -NR50C(=0)R51, -COOR50, -CONR50R51 and -S(0)mR50; wherein optionally substituted C6-C14 aryl means C6-C14 aryl which may be optionally substituted with one or more F, Cl, Br, I, -CN, -NO2, -CHO, heterocyclyl, -OR50, -NR50R51, -NRSOC(=0)R51, -COOR50, -CONR50R51 and -S(O)mR50; wherein optionally substituted heterocyclyl means heterocyclyl which may be optionally substituted with one or more F, Cl, Br, I, -CN, -NO2, -CHO, heterocyclyi, -OR50, -NR50RS1, -NR50q=0)R51, -COOR50, -CONR50R51 and -S^R50; R47, R48, R49, R50 and R51, which may be the same or different, are hydrogen, C1-C8 alkjd, C3-C8 cycloalkyl C6-C14 aryl, heterocyclyl, arylalkyl or heterocyclylalkyl; m= 0,1 or 2. R1 is preferably hydrogen or C1-C6 optionally substituted alkyl. More preferably R1 is hydrogen. R2 is preferably selected from hydrogen, halogen, -CN, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, -OR8 (R3 is hydrogen or Cl-CS optionally substituted alkyl), -HP9F,10 (P.9 and R10, which may be the same or different, hydrogen or Cl-CS optionally substituted alkyl), -C(=0)iTF/F10 (F,? and R10, which may be the same or different, are hydrogen, Cl-CS optionally substituted alkyl, C3-CS optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9C(=0)R12 (R9 is hydrogen or Cl-CS optionally substituted alkyl; R12 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9C(=0)OR13 (R9 is hydrogen or C1-C8 optionally substituted alkyl; R13 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9C(=O)NR13R14 (R9 and R13, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl; R14 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -NR9SO2R13 (R9 is hydrogen or C1-C8 optionally substituted alkyl; R13 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl), -SR (R is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) or -S02R (R is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl). More preferably R2 is hydrogen, halogen, -CN or -SCHa. Still more preferably R2 is hydrogen; R3 is preferably selected from C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, -CM, -HO2, -G-R15 {G is a bond or -C(=0)-; R15 is Cl-CS optionally substituted alkyl, C2-CS optionally substituted alkenyl, C2-CS optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -ORlb (RltJ is hydrogen, C1-C8 optionally substituted, alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl) or -NR17R18 (R17 and R18, which may be the same or different, are hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)}, -NR17C(=O)R19 (R17 is hydrogen or C1-C8 optionally substituted alkyl; R19 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally 1*7 1*7 substituted aryl or optionally substituted heterocyclyl) and -S(O)mR (R is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl; m is 0 or 2)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CN, -N02, -G-R23 {G is a bond or -C(=O)-; R23 is C1-C8 optionally substituted alkyl, C3-CS optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) or -NR17R18 (R17 and R18, which may be the same or different, are hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)}, -NR24C(=O)R25 (R24 is hydrogen or C1-C8 optionally substituted alkyl; R25 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) and -S(O)mR24 (F24 b C1-C3 optionally substituted alkyl or C3-CS optionally substituted, cycloalkyl; m is 0 or 2)]. More preferably R3 is substituted phenyl [As substituents of phenyl may be mentioned one or more selected from the group consisting of halogen, -CM, -NO2, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkynyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl) and -C(=O)NR17R18 (R17 1 Q and R , which may be the same or different, are hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)], unsubstituted bicyclic heteroaryl, substituted bicyclic heteroaryl [As substituents of bicyclic heteroaryl may be mentioned one or more selected from the group consisting of halogen, -CN, -NOz, C1-C8 optionally substituted alkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl), -NHC(=O)R19 (R19 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) and -SR17 (R17 is C1-C8 optionally substituted alkyl)]. R4 is preferably selected from hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, optionally substituted aryl. More preferably R4 is hydrogen, methyl or ethyl. R3 is preferably selected from C3-C3 substituted cycloalkyl [As cutctitue-ntc of C3-C8 cycloalkyl may be mentioned one or more selected from the group consisting of halogen, -CM, C1-C8 optionally substituted alkyl, -OR30 (R30 is hydrogen or Cl-CS optionally substituted alkyl), -NR30R31 (R30 and R31, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl) and -NHC(=O)R32 (R32 is C1-C8 optionally substituted alkyl, C3-C8 substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, -CN, Cl-CS optionally substituted alkyl, -OR16 (R16 is hydrogen or C1-C8 optionaUy substituted alkyl), -NR17R18 (R17 and R1S, which may be the same or different, are hydrogen or C1-C8 optionaUy substituted alkyl) and -NHC(=O)R41 (R41 is C1-C8 optionally substituted alkyl, C3-CS substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)]. More preferably R5 is preferably selected from cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl -OH and -'NHb], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, Cl-CS optionally substituted alkyl -OH and -NHa]. Still more preferably R3 is 4-amino-cyclohesyl, piperidin-3-yl, piperidin-4-yl or pyrrolidin-3-yl. R6is preferably selected from hydrogen and C1-C8 optionally substituted alkyl. More preferably R6 is hydrogen. As preferred combinations of the groups mentioned as preferred examples of R1 - R6 in formula I according to the invention, there may be mentioned the following combinations 1) to 10). 1) In formula I, wherein R1 is hydrogen, R2 is hydrogen, R3 is C6-C14 aryl group substituted by C6-C14 optionally substituted aryl or optionally substituted heterocyclyl [wherein C6-C14 aryl group as R3 may be substituted by one or more substituents selected from the group consisting of halogen, -CN, -NO2, Cl-CS optionally substituted alkyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl)], R4 is C1-C8 optionally substituted alkyl, R5 is cyclohexyl [As substituents of cyciohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHi], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHa] and R6 is hydrogen. 2) In formula I, wherein R1 is hydrogen, R2 is hydrogen, R3 is C6-C14 aryl group substituted by -OR16 (R16 is Cl-CS optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl) [wherein C6-C14 aryl group as R3 may be substituted by one or more substituents selected from the group consisting of halogen, -CN, -NO2, Cl-CS optionally substituted alkyl, -OR16 (R16 is hydrogen, Cl-CS optionally substituted alkyl), -NE.17F,18 (R17 and R1S, which may be the same or different, are hydrogen or Cl-CS optionally substituted alkyl)], R4 is Cl-CS optionally substituted alkyl, R5 is cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHa], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned, one or more selected from i:he group consisting of halogen, C1-C3 optionally substituted alkyl, -OH and -ITU?] and F.6 is hydrogen. 3) In formula I, wherein R is hydrogen, R" is hydrogen, R is C6-C14 aryl group substituted by -G-R15 {G is -(CO)-; R15 is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl) or -NR17R18 (R17 and R18, which may be the same or different, are hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl)} [wherein C6-C14 aryl group as R3 may be substituted by one or more substituents selected from the group consisting of halogen, -CN, -NO2, C1-C8 optionally substituted alkyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl)], R4 is Cl-CS optionally substituted alkyl, R5 is cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NH2], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, Cl-CS optionally substituted alkyl, -OH and -lIHi] and R6 is hydrogen. 4) In formula I, wherein R1 is hydrogen, R2 is hydrogen, R3 is unsubstituted bicyclic heteroaryl or substituted bicyclic heteroaryl [As substituents of bicyclic heteroaryl may be mentioned one or more- selected, from the group consisting of halogen, -CIJ, -NO2, C1-C8 optionally substituted, alfcyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -ORlb (RlD is hydrogen, C1-C8 optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocj'clylalkyl), -MR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl), -NH(CO)R19 (R19 is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) and -SR17 (R17 is C1-C8 optionally substituted alkyl)], R4 is C1-C8 optionally substituted alkyl, R5 is cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NH2], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NH2] and R6 is hydrogen. 5) In formula I, wherein R1 is hydrogen, R2 is F, R3 is C6-C14 aryl group substituted by C6-C14 optionally substituted aryl or optionally substituted heterocyclyl [wherein C6-C14 aryl group as R3 may be substituted by one or more substituents selected from the group consisting of halogen, -CN, -NOo, C1-C8 optionally substituted alkyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl), -NR17R18 (R17 and i f* R ', which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl)], R4 is hydrogen, R5 is cyclohexyl [As substituents of cyc).ohe;:yl may be mentioned one or more selected from the group consisting of halogen, Cl-CS optionally substituted alkyl, -OH and -NH2], unsubstituted saturated heterocyctyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C3 optionally substituted alkyl, -OH and -MH2] and R6 is hydrogen. In fonnula I. wherein R1 is hydrogen, R2 is F, R3 is C6-C14 aryl group substituted by -OR16 (R16 is Cl-CS optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl) [wherein C6-C14 aryl group as R3 may be substituted by one or more substituents selected from the group consisting of halogen, -CN, -NO2, C1-C8 optionally substituted alkyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl)., -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl)], R4 is hydrogen, R5 is cyclohexyl [As substituents of cyclohexj'l may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -Nlfe], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may. be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NH2] and R6 is hydrogen. In formula I, wherein R1 is hydrogen, R2 is F, R3 is C6-C14 aryl group substituted by -G-R15 {G is -(CO)-; R15 is C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl) or -NR17R18 (R17 and R1G, v/hich may be the same or different, are hydrogen. Cl-CS optionally substituted aLkyl C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocj'clyl)} [wherein C6-C14 aryl group as R3 may be substituted by one or more substituents selected from the group consisting of halogen, -CN, -NO2, Cl-CS optionally substituted alkyl, -OR16 (R16 is hydrogen, Cl-CS optionally substituted, alfcyl), -i TR17R1S (R17 and R1S, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl)]. R4 is hydrogen, R5 is cyclohenyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, Cl-CS optionally substituted alkyl, -OH and -NHz], unsubstiluted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHfe] and R6 is hydrogen. 8) In formula I, wherein R is hydrogen, R is F, R is unsubstituted bicyclic heteroaryl or substituted bicyclic heteroaryl [As substituents of bicyclic heteroaryl may be mentioned one or more selected from the group consisting of halogen, -CN, -NO2, Cl-CS optionally substituted alkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, -OR16 (R16 is hydrogen, C1-C8 optionally substituted alkyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), -NR17R18 (R17 and R18, which may be the same or different, are hydrogen or C1-C8 optionally substituted alkyl), -NH(CO)R19 (R19 is Cl-CS optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl or optionally substituted heterocyclyl) and -SR17 (R17 is Cl-CS optionally substituted alkyl)], R4 is hydrogen, R5 is cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, Cl-CS optionally substituted alkyl, -OH and -Mlnfe]. unaubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHo] and R6 is hydrogen. In formula 1, wherein R1 is hydrogen., R2 is halogen, -CH or -SCH3, R3 is C6-C14 optionally substituted aryl, optionally substituted bicyclic heteroaryl, F.4 is hydrogen, R^ is cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHz], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHo] and R6 is hydrogen. In formula I, wherein R1 is hydrogen, R2 is halogen or -CN, R3 is C6-C14 optionally substituted aryl, optionally substituted bicyclic heteroaryl, R4 is C1-C8 optionally substituted alkyl, R5 is cyclohexyl [As substituents of cyclohexyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHa], unsubstituted saturated heterocyclyl or substituted saturated heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, C1-C8 optionally substituted alkyl, -OH and -NHa] and R6 is hydrogen. The compounds of the first aspect may be provided as a salt, preferably as a pharmaceutically acceptable salt of the compounds of formula I. Examples of pharmaceutically acceptable salts of these compounds include those derived from organic acids such as acetic acid, malic acid, tartaric acid, citric acid, lactic acid, ozalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, mandelic acid, methanesulphonic acid, benzenesulphonic acid, trifluoroacetic acid and /7-toluenesulphonic acid, mineral acids such as hydrochloric and sulphuric acid and the like, giving methanesulphonate, bemenesulphonate, p-toluenesulphonate, hydroehloride and sulphate, and the like, respectively or those derived from bases such as organic and inorganic bases. Examples of suitable inorganic bases for the formation of salts of compounds for this invention include the hydroxides, carbonates, and bicarbonate-s of ammonia, lithium, sodium, calcium, potassium, aluminium, iron, magnesium, zinc and the like. Salts can also be formed with suitable organic bases. Such bases suitable for the formation of pharmaceutically acceptable base addition salts with compounds of the present invention include organic bases which are non-toxic and strong enough to form salts. Such organic bases are already well known in the art and may include amino acids such as arginine and lysine, mono-, di-, or trihydroxyalkylamines such as mono-, di-, and triethanolamine, choline, mono-, di-, and trialkylamines, such as methylamine, dimethylamine, and trimethylamine, guanidine; AT-methylglucosamine; JV-methylpiperazine; morpholine; ethylenediamine; JV-benzylphenethylamine; tris(hydroxymethyl) aminomethane; and the like. Salts may be prepared in a conventional manner using methods well known in the art. Acid addition salts of said basic compounds may be prepared by dissolving the free base compounds of the invention in aqueous or aqueous alcohol solution or other suitable solvents containing the required acid. Where a compound of the invention contains an acidic function, a base salt of said compound may be prepared by reacting said compound with a suitable base. The acid or base salt may separate directly or can be obtained by concentrating the solution e.g. by evaporation. The compounds of this invention may also exist in solvated or hydrated forms. The invention also extends to a prodrug of the aforementioned compounds such a? an ester or amide thereof. A prodrug is any compound that may be converted under physiological conditions or by solvolysis to any of the compounds of the invention or to a pharmaceutically acceptable salt of the compounds of the invention. A prodrug may be inactive when administered to a subject but is converted in vivo to an active compound of the invention. The compounds of the invention may contain one or more asymmetric carbon atoms and may exist in racemic and optically active forms. The compounds of the invention may exist in trans or cis form. The first aspect of the invention covers all of these compounds. As specific examples of compounds of the formula I above there may be mentioned compounds listed in Table A below. Wherein "Me", "Et", "n-Pr", "i-Pr", "n-Bu", "t-Bu" and "Ph" mean "methyl group", "ethyl group", 'Vpropyl group", "isopropyl group", ";i-butyl group", "terf-butyl group" and "phenyl group" respectively. Table A (Table Removed) In a second aspect, the present invention provides a compound of formula 11-26, III-OI and IV which are useful as synthetic intermediates for a compound of formula I: 1) A compound of (he formula 11-26 (Figure Removed) wherein R1 - R6 are as defined for formula I above; R45 is C1-C8 optionally substituted alkyl or optionally substituted arylalkyl; with the provisos: that R1, R2 and R4 are not all H; R45 is preferably tert-butyl or benzyl. 2) A compound of the formula III-OI (Figure Removed) wherein R1 - R6 are as defined for formula I above; R45 is C1-C8 optionally substituted alkyl or optionally substituted arylalkyl; with the provisos: that R,1. R2 and R4 are not all H; R45 is preferably terr-butyl or benzyl. 3) A compound of the formula IV (Figure Removed) wherein R1 - R6 are as defined for formula I above; with the provisos: that R1, R2 and R4 are not all H; that R4 is not optionally substituted aryl or optionally substituted heteroaryl. The pyrazolo[l,5-fl]pyrimidine derivatives represented by formula I above exist as tautomers represented by the following formula X and XI: (Figure Removed) wherein R1 - R6 are as defined for formula I above; These tautomers are also encompassed within the scope of the present invention. In a third aspect, the present invention provides a process for the manufacture of a compound of the invention by reaction of a compound of formula II, III, TV, V, VI, VII, V-01, IV-01,11-01, H-03,11-04,11-06, H-08, n-13,11-15,11-18, 11-20, 11-22, 11-24, 1-26,1-28 or V-04 as follows, wherein R^R6 are as defined above: 1) reacting a compound of the formula.II (Figure Removed) with acid e.g. trifluoroacetic acid for removal of *-butoxycarbonyl groups of a compound (for example as described in Protective Groups in Organic Synthesis, 3rd Ed, John Wiley & Sons Lnc) 2) reacting a compound of the formula III (Figure Removed) with a compound of the formula R5R6NH either in the absence or presence of transition metal catalyst under e.g. Buchwald conditions (for example as described in J. Am. Chem. Soc. 1994,116,7901.) 3) reacting a compound of the formula IV (Figure Removed) with a compound of the formula R5R6NH 4) reacting a compound of the formula IV (Figure Removed) with a compound of the formula di /-butyl dicarbonate (for example as described in Protective Groups in Organic Synthesis, 3rd Ed, John Wiley & Sons Inc) 5) reacting a compound of the formula V (Figure Removed) with a compound of the formula R3NH2 or R3NHAc in the presence of base e.g. triethylamine and sodium hydride 6) reacting a compound of the formula VI (Figure Removed) with a halogenating agent e.g. phosphorus oxychloride or phenyl phosphonic dichloride (for example as described in US 3907799 (CA 1975, 84, 4998p), J. Med. Chem. 1977, 20,296, Monatsh Chem. 1986,117,1305.) 7) reacting a compound of the formula VII (Figure Removed) (VII) with a compound of the formula R4CH(CO2Me)2 or R4CH(C02Et)a (for example as described in J. Med. Chem. 1976,19, 296 and J. Med. Chem. 1977, 20, 296.) 8) reacting a compound of the formula V-01 (Figure Removed) (V-01) with a halogenating agent e.g. ^-chlorosuccinimide, JV-brornosuccinirnide (for example as described in J. Med. Chem. 1976,19,517.) or iodine monochloride 9) reacting a compound of the formula V-01 (Figure Removed) with a thiocyanating agent e.g. combination of potassium thiocyanate and bromine 10) reacting a compound of the formula V-01 (Figure Removed) (V-01) with an acylating agent e,g. dimethyl fonnamide/phosphorus ox3'chloride or acetyi chloride/aluminium trichloride 11) reacting a compound of the formula IV-01 (Figure Removed) with a Grignard reagent e.g. methyl magnesium chloride 12) reacting a compound of the formula 11-01 (Figure Removed) with an acylating agent e.g. trifluoroacetic anhydride 13) reacting a compound of the formula 11-01 (Figure Removed) with fluorinating agent e.g. l-chloromethyl-4-fluoro-l,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate) (3. Chem. Soc. Perkin 1, 1996, 2069.) 14) reacting a compound of the formula 11-03 (Figure Removed) with aqueous sodium hydroxide for the hydrolysis of ester group in compound; R67 is methyl or ethyl (Figure Removed) 15) reacting a compound of the formula 11-04 with amine derivatives in the presence of peptide coupling agent e.g. etliyl-S-^'-dimethylarninopropyl) carbodiimide hydrochloride, W-hydorojiybenzolriasoIe monohydrale and tri&thyla.min£ 16) reacting a compound of the formula 11-06 (Figure Removed) with oxidizing agent e.g. iodosobenzene diacetate for Hofmann rearrangement in the presence of benzyl alcohol (for example as described in J. Org. Chem. 1979, 44, 1746 and Synthesis 1981, 266. ), followed by removal of the benzyloxy carbonyl group by hydrogenolysis in the presence of palladium on carbon (for example as described in Protective Groups in Organic Synthesis, 3rd Ed, John Wiley & Sons Inc) 17) reacting a compound of the formula 11-08 (Figure Removed) with a compound of the formula R12COC1, R12COOH, R10SO2C1, R10NCO or R10NCS 18) reacting a compound of the formula 11-13 (Figure Removed) with alcohol derivatives in the presence of e.g. diisopropyl azodicarboxylate and polymer supported triphenylphosphine under e.g. Mitsunobu conditions (for example as described in Synthesis 1981,1.); Ar1 represents C6-C14 optionally substituted aryl or optionally substituted heteroaryl 19) reacting a compound of the formula 11-15 (Table Removed) with boronic acid derivatives in the presence of transition metal catalyst under e.g. Suzuki coupling conditions (for example as described in Chem. Rev. 1995,95,2457.); Ar1 represents C6-C14 optionally substituted aryl or optionally substituted heteroar)'! 20) reacting a compound of the formula 11-15 (Figure Removed) with a 1-alkyne in the presence of transition metal catalyst under Sonogashira coupling conditions (Synthesis 1980, 627, and Comprehensive Organic Synthesis, Vol. 3, p. 521, 1991.); Ar1 represents C6-C14 optionally subGlituted aryl or optionally subctituled hete.roaryl 21) reacting a compound of the formula 11-18 (Formula Removed) with a compound of the formula R16R17NH in the presence of peptide coupling agent; Ar1 represents C6-C14 optionally substituted aryl or optionally substituted heteroaryl 22) reacting a compound of the formula 11-20 (Figure Removed) with an alkyl lithium e.g. n-butyl lithium under Weinreb conditions (for example as described in Tetrahedron Lett. 1981,22,3815.) 23) reacting a compound of the formula 11-22 (Figure Removed) with alkyl halide e. g. methyl iodide in the presence of base, followed by trifluoroacetic acid and sodium hydroxide, respectively, for removal of f-butoxycarbonyl and trifluoroacetyl group from a compound 24) reacting a compound of the formula 11-08 (Figure Removed) with an aldehyde e.g. benzyl aldehyde in the presence of reducing agent e.g. sodium acetoxyborohydride 25) reacting a compound of the formula 11-24 (Figure Removed) v/ith alkyl halide e. g. methj'l iodide in the presence of base e. g. sodium hydride 26) reacting a compound of the formula 1-26 (Figure Removed) with H2 in the presence of Pd(OH)2-C or alpha-chloioethyl chloroformate followed by methanol for removal of R60 group from a compound (for example as described in Protective Groups in Organic Synthesis, 3rd Ed, John Wiley & Sons Inc); R60 is benzyl orp-MeO-benzyl; n is 1, 2 or 3 27) reacting a compound of the formula 1-28 (Figure Removed) with halogenating agent e.g. iodine monochloride 28) reacting a compound of the formula V-04 (Figure Removed) with reducing agent e.g. sodium borohj'dride or with diol derivative e.g. propane 1,3-diol and ethane 1,2-diol for formation of acetal. A compound of formula I may undergo one or more further reactions to provide a different compound of formula I. For example, a compound may undergo a reduction, oxidation, elimination, substitution and/or addition reaction. Figure 2-8 shows a general reaction scheme for the preparation of compounds of Formula I. The compounds of formula V, VI, VII and VIII are either known or can be prepared by methods analogous to those known for preparing analogous known compounds. Other methods will be apparent to the chemist skilled in the art, as will the methods for preparing starting materials and intermediates. The Examples also make apparent various methods of preparing compounds of the invention as well as starting materials and intermediates. In a fourth aspect, the present invention provides a composition comprising a compound of the invention in combination with a pharmaceutically acceptable carrier, diluent or excipient. The composition may also comprise one or more additional active agents, such as an anti-inflammatory agent (for example a p38 inhibitor, glutamate receptor antagonist, or a calcium channel antagonist), a chemotherapeutic agent and/or an antiproliferative agent. Suitable carriers and/or diluents are well known in the art and include pharmaceutical grade starch, mannitol, lactose, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, (or other sugar), magnesium carbonate, gelatin, oil. alcohol, detergents, emulsifiers or water (preferably sterile). The composition may be a mixed preparation of a composition or may be a combined preparation for simultaneous, separate or sequential use (including administration). The composition according to the indention for use in the aforementioned indications ma.j' be administered by any convenient method, fcr example by oral (including by inhalation), parenteral, mucosal (e.g. buccal, sublingual, nasal), rectal or transdermal administration and the compositions adapted accordingly. For oral administration, the composition can be formulated as liquids or solids, for example solutions, syrups, suspensions or emulsions, tablets, capsules and lozenges. A liquid formulation will generally consist of a suspension or solution of the compound or physiologically acceptable salt in a suitable aqueous or non-aqueous liquid carriers) for example water, ethanol, glycerine, polyethylene glycol or an oil. The formulation may also contain a suspending agent, preservative, flavouring or colouring agent. A composition in the form of a tablet can be prepared using any suitable pharmaceutical carrier(s) routinely used for preparing solid formulations. Examples of such carriers include magnesium stearate, starch, lactose, sucrose and microcrystalline cellulose. A composition in the form of a capsule can be prepared using routine encapsulation procedures. For example, powders, granules or pellets containing the active ingredient can be prepared using standard carriers and then rilled into a hard gelatin capsule; alternativel}', a dispersion or suspension can be prepared using any suitable pharmaceutical carriers), for example aqueous gums, celluloses, silicates or oils and the dispersion or suspension then filled into a soft gelatin capsule. Compositions for oral administration may be designed to protect the active ingredient against degradation as it passes through the alimentary tract, for example by an outer coating of the formulation on a tablet or capsule. Topical parenteral compositions consist of a solution or suspension of the compound or physiologically acceptable salt in a sterile aqueous or non-aqueous carrier or parenterally acceptable oil, for example polyethylene gtycol, polj'vinyl pyrrolidone, lecithin, arachis oil or sesame oil. Alternatively, the solution can be lyophilised and then reconstituted with a suitable solvent just prior to administration. Compositions for nasal or oral administration may conveniently be formulated as aerosols, drops, gels and powders. Aerosol formulations typically comprise a solution or fine suspension of the active substance in a physiologically acceptable aqueous or non-aqueous solvent and are usually presented in single or multidose quantities in sterile form in a sealed container, which can take the form of a cartridge or refill for use with an atomising device. Alternatively the sealed container may be a unitary dispensing device such as a single dose nasal inhaler or an aerosol dispenser fitted with a metering valve which is intended for disposal once the contents of the container have been exhausted. Where the dosage form comprises an aerosol dispenser, it will contain a pharmaceutically acceptable propellant. The aerosol dosage forms can also take the form of a pump-atomiser. Compositions suitable for buccal or sublingual administration include tablets, lozenges and pastilles, wherein the active ingredient is formulated with a carrier such as sugar and acacia, tragacanth, or gelatin and glycerin. Compositions for rectal or vaginal administration are convenientl3'in the form of suppositories (containing a conventional suppository base such .as cocoa butter), pessaries, vaginal tabs, foams or enemas. Compositions suitable for transdermal administration include ointments, gels, patches and injections including powder injections. Conveniently the composition is in unit dose form such as a tablet, capsule or ampoule. In a fifth aspect, the present invention provides a process for the manufacture of a composition according of the invention which comprises admirdng one or more compounds of the invention with one more pharmaceutically acceptable excipients, carriers or diluents. The manufacture can be carried out by standard techniques well known in the art and involves combining a compound according to the first aspect of the invention and the pharmaceutically acceptable carrier or diluent. The composition may be in any form including a tablet, a liquid, a capsule, and a powder or in the form of a food product, e.g. a functional food. In the latter case the food product itself may act as the pharmaceutically acceptable carrier. In a sixth aspect, the present invention provides a compound or composition of the invention, for use in medicine. The compounds of the present invention are inhibitors of protein kinases such as mitogen-activated protein kinases, particularly mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2), or cyclin dependent kinases (CDK) e.g,, CDK1 and CDK2. Preferably, the compounds of the invention inhibit MAPKAP-K2 or CDK selectively (Le., the compounds of the present invention show greater activity against one kinase than the other). For the purpose of this invention, an inhibitor is any compound which reduces or prevents the activity of a protein kinase. The compounds are therefore useful for conditions for which inhibition of protein kinase activity is beneficial. Thus, preferably, this aspect provides a compound of the first aspect, or a composition of the third aspect of the present invention, for the prevention or treatment of a protein kinase-mediated disorder. The compounds of the first aspect of the indention may thus be used for the inhibition of protein Irjnase. A "protein kinase-mediated disorder" is nuy disease or deleterious condition in which protein kinase plays a role. Examples include neurological disorder (including dementia), inflammatory disease, a disorder linked to apoptosis, particularly neuronal apoptosis, stroke, sepsis, autoimmune disease, destructive bone disorder, proliferative disorder, cancer, tumour growth, infectious disease, allergy, ischemia reperfusion injury, heart attack, angiogenic disorder, organ hyppxia, vascular hyperplasia, cardiac hypertrophy and thrombin induced platelet aggregation. The compounds of the present invention are particularly useful for the prevention or treatment of a neurodegenerative disorder. In particular, the neurodegenerative disorder results from apoptosis and/or inflammation. Examples of neurodegenerative disorders are: dementia; Alzheimer's disease; Parkinson's disease; Amyotrophic Lateral Sclerosis; Huntington's disease; senile chorea; Sydenham's chorea; hypoglycemia; head and spinal cord trauma including traumatic head injury; acute and chronic pain; epilepsy and seizures; olivopontocerebellar dementia; neuronal cell death; hypoxia-related neurodegeneration; acute hypoxia; glutamate toxicity including glutamate neurotoxicity; cerebral ischemia; dementia linked to meningitis and/or neurosis; cerebrovascular dementia; or dementia in an HIV-infected patient. The compounds of the invention can also be used to prevent or treat disorders resulting from inflammation. These include, for example, inflammatory bowel disorder, bronchitis, asthma, acute pancreatitis, chronic pancreatitis, allergies of various types, and possibly Alzheimer's disease. Autoimmune diseases which may also be treated or prevented by the compounds of the present invention include rheumatoid arthritis, systemic lupus erythematosus, Sjogren S3Tidrome, psoriatic arthritis, glomerulonephritis. cc-ltroderma, chronic thyroiditis, Graves's disease, autoimmune gastritis, diabetes, autoimmune juaemolylis anaemia, autoimmune neutropaenia, tlirombocytopenia, atopic dermatitis, chronic active hepatitis, inyasthenia gravis, multiple sclerosis, ulcerative coh'tis, Crohn's disease, psoriasis or graft \>s host disease. A compound of the present invention may be administered simultaneously, subsequently or sequentially with one or more other active agent, such as an anti-inflammatory agent e.g, p38 inhibitor, glutamate receptor antagonist, calcium channel antagonist, a chemotherapeutic agent or an antiproliferative agent. For example, for acute treatment, a p38 inhibitor may be administered to 'a patient prior to administering a compound of the present invention. The compounds of the invention will normally be administered in a daily dosage regimen (for an adult patient) of, for example, an oral dose of between 1 mg and 2000 mg, preferably between 30 mg and 1000 mg, e.g. between 10 and 250 mg or an intravenous, subcutaneous, or intramuscular dose of between 0.1 mg and 100 mg, preferably between 0.1 mg and 50 rag, e.g. between 1 and 25 mg of the compound of the formula I, or a physiologically acceptable salt thereof calculated as the free base, the compound being administered 1 to 4 times per day. Suitably the compounds will be administered for a period of continuous therapy, for example for a week or more. In a seventh aspect, the present invention provides a method of treating or preventing a protein kinase-mediated disorder in an individual, which method comprises administering to said individual one or more compounds of the invention or a composition of the invention. The active compound is preferably administered in a cumulative effective amount. The individual ma)' be in need of the treatment or prevention. Any of the protein kinase-mediated disorders listed above in relation to the fifth aspect may be the subject of treatment or prevention according to the si:;:th aspect. One or more oilier active agent may be administered to the individual simultaneously, subsequently or sequentially to administering the compound. The other active agent may be an anti-inflammatory agent such as a p3S inhibitor, glutamate receptor antagonist, calcium channel antagonist, a chemotherapeutic agent or an antiproliferative agent. In an eighth aspect, the present invention provides the use of a compound of the invention in the manufacture of a medicament for the prevention or treatment of a protein kinase-mediated disorder. The medicament may be used for treatment or prevention of any of the protein kinase-mediated disorders listed above in relation to the fifth aspect. Again, the compounds of the present invention may be administered simultaneously, subsequently or sequentially with one or more other active agent such as a p38 inhibitor. In a ninth aspect, the present invention provides an assay for determining the activity of the compounds of the present invention, comprising providing a system for assaying the activity and assaying the activity of the compound. Preferably the assay is for the protein kinase inhibiting activity of the compound. The compounds of the invention may be assayed in vitro, in vivo, in silica, or in a primary cell culture or a cell line. In vitro assays include assays that determine inhibition of the kinase activity of activated protein kinase. Alternatively, in vitro assays may quantitate the ability of a compound to bind protein kinase and may be measured either by radiolabelling the compound prior to binding, then isolating the inhibitor/ protein kinase complex and determining the amount of the radiolabel bound or by running a competition experiment where new inhibitors are incubated with protein kinase bound to known radioligands. An ezample of an assay which ma}' be used is Scintillation Frccirnity Assay ("PAX preferably using radiolabelled ATP. Another example is ELISA. An;1 type or isoforrn of protein kinase may be used in these assays. In a tenth aspect, the present invention provides a method of inhibiting the activity or function of a protein kinase. which method comprises exposing a protein kinase to a compound or a composition of the invention. The method may be performed in a research model, in vitro, in silica, or in vivo such as in an animal model. A suitable animal model may be a kainic acid model in rat or mice, traumatic brain injury model in rat, or MPTP in mice for neurodegenerative disorder and a collagen induced arthritis model in rat or mice, type II collagen-antibodies induced arthritis in mice, or a LPS induced endotoxin shock model in mice for inflammatory disease. All features of each of the aspects apply to all other aspects mutatis mutandis. Examples The invention will now be explained in greater detail by the following examples, with the understanding that the scope of the invention is not in any sense restricted by these examples. The numbers assigned to each of the compounds in the examples correspond to the Compound Nos. of the compounds listed as specific examples in Tables A above. Structures of isolated novel compounds were confirmed by !H NMR and/or other appropriate anatyses. Compounds were characterised by mass spectrometry using single quadrupole instrumentation with an electrospray source. M+H indicates values obtained for compound molecular mass (M) with proton (H) capture and M-H compound molecular mass (M) with proton (H) loss. Melting points (mp) are uncorrected; (d) denotes decomposition at or near the melting point. Compounds which were not solids were gums. The JLH-MMR spectra (400 MHz, DMSO-d6 or CDC13) of selected compounds of the invention were measured. The data for the chemical shifts (d: ppm) and coupling constants (J: Hz) are shown. The "HFLC retention time" data for the compounds synthesized in the examples are the retention time for the compounds in HPLC analysis carried out under the following conditions. HPLC (High Performance Liquid Chromatography) conditions System: Hewlett-Packard 1100 HPLC Column: Cadenza CD-CIS (Imtakt) 100 mm x 4.6 mmf [Method AJ Solvent: A: H2O/acetonitrile = 95/5 0.05% TFA (trifluoroacetic acid) B: H2O/acetonitrile = 5/95 0.05% TFA (trifluoroacetic acid) Flow rate: 1.0 mL/min Gradient: 0-1 min, solvent B: 10% solvent A: 90% 1-13 min, solvent B: 10% -+ 70% solvent A: 90% -»• 30% 13-14 min, solvent B: 70% -*• 100% solvent A: 30% —:• 0% 14-16 min, solvent B: 100% solvent A: 0% 16-19 min, solvent B: 100% -=•• 10% solvent A: 0% -?• 90% Calculation of purity: Area % of UV absorption (254 nm) [Method B] Solvent: A: H20/ace1:onitrile = 95/5 0.05% TFA (trifluoroacetic acid) B: H20/acetonitrile = 5/95 0.05% TFA (trifluoroacetic acid) Flow rate: 1.0 mL/min Gradient: 0-1 min, solvent B: 5% solvent A: 95% 1-13 min, solvent B: 5% -* 55% solvent A: 95% -»• 45% 13-14 min, solvent B; 55% -»• 100% solvent A: 45% -»0% 14-17 min, solvent B: 100% solvent A: 0% 17-18 min, solvent B: 100% -» 5% solvent A: 0% -»95% Calculation of purity: Area % of UV absorption (254 nm) [Method C] Solvent: A: H20/acetonitrile = 95/5 0.05% TFA (trifluoroacetic acid) B: H2O/acetonitrile = 5/95 0.05% TFA (trifluoroacetic acid) Flow rate: 1.5 mL/min Gradient: 0-1 miri. solvent B: 2% solvent A: 98% 1-9 min, solvent B: 2% -* 30% solvent A: 98% -* 70% 9-13 min, solvent B: 30% -> 100% solvent A: 70% -* 0% 13-16 min, solvent B: 100% solvent A: 0% 16-17.5min, solvent B: 100% -+ 2% solvent A: 0% -* 9S% Calculation of purity: Area % of UV absorption (254 run) [Method D] Solvent: A: H2O/acetonitrile = 95/5 0.1% MEt3 (triethyl amine) B: H2O/acetonitrile = 5/95 0.1 % NEt3 (triethyl amine) Flow rate: 1.5 mL/min Gradient: 0-1 min, solvent B: 10% solvent A: 90% 1-14 min, solvent B: 10% -»100% solvent A: 90% -»0% 14-16 min, solvent B: 100% solvent A: 0% 16-17 min, solvent B: 100% -»10% solvent A: 0% -> 90% 17-20min, solvent B: 10 solvent A: 90% Calculation of purity: Area % of UV absorption (254 nm) EXAMPLE 1 [General Procedure for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (VI)] To a stirred solution of sodium ethoxide (50 mmol) in ethanol (100 mL) was added the appropriately 2-substituted malonic acid diester (20 mmol) and appropriately substituted 3-aminopyrazole (VII) (20 mmol). The mi?:ture was heated at refluj; for 18 h, during which a precipitate formed." The reaction was cooled to room temperature and the mixture was filtered through an A4 sinter (whilst washing with a minimum of cool ethanol). The residue was dried under vacuum. The dried precipitate was dissolved in water (ca. 100 mL) and the resulting solution was acidified (pH 2) with concentrated HC1. This rendered a pale-white precipitate (VI), which v/as filtered, and dried. Typical unoptimisec! yields ranged from 20-40%. *In several cases where the substituent was an alkyl chain, little or no precipitate v/as formed. In these situations, the ethanol was removed under reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous phase was acidified (pH 2) with concentrated HC1 and back-extracted with ethyl acetate. The organic phase was washed (water and saturated aqueous Nad) and dried (MgS04) to give the desired bis-hydroxy compound (VI). (Figure or Table Removed) EXAMPLE 2 [General Procedure for the Synthesis of Fyrazolo[l,5-«]pyrimidines of General Formula To a suspension of bis-hydroxy compound (VI) (2 g) in .A/.W-dimethylaniline (2 mL) was added phosphorous oxychloride (or phenyl phosphonic dichloride) (20 mL). The mixture v/as heated at reflux for 18 h, and excess phosphorus oxychloride (or phenyl phosphonic dichloride) was removed in mcuc. The. residue v/as poured onto ice (50 g) and extracted with CffcClo (5 ji). The organic phase was adsorbed, onto neutral (activity I) alumina and chroraatographed (typically using petrol—> 30% ethyl acetate/petrol as eluent). To gave the appropriately substituted 5,7-dichlorop3'razolo[l,5-tf]pyrimidine intermediate (V) in yields of ca. 40 % values. (Figure or Table Removed) EXAMPLE 3 [General Procedure for the Synthesis of Pyrazolo[l,5-tf]pyrimidmes of General Formula (Y-02)] A solution of the 5,7-dichloropyrazolo[l,5- chloroform (50 mL) was treated with W-chlorosuccinimide, //-broinosuccinimide or iodine monochloride (0.011 mol) at room temperature. The mixture was boiled under re-flic: until all solidc were dissolved and no starting material remained (by TLC). The mixture was poured onto ice/water and. the organic layer was separated, washed with aqueous NaaCOs, dried over MgSO^, and the solvent removed in vacuo. The residual material was purified by chromatography over silica gel to provide the 3-halo-5,7-dichloropyrazolo[l,5-0]pyriimdme(V-02). (Table Removed) EXAMPLE 4 [General Procedures for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (V-03)] Synthesis of {5,7-dichloro(pyrazolo[l,5-a]pyramidin-7-yl)}thiocarbonitrile. Cl (Figure Removed) To a solution of powdered potassium thiocyanate (2.66 g) in acetic acid (20 mL) was added slowly a solution of bromine (0.72 mL) in acetic acid (3 mL) whilst maintaining the temperature between 10 - 15 °C. 5,7-Pichloropyrazolc»[1.5-(?]pyrimidine (2.5 g) in acetic acid (30 mL) v/ac added and the resulting solution was stirred at 15 °C for 30 min and then room temperature for 3 h after which, the solvent was removed under reduced pressure. Water and ethyl acetate were added and the product was extracted with ethyl acetate (3x). The combined organic phace was dried (HasSO^), evaporated and. subjected to flash chromatography to give the title compound (780 mg, 73 % pure by 'H-HMR); ^I-MvlF, (40U MHz, CPC13) d(ppm): 8.27 (1H, s, 2-H), 7.10 (1H, s, 6-H). EXAMPLE 5 [General Procedures for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (V-04)] Synthesis of 5,7-dichloro-6-methylpyrazolo[l,5-o]pyrimidine-3-carbaldehyde. (Figure Removed) To 7/^V-dimethyl formamide (9 mL) under nitrogen at room temperature was added POC13 (3mL) and the resulting slurry was stirred for 5 min. 5,7-Dichloro-6-methylpyrazolo[l,5-fl]pyrimidine (5g) was slowly added and resulting thick mixture was heated at 70°C for 3 h. The mixture was poured onto ice and basified with sodium hydroxide (5g). The residue was filtered and the dried precipitate chroma'tographed on silica gel (eluting with CH2C12-*20 % ethyl acetate/ CH2C12) to give the title compound (3.74 g); mp 137-139 °C. EXAMPLE 6 [General Procedures for the Synthesis of Pyra£olo[l55-a]pyrimidmes of General Formula (V-05)] Synthesis of {5,7-dichloro-6-methyl(pyra2olo[l,5-a]pyrimidin-3-yl)}methanol. Gl HO- To 5;7-dichloro-6-methylp)'razolo[l,5-c]pyrimidine-3-carbaIdehyde (200 mg) in ethanol (20 mL) was added sodium borohydride (70mg) and the reaction mixture was stirred at room temperature for 15 min. Saturated aqueous NTttCl (1 mL) was added and the reaction mixture was stirred for a further 10 min then the solvent was removed under reduced pressure. Water and ethyl acetate were added and the product was extracted with ethyl acetate (3x). The combined organic phase was washed (water, saturated aqueous NaCl) and dried (MgS04) to give the title compound (150 mg); 'H-NMR (400 MHz, CDC13) d(ppm): 8.22 (1H, s, 2-H), 4.90 (1H, s, CH2OH). EXAMPLE? [General Procedures for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (V-06)] Synthesis of 2-{5,7-dichloro-6-meth3'l(p)'razolo[l,5-«]p3'rimidin-3-yl)}-l,3-dioxane. Cl (Figure Removed) To 5,7-dichloro-6-meth)'lpyrazolo[l,5-a]p3'rirnidine-3-carbaldehyde (290 mg) in toluene (40 mL) was added pyridinium p-toluenesulfonate (60 mg) and propan-l,3-diol. The rriL.ture was then heated under refiui: for 2h, with aseotropic removal of water. The solution was cooled and evaporated under reduced pressure. The residue was chroraatographed on silica gel using ethyl acetate/petroleum ether 2/3 as eluent to give the title compound (310 mg) as a white solid; ]H-i TMR (400 MHz, CPC13) d(ppm): S.32 (1H, s, 2-HX 5.97 (1H, s, Cff02R), 4.25 (2H, br dd, OCH^), 4.05 (2H, br t, OCH«), 2.50 (3H, s, 6-Me), 2.25 (1R m, CCHegRC), 1.48 (1H, br d, CCHff«C). EXAMPLE 8 [General Procedures for the Synthesis of Pj'razolo[l,5-fl]pyrimidines of General Formula (IV) and (IV-01)] a) To a solution of (appropriately substituted) 5,7-dichloropyrazolo[l,5-ojpyrimidine (V) or {5,7-dichloro(pyrazolo[l,5-fl]pyramidin-7-yl)}thiocarbonitrile and triethylamine (2 equivalents) in 2-propanol (20 mL) was added the amine R3NH2 (1 or 1.1 equivalents) and the mixture was stirred at room temperature overnight. The mixture was concentrated in vacua and the residue was then partitioned between water and CHjCla. The organic phase was washed twice with water and the combined aqueous phases back-extracted with CHzClz- The organic layer was combined, washed with saturated aqueous NaCl and dried over Na2SC>4. Removal of the solvent in vacua yielded the precursor (IV). [Purification performed - normally the products did not require any further purification, if they did, they were recrystallised. Analysis performed - JH-NMR, HPLC and MS]. Should the above room-temperature reaction not occur satisfactorily, the following may be applied: b) To a solution of the 5,7-dichlorop3'razolo[l,5-fl]pyrimidine (V) (2 g) in 2-propanol (25 mL) containing 7V,Af-diisopropylethylamine (2 equivalents) was added the amine R'NHi (1.2 equivalents). The reaction was heated overnight at 80 °C and the solvent removed in vacuo. The residue was partitioned between water and CH^Cla and the organic phase v/ac \vashed with water, saturated aqueous Had and dried, oyer MgSC'4. Removal of the solvent in vacua yielded the product (TV). c) To a stirred suspension of sodium hydride (50 mmol) in /^//-dirnethylformamide (30 mL) was added appropriately substituted aniline derivative (25 mmol) and then appropriately substituted 5,7-dichloropyrazolo[l,5-0]pyrimidine (V) (25 mmol) in tetrahydrofuran (50 mL). The resulting mixture was stirred at 50 °C for 2 h. The reaction was quenched with saturated aqueous NELiCl. After extraction with ethyl acetate, the combined organic layer was washed with saturated aqueous Nad and dried over MgSO4. The solvent was removed in vacuo to give the crude title compound (IV). Typical unoptimised yields for d) 60 - 80 %. d) To a solution of 2-chloroacetanilide (2.2 mmol) in toluene (3 mL) at room temperature was added sodium hydride (3 mmol) after the addition the mixture was heated until effervescence ceased and the solution became homogenous. The appropriately substituted 5,7-dichloropyrazolo[l,5-a]pyrimidine (V) (1 mmol) was added and the mixture heated at reflux for 5 h. (The solution became heterogeneous during this time). Upon cooling, acetic acid (1 mL) and water (1 mL) were cautiously added and the mixture was stirred for 15 min. The solvent was removed in vacua and the residual acetic acid removed by azeotropic evaporation with toluene (3x). The residue was partitioned between water and ethyl acetate. The organic phase was washed (water and saturated aqueous HaCl) and dried. The solvent was removed in vacuo and. the residue was chromatographed to afford the desired compound (TV). Typical unoptimised yields for c) 50 - 70 %. The R/ of starting material (V) and product (IV) are chromatographically indistinguishable, making complete reaction difficult to detennine. It appears that at least 5 h is required for significant reaction to occur. (Table Removed) EXAMPLE 9 [General Procedure for the Sj'nthesis of Pyrazolo[l,5-c]pyrimidines of General Formula (IV-02)] Synthesis of (3-chloro-4-fluorophenyl) {5-chloro-3-methylthio(pyrazolo[l,5-ar]pyrimidin-7-3'l)}amine. (Figure Removed) Methyl magnesium chloride (0.25 mL, 3M solution) was added cautiously to a solution of {5-chloro-7-[(?-chloro-4-fluorophen^ } thiocarbonitrile (100 mg) in dry letrahydrofuran (5 mL) while maintaining the temperature between 0 - 4 °C for 2 h. Acetic acid. (2 equivalents.) was added and the solvent was removed under reduced pressure. Water and ethyl acetate were added and the product was extracted with ethyl acetate (3x). The combined organic phase was dried (NaoSC^) and evaporated to give the title compound (98 mg); mp 156-158 °C. EXAMPLE 10 [General Procedure for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (III)] To a solution of the precursor (IV) formed above (2 g) in 1,4-dioxane (10 mL) was added di-terf-butyl dicarbonate (2 equivalents) in 1,4-dioxane (10 mL) followed by a catalytic amount of 4-dimethylaminopyridine. The reaction was stirred at room temperature overnight and if starting material was detected by TLC, the reaction was left for longer. The mixture was concentrated in vacua and the residue was then partitioned between water and CHsCb. The organic phase was washed with 10% citric acid, water and saturated aqueous NaCl and then dried over MgSO,*. Removal of the solvent in vacua gave the Boc protected intermediate (III). [Purification performed -filter column to remove any residual 4-dimethylaminopyridine. Analysis performed -1H-NMR,HPLCandMS]. (Table Removed) EXAMPLE 11 (General Procedures for the Synthesis of Fyrazolo[1.5-fl]pyrimidines of General Formula (II)] An intimate mixture (III) (100 mg) and amine (HNR5R6) (1.5 g) were heated together at 80 - 85 °C for 18 h, then cooled. The crude material was then partitioned between ethyl acetate and saturated aqueous NaHCOa. The organic phase was then separated, washed with water and dried over MgSO4 and concentrated in vacua. The crude material was then subjected to column chromatography over silica gel. CHbCk was used as eluent, then gradient elution up to 95% CH2Cl2 + 5% (10 M NHa in methanol). Typical purified yield 20 mg. A solution of the Boc intermediate (III) (0.248 mmol), the amine (HNR5R6) (0.496 mmol), copper iodide (0.496 mmol), and potassium carbonate (0.496 mmol) in DMSO (0.8 mL) was stirred at 85 °C for 2 days. The reaction mixture was cooled to room temperature, followed by quenched with saturated aqueous NTLtCl. The mixture was extracted with Et2O. The combined extract was washed with saturated aqueous Nad, dried over NaoSO^ filtered, and evaporated. The residue was purified by column cliromatography (5-10% MeOH-GHbCk) to give the title compound (II). c) Synthesis of 4-{7-[tert-Buto::ycarbonyl-(4-etho;:y-phenyl)-amino]-6-meth)'l-pyra2;olo[l,5-fl] pyrimidin-5-ylarnmo}-pyrrolidine-l,2-dicarboxylic acid 1-tert-butyl ester (Figure Removed) A solution of the Boc intermediate (0.24S mmol), the (S)-4-amino L-proline (114 mg, 0.496 mmol). copper iodide (94.4 mg. €.496 mmol) and potassium carbonate (6S.5 mg, 0.496 mmol) in DMSO (0.8 mL) was stirred at 85 °C for 2 days. The reaction mixture was cooled to room temperature, followed by quenched with saturated aqueous NHjCl. The mixture was extracted with EtiO. The combined extract was washed with saturated aqueous NaCl, dried over NaaSO,*, filtered, and evaporated. The residue was purified by column chromatography (5-10% MeOH-CHaCla) to give coupling compound (66.0 mg, 44.6%). The title compound was obtained. The !H-NMR for this compound was shown bellow. 'H-NMR (400 MHz, CD3OD) (ppm): 1.25 (t, J=7.1Hz, 3H), 1.34 (s, 18H), 1.95 (m, 1H), 2.56 (m, 1H), 3.44 (m, 1H), 3.69 (m, 1H), 3.89 (q, /=7.1Hz, 2H), 4.16 (m, 1H), 6.05 (m, 1H), 6.74 (d, J=7.1Hz, 2H), 7.14 (d,J = S.5Hz, 2H), 7.68 (s, 1H). (Table Removed) EXAMPLE 12 [General Procedures for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (I)] An intimate mixture of the Boc intermediate (III) (100 mg) and the amine (HNR5R6) (1.5 g) were heated together at 80 - 85 °C for 90 min, then cooled. The crude material was then partitioned between CH2Cl2 and saturated aqueous NaHCOa. The organic phase was then separated and washed with water, dried over MgS04 and concentrated in vacuo. The crude material dissolved in OHfeCla (10 mL) and trifluoroacetic acid (5 mL). The mixture was stirred for 1 h at room temperature, then evaporated in vacuo. The residue was partitioned between saturated aqueous NaHCOa and CPkClo, the organic phase was separated, dried over MgSC>4 then subjected to column chromatography over silica gel. ClrfeCl? vi-as used as eluent, then gradient elution up to 95% CH^Clo + 5% (10 M MHs in methanol). Typical purified yield 20 mg. The Boc intermediate (III) (0.1 rnmol) was dissolved in toluene (1 ml) and the amine (HNR5R6) (1.2 equivalents) was added. Tris(dibenzylideneacetone)dipalladiurn (0) (2 mol %), 2,2'-bis(diphenylphosphino)-l,r-binaphtyl (4 mol %) and sodium ten-butozide (1.2 equivalents) were added sequentially under an atmosphere of nitrogen. The reaction was heated and agitated overnight at SO °C following which the reaction was filtered through a 0.45 micron filter. The solvent was removed in vacua and the residue was resuspended in CHaCla (0.2 mL). Trifluoroacetic acid (0.8 mL) was added and the reactions allowed to stand for 1 h at room temperature. The mixture was evaporated to dryness, in vacua, and the resultant residue was dissolved in jty, JV-dimethylformamide (1 mL), filtered and purified by preparative HPLC to give the product (I). [Analysis performed - LC/MS]. EXAMPLE 13 [General Procedure for the Synthesis of Pyrazolo[l,5-o]pyrimidines of General Formula (1-01)] Synthesis of l-{5-[(rrfl;»j-4-aminocyclohexyl)amino]-7-[(4-iodophenyl)amino]-6-methyl(pyrazolo[lJ To a solution of yclohezy 5-o]pyrimidin-3-yl)}-252,2-trifluoroethan-l-one (compound No: 417). -butoxy)-Af-(4-iodophenyl)carboxamide (50 mg) in 1,2-dichloroethane (1.8 mL) was added trifluoroacetic anhydride (1.8 mL). The resulting mijrture was stirred at 45 °C for 3 h and (hen the solvent was removed /;/ vacuo. The residue was dissolved in CH^C^ (1.25 mL). To this stirred solution was added trifluoroacetic acid (0.53 mL). The resulting mixture was stirred at room temperature for 3 h, and then the solvent was removed in vacuo. The residue was dissolved in letrahydrofuran (1.6 mL) and methanol (0.18 mL). To this stirred solution was added 2mol/L aqueous NaOH (0.18 mL). The resulting mixture was stirred at room temperature for 15 h. The reaction was quenched with aqueous IN HC1. After extraction with CH^Cla, the combined organic layer was washed with saturated aqueous NaCl, dried over NaoSC>4 and then the solvent was removed in vacuo. The residue was purified by preparative HPLC to give the title compound (33.0 mg, yield 41% as 3 trifluoroacetic acids salt) as a white solid. The , HPLC retention time and ESI/MS data for this compound are shown below. (400MHz, DMSCM6) d(ppm): 1.38-1.56 (m, 4H), 1.79 (s, 3H), 1.97-2.12(m, 4H), 3.04(brs, 1H), 4.09(brs, 1H), 6.73(d, /=8.52Hz, 2H), 7.11(d, J=7.32Hz, 1H), 7.57(d,/=S.04Hz, 2H) , 7.86(brs, 3H), 8.34(s, 1H), 9.27(s, 1H). HPLC retention time (method A): 14.7 min. ESI/MS: 559.3 (M+H, EXAMPLE 14 [General Procedure for the Synthesis of Pyrazolo[l,5-fl]pyrimidines of General Formula (1-02)] Synthesis of {5-[(f;-fl/i5'-4-aminocyclohexyl)amino]-3-fluoro-6-methyl(pyrazolo[l,5- )}(4-iodophenyl)amine (compound No: 441). A (Figure Removed) ^-{5-[(ftww-4-aminocycloheAyl)amino]-6-methyl(pyrazolo[1.5-a]pyrimidin-7-y l)}(tert-butoxy)-Ar-(4-iodophenyl)carboxamide (20mg) was dissolved in tetrahydrofuran (300//L). To this solution was added l-chloromethyl-4-fluoro-l,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) (63 mg). The resulting mixture was stirred for 19 h at 40 °C. The reaction was quenched with saturated aqueous NaHCOa. After extraction with CH2Cl2, the combined organic layer was washed with saturated aqueous NaCl, dried over NaaSO4, and the solvent was removed in vacua to give the crude Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CHoCk (2.0 mL). To this solution was added trifluoroacetic acid (0.2 mL). After stirring for 4 h, the solvent was removed in vacua. The residue was purified on preparative TLC to give the title compound (1.5 mg, 9 % yield). The ^-NMR, HPLC retention time and ESI/MS data for this compound are shown below. 'H-NMR (400MHz, CDC13) d(ppm): 1.25(m, 2H), 1.36(m, 2H), 1.72(s, 3H), 1.99(m, 2H), 2.22(m, 2H), 2.72(rn, 1H), 4.14 EXAMPLE 15 [General Procedure for the Synthesis of Fyraiok{if5-a]pyrimidme:. of General Formula (11-04)] Synthesis of (Figure Removed) 5-({trans-4-[(lert-butoxy)carbonylamino]cyclohexyl}amino)-7-[(tert-butoxy)-N-(4-eth.o xj'phenyl)carbon5'lamino]-6-methylpyrazolo[l,5-a]pyrimidine-3-carboxylicacjd. 9H3 O To a stirred suspension of ethyl 5-({fra/i5'-4-[(tot-butoxy)carbonylamino]cyclohexyl}aniino)-7-[(to^-butoxy)-//-(4-etho xyphenyl)carbonylaniino]-6-methylpyrazolo[l,5-fl]pyrimidine-3-carboxylate (5.55 g) in 2-propanol (136 mL) was added 2 mol/L aqueous NaOH (34 mL). The resulting mixture was stirred at 50 °C for 40 h, and then at 80 °C for 4 h. The mixture was acidified (pH 4) with 1 mol/L aqueous HC1 and concentrated in vacuo. The residue Avas suspended in water (150mL) and slowly stirred for 1 h. The precipitate was filtered and dried in vacuo to give the title compound (5.35g, yield 78%) as a white solid. The ^-NMR and ESI/MS data for this compound are shown below. 'H-NMR (400MHz, DMSO-4;) d(ppm): 1.19-1.2S(br, 4H), 1.29(t, J=7.08Hz, 3H), 1.38(s, 1SH), 1.73-1.86(br, 2H), 1.86-2.04(br; 5H), 3.15-3.33(ra, 1H), 3.97(q,/=7.08Hz./ 2H), 4.02-4.0S(m5 1H), 6.43(brs, 1H), 6.82(d; J=S.80Hz, 1H), 6.86(d, J=8.76Hz, 2H), 7.20(d,/=7.SOHz, 2H), 7.93(brs, ESI/MS: 625.5 (M+H, t'jreneral Procedure for the Synthesis of r'yrazolo[l,5: (Figure Removed) 5-({/ra/?.5'-4-[(fe/t-butox)Oc^rbonylarnino]cyclohexyl}amino)-7-[(ife7-;>butoxy)-//-(4-etho X3'phen)'l)carbonylamino]-6-methylp3'razolo[l,5-fl]p)'rimidine-3-carboxarnide. 9H3 Q To a stirred solution of 5-({ft-fl/t5-4-[(te7-/'-butoxy)carbonylamino]cyclohexyl}amino)-7-[(re7-/'-butoxy)-^-(4-etho xyphenyl)carbonylamino]-6-methylpyrazolo[l,5-fl]pyrimidine-3-carboxylic acid (1.25 g) in jV,Ar-dimethylformamide (20 mL) were added ethyl-3-(3'-dimethylaminopropyl)carbodiirmde hydrochloride (1.92 g), JV-hydoroxybenzotriazole monohj'drate (0.31 g), triethylamine (2.8 mL) and ammonia (5.0 mL, 2.0 mol/Lin methanol). The resulting mixture was stirred at room temperature for 24 h. The reaction was quenched with saturated aqueous NaCl. After extraction with CHsClo, the combined organic layer was washed with water, dried over MgSCU, and the solvent was removed ///. vacua to give the crude title compound (1.25 g) as a white solid. This crude product was used in the nezt reaction without further purification. ESI/MS data for this compound are shown below. ESI/MS: 624.6 (M+H, example 17 [General Procedure for the Synthesis of Pyrazolo[l,5-.]pyrimidines of General Formula (11-07)] Synthesis of thoxj'phenyl)carbonylamino]-6-methyl(pyrazolo[l,5-fl]pyrimidin-3-yl)](phenylmethoxy l)carboxamide. (Figure Removed) To a stirred solution of crude 5-({fra;w-4-[(ferf-butoxy)carbonylamino]cyclohexyl}amino)-7-[(te7t-butoxy)-JV-(4-etho xyphenyl)carbonylamino]-6-methylpyrazolo[l,5-fl]pyrimidine-3-carboxamide(1.25g) in benzyl alcohol (5.0 mL) was added potassium tert-butoxide (0.561 g). The resulting mixture was stirred at room temperature for 10 min. and then at 0 °C for 10 min. To this stirred solution was added iodobenzene diacetate (0.773 g), stirred at 0 °C for 10 min., and allowed to warm room temperature. The resulting mixture was stirred at room temperature for 12 h. The reaction was quenched with saturated aqueous PiaCl. After extraction with CH:Cl2j the combined organic layer was dried over MgSO4, and solvent was removed in vacua to give the crude title compound (1.46 g) as pale red oil. This crude product was used in the next reaction without further purification. The :H-NMR and. ESJ/MS data for this compound are shov/n beio\v. 1H-iII-,'IF. (400MHz, PMSO-tfe) d(ppm): 1.18-1.30(brs, 4H), 1.29(t, /=7.0SHz; 3H), 1.38(s, 1SH), 1.75-1.86(m,2H), 1.87-1.97(m, 2H), 2.00(brs, 3H), 3.15-3.28(m, IH), 3.97(t /=7.08Hz, 2H), 3.85-4.10(m, IH), 5.12(s, 2H), 6.43-6.53(m, IH), 6.75(d, /=7.56Hz, 2H), 6.86(d, J=8.80Hz, 2H) , 7.15-7.50(m, 7H)? 7.83(brs, IH), S.86(brs, IH). ESI/MS: 730.7 (M+H, EXAMPLE 18 [General Procedure for the Synthesis of Pyrazolo[l,5-c]pyrimidines of General Formula (11-08)] Synthesis of JV-[3-amino-5-({frfl/w-4-[(terr-butoxy)carbonylamino]cyclohexyl}amino)-6-methyl(pyr azolo[l,5-fl]pyrimidin-7-yl)](terf-butoxy)-^-(4-ethoxyphenyl)carboxamide. (Figure Removed) To a stirred solution of the crude tho?:3'phenyl)carbonylamino]-6-meth}1(pj'razolo[l,5-c]pyrimidin-3-yl)](j:«henylmethoz3r l)carboi:amide (1.46 g) in ethanol (100 mL) and acetic acid (0.4-6 mL) was added Pd/C (0.29 g, 10% on carbon). The resulting mixture was stirred at room temperature for 2 days under hydrogen atmosphere, and Pd/C was filtered off. The solvent was removed in vacuo. The residue was purified by silica gel column chxomatography (elute with ethyl ace=tate./;/.-he::ane = 3/1) to give the title compound (0.560 g, yield 47% for 2 step?) k a pale yellow jolid. The 'H-l IMF. and. EGI/iviG data for this compound, are shown below. 'H-HMR (400MHz, DMSO-fk) rffppm): 1.20-1.35(brs, 4H), 1.29(1, /=7.0SHz, 3H), 1.38(s, 1SH), 1.75-1.90(brs, 3H), 1.90-2.05(m, 4H), 3.22(brs, 1H), 3.92-4.00(m, 3H), 6.21(brs, 1H), 6.77(d, J=8.04Hz, 1H), 6.83-6.87(m, 3H), 7.20(brs, 3H), 7.45(brs: ESI/MS: 596.6 (M+H, C^s EXAMPLE 19 [General Procedure for the Synthesis of Pyrazolo[l,5-a]pyrimidines of General Formula (1-09)] Synthesis of//-{5-[(r7-c7i5-4-aminocyclohexyl)amino]-7-[(4-ethoxyphenyl) aminoJ-e-methyltpyrazolofl.S-ajpyrimidin-S-yOlacetamide (compound No: 378). (Figure Removed) To acetyl chloride (7.1 //L) were added [3-amino-5-({rrfl/w^-[(/en-butoxy)carbonylamino]cyclohexyl}amino)-6-methyl(pyr azolo[l55-a]pynmidin-7-yl)](Vert-butozy)-/-(4-ethojr)'plienyl)carb»o?iamide (14.9 mg) in CH2C12 (250 //.L) and Iriethylamine (13. 9 /^L). The resulting mixture was stirred at room temperature for 1 h. The reaction was quenched with saturated aqueous Nad. After extraction with CHoCk, the solvent was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the ne;:t reaction v/ithout further purificaiioii. The crude product was dissolved in QHfeCfe (175/^L). To this solution Was added irifluoroacetic acid (75 /.(L). The resulting mixture was stirred at room temperature for 2 h, and then the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (9.04 mg, 3'ield 46% as 3 trifluoroacetic acids salt) as a white solid. The aH-NMR, HPLC retention time and ESI/MS data for this compound are shown below. :H-NMR (400MHz, DMSO-d6) d(ppm): 1.30(t,7=6.84Hz, 3H), 1.32-1.55 (m, 4H), 1.63 (s, 3H), 1.85-2.05(m, 4H), 2.05(s, 3H), 3.00(brs, 1H), 3.97(q, /=6.SOHz, 2H), 4.05(brs, 1H), 6.24(brs, 1H), 6.85(d, 7=9.00Hz, 2H) , 6.90(d, J=8.80Hz, 2H), 7.78(brs, 3H), S.00(s, 1H), S.54(brs, 1H) , 9.40(brs, 1H). HPLC retention time (method A): S.4 min. ESI/MS: 438.4 (M+H, [General Procedure for the Synthesis of Pyrazolo[l,5-fl]pyrimidines of General Formula (1-10)] Synthesis of {5-[Ora;?5'-4-aminocyclohex3rl)aniinoJ-7-[(4-e.thoxyphenyl) amino]-6-meth)'l(p'yrazolojl,5-fl]pyrimidin-3-yl)}(memylsulfonyl)amme (compound Ho: 386). (Formula Removed) To methanesulfcmyl chloride (11.5 mg) were added Ar-[3-amino-5-({?ra/j5-4-[(tert-butoxy)carbonylaniino]cyclohexyl}araino)-6-methyl(pyr azolo[l,5-a]pyrimidin-7-yl)](tert-butoxy)-A^-(4-ethoxyphenyl)carboxamide (14.9 mg) in CH2C12 (250 fiL) and triethylamine (13.9 juL). The resulting mixture was stirred at room temperature for 1 h. The reaction was quenched with saturated aqueous Nad. After extraction with CHoCb, the solvent was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CHaQb (175 juU). To this solution was added trifluoroacetic acid (75 fiL). The resulting mixture was stirred at room temperature for 2 h, and then the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (2.43 mg, yield 12% as 3 trifluoroacetic acids salt) as a white solid. The !H-NMR, HPLC retention time and ESI/MS data for this compound are shown below. JH-NMR (400MHz, DMSO-d6) d(ppm): 1.26(t, J=7.08Hz., 3H), 1.30-1.45 (m, 4H), 1.60 (s, 3H), l.S7-2.03(ms 4H): 2.93(brs, 1H), 3.06(s,3H), 3.85-3.98(m, 3H), 6.24(d, J=7.32Hz, 1H), 6.Sl(d, J=9.28Hz? 2H) , 6.86(d, J=9.04Hz, 2H), 7.68(s, 1H), 7.72(brs, 3H), 8.56(s, 1H), S.75(s, 1H). HPLC retention time (method A): 10.5 min. ESI/MS: 474.4 (M+H, C22H3iN7O3S). [General Procedure for the Synthesis of Pyraiolo[l,5-a]pyiimiflinc-s of General Formula (1-11)] Synthesis of A7-{5-[(frfl775-4-aminocyclolieryl)amino]-7-[(4-ethox3'phenyl) amino]-6-methj'l(p}'razolo[l,5-fl]p3frimidin-3-)'l)}(phenylamino)carboxaniide (compound No: 389). (Figure Removed) To phenyl isocyanate (11.9 mg) were added A?-[3-amino-5-({/7-a//5'-4-[(te7t-butoxy)carbonylamino]cyclohexyl}amino)-6-methyl(pyr azolo[l,5-a]pyrimidin-7-yl)](re7t-butoxy)-A'"-(4-ethoxyphenyl)carboxaraide (14.9 mg) in CH2C12 (250 /^L) and triethylamine (13.9 //L). The resulting mixture was stirred at room temperature for 1 h. The reaction was quenched with saturated aqueous NaCl. After extraction with CH^C^, the solvent was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CH^C'lo (175 f.iL). To this stirred, solution 'vie added tnfluoroacetie acid. (15 /'L). The resulting mixture v/as stirred at room temperature for 2 h, and then the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (6.59 mg, yield 31% as 3 trifluoroacetic acids salt) as a white solid. The JH-NMR, HPLC retention time and EC I/MS data for this compound are sho-.vn bdov/. 'H-IIMR (400MHz, DMSO-4) d(ppm): 1.30(1, /=7.0SHz, 3H), L36-i.47(m, 4H), 1.65(s, 3H)? 1.90-2.10(m, 4H), 2.9S(brs, 1H), 3.97(q. J=7.0SH2, 2H), 4.03(brs, 1HD, 6.13(brs, 1H), 6.82-6.96(m, 5H). 7.25(t, J=S.2SHz, 2H), 7.45(d, /=7.60Hz, 2H), 7.76(brs, 3H), 7.86(brs, 1H), 7.95(s, 1H), 8.58(brs, 1H), S.76(bis, 1H). HPLC retention time (method A): 10.9 rain. ESI/MS: 515.6 (M+H, QssHW^Oa). EXAMPLE 22 [General Procedure for the Synthesis of Pyrazolo[l,5-ajpyrimidines of General Formula (1-12)] Synthesis of ({5-[(//wz5i-4-aminocyclohexyl)amino]-7-[(4-ethoxyphenyl) amino]-6-meth}'l(pyrazolo[l,5-fl]pyrimidin-3-yl)}arnmo)(methylamino)methane-l-thio ne (compound No: 390). (Figure Removed) To methyl thioisocyanate (7.3 mg) were added. //-[3-amino-5-({/rff77j-4-[{fen'-buto::3')carbon)flamino]cyclohe;:yl}3mino)-6-methyl(pyr lrw CH2C12 (250 //L) and triethylamine (13.9 ,uL). The resulting mixture was stirred at room temperature for 1 h. The reaction was quenched with saturated aqueous NaCl. After e; traction Tyith CTbCK, the foment "•.'•' as removed in vacuo to give the cnj.de di-Boc protected intermediale. This crude product «vas used in the ne:;t reaction without further purification. The cru.de product v, as dissolved in CH2Cl2 (175 ,«L). To this stirred solution was added trifluoroacetic acid (75 /uL). The resulting mixture was stirred at room temperature for 2 h, and then the solvent was removed in vacuo. The residue was purified by preparative HPLC to give the title compound (8.32 mg, yield 41% as 3 trifluoroacetic acids salt) as a white solid. The ^-NMR, HPLC retention time and ESI/MS data for this compound are shown below. 'H-NMR (400MHz, DMSO-^6) d(ppm): 1.30(t, J=6.84Hz, 3H), 1.33-1.50(m, 4H), 1.64(s, 3H), 1.88-2.05(m, 4H), 2.91(d, J=4.40Hz,' 3H), 2.98(brs, 1H), 3.88(brs, 3.97(q, J=6.80Hz, 2H), 6.27(d, J=7.08Hz, 1H), 6.80-6.95(m, 4H), 7.67(s, 7.70-7.90(m, 4H), 8.6l(s, 1H), 9.06(s, 1H). HPLC retention time (method A): 10.3 min. ESI/MS: 469.4 (M+H, Qatfo EXAMPLE 23 [General Procedure for the Synthesis of Pyrazolo[l,5-a]p3'rimidines of General Formula (1-14)] Synthesis of {5-[(;rfl/w-4-aminocj'clohezyl)amino]-6-iTietli)d(pyrazolo[l?5-ff]pjrrimidin-7-3'l)}[4-(rne thylethoxy)phenyl]amine (compound No: 197). (Figure Removed) A solution of A^-{5-[(4-aniinoc}'cloliexyl)aniino]-6-metlij'l(8-hydrc»pyrazolo[l,5-p]pyrimidm-7-yl)}(fe rf-butoxy)-7\'-[4-(phenylmethoxy)phenyl]carboxamide (3.68 g) and Pd/C (0.78 g. 10% on carbon) in methanol (140 niL) was stirred under hydrogen atmosphere for 23 h. The catalyst was filtered off and the solvent was removed in vacua to give the crude intermediate (2.93 g) as a pale brown solid. This crude intermediate was used in the next reaction without further purification. A suspension of crude intermediate (22.7 mg), 2-propanol (19 juL) and polymer-supported triphenylphosphine resin (3.0 mmol/g, 83.5 mg) in CH^Cfe (1.0 mL) was shaken for 0.5 h at room temperature. To this suspension was added a solution of diisopropylazodicarboxylate (39.3 //L) in CEfeCfc (1.1 mL) and then shaken at room temperature for 10 h. The reaction mixture was filtrated and the residual resin was washed with CHoClj (3 x 1.0 mL). The combined filtrate was evaporated in vacuo to give the crude Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CHoCla (1.0 mL). To this solution was added trifluoroacetic acid (O.S7 mL). The resulting mixture was stirred at room temperature for 2.3 h and the solvent was removed in vacuo. The residue was purified by preparative HPLC to give the title compound (7.3 mg, 37 % yield as 3 trifluoroacetic acids salt). The HPLC retention time and ESI/MS data for this compound are shown below. HPLC retention time (method A): 7.6 min. ESI/MS: 395.0 (ivl'+H, C^HsoNeO). Synthesis of {5-[(/7-ffoj-4-aniinocycloheAyl)amino]-6-methyl(p3Tazolo[l,5-a]pyrimidin-7-yl)}[3-(2-p iperazin}'le.thoxy)phenyl]amine (compound No: 259) (Figure Removed) A solution of Ar-{5-[(4-aminocyclohexyl)amino]-6-methyl(8-hydropyrazolo[l,5-fl]pyrimidin-7-yl)}(fe 7t-butoxy)-A43-(jphenyImethoxy)phenyl]carboxamide (11.6 g) and Pd/C (0.62 g, 10% on carbon) in methanol (150 mL) was stirred under hydrogen atmosphere for 23 h. The catalyst was filtered off and the solvent was removed 777 vacua to give the crude intermediate (10.7 g) as a pale brown solid. This crude intermediate was used in the next reaction without further purification. A suspension of crude intermediate (33.9mg), 4-(2-hydroxyethyl)piperazinecarboxylate (86.4mg) and polymer-supported triphenylphosphine resin (3.0 mmol/g. 125 mg) in CH2C12 (1.75 mL) was shaken for 0.5 h at room temperature. To this suspension was added a solution of diisopropylazodicarborrylate (59.0 //L) in CH2C12 (1.0 m.L) and then shaken at room, temperature for 17.5 h. The reaction mixture was filtrated and the residual resin was washed with CH2Cl2 (3 ;: 1.0 rnL). The combined filtrate was evaporated in vacua to give the crude Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CH^Cl: (1.0 m.L). To thi: solution '-.vac1, added trifluoroacetic acid (O.S7 mL). The resulting mixture was stirred at room temperature for 2.3 h and the solvent was removed in vncuo. The residue was purified by preparative HFLC to give the title compound (20.6 rag, 34% yield as 3 trifluoroacetic acids salt). The HPLC retention time and ESI/MS data for this compound are shown below. HPLC retention time (method B): 2.3min. ESI/MS: 465.7 (M+H, C25H36N8O). EXAMPLE 24 [General Procedure for the Synthesis of Pyrazolo[1.5-fl]pyrimidines of General Formula (1-16)] Synthesis of {5-[(r/-fl/z5-4-aminocyclohexyl)amino]-6-methyl(p)'razolo[l,5-a]pyrimidin-7-yl)}(4-phe A mixture of -buto.vy)-/,/'-(4-iodophenyl)carbo:iiamide (30 mg), phenylboronic acid (7.2 mg), Ma2CO3 nylphenyl)amine (compound No: 284). (Figure Removed) /i (67.8 mg), palladium (II) acetate (3.6 mg) and triphenylphosphine (12.5 mg) in -propanol (1.08 mL) and H20 (0.217 mL) was stirred for 19.3 h at 80 °C. The reaction mixture was filtrated, and the filtrate was evaporated in- vacua to give the crude Boc protected intermediate. This crude product was used in the ne^.t reaction without further purification. The crude product was dissolved in CH2Cl2 (1.0 mL). To this solution was added trifluoroacetic acid (0.87 mL). The resulting mixture was stirred for 1.8 h, the solvent was removed in vacuo. The residue was purified by preparative HPLC to give the title compound (9.1 mg, 23% yield as 3 trifluoroacetic acids salt). The HPLC retention time and ESI/MS data for this compound are shown below. HPLC retention time (method B): lO.Smin. ESI/MS: 413.3 (M+H, C25I Synthesis of {5-[(/ra/w-4-aminocyclohexyl)amino]-6-methyl(pyrazolo[l,5-fl]pyrimidin-7-yl)}(3-(3-p yridyl)phen3'l)amine (compound No: 450). (Figure Removed) The title compound and Eoc protected intermediate were synthesised in the same manner as above-. using -^-{5-[(frfl/w-4-aminocyclohexyl)amino]-6-rnethyl(pyrazolo[l,5-fl]pyrirnidin-7-yl)}(ter/ -butoxy)-W-(3-iodophenyl)carboxamide, pyridine-3-boronic acid, Na2C03 palladium (II) acetate and triphenylphosphine. The title compound (6.1 mg, 15% yield as 3 irifluoroacetic acids salt) v/as obtained.. The .HPLC retention time and. ESI./1VIC data for this compound, are shown he-.lov/. HPLC retention time (method A): 6.0 min. ESI/MS: 414.1 (M+H, C24H27N7). EXAMPLE 25 [General Procedure for the S)'nthesis of Pyrazolo[l,5-a]p}'rimidines of General Formula (1-17)] Synthesis of {5-[(r/-fl7W-4-aminocycIohexyl)amino]-6-methyl(pyrazolo[l,5-a]pyrimidin-7-yl)}[4-(2-p henylethynj'OphenylJamine (compound No: 375). (Figure Removed) H To a mixture of /Nr-{5-[(w-«7i5-4-aminocyclohexyI)amino]-6-methyl(pyrazolo[l,5-a]pyrimidin-7-yl)}(fe;t -butox)')-A^-(4-iodophen}'l)carboxamide (30 mg), palladium (II) acetate (6.0 mg), triphenylphosphine (7.0 mg) in telrah)'drofuran (0.5mL) was added ethynylbenzene (17.6 //.L) and. triethylamine (26 ftL). The resulting mixture was stirred for 15 min. To this mi::ture '.vac added cupper (I) iodide (3.0 mg) and stired for 1 h at 50 °C. The reaction mixture was filtrated and the filtrate was evaporated in vacua to give the crude Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved, in CH-Ck (1.0 nxL). To this solution was added trifluoroacetic acid (0.87 mL). Alter stirring for 4 h, the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound. (11.4 nig, 27% yield as 3 trifluoroacetic acids salt). The HPLC retention time and ESI/MS data for this compound are shown below. HPLC retention time (method A): 12.7 min. ESI/MS: 437.2 (M+H, C EXAMPLE 26 [General Procedure for the Synthesis of Pyrazolo[l,5-fl]pyrimidines of General Formula (1-19)] Synthesis of 4-({5-[(trans-4-aminocyclohexyl)amino]-6-methyl(pyrazolo[l,5-o]pyrimidin-7-}'l)} amino)phenyl pyrrolidinyl ketone (compound No.792). Q (Figure Removed) To a stirred solution of 4-{(>t7t-butO;:y)-Ar-[5-({i7^^^ hyl(pyrazolo[l,5-ajpyrimidin-7-yl)]carbonylamino}benzoic acid (50 mg) in Ayy-dimethylformamide (1.0 mL) was added carbonyldiimidazole (69 mg) and stirred at room temperature for 30 minutes. The resulting mixture was added to pyrrolidine 1.100 i!-L) and stirred at room temperature for 15 h. The reaction \vac quenched v/ith samraied aqueous ] FaCl. .Vfi?r extraction with CH^Cl;, the solvent 'was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CH2C12 (700 juL). To this stirred solution was added trifluoroacetic acid (300 ftL). The resulting mixture was stirred at room temperature for 2 h, and then the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (39.43 mg, yield 59% as 3 trifluoroacetic acids salt) as a white solid. The ^-NMR, HPLC retention time and ESI/MS data for this compound are shown below. 'H-NMR (400MHz, DMSO-J6) d(ppm): 1.37-1.53 (m, 4H), 1.73-1.88 (m, 7H), 1.92-2.07 (m, 4H), 2.95-3.05 (m, IH), 3.43 (t, J=6.60Hz, 4H), 3.89-4.00 (m, IH), 6.07 (s, IH), 6.49 (brs, IH), 6.86 (d, 7=8.28Hz, 2H), 7.45 (d, /=S.56Hz, 2H), 7.73-7.91 (m, 4H), 9.18 (brs, IH). HPLC retention time (method A): 6.9 min. ESI/MS: 434.1 (M+H, C24H3iN70). EXAMPLE 27 [General Procedure for the Synthesis of Pyrazolo[l,5-fl]pyrimidines of General Formula (1-21)] Synthesis of !*-{5-[(/:7'a7w-4-aminocyclohexyl)amino]-7-[(4-ethoxyphenyl)amino]-6-methyl(pyrazolo [l,5-o]pyrirnidin-3-yl)}pentan-l-one (compound No:362). (Figure Removed) (ter?-Butoxy)-7vf-[5-({ft'a;;,5'-4-[(j:err-butoxy)carbonylaniino]cyclohexyl}anaino)-3 -(Ar-methoxy-Ar-methylcarbamoyl)-6-methyl(pyrazolo[l,5-fl]pyriniidin-7-yl)]-?^-(4-etho xyphenyl)carboxamide (33.4 mg) was dissolved in tetrahydrofuran (500 //.L) and stirred at -78 °C for 5 min under nitrogen atmosphere. To this stirred solution was added /i-butyl lithium (61.5 //L, 2.44 M in /i-hexane). The resulting mixture was stirred at -78 °C for 1 h, allowed to warm at room temperature and then stirred at room temperature for 23 h. The reaction was quenched with saturated aqueous NILtCl. After extraction with ethyl acetate, the combined organic layer was washed with saturated aqueous NaCL dried over NajSO* and then the solvent was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CHbCfe (175 //L). To this stirred solution was added trifluoroacetic acid (75 ;/L). The resulting mixture was stirred at room temperature for 2 h, and then the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (2.93 mg, yield 6% for 2 steps as 3 trifluoroacetic acids salt) as a white solid. The JH-NMR. HPLC retention time and ESI/MS data for this compound are shown below. !H-j MR (400MHz, DMSO-4) (ppm): 0.91(1, J=7.32Hs, 3H), 1.30(1, /=7.04Hz, 3H), 1.32-1.52 (m, 6H), 1.57-1.67 (m, 5H), 1.90-2.l5(m, 4H), 2.96-3.06(m, 3H), 3.92-4.03(m; 3H), 6.57(d, J=7.32Hz, 1H), 6.85(d, J=9.04Hz, 2H), 6.92(d, J=9.00 Hz, 2H), 7.75-7.?0(m, 3H), S.14(s, 1H\ 8.7S(sf 1H). HPLC retention time (method A): 14.2min. ESI/MS: 465.2 (M+H5 CoeHjeNgOs). EXAMPLE 28 [General Procedure for the Synthesis of Pyrazolo[l,5-c]pyrimidines of General Formula (1-23)] Synthesis of {5-[(//-fl/z5-4-aminocyclohexyl)amino]-6-meth)'l-[3-benzylamino] (pyrazolo[l,5-o]pyrimidin-7-yl)} (4-ethoxyphen)'l)amine (compound No. 436). (Figure Removed) To sodium hydride (1.2 mg) was added N- [5-({frfl7W-4-[(terr-butoxy)carbonylamino] cyclohexyl}amino)-7-[(tert-butox}')-^-(4-ethoxyphenyl)carbonylamino]-6-methyl(pyra zolo[l,5-fl]pyrimidin-3-yI)]-2,2,2-trifluoroacetamide (20.8 mg) in tetrahydrofuran (300 //L). The resulting mixture was stirred at room temperature for 1 h, to this solution was added benzyl bromide (4.3 fiL) and then stirred at room temperature for 15 h. The reaction was quenched with saturated aqueous NaCl. After extraction with CHjCfe, the sobeof v/ac removed in rc.cue. The residue was dissolved in CH2Cl2 (210//L). To this stirred solution was added trifluoroacetic acid (90 //L). The resulting mixture was stirred at room temperature for 2 h. and then the solvent was removed in vacua. The residue 11, •;•: dissolved in rnethanol (300//L). To this stirred solution was added aqueous 2 raol/L I laOH (75 /,/L). The resulting mizture \viii, blirred at room temperature for 2 h. The reaction was quenched with saturated aqueous NaCl. After extraction with CHsCb, the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (12.79 mg, yield 52% as 3 trifluoroacetic acids salt) as a white solid. The ^-NMR, HPLC retention time and ESI/MS data for this compound are shown below. 'H-NMR (400MHz, DMSO-d6) d(ppm): 1.30(t, /=7.08Hz, 3H), 1.38-1.55(m, 4H), 1.65(s, 3H), 1.95-2.13(m, 4H), 3.02(brs, 1H), 3.92-4.05(m, 3H), 4.62(s, 2H), 6.50(d, /=7.02Hz, 1H), 6.S5(d, J=9.28Hz, 2H), 6.89(d, /=9.28Hz, 2H), 7.38-7.46(m, 5H), 7.80(s, 1H), 7.88-7.97(m, 3H), S.73(s, 1H). HPLC retention time (method A): 11.2 min. ESI/MS: 486.4 (M+H, C28H35N7O). Synthesis of [5-[(ft-a/w-4-aminocyclohexyl)amino]-3-({[3-(difluoromethoxy)phenyl]methyl}amino)-6-methyl(p3'razolo[l,5-a]pyrimidin-7-yl)](4-ethoxyphenyl)amine (compound No.791). (Figure Removed) To a solution of 3-(difluoromethoxy)benzaldehyde (5.1 mg) in 1,2-dichloroethane (340 //.L) and acetic acid (35 /.iV) were added /\^[3-amino-5-({nY/;;,v-44(rert-butoxy)carbonylamino]cyclohexyl}amino)-6-methyl(pyr aioJo[lp-^]pyrimidiri-7-yl)](>m (22.4 mg). The resu.liing minturt v-as stined at 70 °C for 30 min. To this solution v,;as added sodium tetrahydroborate (20 mg) and stirred at room temperature for 10 min. The reaction was quenched, with water. After extraction with QrfcCfe, the combined organic layer was washed with saturated aqueous Nad and the solvent was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CHaCfe (280 /uL). To this stirred solution was added trifluoroacetic acid (120 /uL). The resulting mixture was stirred at room temperature for 2 h, and then the solvent was removed in vacua. The residue was purified by preparative HPLC to give the title compound (15.58 mg, }'ield 46% as 3 trifluoroacetic acids salt) as a white solid. The ^-NMR, HPLC retention time and ESI/MS data for this compound are shown below. JH-NMR (400MHz, DMSO-4) d(ppm): 1.30(t, J=6.84Hz, 3H), 1.35-1.52(m, 4H), 1.65(s, 3H), 1.95-2.12(m, 4H), 3.01(m, 1H), 3.92-4.00(m, 3H), 4.63(s, 2H), 6.40-6.47(rn, 1H), 6.82-6.90(m, 4H), 7.16-7.30(m, 4H), 7.45(t, /=8.04Hz, 1H), 7.76(brs, 7.85(brs, 3H), 8.69(brs, 1H). HPLC retention time (method A): 10.9 min. ESI/MS: 552.1 (M+H, EXAJ\iPLE 29 [General Procedure for the Synthesis of Pyrazolo[l,5-0]pyrirnidines of General Formula (1-25)] Synthesis of {74(4-ethcc;yphenyl)amino]-6-me^ )'"lamine (compound No: 340). (Figure Removed) To a solution of tert-butyl 3-({7-[(rert-butoxy)-JV-(4-ethoxyphenyl)carbonylamino]-6-methyl(pyrazolo[l,5-a]pyri midin-5-yl)}methylamino)piperidinecarboxylate (22.3 mg) in JV^-dimethylformamide (0.5 mL) was added sodium hydride (>60 % w/w in oil, 3.1 mg). The resulting mixture was stirred at room temperature for 10 min. To this solution was added methj'l iodide (3.7/*L) and the resulting mixture was stirred for further 15 h. The reaction was quenched with water. After extraction with QfoCla, the combined organic layer was washed with saturated aqueous NaCl, dried over Na2SO4, and the solvent was removed in vacua to give the crude di-Boc protected intermediate. This crude product was used in the next reaction without further purification. The crude product was dissolved in CKbClo (1.0 mL). To this solution was added trifluoroacetic acid (0.87 mL) and stirred for 5.5 h. The solvent was removed in vacua. The residue was purified on preparative TLC to give the title compound (14.6 mg, 64% yield). The ]H-NMR> HPLC retention time and ESI/MS data for this compound are shown below. ]H-NMR (400MHz, DMSO-rf6) rf(ppm): 1.42(1, 3H), 1.78(s, 3H), 1.81(m, 3H), 1.96(m, 1H), 2.57(m, 1H)5 2.S6(s, 3H), 2.89(m, 1H), 3.0S(m, 1H), 3.24(m,. 1H), 3.49(m, 1H), 3.9?(q; 2H), 5.30(brs, 1H), 6.24(d, J=2.:Hz:, 1H), 6.91(m, 2H), 6.?8(m, 2HX 7.6S(brs. 1 HI 7.35(d, /=2.2Hz, 1H) ILFLC retention time (method A): 9.8 min. ESI/MS: 381.2 (M+H, C2iH2SN6O). EXAIslPLE 30 [General Procedure for the Synthesis of Pyrazolo[l,5-o]pyrimidines of General Formula (1-27)] Synthesis of {5-[((31S)(3-piperidyl))amino]-6-rnethyl(pyrazolo[l,5-a]pyrirnidin-7-yl)}(4-ethoxyphen yl)amine (compound No: 193). (Figure Removed) To a stirred solution of N-(5-{[(3S)-l-benzyl(3-piperidyl)]amino}-6-methyl(pyrazolo[l,5-a]p)'rimidin-7-)'l))(ter t-butoxy)-N-(4-ethoxyphenyI)carboxamide (272 mg) in CH2C12 (2 mL) was added trifluoroacetic acid (2 mL). After stirring at room temperature for 3 h, the reaction mixture v/as poured into the saturated, aqueous NaHCOs and extracted with CH^Clo. The combined, extract v/as washed with saturated, aqueous NaCL dried over Na-SCX], filtered, arid the solvent was removed in vacuo. The residue v/as purified by silica gel column chiomatography (96% Cl^C'k + 4% (2 M NHg in methanol) was used as eluent, then gradient elution up to 90% CH2C12 + 10% (2.0 M NH3 in methanol)) to give the intermediate (237 mg). A solution of this intermediate in ethane! (2 mL) was hydrogenated under hydrogen atmosphere in the presence of Fd(O.H)2/C (125 nig, 10% on carbon). After stirring for 5 h, the reaction mixture was filtered, and evaporated in vacuo. The crude residue was purified by column chromatography (96% QtzCla + 4% (2.0 Ivl MHa in methanol)) to give the title compound (107 mg, 60%). The 1H-NMR, HPLC retention time and ESI/MS data for this compound are shown below. 1H-NMR (400MHz, CDC13) d(ppm): 7.76 (d, J=2.2Hz, IH), 7.49 (s, IH), 7.00 (d, J=9.0Hz, 2H), 6.85 (d, J=8.8Hz, 2H), 6.11 (d, J=2.2Hz, IH), 4.95 (m, IH), 4.27 (m, IH), 4.02 (q, J=7.1Hz, 2H), 3.20 (m, IH), 2.83 (m, 2H), 2.71 (dd, J=6.2Hz, 11.4Hz, IH), 1.87 (m, IH), 1.71 (m, 2H), 1.71 (s, 3H), 1.56 (m, IH), 1.49 (t, J=7.1Hz, 3H). HPLC retention time (method A): 8.0 min. ESI/MS: 367.4 (M+H, C2oH26N6O). Synthesis of [5-(azaperhydroepin-3-yl i amino)-6-methyl(pyrazolo[l,5-fl]p3'rimidin-7-yl)](4-ethoxyphenyl)amine (compound No: 272). (Figure Removed) To a solution of (re7t-butoxy)-/^-(4-ethox)'phenyl)-/V-(6-mrthyl-5-{[l-benzylazaperhydoepin-3-yl]amino }(pyrazolo[l,5-fl]pyrimidine-7-yl))carboxamide (6.6 rag) in CH2C12 (0.5 mL) was added trifluoroacetic acid (0.3 mL) at 0 °C. After stirring for 16 h at room temperature. Ihe reaction mixture v/as poured, into saturated, aqueous KaHCOs and extracted -vith elhyl acetate. The combined organic layer v/ao washed with saturated aqueous rlaCl, dried over Na2SO4, filtered, and evaporated ///. vacuo. The residue was purified on preparative TLC to give the intermediate (5.0 mg, 91%). To a stirred solution of this intermediate (2.0 rng) in CHoCb (0.3 mL) was added a-chloroethyl chloroformate (2 jtiL) at 0 °C. After stirring for 0.5 h, to the reaction mixture was added saturated aqueous NaHCOa and then extracted with ethyl acetate. The combined organic layer was washed with saturated aqueous NaCl, dried over NaaSO-t, filtered, and evaporated in vacuo. The residue was dissolved in methanol (0.5 mL). After reflux for 4 h, the reaction mixtire was cooled to room temperature and then evaporated in vacua. The residue was purified on preparative TLC (90% CH2C12 + 10% (2.0 M NH3 in methanol)) to give the title compound (0.9 mg, 59%). The HPLC retention time and ESI/MS data for this compound are shown below. HPLC retention time (method A): 4.4 min. ESI/MS: 381.4 (M-fH, C2iH28N6O). EXAMPLE 31 [General Procedure for the Synthesis of Pyrazolo[l,5- (1-29)] Synthesis of {5-[(w-fl7t5'-4-aminoc}'clohexyl)amino]-3-iodo(pyrazolo[l,5-(7]p}'rirnidin-7-yl)}[(3-chlor ophenyl)methyl]amine (compound No: 297). (Figure Removed) H To a slirrcd solution of )methyl]amine (41.8 mg) in CH2C12 (565 //L) was added IC1 (169 fiL, 1.0 M in CH2C12), and the resulting mixture was stirred at room temperature for 4 h in the dark. The reaction was quenched with saturated aqueous Na^Oa. The resulting precipitate was collected by filtration. After extraction of filtrate by CH2C12, the combined organic layer was washed with saturated aqueous Nad. To this solution, the precipitate collected above was dissolved, and the solvent was removed in vacua. The residue was purified by preparative HPLC, and the fraction contained the title compound was basified (pH 9) with saturated aqueous NaHC03. After extraction with CH2C12, combined organic layer was dried over Na2SC>4. The solvent was removed in vacua, and the title compound (23.11mg, 41% yield) was obtained as a white solid. The ^-NMR, HPLC retention time and ESI/MS data for this compound are shown below. JH-NMR (270MHz, DMSO-4) d(ppra): 1.00-1.40(m, 4H), 1.70-2.00(m, 4H), 2.71(m, 1H), 3.65(m, 1H), 4.44(brs, 2H), 5.10(s, 1H), 6.76(d, /=7.S3Hz, 1H), 7.10-7.50(m, 4H), 7.81(s, 1H), 8.05(brs, 1H). HPLC retention time (method A): 7.6 min. ESI/MS: 497.4 (M+H, C19E22 CUN6). EXAMPLE 32 i General Procedure for the Synthesis of Pyrazolo[l,5-fl]pyrimidines of General Formula (.1-31)] To a solution of py.razolo[1.5-ff]pyrimidin<:-. nig in tetrahydrofuran nil was added cyclohexanone equivalents and the reaction heated for h at to cooled mixture then sodium cyanoborohydride stirred room temperature h. evaporated dryness vacua resultant residue dissolved water ethyl acetate. organic layer separated dried over mgsc>4 then subjected to column chromatography over silica gel. The eluent was CH2C12, then gradient elution up to 95% CH2C12 + 5% (10 Af NH3 in methanol) to give pyrazolo[l,5-a]pyrimidine of General Formula (1-31). EXAMPLE 33 Synthesis of 7-N-(4-Ethoxy-phenyl)-6-methyl-5-N-(4-propyl-piperidin-3-yl)-pyrazolo [l,5- (Figure Removed) To a stirred solution of 4-allyl 3-oxopiperidine (3.39 g, 12.4 mmol) in tetrahydrofuran (31 mL) was added a solution of lithium tris .yec-buyul hydrobororate in tetraltydrofuran (15 mL: IM solution ) at -7S°C. After stirring at -78°C for 3 h, the mixture was acidified with 1 H HC1 and extracted with AcOEt. The combined extract was washed, with saturated aqueous NaHCOs, followed by saturated aqueous NaCl. The organic layer was dried over Na2SC>4, filtered and evaporated in vacuo. The residue was purified by column chromatography (20% AcOEt-hexane) to give 4-/ytyl-3-hydro£y-pipeddme-l-carbo;:ylic acid benzyl ester (3.12 g). 'II-NMR (400 MHz, CDCi3) rf(ppm): 7.35 (m, 5H% 5.79 (m, IE), 5.13 (m, 2H), 5.09 (m, 1H), 5.04 (m, 1H), 4.22 (br, 2H), 3.83 (m, 1H), 2.92 (m, 1H), 2.77 (br, 1H), 2.21 (m, lit), 2.05 (m, 1H), 1.57 (m, 2H), 1.48 (br, 1H). To a stirred solution of 4-All}'l-3-hydroxy-piperidine-l-carboxylic acid benzyl ester (293 ing, 1.06 mmol) were added triphenyl phosphine(362 mg, 1.38 mmol), a solution of diethyl azodicarboxylate in toluene (0.6 mL, 1.38 mmol; 40% solution) and DPPA (297 fiiL, 1.38 mmol). After stirring for 4h, the mixture was evaporated and the residue was purified by column chromatography (15% AcOEt-hexane)to give 4-Allyl-3-azido-piperidine-l-carboxylic acid benzyl ester. To a stirred solution of above residue in tetrahydrofuran (3.5 mL)-H2O (0.35 mL) was added triphenyl phosphine (417 mg, 1.59 mmol). The mixture was stirred under reflux for 16 h, added NaSC>4, filtered and evaporated. The crude mixture was purified by column chromatography to give 4-Allyl-3-amino-piperidine-l-carbox3'lic acid benzyl ester (118 mg, 41% in 2 steps). JH-NMR (400 MHz, CD3OD) d(ppm): 7.2 (m, 5H), 5.71 (m, 1H), 5.00 (s, 2H), 4.99 (m, 1H), 4.93 (m, 1H), 4.05 (m, 1H), 3.96 (m, 1H), 2.70 (br, 1H), 2.47 (br, 1H), 2.39 (m, 1H), 2.30 (m, 1H), 1.S4 (m, 1H), 1.66 (m, 1H), 1.24 (m, 1H), 1.04 (m, 1H). 4-Allyl-3-[7-(4-etnok7,'-pb.enylajmino)-6-melhyl-pyrazolo[l,5-«Jpyrimidin-5-3'lamino]-pi peridine-1-carboxylic acid benzyl ester was prepared by Example 12. A solution of 4-Allyl-3-[7-(4-ethoxy-phenylamino)-6-methyl-pyrazolo[l,5-fl] pyrimidin-5-ylaminoJ-piperidine-l-carboxylic acid benzyl ester (3.1 mg) in EtOH (1.5 mL) was hydrogenated in the presence of 10% palladium on carbon (7.5 mg) for 45 min. The mixture was filtered through a pad. of Celite and evapotrated. The residue was purified, on preparative TLC to give the title compound (1.4 mg). 'H-ITMR (400 MHz, CDC13) d(ppm): 7.77 (d, J=2.2Hz, 1H), 7.51 (s. 1H)T 7.01 (d, J-S.SHZ, 2H), 6.86 (d, /=9.04Hz, 2H), 6.10 (d, /=2.2Hz, 1H), 4.45 (br, 1H), 4.05 (m, 1H), 4.02 (q, J=6.84 Hz, 2H), 3.47 (dd, 1H), 3.09 (m, 1H), 2.6S (m, 1H), 2.48 (m, 1H), 2.02 (m, 1H), 1.91-1.43 (m.. 3H), 1.69 (s, 3H): 1.42 (t, J=6.84 Hz, 3H), 1.26 (m, 2H), O.S9(t,J=7.0SHz,3H). EXAMPLE 34 The compounds of the invention listed in Table B below were synthesized according to the respective methods in Examples 1 to 33 using the corresponding starting materials and reagents. The numbers assigned to each of the compounds in Table B correspond to the Compound Nos. of the compounds listed as specific examples in Table A above. Compounds were characterised by mass spectrometry using single quadrupole instrumentation with an electrospray source. M+H indicates values obtained for compound molecular mass (M) with proton (H) capture and M-H compound molecular mass (M) with proton (H) loss. Melting points (mp) are uncorrected; (d) denotes decomposition at or near the melting point. Compounds which were not solids were gums. The ^-NMR spectra (400 MHz, DMSO-J6 or CDC13) of selected compounds of the invention were measured. The data for the chemical shifts (d: ppm) and coupling constants (/: Hz) are shown in Table B. The "HPLC retention time" are the retention time for the compounds in HPLC analysis carried out under the condition of the Method A, B, C or D above. The "method of preparation" in Table B are the example numbers of the corresponding methods in witch the compounds were synthesized. Table B (Table Removed) EXAMPLE35 [General Procedure for Measurement of MAPKAF-K2 Enzj'me Activity Inhibition] (Compound, preparation) '-Compounds \vere dissolved in DM30 at a concentration of 10 mM and. stored in aliquots at -20oC. Compounds in DMSO from these stock aliquots v/ere diluted in DMSO to produce the required range of 3Ox stock solutions. These stock solutions were then subjected to 1:3 dilutions in order to prepare the required range of lOx stock solutions and 5 //.L of each solution was used per 50 fiL reaction. A final DMSO concentration of 3% was maintained throughout all compound dilution series to maximise compound solubility. Compounds were routinely tested at final i concentrations ranging from 300 //M to 0.001 ^M, but may have been tested at lower concentrations depending upon their activity. (MAPKAP-K2 Assay) The kinase reaction was conducted in a round-bottomed polypropylene 96-well plate. MAPKAP-Kinase 2 was diluted to 0.5 mV/juL in diluent buffer (50 mM Tris/HCl. pH7.5; 0.1 mM EGTA, 0.1% (v/v) p-mercaptoethanol, 1 mg/mL BSA). 5 //Lcompound or 30% DMSO was added to each well followed by 25 //.Lsubstrate cocktail (final concentration: 10 ^M ATP, 30 yuM peptide (KKLNRTLSVA), 0.5 //Ci 33P-y-ATP in 50 mM Tris pH7.5, 0.1 mM EGTA, lOmM Mg-acetate and 0.1% P-mercaptoethanol). The reaction was initiated with the addition of 20 /.iL enzyme solution per well or 20 fiL diluent buffer without enzyme. The plate was shaken for 10 seconds and. then left at room temperature: for 30 minutes. The reaction was terminated with 50 //.L 150 mM phosphoric acid. 90 /.iL of the reaction mixture was then transferred into a 96-well P81 filter plate (Whatmann) and incubated at room temperature for 5 minutes. The filter plate was then washed 4 times with 200 //L 75 mM phosphoric acid per well on a plate vacuum manifold (Millipore) and dried in an oven for 2-3 hours. Packard. MicroScint '0' (jQ ;/L) was then added to each well, the plate was mixed for 30 minutes and subjected to liquid scintillation counting on a Packard TopCount. .After adding 25 /.(L of peptide substrate solution [60 juM substrate peptide. 20 /uM ATP, 50 mM Tris buffer (pH 7.5), 0.1 mM EGTA, 0.1 % p-mercaptoethanol, 20 mM magnesium acetate, 0.1 //Ci [y-33P]ATP (specific activity: approximately 110 TBq/mmol)] to 5 /j,L of the test compound using 5% dimethylsulfoxide as the solvent, reaction was initiated by further addition of 20 /.iL of a MAPKAP-K2 enzyme solution [10 mU recombinant human MAPKAP-K2, 50 mM Tris buffer (pH 7.5), 0.1 mM EGTA, 0.1 % p-mercaptoethanol, 0.1% BSA]. After conducting the reaction for 30 'minutes at room temperature, an equivalent volume of a 200 mM phosphoric acid solution was added to suspend the reaction, and 90 f.iL of the reaction product was adsorbed onto a MultiScreen PH plate (Millipore) and rinsed with a 100 mM phosphoric acid solution. After drying the plate, 30 [*L of MicroScint-O (Packard BioScience) was added, .and the cpm was measured with a scintillation counter to determine the inhibiting activity. Substrate peptide is Lys-Lys-Leu-Asn-Arg-Thr-Leu-Ser-Val-Ala. (Interpretation) % Control = (X-B)/(Tot-B) x 100 % Inhibition = 100 - % Contr X = cpm of the test compound wells B = cpm of \velb without enzyme Tot = cpm of wells with DMSO vehicle only (MAPKAP-K2 inhibitory activity) The efficacy of the compounds in Table A against 1VJAPKAP-K2 is shown in Table C below. (The activity is presented as -f. ++, or +++ representing active, mure active and very active based on assays conducted at typically 1 - 100 ftM). Table C (Table Removed) EXAMPLE 36 [General Procedure for Measurement of CDK-1 Enzyme Activity Inhibition] (Compound preparation) Compound? were dissolved in DMSO at a concentration of 10 hum and stored in aliquots at -20°C. Compounds in DIviSO from these stock aliquots were diluted in DMSO to produce the required range of 30x stock solutions. These stock solutions were then subjected to 1:3 dilutions in order to prepare the required range of lOx stock solutions and 5 //L of each solution was used per 50 //L reaction. A final DMSO concentration of 3% was maintained throughout all compound dilution series to maximise compound solubility. Compounds were routinely tested at final concentrations ranging from 300 /*M to 0.001 //M, but may have been tested at lower concentrations depending upon their activity. (CDK-1 Assay) The kinase reaction was conducted in a round-bottomed polypropylene 96-well plate. CDK-1 was diluted to 0.5 U/pL in diluent buffer (50 mM Tris/HCl. pH7.5, 0.1 mM EGTA, 0.1% (v/v) (3-mercaptoethanol, 1 ing/mL BSA). 5 //.L compound or 30% DMSO was added to each well followed by 25 f.iL substrate cocktail (final concentration: 10 //M ATP5 50 pM peptide (HSTPPKKKAK), 0.5 /*Ci 33P-Y-ATP in 50 mM Tris-HCl (pH 7.5), 1 mM EGTA, 2 mM DTT, 10 mM MgCl2, 0.01% Brij-35). The reaction was initiated with the addition of 20 /^.L enzyme solution per well or 20 /./.L of diluent buffer without enzyme. The plate was shaken for 10 seconds and then left at room temperature for 15 minutes. The reaction was terminated with 50 //L 150 mM phosphoric acid. 90 //L of the reaction mixture was then transferred into a 96-well P81 filter plate (Whatmann) and incubated at room temperature for 5 minutes. The filter plate v/as then washed 4 times with 200 tuL 75 mM phosphoric acid, per v/ell on a plate vacuum manifold (Miilipore) and dried in an oven for 2-3 hours. Packard. MicroScint t>:/ (30 jU-L) v/as then added to each well, the plate v/as mixed for 30 minutes and subjected to liquid scintillation counting on a Packard TopCount. (Interpretation) % Control = (X-B)/(Tot-B) x 100 % Inhibition = 100 - % Control X = cpm of the test compound wells B = cpm of wells without enzyme Tot = cpm of wells with DMSO vehicle only (CDK-1 inhibitory activity) Compounds that inhibit CDK-1 (IC50 18, 19, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 35 and 36. EXAMPLE 37 [General Procedure for Measurement of CDK-2 Enzyme Activity Inhibition] (Compound preparation) Compounds were dissolved in DMSO at a concentration of 10 mM and stored in aliquots at: -20°C. Compounds in DMSO from these stock aliquots were diluted in DMSO to produce the required range of 30s stock solutions. These stock solutions were then subjected to 1:3 dilutions in order to prepare the required range of lOx stock solutions and 5 //L of each solution was used per 50 [iL reaction. A final DMSO concentration of 3% was maintained throughout all compound dilution series to w.ar.irnise compound solubility. Compounds were routinely tested at final concentraiionc ranging from 300//ivi to 0.001 //Ivi, but may ha\>e been tested at iov,*er concentrations depending upon their activity. (CDK-2 Assay) a) The kinase reaction was conducted in a round-bottomed polypropylene 96-well plate. CDK-2 was diluted to 0.5 ng/wL in diluent buffer (50 mM Tris/HCl. pH7.5, 0.1 mM EGTA, 0.1% (v/v) p-mercaptoethanol, 1 mg/ml BSA). 5 fiL compound or 30% DMSO was added to each well followed by 25 ju.L substrate cocktail (final 10 juM ATP, 0.1 mg/ml Histone type III-S, 0.2 //Ci 33P-y-ATP in 50 mM Tris-HCl (pH 7.5), 1 mM EGTA, 2 mM DTT, 10 mM MgCl2, 0.01% Brij-35). The reaction was initiated with the addition of 20 //L enzyme solution per well or 20 /uL of diluent buffer without enzyme. The plate was shaken for 10 seconds and then left at room temperature for 60 minutes. The reaction was terminated with 50 fiL 150 mM phosphoric acid. 90 [tL of the reaction mixture was then transferred into a 96-well P81 filter plate (Whatmann) and incubated at room temperature for 5 minutes. The filter plate was then washed 4 times with 200 /uL 75 mM phosphoric acid per well on a plate vacuum manifold (Millipore) and dried in an oven for 2-3 hours. Packard MicroScint '0' (30 /uL) was then added to each well, the plate was mixed for 30 minutes and subjected to liquid scintillation counting on a Packard, TopCount. After adding 25 ,//.L of substrate solution [0.2 mg/ml Histone type III-S, 20 /./M ATP, 100 mM Tris buffer (pH 7.5), 2 mM EGTA, 4 mM DTT, 0.02 % polyoxyethylene lauryl ether (23 Lauryl Ether; Brij 35), 20 mM magnesium chloride, 0.2 jud [y-33P]ATP (specific activity: approximately 110 TBq/mmol)] to 5 /J.L of the test compound using 5% dimethylsulfo:iide as the solvent, reaction was initiated by further addition of 20 //.L of a CPK2 enzyme solution [2.5 mU recombinant human CDK2/cyclin A, 50 mM Tris buffer (pH 7.5), 0.1 mM EGTA, 0.1 % p-mercaptoethanol, 0.1% BSA]. After conducting the reaction for 15 minutes at room temperature, an equivalent volume of a 70 % trichloroacelic acid (TCA) solution was added to suspend the reaction, and 90 ju.L of the reaction product was adsorbed onto a Multiscreen HV plate (Millipore) and rinsed with a 25 % TCA solution. After drying the plate, 30 //L of MicrpScint-O (Packard BioScience) was added, and the cpm was measured with a scintillation counter to determine the inhibiting activity. (Interpretation) % Control = (X-B)/(Tot-B) x 100 % Inhibition = 100 - % Control X = cpm of the test compound wells B = cpm of wells without enzyme Tot = cpm of wells with DMSO vehicle only (CDK-2 inhibitory activity) Compounds that inhibit CDK-2 (IC50 14, 15, 16, 23, 23, 31, 32, 35, 37, 38, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56, 57, 58, 59, 60, 61, 63, 64, 65, 68. 70, 71, 72, 74, 75? 76, 77, 78, 80. 81, 83, 84. 85, 86, 87, 88, 89, 91, 92, 93, 95, 97, 98, 102, 103, 105, 107, 111, 112, 113, 114, 115, 116, 118, 125, 126, 128, 129, 131, 137, 140, 148, 149, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 163, 164, 165, 166, 167, 168,. 169, 170, 171, 172, 173, 175, 176, 178, 179, 191, 193, 196, 197, 198, 1??, 200, 201, 202, 203, 204, 205, 203, 211, 212, 213, 214, 215, 216, 217, 219, 221. 222; 223, 224. 225, 226, 228, 229, 231, 234, 23/, 238, 239, 240, 243, 246, 247, 248, 250, 251. 252, 253, 254, 256, 267, 274, 282, 284, 285, 286, 287, 288, 2S9, 290, 291, 292, 293, 294, 295, 297, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 333, 335, 340, 341, 343, 350, 351, 352, 353, 354, 355, 356, 357, 359, 360, 361, 362, 366, 368, 371, 410, 411, 412, 417, 418, 419, 420, 421, 422, 423, 425, 437, 441, 442, 443, 444, 445, 460, 463, 511, 514, 762, 764, 765, 772, 773, 776, 778 and 785. Industrial Applicability The Pyrazolo[l,5-a]pyrimidine derivatives represented by formula I and their pharmaceutically acceptable salts exhibit excellent kinase inhibiting activity (particularly MAPKAP-K2 inhibiting activity). Drugs comprising the compounds as effective ingredients are therefore expected to be useful as therapeutic or prophylactic agents for a protein kinase mediated disorder in which kinase is implicated, such as such as inflammatory disease, autoimmune disease, destructive bone disorder, cancer and/or tumour growth. We claim: 1. Pyrazolo [1,5-a] pyrimidine compound of formula I (Formula Removed) wherein R1 is hydrogen, C1-C8 substituted or unsubstituted alkyl. C2-C8 substituted or unsubstituted alkenyl. C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 substituted or unsubstituted aryl. substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted heterocyclylalkenyl, substituted or unsubstituted arylalkynyl or substituted or unsubstituted heterocyclylalkynyl, all of the above being such as hereinbefore described; R2 is hydrogen, halogen,-CN, -NO2, -CHO, -G-R7 where G is a bond, -C (=O)-or-0-C (=0)-; and R7 is C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted heterocyclylalkenyl, substituted or unsubstituted arylalkynyl, substituted or unsubstituted heterocyclylalkynyl, -OR8 wherein R8 is hydrogen, C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl or substituted or unsubstituted heterocyclylalkyl, -NR R10 wherein R9 is as defined for R8; R10 is hydrogen, C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl or -OCH3, -R wherein R is an substituted or unsubstituted saturated heterocyclyl with 5 to 7 members containing one to four heteroatoms selected from N, O and S, C6-C14 substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; provided that when R is C6-C14 substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl. then G is not a bond, -NR9C(=O)Rn wherein R9 is as defined for R8; R11 is hydrogen, C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl, C6- C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted heterocyclylalkenyl, substituted or unsubstituted arylalkynyl or substituted or unsubstituted heterocyclylalkynyl, -NR9C(=X)OR13 wherein R9 and R13. which may be the same or different, are as defined for R8; X is O, S, N-CN or NH, - NR9C(=X)NR13R14 wherein R9, R11 and R14, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH, -NR9SO2R13 wherein R9 and R13. which may be the same or different, are as defined for R , -SR wherein R is as defined for R or - S(0)mR9 wherein R9 is as defined for R8; m is 1 or 2; R3 is C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 unsubstituted aryl, C6-C14 substituted aryl wherein said substituents are selected from the group consisting of halogen,-CN.-NO2, -CHO, -G-R15 wherein G is a bond, -C(=O)- or -0-C(=0)-; R15 is C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl. substituted or unsubstituted heterocyclylalkenyl, substituted or unsubstituted arylalkynyl, substituted or unsubstituted heterocyclylalkynyl, -OR16 wherein R16 is as defined for R or - NRI7R18 wherein R17 and R18 which may be the same or different, are as defined for R , -NRl7C(=O)R19 wherein R17 is as defined for R8; R19 is as defined for R12. - NR17C(=X)OR18 wherein R17 and R18, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH, -NRI7C(=X)NRI8R20 wherein R17, R18 and R20, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH, - NR17SO2R18 wherein R17 and R18, which may be the same or different, are as defined for R8. -S(O)mR17 wherein R17 is as defined for R18; m is 0. 1 or 2 and -SO2NR21R22 wherein R21 and R22 , which may be the same or different, are as defined for R8; R21 and R21 together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N. O and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents, unsubstituted heterocyclyl, substituted heterocyclyl wherein said substituents are one or more selected from the group consisting of halogen, -CN. -NO2, -CHO. -G-R23 wherein G is a bond, -C(=O)- or -O-C(=O)-; R23 is as defined for R15-NR24C(=O)R25 wherein R24 is as defined for R8; R25 is as defined for R12, -NR24C(=X)OR26 wherein R24 and R26. which may be the same or different, are as defined for R8; X is O. S, N-CN or NH, -NR24C(=X)NR26R27 wherein R24, R26 and R27 which may be the same or different, are as defined for R8; X is O, S, N-CN or NH. -NR24SO2R26 wherein R24 and R26. which may be the same or different, are as defined for R8, -S(0)mR24 wherein R24 is as defined for R8; m is 0, 1 or 2 and -SO2NR28R29 wherein R and R , which may be the same or different, are as defined for R8; R28 and R29 together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said monocyclic or bicyclic heterocycle may be unsubstituted or substituted with one or more substituents, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted heterocyclylalkenyl, substituted or unsubstituted arylalkynyl or substituted or unsubstituted heterocyclylalkynyl, all of the above being such as hereinbefore described; R4 is hydrogen, halogen, C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl. C6-C14 substituted or unsubstituted aryl. substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted heterocyclylalkenyl. substituted or unsubstituted arylalkynyl, substituted or unsubstituted heterocyclylalkynyl, -OR30 wherein R30 is as defined for R , -SR wherein R30 is as defined for R8, -NR30R31 wherein R30 and R31, which may be the same or different, are as defined for R8, -NR30C(=O)R32 wherein R30 is as defined for R8; and R32 is as defined for R12, -NR30C(=X)OR31 wherein R30 and R31 which may be the same or different, are as defined for R8; X is O, S. N-CN or NH, -NR30C(=X)NR31R33 wherein R30, R3' and R33, which may be the same or different, are as defined for R ; X is 0, S, N-CN or NH or -NR30SO2R31 wherein R30 and R31. which may be the same or different, are as defined for R ; all of the above being such as hereinbefore described; R5 is C1-C8 substituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted cycloalkyl wherein said substituents of C3-C8 cycloalkyl are one or more selected from the group consisting of halogen, -CN, -NO2, -CHO, -G-R34 wherein G is a bond, -C(=O)- or -O-C(=O)-; R34 is as defined for R15, -NR35C(=0)R36 wherein R35 is as defined for R8; R36 is as defined for R12, -NR35C(=X)OR37 wherein R35 and R37. which may be the same or different, are as defined for R8; X is O, S, N-CN or NH; -NR35C(=X)NR37R38 wherein R35, R37 and R38, which may be the same or different, are as defined for R38; X is O, S, N-CN or NH and -NR35SO2R37 wherein R35 and R37, which may be the same or different, are as Q defined for R , unsubstituted heterocyclyl, substituted heterocyclyl wherein said substituents of heterocyclyl are one or more selected from the group consisting of halogen, -CN, -NO2, -CHO, -G-R39 wherein G is a bond, -C(=0)- or -0-C(=0)-; R39 is as defined for R15, -NR40C(=O)R41 wherein R40 is as defined for R8; R41 is as defined for R12, -NR40C(=X)OR42 wherein R40 and R42, which may be the same or different, are as defined for R8; X is O, S, N-CN or NH, -NR40C(=X) NR42R43 wherein R40, R42 and R43, which may be the same or different, are as defined for R°; X is O, S, N-CN or NH and -NR40SO2R42 wherein R40 and R42, which may be the same or different, are as defined for R , substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted heterocyclylalkenyl, substituted or unsubstituted arylalkynyl, substituted or unsubstituted heterocyclylalkynyl or -NR44R ' wherein R44 and R45 which may be the same or different, are C1-C8 substituted or unsubstituted alkyl ; R44 and R45 together may be taken together with the nitrogen to which they are attached to form a mono heterocycle with 5-7 members and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N. O and S. the said mono heterocycle being unsubstituted or substituted with one or more substituents; all of the above being such as hereinbefore described; R6 is hydrogen, C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl. substituted or unsubstituted arylalkyl or substituted or unsubstituted heterocyclylalkyl; all of the above being such as hereinbefore described; with the provisos: that R1, R2 and R4 are not all H; that R is not pentafluorophenyl; that R" is not a group represented as the following C1-C6 alkyl or C3-C6 cycloalkyl, in which an alkyl group or a cycloalkyl group may be unsubstituted or substituted by phenyl or by one or more fluoro substituents ; wherein the aryl means an aromatic 6-10 membered hydrocarbon containing one ring or being fused to one or more saturated or unsaturated rings; wherein the heterocyclyl means a 3-10 membered ring system containing 1 to 4 heteroatoms selected from N, O, or S; wherein the arylalkyl is a group comprising a combination of the aryl and the alkyl, wherein the alkyl relates to both straight chain or branched alkyl radicals of 1 to 8 carbon atoms; wherein the heterocyclylalkyl is a group comprising a combination of the heterocyclyl and the alkyl, wherein the alkyl relates to both straight chain or branched alkyl radicals of 1 to 8 carbon atoms. 2. The compound as claimed in claim 1 wherein R is hydrogen or C1-C8 substituted or unsubstituted alkyl. 3. The compound as claimed in claim 1 wherein R1 is hydrogen. 4. The compound as claimed in any one of claims 1 to 3 wherein R is –NO2, -OC(=O)R7 , -CO2R8 or -CONR9R10; wherein R7, R8, R9 and R10 are as defined in claim 1. 5. The compound as claimed in any one of claims 1 to 3 wherein R is -NR C(=O)R , -NR9C(=X)OR13, -NR9C(=X)NR13R14. -NR9SO2R13, -SR9 or -S(O)mR9; wherein R9, R12, R13, R14 and X are as defined in claim 1; m is 1 or 2. 6. The compound as claimed in any one of claims 1 to 3 wherein R is C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl or substituted or unsubstituted arylalkyl. 7. The compound as claimed in any one of claims 1, 3 or 4 wherein R2 is hydrogen, halogen,-CN or -SCH3. 8. The compound as claimed in any one of claims 1 to 3 wherein R is halogen. 9. The compound as claimed in any one of claims 1 to 3 wherein R2 is F. 10. The compound as claimed in any one of claims 1 to 3 wherein R is hydrogen. 11. The compound as claimed in any one of claims 1 to 10 wherein R3 is C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C2-C8 substituted or unsubstituted alkynyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 unsubstituted aryl, C6-C14 substituted aryl, unsubstituted heteroaryl. substituted heteroaryl, substituted or unsubstituted arylalkyl or substituted or unsubstituted heteroarylalkyl. 12. The compound as claimed in any one of claims 1 to 10 wherein R3 is C6-C14 substituted aryl. 13. The compound as claimed in any one of claims 1 to 10 wherein R3 is C6-C14 substituted aryl wherein said substituents are one or more selected from the group consisting of halogen, -CN. -NO2, -G-R15, -NRl7C(=O)R19 and -S(O)mR17; wherein R15, R17,R19 or G are as defined in claim 1 ; m is 0, 1 or 2. 14. The compound as claimed in any one of claims 1 to 10 wherein R3 is C6-C14 substituted aryl wherein said substituents are one or more selected from the group consisting of halogen, -CN, -NO2, -G-R15 wherein G is a bond or -C(=O)-; R15 is C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl, C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclylalkyl,-OR16 or -NR17R18, -NR17C(=O)R19 and S(O)mR17; wherein R16, R17, R18 or R19 are as defined in claim 1; m is 0, 1 or 2. 15. The compound as claimed in any one of claims 1 to 10 wherein R3 is C6-C14 substituted aryl wherein said substituents are one or more selected from the group consisting of halogen, -CN, -NO2, -G-R15 wherein G is a bond; Rb is C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, -OR16 or -NRI7R18, -NR17C(=O)R19 and -S(O)mR17; wherein R16,R17,R18 or R19 are as defined in claim 1; m is 0, 1 or 2. 16. The compound as claimed in any one of claims 1 to 10 wherein R is C6-C14 substituted aryl wherein the substituents are one or more selected from the group consisting of halogen, -CN, -NO2, -G-R15 where G is a bond or -C(=O)-; R15 is C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl, -OR16 or -NR17R18, -NR17C(=O)R19 and -S(O)mR17; wherein R16, R17, R18 or R19 are as defined in claim 1 ; m is 0, 1 or 2. 17. The compound as claimed in any one of claims 1 to 10 wherein R is C6-C14 substituted aryl wherein said substituents are one or more selected from the group consisting of halogen, -CN, -NO2, -G-R1' wherein G is a bond or -C(=O)-; R15 is C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl, -OR or -NR17R18, -NR17C(=0)R19 and -S(O)mR17; wherein R16, R17, R18 or R19, which may be the same or different, are hydrogen, C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl; m is 0, 1 or 2. 18. The compound as claimed in any one of claims 1 to 10 wherein R3 is C6-C14 substituted aryl wherein said substituents are one or more selected from the group consisting of halogen, -CN, -NO2 and -G-R15 wherein G is -C(=O)-; R15 is C1-C8 substituted or unsubstituted alkyl, C3-C8 substituted or unsubstituted cycloalkyl. C6-C14 substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, -OR16 or -NR R ; wherein R . R or R are as defined in claim 1. 19. The compound as claimed in any one of claims 1 to 10 wherein R3 is unsubstituted heterocyclyl. 20. The compound as claimed in any one of claims 1 to 10 wherein R' is substituted heterocyclyl. 21. The compound as claimed in any one of claims 1 to 10 wherein R' is substituted heterocyclyl wherein said substituents are one or more selected from the group consisting of halogen, -CN, -NO2, -G-R23, -NR24C(=0)R25 and -S(O)mR24; wherein R23. R24, R25 or G are as defined in claim 1 ; m is 0, 1 or 2. 22. The compound as claimed in any one of claims 1 to 10 wherein R is unsubstituted bicyclic heteroaryl. 23. The compound as claimed in any one of claims 1 to 10 wherein R is substituted bicyclic heteroaryl wherein said substituents are one or more selected from the group consisting of halogen, -CN, -NO2, -G-R23, -NR24C(=O)R25 and -S(O)mR24; wherein R23. R24, R25 or G are as defined in claim 1 ; m is 0, 1 or 2. 24. The compound as claimed in any one of claims 1 to 23 wherein R4 is halogen, C1-C8 substituted or unsubstituted alkyl. C3-C8 substituted or unsubstituted cycloalkyl, substituted or unsubstituted arylalkyl. substituted or unsubstituted heterocyclylalkyl. -OR30 wherein R30 is as defined in claim 1. 25. The compound as claimed in any one of claims 1 to 23 wherein R4 is C1-C8 substituted or unsubstituted alkyl. 26. The compound as claimed in any one of claims 1 to 23 wherein R is methyl. 27. The compound as claimed in any one of claims 1 to 23 wherein R is hydrogen. 28. The compound as claimed in any one of claims 1 to 27 wherein R5 is C3-C8 substituted cycloalkyl, unsubstituted heterocyclyl or substituted heterocyclyl. -29. The compound as claimed in any one of claims 1 to 27 wherein R5is C3-C8 substituted cycloalkyl wherein said substituents are one or more selected from the group consisting of halogen, -CN, C1-C8 substituted or unsubstituted alkyl. C2-C8 substituted or unsubstituted alkenyl, C3-C8 substituted or unsubstituted cycloalkyl and -NRI7R18; wherein R or R is as defined in claim 1. 30. The compound as claimed in any one of claims 1 to 27 wherein R3 is substituted cyclohexyl wherein said substituents are one or more selected from the group consisting of halogen, -CN, C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C3-C8 substituted or unsubstituted cycloalkyl and -NRI7R18; wherein R17 or R18 is as defined in claim 1. 31. The compound as claimed in any one of claims 1 to 27 wherein R^ is 4-amino-cyclohexyl. 32. The compound as claimed in any one of claims 1 to 27 wherein R'*1 is unsubstituted heterocyclyl or substituted heterocyclyl wherein the substituents of heterocyclyl are one or more selected from the group consisting of halogen, -CN. C1-C8 substituted or unsubstituted alkyl, C2-C8 substituted or unsubstituted alkenyl, C3-C8 substituted or unsubstituted cycloalkyl and -NRI7R18; wherein R17 or R18 is as defined in claim 1. 33. The compound as claimed in any one of claims 1 to 27 wherein R5 is unsubstituted piperidin-3-yl, unsubstituted piperidin-4-yl or unsubstituted pyrrolidin-3-yl. 34. The compound as claimed in any one of claims 1 to 27 wherein R5 is substituted piperidin-3-yl, substituted piperidin-4-yl or substituted pyrrolidin-3-yl. 35. The compound as claimed in any one of claims 1 to 27 wherein R5 is substituted piperidin-3-yl, substituted piperidin-4-yl or substituted pyrrolidin-3-yl, wherein the substituents are one or more selected from the group consisting of halogen,-CM, C1-C8 substituted or unsubstituted alkyl. C2-C8 substituted or unsubstituted alkenyl and C3-C8 substituted or unsubstituted cycloalkyl. 36. The compound as claimed in any one of claims 1 to 35 wherein R6 is hydrogen. 37. The compound as claimed in any one of claims 1 to 35 wherein R6 is C1-C8 substituted or unsubstituted alkyl or substituted or unsubstituted arylalkyl. .

Documents:

3714-DELNP-2005-Abstract-(02-02-2009).pdf

3714-DELNP-2005-Abstract-(12-02-2009).pdf

3714-DELNP-2005-Abstract-(23-09-2008).pdf

3714-delnp-2005-abstract.pdf

3714-delnp-2005-assignment.pdf

3714-DELNP-2005-Claims-(02-02-2009).pdf

3714-DELNP-2005-Claims-(12-02-2009).pdf

3714-DELNP-2005-Claims-(23-09-2008).pdf

3714-delnp-2005-claims.pdf

3714-delnp-2005-complete specification (granted).pdf

3714-DELNP-2005-Correspondence-Others-(02-02-2009).pdf

3714-DELNP-2005-Correspondence-Others-(05-02-2009).pdf

3714-DELNP-2005-Correspondence-Others-(23-09-2008).pdf

3714-DELNP-2005-Correspondence-Others-(24-09-2008).pdf

3714-DELNP-2005-Correspondence-Others-(26-09-2008).pdf

3714-delnp-2005-correspondence-others.pdf

3714-delnp-2005-description (complete).pdf

3714-delnp-2005-drawings.pdf

3714-DELNP-2005-Form-1-(23-09-2008).pdf

3714-delnp-2005-form-1.pdf

3714-delnp-2005-form-18.pdf

3714-DELNP-2005-Form-2-(26-09-2008).pdf

3714-delnp-2005-form-2.pdf

3714-DELNP-2005-Form-26-(12-02-2009).pdf

3714-delnp-2005-form-26.pdf

3714-DELNP-2005-Form-3-(05-02-2009).pdf

3714-DELNP-2005-Form-3-(23-09-2008).pdf

3714-delnp-2005-form-3.pdf

3714-delnp-2005-form-5.pdf

3714-delnp-2005-gpa.pdf

3714-delnp-2005-pct-101.pdf

3714-delnp-2005-pct-210.pdf

3714-delnp-2005-pct-304.pdf

3714-delnp-2005-pct-308.pdf

3714-delnp-2005-pct-311.pdf

3714-DELNP-2005-Petition-137-(05-02-2009).pdf

3714-DELNP-2005-Petition-137-(24-09-2008).pdf

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