ZA200502185B - Pyrazolo[3,4-b]pyridine compounds, and their use as phosphodiesterase inhibitors - Google Patents

Pyrazolo[3,4-b]pyridine compounds, and their use as phosphodiesterase inhibitors Download PDF

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ZA200502185B
ZA200502185B ZA200502185A ZA200502185A ZA200502185B ZA 200502185 B ZA200502185 B ZA 200502185B ZA 200502185 A ZA200502185 A ZA 200502185A ZA 200502185 A ZA200502185 A ZA 200502185A ZA 200502185 B ZA200502185 B ZA 200502185B
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South Africa
Prior art keywords
ethyl
pyrazolo
pyridine
carboxamide
ylamino
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ZA200502185A
Inventor
Allen David George
Cook Caroline Mary
Edlin Christopher David
Johnson Martin Redpath
Knowles Richard Graham
Mitchell Charlotte Jane
Ward Peter
Coe Diane Mary
Dowle Michael Dennis
Hamblin Julie Nicole
Jones Paul Spencer
Lindvall Mika Kristian
Redgrave Alison Judith
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Glaxo Group Ltd
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Publication of ZA200502185B publication Critical patent/ZA200502185B/en

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Pyrazolo[3,4-b]pyridine compounds, and their use as phosphodiesterase inhibitors
The present invention relates to pyrazolopyridine compounds, processes for their preparation, intermediates usable in these processes, and pharmaceutical compositions
B containing the compounds. The invention also relates to the use of the pyrazolopyridine compounds in therapy, for example as inhibitors of phosphodiesterases and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis or allergic rhinitis.
US 3,979,399, US 3,840,546, and US 3,966,746 (E.R.Squibb & Sons) disclose 4-amino derivatives of pyrazolo[3,4-b]pyridine-5-carboxamides wherein the 4-amino group
NR3R4 can be an acyclic amino group wherein R3 and R4 may each be hydrogen, lower alkyl (e.g. butyl), phenyl, etc.; NR3R4 can alternatively be a 3-6-membered heterocyclic group such as pyrrolidino, piperidino and piperazino. The compounds are disclosed as central nervous system depressants useful as ataractic, analgesic and hypotensive agents.
US 3,925,388, US 3,856,799, US 3,833,594 and US 3,755,340 (E.R.Squibb & Sons) disclose 4-amino derivatives of pyrazolo[3,4-b]pyridine-5-carboxylic acids and esters.
The 4-amino group NR3R4 can be an acyclic amino group wherein R3 and R4 may each be hydrogen, lower alkyl (e.g. butyl), phenyl, etc.; NR3R4 can alternatively be a 5-6- membered heterocyclic group in which an additional nitrogen is present such as pyrrolidino, piperidino, pyrazolyl, pyrimidinyl, pyridazinyl or piperazinyl. The compounds are mentioned as being central nervous system depressants useful as ataractic agents or tranquilisers, as having antiinflammatory and analgesic properties. The compounds are mentioned as increasing the intracellular concentration of adenosine-3',5"- cyclic monophosphate and for alleviating the symptoms of asthma.
H. Hoehn et al., J. Heterocycl. Chem., 1972, 9(2), 235-253 discloses a series of 1H- pyrazolo[3,4-b]pyridine-5S-carboxylic acid derivatives with 4-hydroxy, 4-chloro, 4-alkoxy, 4-hydrazino, and 4-amino substituents.
CA 1003419, CH 553 799 and T.Denzel, Archiv der Pharmazie, 1974, 307(3), 177-186 disclose 4,5-disubstituted 1H-pyrazolo[3,4-b]pyridines unsubstituted at the 1-position. ) Japanese laid-open patent application JP-2002-20386-A (Ono Yakuhin Kogyo KK) published on 23 January 2002 discloses pyrazolopyridine compounds of the following ' formula:
rR - Bog 0
R JP-2002-20386-A
N / | IAN NH, (Ono)
VY J — /
R® wherein R' denotes 1) a group -ORS, 2) a group -SR’, 3) a C2-8 alkynyl group, 4) a nitro group, 5) a cyano group, 6) a C1-8 alkyl group substituted by a hydroxy group or a C1-8 alkoxy group, 7) a phenyl group, 8) a group -C(O)R?, 9) a group -SO.NR°R'?, 10) a group -NR''SO;R'?, 11) a group -NR'*C(O)R** or 12) a group -CH=NR". R®and R’ denote i) a hydrogen atom, ii) a C1-8 alkyl group, iii) a C1-8 alkyl group substituted by a
C1-8 alkoxy group, iv) a trihalomethyl group, v) a C3-7 cycloalkyl group, vi) a C1-8 alkyl group substituted by a phenyl group or vii) a 3-15 membered mono-, di- or tricyclic hetero ring containing 1-4 nitrogen atoms, 1-3 oxygen atoms and/or 1-3 sulphur atoms.
RZ? denotes 1) a hydrogen atom or 2) a C1-8 alkoxy group. R? denotes 1) a hydrogen atom or 2) a C1-8 alkyl group. R* denotes 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3-7 cycloalkyl group, 4) a C1-8 alkyl group substituted by a C3-7 cycloalkyl group, 5) a phenyl group which may be substituted by 1-3 halogen atoms or 6) a 3-15 membered mono-, di- or tricyclic hetero ring containing 1-4 nitrogen atoms, 1-3 oxygen atoms and/or 1-3 sulphur atoms. R> denotes 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3- 7 cycloalkyl group, 4) a C1-8 alkyl group substituted by a C3-7 cycloalkyl group or 5) a phenyl group which may be substituted by 1-3 substituents. In group R?, a hydrogen atom is preferred. In group R4 , methyl, ethyl, cyclopropyl, cyclobutyl or cyclopentyl are preferred. The compounds of JP-2002-20386-A are stated as having PDE4 inhibitory activity and as being useful in the prevention and/or treatment of inflammatory diseases and many other diseases.
EP 0 076 035 Al (ICI Americas) discloses pyrazolo{3,4-b]pyridine derivatives as central nervous system depressants useful as tranquilisers or ataractic agents for the relief of anxiety and tension states.
The compound cartazolate, ethyl 4-(n-butylamino)-1-ethyl-1H-pyrazolo[3,4-b]-pyridine- 5-carboxylate, is known. JW. Daly et al., Med. Chem. Res., 1994, 4, 293-306 and D. Shi et al., Drug Development Research, 1997, 42, 41-56 disclose a series of 4- (amino)substituted 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid derivatives, including ethyl 4-cyclopentylamino-1-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, and their affinities and antagonist activities at A1- and Aj A-adenosine receptors, and the latter paper discloses their affinities at various binding sites of the GABA A-receptor channel.
S. Schenone et al., Bioorg. Med. Chem. Lett., 2001, 11, 2529-2531 and F. Bondavalli et al., J. Med. Chem., 2002, vol. 45 (Issue 22, 24 October 2002, allegedly published on Web 09/24/2002), pp. 4875-4887 disclose a series of 4-amino-1-(2-chloro-2-phenylethyl)-1H- pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl esters as A 1-adenosine receptor ligands.
WO 02/060900 A2 appears to disclose, as MCP-1 antagonists for treatment of allergic,
RB inflammatory or autoimmune disorders or diseases, a series of bicyclic heterocyclic compounds with a -C(0)-NR#-C(0)-NRSRO substituent, including isoxazolo[5,4- b]pyridines and 1H-pyrazolo[3,4-b]pyridines (named as pyrazolo[5,4-b]pyridines) with the -C(0)-NR4-C(0)-NRSRO group as the 5-substituent and optionally substituted at the 1-3, 4-, and/or 6-positions. Bicyclic heterocyclic compounds with a ~C(O)NH» substituent instead of the -C(O)-NR4-C(0)-NRSRO substituent are alleged to be disclosed in WO 02/060900 as intermediates in the synthesis of the -C(O)-NR4-C(O)-NRSR6 substituted compounds. Itis desirable to find new compounds which bind to, and preferably inhibit, phosphodiesterase type IV (PDE4).
The present invention provides a compound of formula (I) or a salt thereof (in particular, a pharmaceutically acceptable salt thereof): 3
R
HN" O 7 Nr X
S00 0
NT ONT CR?
R’ wherein:
Rls C1-4alkyl, Cj_3fluoroalkyl, -CHyCH»>OH or -CH2CH7CO,C1 .palkyl;
R2 is a hydrogen atom (H), methyl or Cy fluoroalkyl;
R3 is optionally substituted Cj3_geycloalky! or optionally substituted mono-unsaturated-C5_7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc);
Y
Cp, On . bY ) nt h Y (aa) (bb) (cc) in which nl and n2 independently are 1 or 2; and in which Y is O, S, SO», or NR10, where R10 is a hydrogen atom (H), Cj.4alkyl (e.g. methyl or ethyl), C1. fluoroalkyl,
CH,C(O)NH,, C(O)NH3, C(0)-Cj.2alkyl, C(O)-C1fluoroalkyl or -C(0)-CHpO-Cj.palkyl; and wherein in R3 the C3_gcycloalkyl or the heterocyclic group of sub-formula (aa), (bb) or (cc) is optionally substituted with one or two substituents independently being (e.g. being) oxo (=0); OH; Cj_palkoxy; C1.2fluoroalkoxy (e.g. trifluoromethoxy); NHR21 wherein R21 is a hydrogen atom (H) or Cy_g straight-chain alkyl (e.g. H or C4 straight- chain alkyl); Cj_palkyl; Cj.2fluoroalkyl (e.g. Cifluoroalkyl such as -CH)F or -CHF?); -CH,OH; -CH,CH,OH; -CHoNHR22 wherein R22 is H or C1 _palkyl; -C(O)OR23 wherein R23 is H or C1 _palkyl; -C(O)NHR24 wherein R24 is H or C1.palkyl; -C(O)R2> wherein R25 is C1-2alkyl; fluoro; hydroxyimino (=N-OH); or (C|_4alkoxy)imino (=N-OR26 where R20 is C1-4alkyl); and wherein any OH, alkoxy, fluoroalkoxy or
NHR2! substituent is not substituted at the R3 ring carbon attached (bonded) to the -NH- group of formula (I) and is not substituted at either R3 ring carbon bonded to the Y group of the heterocyclic group (aa), (bb) or (cc); and wherein, when R3 is optionally substituted mono-unsaturated-Cg_7cycloalkenyl, then the cycloalkenyl is optionally substituted with one or two substituents being fluoro or
Cj.palkyl provided that if there are two substituents then they are not both Cpalkyl, and the R3 ring carbon bonded to the -NH- group of formula (I) does not partake in the cycloalkenyl double bond; =) or R3 is a bicyclic group of sub-formula (dd): (dd) or of sub-formula (ee): , Y!
YK
. 3
YON
(ee) wherein Y1, Y2 and Y3 independently are CH; or oxygen (O) provided that no more than one of Y1, Y2 and Y3 is oxygen (0);
and X is NR4R5 or OR4, in which: h R4 is a hydrogen atom (H); C1-galkyl; C1_3fluoroalkyl; or Cp_galkyl substituted by one substituent R11; and
RJ is a hydrogen atom (H); C1 .galkyl; C1.g fluoroalkyl; C3_gcycloalkyl optionally substituted by a Cq_2alkyl group; or -(CHp)p4-C3_geycloalkyl optionally substituted, in the -(CHp)%*- moiety or in the C3.gcycloalkyl moiety, by a Cj.palkyl group, wherein n% is1,2 or 3; orR3is Cp_galkyl substituted by one or two independent substituents R1 1, wherein each substituent R11, independently of any other R11 substituent present, is: hydroxy (OH); C1.galkoxy; phenyloxy; benzyloxy; -NRI12R13; .NR15 -C(O)R1 6,
NR15.C(0)-0-R16; -NR15-C(0)-NH-R15; or -NR13-SO7R 16; and wherein any R11 substituent which is OH, alkoxy or -NR12R13 js not substituted at any carbon atom, of any R4 or RS substituted alkyl, which is bonded to the nitrogen of NR4RS; or RS is (CH) I-C(O)R16; -(CH,), 12-C(O)NR12R 13; -CHR19-C(O)NR1ZR13; (CHp)p12-C(0)OR16; -(CH,),12-C(0)OH; -CHR19-C(0)OR 16; -CHR19-C(O)OH; -(CHp)y!2-809-NR12R13; (CHp),12-S02R 16; or <(CHp)p 12-CN; wherein nll is 0, 1, 2,3or4andnl2is 1,2,3 or 4; orR3 is -(CHp), 13-Het wherein nl3 is 0, 1, 2, 3 or 4 and Het is a 4-, 5-, 6- or 7-membered saturated or partly-saturated heterocyclic ring containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-hetero-atoms present are not bound to the (CHp),13- moiety when n!3 is 1 and are not bound to the nitrogen of NR4RS5 when nl3 is 0; wherein any ring-nitrogens which are ‘ present and which are not unsaturated (i.e. which do not partake in a double bond) are present as NR17 where R17 is as defined herein; and wherein one or two of the carbon : 35 ring-atoms independently are optionally substituted by C1.palkyl; or RY is phenyl optionally substituted with, independently, one, two or three of: a halogen atom; Cj_galkyl (e.g. C1_galkyl or Cq.nalkyl); Cj.2fluoroalkyl (e.g. trifluoromethyl);
C1_4alkoxy (e.g. C1.palkoxy); C1.2fluoroalkoxy (e.g. trifluoromethoxy);
C3_gcycloalkyloxy; -C(O)R! 6a; .C(O)OR30; -S(O)-R! 6a (e.g. C1_palkylsulphonyl or
C1.9alkyl-SO,-); R162.5(0)p-NR152- (e.g. C1 palkyl-SO,-NH-); R7TREN-S(0)-; : C1.2alkyl-C(0)-R15aN-5(0);-; Cy_4alkyl-S(O)-, Ph-S(O)-, R7R8N-CO-; “NR15-C(O)R!6; R7R8N; OH; C1 _galkoxymethyl; C1-gqalkoxyethyl;
X 5 Cj.palkyl-S(0)3-CHy-; RTR8N-S(0)2-CHp-; C1 _palkyl-S(0)2-NR153.CHy-; -CH,-OH; -CH,CHj-OH; -CH,-NR7R8; -CH,-CHp-NR7RS; -CHp-C(0)OR30; _CH,-C(0)-NR7RS8; -CH,-NR 152.C(0)-C1_3alkyl; -(CHp)p!4-Het! where nl4is 0 or 1; cyano (CN); Ar>2; or phenyl, pyridinyl or pyrimidinyl wherein the phenyl, pyridinyl or pyrimidinyl independently are optionally substituted by one or two of fluoro, chloro, Cj-palkyl, Cqfluoroalkyl, C1_palkoxy or Cqfluoroalkoxy; or where two adjacent substituents taken together are -O~(CMep)-O- or ~0—(CHp) 14-0O- where nl4is1or2; wherein R7 and R8 are independently a hydrogen atom (H); C1 _4alkyl (e.g.
C1.nalkyl such as methyl); C3_gcycloalkyl; or phenyl optionally substituted by one or two of: fluoro, chloro, C1_palkyl, C1fluoroalkyl, Cj.palkoxy or Cj fluoroalkoxy; or R7 and R8 together are -(CHp)y6- or -C(0)-(CHp)p’- or -C(0)-(CHR)n’-C(0)- or -(CHp)y8-X7-(CHy)p%- or -C(0)-X7-(CHp) 1 0- in which: nS is 3, 4,5 or 6, n’ is 2, 3, 4, or 5 (preferably n’ is 2, 3 or 4), n8 and n9 and n!0 independently are 2 or 3 (preferably independently 2), and X7 is O or NR14 wherein R14 is H, C1_palkyl or C(O)Me (preferably H or Cq_palkyl); or RS has the sub-formula (x), (¥), (y1) or (2): -(CH A A A —G ( ho? “8 —X “8 ne 8 cH — pr
Fag P F XP r NP 2 ~L (x) vy) (v1) (2) wherein in sub-formula (x), n= 0, 1 or 2; in sub-formula (y) and (yl), m= 1 or 2; and in sub-formula (z), r= 0, 1 or 2; ' wherein in sub-formula (x) and (y) and (y1), none, one or two of A, B, D, E and F are independently nitrogen or nitrogen-oxide (N*-0-) provided that no more than one of A,
B,D, E and F is nitrogen-oxide; and the remaining of A, B, D, E and F are independently
CH or CRY;
provided that when n is 0 in sub-formula (x) then one or two of A, B, D, E and F are independently nitrogen or nitrogen-oxide (N*-0-) and no more than one of A,B, D, E and F is nitrogen-oxide; wherein, each R9, independently of any other RO present, is: a halogen atom; C}_galkyl ’ (e.g. C.4alkyl or Cy_palkyl); Cj_gfluoroalkyl (e.g. Ci-pfluoroalkyl); Cq_galkoxy (e.g.
Cj-palkoxy); Cy_afluoroalkoxy; C3_gcycloalkyloxy; -C(O)R163; -C(O)OR30; -S(O)p-R162 (e.g. C1_oalkylsulphonyl, that is C1 _palkyl-SOy-); R162-§(0),-NR152. (e.g. C.nalkyl-SO5-NH-); R7R8N-S(0);-; C1.2alkyl-C(O)-R153N-S(0)2-; Cj.4alkyl-S(0)-, Ph-S(0)-, R7R8N-CO-; -NR15-C(O)R16; R7R8N; OH;
C1-4alkoxymethyl; C1 _galkoxyethyl; Cy_palkyl-S(0)2-CHp-; R7R8N-S(0),-CHy-;
C1.0alkyl-S(O),-NR152.CHj,-; -CHy-OH; -CHCHy-OH; -CH-NRRS; -CH,-CH5-NRR8; -CH-C(0)OR30; -CH,-C(O)-NR7RS; -CHy-NR152.C(0)-C _3alkyl; -(CHp),14-Hetl where nl4 is 0 or 1; cyano (CN); Arb; or phenyl, pyridinyl or pyrimidinyl wherein the phenyl, pyridinyl or pyrimidinyl independently are optionally substituted by one or two of fluoro, chloro, C1_palkyl,
C1 fluoroalkyl, C1.palkoxy or Cj fluoroalkoxy; or where two adjacent RO taken to gether are ~O—(CMep)—-O— or -O—(CHp),, 14-0~ where n14 is 1 or 2; wherein R7 and R38 are as herein defined; wherein sub-formula (y) and (y1), independently, are optionally substituted by oxo (=O) at a ring carbon adjacent the 6-membered aromatic ring (for example, sub-formula (y) can o p ; 1 Ne _D x 0D optionally be mF or 0 , or sub-formula (y1) can optionally
Za a
Ng Ng hn be © or © ); wherein in sub-formula (z), G is O or S or NR9 wherein R9 is a hydrogen atom (H),
Cj-4alkyl or C1_4fluoroalkyl; none, one, two or three of J, L, M and Q are nitrogen; and the remaining of J, L, M and Q are independently CH or CR where RY, independently of any other RY present, is as defined herein;
or R4 and RS taken together are ~(CH)p!- or -C(0)-(CHp)p?- or -(CHp)p3-X5-(CH)p#- or -C(0)-X’-(CHp)p>-, in which: pl =3, 4, 5 or 6 (preferably p =4o0r5),p2is2,3,4,0r5 (preferably p2 is 2, 3 or 4), and p3 and p4 and p> independently are 2 or 3 (independently preferably 2) and X35 is O or NR17; and wherein, when R4 and RS taken together are —(CH2)p Lor -C(O)-(CH2)p2-, the NR4R> heterocycle is optionally substituted by one R18 substituent wherein R18 is:
C1-4alkyl (e.g. C1.palkyl); Cy.2fluoroalkyl; C3.gcycloalkyl; Cq.palkoxy (not substituted at a ring-carbon bonded to the NR4R3 ring-nitrogen); C1fluoroalkoxy (not substituted at a ring-carbon bonded to the NR4R3 ring-nitrogen); OH (not substituted at a ring-carbon bonded to the NR4R5 ring-nitrogen); -(CHp)p’-C(O)R16 wherein p7 is 0, 1,2 or 3 (preferably p? is 0 or 1); -(CHp)p7-C(O)OR16; (CH), 7-OC(O)R!16; -(CHp)p-C(O)NRIZR13; (CH), 7-NR15C(O)R 16; -(CHp), -NRISC(O)NR12R13; -(CHp)p-NR15C(0)OR16; -(CHp)7-SOoR16; -(CHp)p 7-802 NRI2R13; -(CHy)p -NR15SO,R16; -(CH),7-OH; -(CH2)p 7-OR16; or phenyl optionally substituted by one or two of: a halogen atom, C1.palkyl, Cfluoroalkyl, C.palkoxy or
C1 fluoroalkoxy; or R4 and R3 taken together are —(CHp)p1- or -C(0)-(CHp),2- or -(CH2)p3-X5-(CHp)p?- or -C(0)-X3-(CHp)p>- as defined herein, and wherein the NR4RS heterocycle is fused to a phenyl ring optionally substituted on the phenyl by one or two of: a halogen atom, C1._palkyl, C1 fluoroalkyl, Cq_palkoxy or Cifluoroalkoxy; and
R52 is Cy _galkyl; Cj.g fluoroalkyl; C3.gcycloalkyl; -(CHy),43-C3_gcycloalkyl wherein n#is 1 or 2; phenyl optionally substituted with one or two of: a halogen atom, C- 1-2alkyl, trifluoromethyl, Cj _palkoxy or trifluoromethoxy; or R32 has the sub-formula (x), (y) or (2) as defined herein and wherein:
R12 and R13 independently are H; C1-salkyl (e.g. Cq.3alkyl); C3_geycloalkyl; or phenyl optionally substituted by one or two of: a halogen atom, Cj.palkyl, Cfluoroalkyl,
C1-palkoxy or C1fluoroalkoxy; or R12 and R13 together are -(CH2),0- or -C(0)-(CHp)y,7- or -C(0)-(CHp)7-C(O)- or -(CH2)5,8-X12-(CHp),9- or -C(0)-X12-(CH)10- in which: nb is 3,4, 5 or 6 (preferably n is 4 or 5), n7 is 2, 3, 4, or 5 (preferably n’ is 2, 3 or 4), n8 and n9 and n10 independently are 2 or 3 (independently preferably 2) and X12 is O or NR 142 wherein
R142 is H, C1_palkyl or C(O)Me (preferably H or Cj.palkyl);
R15 is a hydrogen atom (H); Ci-4akkyl (e.g. Bu or C_palkyl e.g. methyl); Cj3.gceycloalkyl; or phenyl optionally substituted by one or two of: a halogen atom,
C1.2alkyl, Cqfluoroalkyl, Cq.palkoxy or Cqfluoroalkoxy;
R152 independent of other R152, is a hydrogen atom (H) or Cj_galkyl (e.g. H, tBu or
C1.2alkyl such as methyl; preferably R152 is H or Cj_palkyl, more preferably H);
R16 and R162 independently are:
C1-6alkyl (e.g. Cq.-galkyl or Cj_palkyl);
C3.gcycloalkyl (e.g. Cs.geycloalkyl) optionally substituted by one oxo (=O), OH or Cy_palkyl substituent (e.g. optionally substituted at the 3- or 4-position of a Cs_gcycloalkyl ring; and/or preferably unsubstituted C3_gcycloalkyl);
Cj_geycloalkyl-CHy- (e.g. Cs_geycloalkyl-CHjp-); pyridinyl (e.g. pyridin-2-yl) optionally substituted on a ring carbon atom by one of: a halogen atom, C1_salkyl, C{fluoroalkyl, C;_palkoxy or Cj fluoroalkoxy;
Ard¢; ’ phenyl optionally substituted by one or two of: a halogen atom, Cy _palkyl,
Cy fluoroalkyl, Cj_palkoxy or Cj fluoroalkoxy; benzyl optionally substituted at an aromatic carbon atom by one or two of: a halogen atom, C1_salkyl, Cy fluoroalkyl, Ci_palkoxy or C1fluoroalkoxy; or a 4-, 5-, 6- or 7-membered saturated heterocyclic ring connected at a ring-carbon and containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-nitrogens which are present are present as NR27 where R27 is H,
C1-2alkyl or -C(O)Me; and wherein the ring is optionally substituted at carbon by one
C1.palkyl or oxo (=O) substituent, provided that any oxo (=O) substituent is substituted at a ring-carbon atom bonded to a ring-nitrogen; wherein Ar3@ | ArSb and Aro¢ independently is/are a 5-membered aromatic heterocyclic ring containing one O, S or NR 152 in the 5-membered ring, wherein the 5-membered ring can optionally additionally contain one or two N atoms, and wherein the heterocyclic ring , is optionally substituted on a ring carbon atom by one of: a halogen atom, Cq_palkyl, Cjfluoroalkyl, -CHyOH, -CH2-OCj_palkyl, OH (including the keto tautomer thereof) or ~CH,-NR28R29 wherein R28 and R29 independently are H or methyl, and R17 is a hydrogen atom (H); Cy_4alkyl (e.g. C1_palkyl); C1 _pfluoroalkyl;
Cj.gcycloalkyl; -(CHp)p0-C(O)R16 wherein p®is 0, 1, 2 or 3 (preferably p0 is 0);
-(CH2)pS-C(O)NRI2R13; -(CH}),6-C(0)OR16; -(CH2),6-C(O)OH; -SOR16; -C(0)-CH2-NR12R13; -C(0)-CH,-NR153.C(0)-C} _3alkyl; -C(0)-CHy-0-C _3alkyl; or phenyl or benzyl wherein the phenyl or benzyl is optionally substituted at an aromatic carbon atom by one or two of: a halogen atom, Cy _palkyl, Cj fluoroalkyl, C1 _palkoxy or
Cjfluoroalkoxy;
R1%s Cy_galkyl; -(CHy)20-OR20 wherein n20 is 1, 2, 3 or 4 and R20 is a hydrogen atom (H) or C_galkyl; -CH(Me)-OH; -CH3-SH; -CH»-CH3-S-Me; benzyl; or (4-hydroxyphenyl)methyl (i.e. 4-hydroxy-benzyl); and
R30, independent of other R30, is a hydrogen atom (H), C1-4alkyl or C3_gcycloalkyl; and
Hetl | independent of other Hetl, is a 4-, 5-, 6- or 7-membered saturated heterocyclic ring connected at a ring-carbon and containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-nitrogens which are present are present as
NR31 where R31 is H, C1.2alkyl or -C(O)Me; and wherein the ring is optionally substituted at carbon by one Cj_jalkyl or oxo (=O) substituent, provided that any oxo (=O) substituent is substituted at a ring-carbon atom bonded to a ring-nitrogen; 20provided that: when R3 is the heterocyclic group of sub-formula (bb), nl is 1, and Y is NR10, then: either (a) R19 is not Cq_galkyl, C1-2fluoroalkyl or CHyC(O)NHo; or (b) R10 is methyl and the compound is: 1-ethyl-N-(2-ethylbutyl)-4-[(1- methylpiperidin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide or 1-ethyl-N-(4- fluorophenyl)-4-[(1-methylpiperidin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5- carboxamide.
Preferably, where X is OR52, the compound is other than the compound wherein R! is methyl, X is OEt, and R3 is cyclopentyl.
In one optional embodiment of the invention, R! is C1_4alkyl or Cy_pfluoroalkyi.
Alternatively or additionally, in one optional embodiment of the invention, RZ is a hydrogen atom (H).
Alternatively or additionally, in one optional embodiment of the invention, R3 is
Y y
SINS
C3_gcycloalkyl or a heterocyclic group being ~ in which Y is 0, S, SOy, or NR10; where R10 is hydrogen, Cj-4alkyl, Cq_2fluoroalkyl, C(O)-Cy. 2alkyl, or C(O)-CF3; and wherein in R3 the C3_gcycloalkyl or heterocyclic group is optionally substituted with one or two substituents being OH, C1_palkoxy, trimethoxy, or C1_palkyl; and wherein any OH, alkoxy or trimethoxy substituent is not substituted at the (R3) ring carbon attached (bonded) to the -NH- group of formula (I) and is not substituted at either (R3) ring carbon bonded to the Y group of the heterocyclic group.
Alternatively or additionally, in one optional embodiment of the invention, R4is hydrogen, Cy_palkyl or Cq_2fluoroalkyl.
Alternatively or additionally, in one optional embodiment of the invention, Ris hydrogen, C1_galkyl, C1.g fluoroalkyl, or C3_gcycloalkyl; or phenyl optionally substituted with one or two of: a halogen atom, Cy_salkyl, trifluoromethyl, C{_palkoxy or trifluoromethoxy; or R? has the sub-formula (x), (y) or (2): -(CH,), A A o—& 1 | —K i (CH)
SN . Ne _D (x) (vy) (2) wherein in sub-formula (x), n = 1 or 2; in sub-formula (y), m = 1 or 2; and in sub- formula (z),r=1o0r2; wherein in sub-formula (x) and (y), none, one or two of A, B, D, E and F are nitrogen; and the remaining of A, B, D, E and F are CH or CRO where RO is a halogen atom, C1_galkyl, Cj_g4fluoroalkyl, C1_palkoxy, Cj.2fluoroalkoxy, Cj_salkylsulphonyl (C1.2alkyl-SO5-), C1 _palkyl-SO2-NH-, R7R8N-S07-, R7R8N-CO-, R7R8N, OH, Cj.4alkoxymethyl, or Cy_palkyl-SO2-CH2-, wherein R7 and RS are independently hydrogen or Cj_palkyl; wherein in sub-formula (z), G is O or S or NR? wherein R? is C}_galkyl or
C1 -4fluoroalkyl; none, one or two of J, L, M and Q are nitrogen; and the remaining of J,
L, M and Q are CH or CRS where RO is as defined herein.
In the alternative to the above R4 and/or R3 optional embodiments, in one optional embodiment of the invention, R4 and RS taken together can be ~(CHp)p!- where pl = 3, 4 or 5 (preferably pl=4o0r5).
In one optional embodiment of the invention, R3is optionally substituted
C3_gcycloalkyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb)
S or(cc);
Y. oe Lh, LA or 8 ) . or . Y (aa) (bb) (cc) in which nl and n2 independently are 1 or 2; and in which Y is O, S, SO», or NR 10; where R10 is a hydrogen atom (H), C;_galkyl (e.g. methyl or ethyl), C1_pfluoroalkyl,
CH,C(O)NHj3, C(O)NHjp, C(0)-C1-2alkyl, or C(0O)-Cj fluoroalkyl; and wherein in R3 the C3.gcycloalkyl or the heterocyclic group of sub-formula (aa), (bb) or (cc) is optionally substituted with one or two substituents being oxo (<0),
OH, C1.palkoxy, C1_pfluoroatkoxy (e.g. trifluoromethoxy), or Cy_palkyl; and wherein any OH, alkoxy or fluoroalkoxy substituent is not substituted at the R3 ring carbon attached (bonded) to the -NH- group of formula (I) and is not substituted at either R3 ring carbon bonded to the Y group of the heterocyclic group (aa), (bb) or (cc).
Alternatively or additionally to the above optional R3 definition, in one optional embodiment of the invention, X is NR4RS or OR32, in which:
R4 is a hydrogen atom (H); Cj_galkyl; C1_3fluoroalkyl; or Co_galkyl substituted by one substituent R11; and
RS is a hydrogen atom (H); Cj.galkyl; Cj.g fluoroalkyl; C3_gcycloalkyl optionally substituted by a C1_palkyl group; or -(CH2)n*-C3_gcycloalkyl optionally substituted, in the -(CHp)p4- moiety or in the C3_gcycloalkyl moiety, by a Cy.palkyl group, wherein n4 isl,2o0r3; or RS is Cy_galkyl substituted by one or two independent substituents RIL; wherein each substituent R11, independently of any other R11 substituent present, is: hydroxy (OH); C1._galkoxy; phenyloxy; benzyloxy; -NRI12R13; -NR15-C(O)R16;
NR15-C(0)-0-R16; -NR1 5.C(O)-NH-R13; or -NR1 5-SO5R1 6; and wherein any R11 substituent which is OH, alkoxy or -NR12R13 is not substituted at any carbon atom, of any R4 or RS substituted alkyl, which is bonded to the nitrogen of NR4R3;
or RS is -(CHp),, 1 1-C(O)R16; -(CHp),12-C(O)NR12R 13; -CHR 19-C(O)NRI2R 13; -(CH),12-C(0)OR 16; -CHR 19-C(0)OR 16; -(CHy) 12-S02-NR12R 13; (CH) 12-S09R 16; or -(CH2),, 1 2-CN; wherein nll is 0, 1,2,3 or 4 and nl12 is 1,2, 3 . 5 oré4 or RJ is ~(CHp)13-Het whereinnl31is 0, 1, 2, 3 or 4 and Het is a 4-, 5-, 6- or 7-membered saturated or partly-saturated heterocyclic ring containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-hetero-atoms present are not bound to the -(CHp)p13- moiety when n13 is 1 and are not bound to the nitrogen of NR4R5 when n13 is 0; wherein any ring-nitrogens which are present and which are not unsaturated (i.e. which do not partake in a double bond) are present as NR17 where R17 is as defined herein; and wherein one or two of the carbon ring-atoms independently are optionally substituted by Cy .palkyl; or R3 is phenyl optionally substituted with one or two of: a halogen atom; Cj_4alkyl (e.g.
C1 -palkyl); Cj_ofluoroalkyl (e.g. trifluoromethyl); Cj._galkoxy (e.g. Cy.palkoxy); C1. sfluoroalkoxy (e.g. trifluoromethoxy); C1-palkyisulphonyl (Cq_palkyl-SO3-);
C1_palkyl-SO-NH-; R7R8N-80,-; R7TR8N-CO-; -NR15-C(O)R 16; R7R8N; OH; Cj.4alkoxymethyl; C_galkoxyethyl; Cq.2alkyl-SO2-CHjp-; cyano (CN); or phenyl optionally substituted by one or two of fluoro, chloro, Cy_palkyl, C1 fluoroalkyl,
C1.-palkoxy or Ci fluoroalkoxy; wherein R7 and R83 are independently a hydrogen atom (H); C1.4alkyl (e.g.
C1-palkyl such as methyl); C3._gcycloalkyl; or phenyl optionally substituted by one or two of: fluoro, chloro, Cq.palkyl, Cqfluoroalkyl, C;_palkoxy or C1 fluoroalkoxy; or R7 and R8 together are ~(CHy),0- or -C(0)-(CHp)p,- or -C(0)-(CHp)y,7-C(O)- or -(CHy)8-X7-(CHp)p?- or -C(0)-X7-(CHp)p 10- in which: nis 3,4,50r6,n7 is 2,3, 4, or 5 (preferably n’ is2, 3 or 4), 1n8 and n and n19 independently are 2 or 3, and X7 is
O or NR14 wherein R14 is H or C1_palkyl; or R3 has the sub-formula (x), (y) or (2):
ACH) AN A a
Ng” I Se” (x) (v) (2)

Claims (1)

  1. CL IS PCT/EP2003/011814 . > -246 - p
    ® ». CLAIMS
    1. A compound of formula (I) or a salt thereof: 3 R HN" O J ~~ X S00 (0) NT SN SR? / R' 5S wherein: R1 is Cj_3alkyl, Cj.ofluoroalkyl or -CHpCH,OH; R2isa hydrogen atom (H), methyl or Cj fluoroalkyl; R3 is substituted Cj3._geycloalkyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); Y (3 ‘oy n or or . ) os . v (aa) (bb) (co) in which n! and n2 independently are 1 or 2; and in which Y is O, S, SO», or NR10; where R10 is a hydrogen atom (H), methyl, ethyl, Cj-2fluoroalkyl, C(O)NH3>, C(0)-Cj.palkyl, C(0)-Cqfluoroalkyl or -C(O)-CH»O-Cjalkyl; and wherein, when R3 is substituted Cj3.gcycloalkyl, then R3 is cyclohexyl substituted by one substituent being oxo (=O), OH, NHR2! wherein R21 is a hydrogen atom (H) or C] 5 straight-chain alkyl, -CH>OH, -C(O)OR23 wherein R23 is H or methyl, -C(O)NHR24 wherein R24 is H or methyl, -C(O)R25 wherein R23 is
    Cj.palkyl, hydroxyimino (=N-OH), or (C}_galkoxy)imino (=N-ORZ26 where R26 is
    Cj.galkyl); and wherein in R3 the heterocyclic group of sub-formula (aa), (bb) or (cc) is optionally substituted with one or two substituents independently being oxo (=O) or OH; AMENDED SHEET
    PCT/EP2003/011814
    ® and wherein any OH or NHR2! substituent is not substituted at the R3 ring carbon attached (bonded) to the -NH- group of formula (I) and is not substituted at either R3 ring carbon bonded to the Y group of the heterocyclic group (aa), (bb) or (cc);
    and X is NR4RS or OR52, in which: R4isa hydrogen atom (H); and
    RS is Cj _galkyl; Cy _g fluoroalkyl; C3_gcycloalkyl optionally substituted by a Cy-palkyl group; or -(CH)p*-C3_geycloalkyl optionally substituted, in the -(CHp)p%- moiety or in the C3_gcycloalkyl moiety, by a Cj.palkyl group, wherein n4 is1,2or3; or RJ is Cy_galkyl substituted by one or two independent substituents R11; wherein each substituent R11, independently of any other R1 I substituent present, is: hydroxy (OH); Cj.galkoxy; phenyloxy; benzyloxy; -NRI2R13; NRI15-C(O)R16; -NR15.C(0)-0-R16; .NR15-C(0)-NH-R13; or -NR13-SO7R 16; and wherein any AMENDED SHEET
    PCT/EP2003/011814 ® R11 substituent which is OH, alkoxy or -NR12R13 is not substituted at any carbon atom, of any R4 or R3 substituted alkyl, which is bonded to the nitrogen of NR4R5; or RS is (CH), 1 1-C(O)R16; -(CHp), 12-C(O)NRI2R 13; -CHR 19-C(O)NR12R 13; «(CHp),12-C(0)OR16; -(CHy), 12-C(0)OH; -CHR19-C(0)OR 16; -CHR19-C(0)OH; -(CHp),12-S05-NR12R 13; -(CHp),12-SO5R 16; or -(CHp), 1 2-CN; wherein nll is 0,1,2,3 0r4 and nl2is 1,2, 3 or 4; or RY is -(CHp)q13-Het wherein n13 is 0, 1,2,3 or4 and Het is a 4-, 5-, 6- or 7-membered saturated or partly-saturated heterocyclic ring containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-hetero-atoms present are not bound to the «(CHp),! 3. moiety when n!3is1and are not bound to the nitrogen of NRARS5 when n!3 is 0; wherein any ring-nitrogens which are present and which are not unsaturated (i.e. which do not partake in a double bond) are present as NR17 where R17 is as defined herein; and wherein one or two of the carbon ring-atoms independently are optionally substituted by C_palkyl; or RJ is phenyl optionally substituted with, independently, one, two or three of: a halogen atom; Cy _galkyl; C_pfluoroalkyl; Cj _galkoxy; Cj_pfluoroalkoxy;
    C3.geycloalkyloxy; -C(O)R 162; .C(0)OR30; -S(0),-R 162; R162.5(0),-NR 152; R7R8N-S(0)y-; Cj.nalkyl-C(0)-R15a8N-S(0);-; C_4alkyl-S(0)-; Ph-S(O)-; R7R8N-CO-; -NR15-C(O)R16; R7R8N; OH; C;_galkoxymethyl; C_galkoxyethyl;
    C.-alkyl-S(0)2-CHy-; R7R8N-S(0)5-CHy-; C1 palkyl-S(0)-NR152-CHy-; -CH,-OH; -CH,CH,-OH; -CH,-NR7RS; -CH,-CH;-NR7R8; -CH;-C(0)OR30; -CHy-C(0)-NR7R8; -CHy-NR152.C(0)-C.3alkyl; -(CHp), 14-Het! where nl4 is 0 or 1; cyano (CN); Ar33; or phenyl, pyridinyl or pyrimidinyl wherein the phenyl, pyridinyl or pyrimidinyl independently are optionally substituted by one or two of fluoro, chloro, C1_salkyl, C1fluoroalkyl, C}_palkoxy or C1fluoroalkoxy; or where two adjacent substituents, on the RS optionally substituted phenyl, taken together are -O—-CMep)—O- or —O—(CHp),142-0- where nl43 is 1 or 2; wherein R7 and R8 are independently a hydrogen atom (H); Cj_galkyl;
    C3.gcycloalkyl; or phenyl optionally substituted by one or two of: fluoro, chloro,
    C1.palkyl, Cifluoroalkyl, C1.palkoxy or C1 fluoroalkoxy; or R7 and R8 together are -(CH)6- or -C(0)-(CHo)p7- or -C(0)-(CH2)57-C(O)- or -(CHp)p8-X7-(CH2)p”- or -C(O)-X7-(CHp),10- in which: nis 3,4, 5 or 6,n7 is 2,3,4, or 5, n8 and n% and nl0 independently are 2 or 3 , and X7 is O or NR14 wherein R14 is H, Cj-palkyl or C(O)Me; CLEAN COPY
    PCT/EP2003/011814 ® or R3 has the sub-formula (x), (¥), (y1) or (2): -(CH,), A A A aC ~ 8 : ZB ~ TB \ T [] : I ll «CH — , Fs D x __D xD 2/r ~L E In E A - x) v) (v1) (2) 5S wherein in sub-formula (x), n = 0, 1 or 2; in sub-formula (y) and (yl), m = 1 or 2; and in sub-formula (z), r=0, 1 or 2; wherein in sub-formula (x) and (y) and (y1), none, one or two of A, B,D, E and F are independently nitrogen or nitrogen-oxide (N*-O-) provided that no more than one of A, B,D, E and F is nitrogen-oxide; and the remaining of A, B, D, E and F are independently CH or CRS; provided that when n is 0 in sub-formula (x) then one or two of A, B, D, E and F are independently nitrogen or nitrogen-oxide (N*-O-) and no more than one of A, B, D, E and F is nitrogen-oxide; wherein, each R9, independently of any other RO present, is: a halogen atom; C1-galkyl; Cj_gfluoroalkyl; Ci_galkoxy; Cy_pflucroalkoxy; C3_gcycloalkyloxy; -C(O)R162; .C(0)OR30; -§(0),-R 163; R162.5(0),-NR 152.; R7REN-S(0),-;
    Cj.oalkyl-C(0)-R158N-S(0),-; C1 _4alkyl-S(0)-; Ph-S(0)-; RTR8N-CO-; -NRI5.C(0)R16; R7R8N; OH; C_galkoxymethyl; Cj _4alkoxyethyl;
    C1.9alkyl-S(0)p-CHp-; R7R8N-S(0),-CHj-; Cy palkyl-S(0)y-NR132-CHy-; _CH»-OH; -CH,CH5-OH; -CHy-NR7R8; -CH,-CHp-NR7R8; -CH;-C(0)OR30; _CH,-C(0)-NR7R8; -CH,-NR152-C(0)-C} _3alkyl; (CHp),!4-Het! where nl4 is 0 or 1; cyano (CN); Ar3b; or phenyl, pyridinyl or pyrimidinyl wherein the phenyl, pyridinyl or pyrimidinyl independently are optionally substituted by one or two of fluoro, chloro, Cy_oalkyl, Cjfluoroalkyl, Cj_palkoxy or C1fluoroalkoxy; or where two adjacent RO taken together are -O—(CMe7)-O- or ~0—(CHy), 148-0- where n142 is 1 or 2; wherein R7 and R8 are as herein defined; wherein sub-formula (y) and (y1), independently, are optionally substituted by oxo (=O) at a ring carbon adjacent the 6-membered aromatic ring; wherein in sub-formula (z), Gis O or S or NR? wherein R? is a hydrogen atom (H), C1-4alkyl or Cj_4fluoroalkyl; none, one, two or three of J, L, M and Q are nitrogen; CLEAN COPY
    PCT/EP2003/011814 ® and the remaining of J, L, M and Q are independently CH or CRS where RO, independently of any other RO present, is as defined herein; and Rais Cq_galkyl; C;_g fluoroalkyl; C3_gcycloalkyl; -(CHp)p%2-C3_gcycloalkyl wherein n42 is 1 or 2; phenyl optionally substituted with one or two of: a halogen atom, C1_palkyl, trifluoromethyl, C{_palkoxy or trifluoromethoxy; or R52 has the sub-formula (x), (y), (v1) or (z) as defined herein; and wherein: R12 and R13 independently are H; C_salkyl; C3_gcycloalkyl; or phenyl optionally substituted by one or two of: a halogen atom, Cj_jalkyl, Cj fluoroalkyl, Cj_palkoxy or Cj fluoroalkoxy; or R12 and R13 together are -(CH2)p6- or -C(0)-(CHp),7- or -C(0)-(CHp),7-C(O)- or -(CHp)8-X12-(CHy),%- or -C(0)-X12-(CHy),10- in which: nb is 3,4, 5 or 6, n7 1s2,3,4,o0r5, n8 and n% and n10 independently are 2 or 3 and X12 is 0 or NR142 wherein R142 is H, C; alkyl or C(O)Me; R13 is a hydrogen atom (H); C|-4alkyl; C3_gcycloalkyl; or phenyl optionally substituted by one or two of: a halogen atom, C_jalkyl, C{fluoroalkyl, Cj_palkoxy or Cjfluoroalkoxy; R153 independent of other R152 is a hydrogen atom (H) or C| _galkyl; R16 and R162 independently are: C1-6alkyl; C3_gcycloalkyl optionally substituted by one oxo (=0), OH or C1 _palkyl substituent;
    Cj3.gcycloalkyl-CHp-; pyridinyl optionally substituted on a ring carbon atom by one of: a halogen atom, C1_palkyl, Cqfluoroalkyl, Cj.palkoxy or Cjfluoroalkoxy; AC; phenyl optionally substituted by one or two of: a halogen atom, C_palkyl, C1fluoroalkyl, C1_jalkoxy or Cj fluoroalkoxy; : benzyl optionally substituted at an aromatic carbon atom by one or two of: a halogen atom, C1_2alkyl, C1 fluoroalkyl, C;.palkoxy or Cifluoroalkoxy; or a 4-, 5-, 6- or 7-membered saturated heterocyclic ring connected at a ring- 40 carbon and containing one or two ring-hetero-atoms independently selected from O, CLEAN COPY
    PCT/EP2003/011814
    ® S, and N; wherein any ring-nitrogens which are present are present as NR27 where R27 is H, C1-palkyl or -C(O)Me; and wherein the ring is optionally substituted at carbon by one C1_palkyl or oxo (=O) substituent, provided that any oxo (=O) substituent is substituted at a ring-carbon atom bonded to a ring-nitrogen; S wherein Ar32 , Ar5b and Ar3¢ independently is/are a S-membered aromatic heterocyclic ring containing one O, S or NR154a in the 5-membered ring, wherein the 5-membered ring can optionally additionally contain one or two N atoms, and wherein the heterocyclic ring is optionally substituted on a ring carbon atom by one of: a halogen atom, C}_»alkyl, C1fluoroalkyl, -CHpOH, -CH3-OC|_salkyl, OH (including the keto tautomer thereof) or —CH,-NR28R29 wherein R28 and R29 independently are H or methyl; and R17 is a hydrogen atom (H); C1 .4alkyl; C}_afluoroalkyl; C3_gcycloalkyl;
    «(CHp)pd-C(O)R16 wherein pb is 0, 1,2 or 3; -(CH2)p0-C(O)NRIZR 13; -(CH2)p0-C(0)OR16; -(CH)0-C(O)OH; -SO9R16; -C(0)-CHy-NR12R 13; -C(0)-CHy-NR152.C(0)-C _3alkyl; -C(0)-CH3-0-C] _3alkyl; or phenyl or benzyl wherein the phenyl or benzyl is optionally substituted at an aromatic carbon atom by one or two of: a halogen atom, C1_»alkyl, Cyfluoroalkyl, Cy_palkoxy or
    Cjfluoroalkoxy;
    R19is C{_galkyl; -(CHp)20-OR20 wherein n20 is 1, 2, 3 or 4 and R20 is a hydrogen atom (H) or Cj_galkyl; -CH(Me)-OH; -CHp-SH; -CH)-CH3-S-Me; benzyl; or (4-hydroxyphenyl)methy! (i.e. 4-hydroxy-benzyl); and
    R30, independent of other R30, is a hydrogen atom (H), C|_4alkyl or C3_gcycloalkyl; and Het! | independent of other Hetl, is a 4-, 5-, 6- or 7-membered saturated heterocyclic ring connected at a ring-carbon and containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-nitrogens which are present are present as NR31 where R31 is H, Cj.palkyl or -C(O)Me; and wherein the ring is optionally substituted at carbon by one Cj_palkyl or oxo (=O) substituent, provided that any oxo (=O) substituent is substituted at a ring-carbon atom bonded to aring-nitrogen; : provided that: when R3 is the heterocyclic group of sub-formula (aa) and Y is NR10, then R10 is not C(O)NH;, C(0)-C1_palkyl or C(O)-C|fluoroalkyl;
    40
    CLEAN COPY
    PCT/EP2003/011814
    @ provided that: when R3 is the heterocyclic group of sub-formula (bb), nlis1,and Y is NR1O, then: either (a) R10 is not methyl, ethyl or C1 -ofluoroalkyl; or (b) R10 js methyl and the compound is: 1-ethyl-N-(2-ethylbutyl)-4-[(1- methylpiperidin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide or 1-ethyl- N-(4-fluorophenyl)-4-[(1-methylpiperidin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5- carboxamide; provided that: when R3 is the heterocyclic group of sub-formula (cc), then NHR3 is of sub-formula (L), (m), (m1) or (m2), wherein the -NH- connection point of the NHR3 group to the 4-position of the pyrazolopyridine of formula (I) is underlined:
    Oo @ La HHT SN JQ HN HN H NH 0] (L) (m) (m1) (m2) :
    and provided that: where R3 is optionally substituted C3_gcycloalkyl, then any OH, -CH,OH, -C(0)OR23, -C(O)NHR?24 or -C(O)R25 substituent is at the 3-, 4- or 5-
    position of the R3 cycloalkyl ring (wherein, in this connection, the 1-position of the
    R3 cycloalkyl ring is deemed to be the connection point to the -NH- in formula (I)).
    AMENDED SHEET
    PCT/EP2003/011814
    ® 2. A compound of formula (IA) or a salt thereof: R® HN” 0 X N — / N R' wherein: X is NR4R5 or OR5a in which: R4 is hydrogen, and Ris Cq_galkyl, Cy_g fluoroalkyl, or C3_gcycloalkyl, phenyl optionally substituted with one or two of: a halogen atom, Cj _palkyl, trifluoromethyl, Cj_palkoxy or trifluoromethoxy; or RS has the sub-formula (x), (y) or (2): G -(CH,), A A QQ \ ~ TB ~ °B J TH i (CH) he Fae-P A Xg-P (x) (¥) (2) wherein in sub-formula (x) and (z), n = 1 or 2; and in sub-formula (y), m = 1 or 2; wherein in sub-formula (x) and (y), none, one or two of A, B, D, E and F are nitrogen; and the remaining of A, B, D, E and F are CH or CRS where RO is a halogen atom, Cj_galkyl, Cj.4fluoroalkyl, C;_palkoxy, Cj_>fluoroalkoxy, C1 -palkylsulphonyl (C1.palkyl-SO5-), C1_palkyl-SO»-NH-, R7REN-SO5-, R7R8N-CO-, R7R8N, OH, C_salkoxymethyl, or Cj _palkyl-SO»-CHy-, wherein R7 and RS are independently hydrogen or Cj_.palkyl; wherein in sub-formula (z), G is O or S or NR? wherein RY is Cy _galkyl or Cjp_g4fluoroalkyl; none, one or two of J, L, M and Q are nitrogen; and the remaining of J,L,M and Q are CH or CRO where RO is as defined herein; R32 is C_galkyl; Cj_g fluoroalkyl; C3_gcycloalkyl; phenyl optionally substituted with one or two of: a halogen atom, C1 _»alkyl, trifluoromethyl, C_palkoxy or trifluoromethoxy; or R32 has the sub-formula (x), (y) or (z) as defined herein; AMENDED SHEET
    PCT/EP2003/011814 ® Y Y or R3 is C3_geycloalkyl or a heterocyclic group being o in which Y is O, S, SO, or NR10; where R10 is hydrogen, C| alkyl, Cj _afluoroalkyl, C(0)-Cq.palkyl, or C(0)-CF3; and wherein in R3 the Cj.gcycloalkyl is cyclohexyl substituted with one OH substituent; and wherein in R3 the heterocyclic group is optionally substituted with one or two substituents being OH; and wherein any OH substituent is not substituted at the ring carbon attached to the -NH- group of formula (IA) and is not substituted at either ring carbon bonded to the Y group of the heterocyclic group; and Rl =Cy_zalkyl or Cj _»fluoroalkyl;
    J. provided that: when R3 is the heterocyclic group being o and Y is NR10, then R10 is not C(0)-Cj.palkyl or C(0)-CF3; provided that: Se when R3 is the heterocyclic group being , and Y is NR10, then: either (a) R10 js hydrogen, C(0O)-Cj.palkyl, or C(O)-CF3; or (b) R10 is methyl and the compound is: 1-ethyl-N-(2-ethylbutyl)-4-[(1- methylpiperidin-4-yl)amino]- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide or 1-ethyl- N-(4-fluorophenyl)-4-{(1-methylpiperidin-4-yl)amino}-1H-pyrazolo[3,4-b]pyridine-5- carboxamide; and provided that: where R3 is substituted C3_gcycloalkyl, then the one substituent is a substituent at the 3-, 4- or 5- position of the R3 cycloalkyl ring (wherein, in this connection, the 1-position of the R3 cycloalkyl ring is deemed to be the connection point to the -NH- in formula (IA)). AMENDED SHEET
    PCT/EP2003/011814
    ® 3. A compound of formula (IB) or a salt thereof: 3 R HN” O J oN X 00 ® = NT ONT OR R' wherein: S R1 is Cj _3alkyl, Cy_pfluoroalkyl or -CHpCH,OH; RZ is a hydrogen atom (H), methyl or C1 fluoroalkyl, R3 is substituted Cj_gcycloalkyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); Y Lh, Wm or or . ) os . Y (aa) (bb) (co) in which nl and n2 independently are 1 or 2; and in which Y is O, S, SO», or NR!0; where R10 is a hydrogen atom (H), methyl, ethyl, C1 -ofluoroalkyl, C(O)NH>, C(0)-Cj.palkyl, or C(0)-Cjfluoroalkyl; and wherein, when R3 is substituted C3.gceycloalkyl, then R3 is cyclohexyl substituted by one substituent being oxo (=O) or OH; and wherein in R3 the heterocyclic group of sub-formula (aa), (bb) or (cc) is optionally substituted with one or two substituents being oxo (=O) or OH; and wherein any OH substituent is not substituted at the R3 ring carbon attached (bonded) to the -NH- group of formula (IB) and is not substituted at either R3 ring carbon bonded to the Y group of the heterocyclic group (aa), (bb) or (cc); and X is NR4R> or OR32, in which: R#4is a hydrogen atom (H); and AMENDED SHEET
    PCT/EP2003/011814 ® RS is C1.galkyl; Cy_g fluoroalkyl; C3_gcycloalkyl optionally substituted by a C1-2alkyl group; or -(CHp)#-C3_gcycloalkyl optionally substituted, in the -(CHp)p?- moiety or in the C3_gcycloalkyl moiety, by a C1_palkyl group, wherein n4 is1,2o0r3; orR3 is Cy _galkyl substituted by one or two independent substituents R11; wherein each substituent R11, independently of any other R11 substituent present, is: hydroxy (OH); Cj .galkoxy; phenyloxy; benzyloxy; -NRI12R13; NR 5-c(O)R16; -NR15-C(0)-0-R16; -NR15-C(0)-NH-R!5; or -NR15-SOyR 16; and wherein any R11 substituent which is OH, alkoxy or -NR12R13 is not substituted at any carbon atom, of any R4 or RS substituted alkyl, which is bonded to the nitrogen of NR4R5; or RS is -(CH3), 1 1-C(O)R16; -(CHp), | I-C(O)NR12R 13; -CHR19-C(O)NR12R 13; -(CHp)n12-C(0)OR!6; -CHR19-C(O)OR16; -(CH3),12-S0»-NR12R 13; (CH), 12-SO5R 16; or -(CH2) 12-CN; wherein n11 is 0, 1,2, 3 or4 and n12 is 1, 2, Jord; or RJ is -(CHp)p13-Het wherein n!3 is 0,1,2,3 0r4 and Hetis a 4-, 5-, 6- or 7-membered saturated or partly-saturated heterocyclic ring containing one or two ring-hetero-atoms independently selected from O, S, and N; wherein any ring-hetero-atoms present are not bound to the -(CHp),13- moiety when nl3is 1 and are not bound to the nitrogen of NR4R5 when nl3 is 0; wherein any ring-nitrogens which are present and which are not unsaturated (i.e. which do not partake in a double bond) are present as NR!7 where R17 is as defined herein; and wherein one or two of the carbon ring-atoms independently are optionally substituted by C1_palkyl; or R3 is phenyl optionally substituted with one or two of: a halogen atom; C1_galkyl; Ci-2fluoroalkyl; Ci_galkoxy; Cy_pfluoroalkoxy; C)_palkylsulphonyl
    (Cj.palkyl-SO5-); Cq.oalkyl-SOp-NH-; R7R8N-SO;-; R7R8N-CO-; -NR15-C(O)R16; R7R8N; OH; Cj_galkoxymethyl; C1_qalkoxyethyl;
    C1.2alkyl-SO2-CHj-; cyano (CN); or phenyl optionally substituted by one or two of fluoro, chloro, Ci_2alkyl, Cyfluoroalkyl, Cj_palkoxy or Ci fluoroalkoxy; wherein R7 and R8 are independently a hydrogen atom (H); C|.4alkyl; Cj3_geycloalkyl; or phenyl optionally substituted by one or two of: fluoro, chloro, C1-palkyl, Cyfluoroalkyl, Cj_palkoxy or Cfluoroalkoxy; or R7 and R8 together are -(CHp)p6- or -C(0)-(CH)y- or -C(0)-(CH2)p7-C(0)- or -(CH2)p8-X7-(CHp)p®- or CLEAN COPY
    PCT/EP2003/011814 ® -C(0)-X7-(CH2), 10- in which: nis 3,4, 50r6,n7 is 2,3, 4, or 5, n8 and n? and nl0 independently are 2 or 3, and X7 is O or NR14 wherein R14 is H or Cj.palkyl; or R3 has the sub-formula (x), (y) or (2): {(CH,) ~___A Ae a—S ~ OB ' ~~ TB J Th i (CH) Hi” FS D x __D L E fn E ’ (x) (y) (2) wherein in sub-formula (x), n = 1 or 2; in sub-formula (y), m = 1 or 2; and in sub- formula (z),r=0, 1 or 2; wherein in sub-formula (x) and (y), none, one or two of A, B, D, E and F are nitrogen; and the remaining of A, B, D, E and F are independently CH or CRS; where RO is a halogen atom; Cy _galkyl; Cj_4fluoroalkyl; Cj.4alkoxy; Cj_»fluoroalkoxy; Cj.palkylsulphonyl (C1.palkyl-SO3-); C1.palkyl-SO2-NH-; R7R8N-SO5-; R7TR8N-CO-; -NR15-C(0)R16; R7R8N; OH; C;_galkoxymethyl; C1 -4alkoxyethyl; C1 _oalkyl-SO2-CHj-; cyano (CN); or phenyl optionally substituted by one or two of fluoro, chloro, C1 _palkyl, Cifluoroalkyl, Cj_palkoxy or C1fluoroalkoxy; wherein R7 and R8 are as herein defined; wherein in sub-formula (z), Gis O or S or NR? wherein RY is a hydrogen atom (H),
    C1.4alkyl or Cq_4fluoroalkyl; none, one, two or three of J, L, M and Q are nitrogen; and the remaining of J, L, M and Q are independently CH or CRO where RO is as defined herein; and RA2 js C1-galkyl; Cj_g fluoroalkyl; C3_gcycloalkyl; phenyl optionally substituted with one or two of: a halogen atom, Cj_palkyl, trifluoromethyl, C{_palkoxy or trifluoromethoxy; or R32 has the sub-formula (x), (y) or (z) as defined herein and wherein: R12 and R13 independently are H; Cj_salkyl; C3_gcycloalkyl; or phenyl optionally substituted by one or two of: a halogen atom, C.palkyl, Cfluoroalkyl, Cj _palkoxy : or C1 fluoroalkoxy; CLEAN COPY
    PCT/EP2003/011814
    ® or R12 and R13 together are -(CHy),0- or -C(0)-(CHy),’- or -C(0)-(CHy)p7-C(O)- or -(CHp)8-X12-(CH9)p9- or -C(0)-X12-(CHy)p,10- in which: nis 3, 4, 5 or 6, n’ 1s 2, 3,4, or 5, n8 and n9 and n10 independently are 2 or 3 and X12 is 0 or NR14 wherein R14 is H or Cj _jalkyl;
    R1Sisa hydrogen atom (H); C1 _galkyl; C3_gcycloalkyl; or phenyl optionally substituted by one or two of: a halogen atom, C_palkyl, Cjfluoroalkyl, C_oalkoxy or Cj fluoroalkoxy;
    Rl6js C1.4alkyl; C3_gcycloalkyl; pyridinyl; or phenyl optionally substituted by one or two of: a halogen atom, C1 _palkyl, C{fluoroalkyl, Cj_palkoxy or C1fluoroalkoxy; and R19s a hydrogen atom (H); Cj_galkyl; -(CH3),20-0R20 wherein n20is 1,2, 3 or 4 andR20isa hydrogen atom (H) or Cy_galkyl; -CH(Me)-OH; -CH3-SH,; -CH»-CH3-S-Me; benzyl; or (4-hydroxyphenyl)methyl (i.e. 4-hydroxy-benzyl); provided that: when R3 is the heterocyclic group of sub-formula (aa) and Y is NR10, then R10 is not C(O)NH>, C(0)-C1_salkyl or C(O)-Cfluoroalkyl;
    provided that: when R3 is the heterocyclic group of sub-formula (bb), nl is 1, and Y is NR10, then: either (a) R10 is not methyl, ethyl or C1-ofluoroalkyl; or (b) R10 is methyl and the compound is: 1-ethyl-N-(2-ethylbutyl)-4-[(1-
    methylpiperidin-4-yl)amino]-1H-pyrazolo{3,4-b]pyridine-5-carboxamide or 1-ethyl- N-(4-fluorophenyl)-4-[(1-methylpiperidin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5- carboxamide; provided that: when R3 is the heterocyclic group of sub-formula (cc), then NHR3 is of sub-formula (L), (m) or (m1), wherein the -NH- connection point of the NHR3 group to the 4-position of the pyrazolopyridine of formula (IB) is underlined:
    J @ J@R wl) HN HN H (L) © (m) (m1) and provided that: where R3 is substituted C3_gcycloalkyl, then the one substituent is a substituent at the 3-, 4- or 5- position of the R3 cycloalkyl ring (wherein, in this connection, the 1-position of the R3 cycloalkyl ring is deemed to be the connection point to the -NH- in formula (IB)).
    AMENDED SHEET
    PCT/EP2003/011814
    J 4. A compound or salt as claimed in claim 1 or 3, wherein RZ is a hydrogen atom (H) or methyl.
    5. A compound or salt as claimed in claim 1 or 3, wherein RZ is a hydrogen atom
    (H).
    6. A compound or salt as claimed in any preceding claim, wherein R1 is ethyl, n-propyl, Cofluoroalkyl or -CH>CH»>OH.
    7. A compound or salt as claimed in any preceding claim, wherein R! is ethyl.
    8. A compound or salt as claimed in any preceding claim, wherein in R3 there is one substituent or no substituent.
    9. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted C3_gcycloalkyl, then the one substituent is oxo (=O); OH; NHR?21 wherein R21 is a hydrogen atom (H); -C(O)OR23 wherein R23 is H; -C(O)NHR24 wherein R24 is H; hydroxyimino (=N-OH); or (C1_.palkoxy)imino (=N-ORZ26 where R26 is Cj _palkyl).
    10. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted C3_gcycloalkyl, then the one substituent is: oxo (=O); OH; NHR21 wherein R21 is a hydrogen atom (H); -C(0O)OR23 wherein R23 is H; hydroxyimino (=N-OH); or (Cj .palkoxy)imino (=N-OR26 where R26 is Cj.palkyl).
    11. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted C3_gcycloalkyl, then the one substituent is OH, oxo (=O) or hydroxyimino (=N-OH).
    12. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted C3_gcycloalkyl, then the one substituent is a substituent at the 3-, 4- or 5- position of the R3 cycloalkyl ring (wherein, in this connection, the 1-position of the R3 cycloalkyl ring is deemed to be the connection point to the -NH- in formula (I) or (1A) or (IB)).
    13. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted C3_gcycloalkyl, then any NHR2! substituent is at the 2-,3-,4-o0r5- position of the R3 cycloalkyl ring; and any oxo (=O), hydroxyimino (=N-OH); or (C1_4alkoxy)imino (=N-ORZ26) substituent is at the 3- or 4-position of the R3 40 cycloalkyl ring (wherein, in this connection, the 1-position of the R3 cycloalkyl ring is deemed to be the connection point to the -NH- in formula (I) or (IA) or (IB)); AMENDED SHEET
    PCT/EP2003/011814 ® 14. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted C3_gcycloalkyl, then R3 is cyclohexyl substituted by one substituent being oxo (=0), OH, NHR2!, -C(0)OR23, hydroxyimino (=N-OH) or (C1_4alkoxy)imino (=N-ORZ26)
    15. A compound or salt as claimed in claim 14, wherein, where R3 is substituted C3_gcycloalkyl, then R3 is cyclohexyl substituted by one oxo (=0), hydroxyimino (=N-OH) or OH substituent.
    16. A compound or salt as claimed in any preceding claim, wherein, where R3 is substituted Cgcycloalkyl, then R3 is 3-hydroxy-cyclohexyl (i.e. 3-hydroxycyclohexan-1-yl), 4-oxo-cyclohexyl (i.e. 4-oxocyclohexan-1-yl), 4-(hydroxyimino)cyclohexyl (i.e. 4-(hydroxyimino)cyclohexan-1-yl), or 4-(Cj_palkoxyimino)cyclohexyl.
    17. A compound or salt as claimed in any preceding claim, wherein, where R3 is the heterocyclic group of sub-formula (aa), (bb) or (cc), then Y is O.
    18. A compound or salt as claimed in any preceding claim, wherein R10jsa hydrogen atom (H), methyl, ethyl, C(O)NH», C(O)methyl or C(O)-CF3.
    19. A compound or salt as claimed in any preceding claim, wherein, where R3 is the heterocyclic group of sub-formula (aa), (bb) or (cc), then R3 is the heterocyclic group of sub-formula (aa) or (bb). AMENDED SHEET
    PCT/EP2003/011814 ® 20. A compound or salt as claimed in claim 19, wherein where R3 is the heterocyclic group of sub-formula (aa), (bb) or (cc), then R3 is the heterocyclic group of sub-formula (bb) and nl is 1.
    21. A compound or salt as claimed in any preceding claim, wherein, in R3, the heterocyclic group of sub-formula (aa), (bb) or (cc) is unsubstituted (wherein, in this connection, where Y is NR10, R10 is not classified as a substituent).
    22. A compound or salt as claimed in any of claims 1 to 20, wherein, in the R3 heterocyclic group of sub-formula (aa), (bb) or (cc), the one or two optional substituents is or are oxo (=O).
    23. A compound or salt as claimed in any of claims 1 to 20, wherein, in the R3 heterocyclic group of sub-formula (aa), (bb) or (cc), only oxo (=O) substitution or no substitution is allowed at each of the 2- and 6-positions of the R3 heterocyclic ring.
    24. A compound or salt as claimed in any preceding claim, wherein when R3 is the heterocyclic group of sub-formula (aa) then Y is O, S, SO or NH, and when R3 is the heterocyclic group of sub-formula (bb) and Y is NR10, then R10 is not methyl, ethyl or Cj -2fluoroalkyl.
    25. A compound or salt as claimed in any preceding claim, wherein, when R3 is the heterocyclic group of sub-formula (bb), then Y is O, S, SO5 or NR 10, wherein RIO0isH, C(O)NHj, C(0)-Cj _palkyl or C(O)-Cfluoroalkyl.
    26. A compound or salt as claimed in any preceding claim, wherein: R3 is the heterocyclic group of sub-formula (bb), nlis1,and Y is O or NR1O, wherein R10 is H, C(O)NH,, C(0)-C] -palkyl or C(0)-C| fluoroalkyl; wherein, in R3, the heterocyclic group of sub-formula (bb) is unsubstituted (wherein, in this connection, where Y 1s NR10, R10 is not classified as a substituent); or R3 is substituted Cecycloalkyl and is: 3-hydroxy-cyclohexyl (i.e. 3-hydroxycyclohexan-1-yl), 4-oxo-cyclohexyl (i.e. 4-oxocyclohexan-1-yl), 4-(hydroxyimino)cyclohexyl (i.e. 4-(hydroxyimino)cyclohexan-1-yl), or 4-(Cjy.palkoxyimino)cyclohexyl.
    27. A compound or salt as claimed in any preceding claim, wherein NHR3 is of sub-formula (d), (e), (f), (8), (g1), (82), (g3), (g4), (h), (1), (9), (k), (k1), (L), (m), (m1), (m2), (m3), (n), (0), (01), (02), (03), (04), (05), (p), (P1), (p2), (3), (p4), (p7) or (p8), 40 wherein the -NH- connection point of the NHR3 group to the 4-position of the pyrazolopyridine of formula (I) or (1A) or (IB) is underlined: AMENDED SHEET
    PCT/EP2003/011814 ® NH NH NH NH A NH o NH Nd Nd 0 NH sels "S HSE 0 6] S Sa HN co 0) 0} lo} (d) (e) (f) (9) (91) (92) (93) (94) 0] 0 isieNe Neale le HN HN HN HN NH HN © (h) (i) ) (k) (k1) (L) Qn 00 NH HN NH NH NH @] =E N Oo (m) (m2) NH (m3) (m1) OH NH, Nelicaieogicieoles! (n) (p) (p1) (p2) (p3) (p4) COH CO,Me HN HN HN (p7) (p8) (0) f N 0 re [r “OMe ISI: HN NH NH NH NH Bu (01) (02) (03) (04) (05)
    28. A compound or salt as claimed in claim 27, wherein NHR3 is of sub-formula (d), (e), (0), (g4), (h), (1), (5), (k), (k1), (L), (m), (m1), (m2), (m3), (n), (0), (01), (02), (03), (04), (05), (p), (2), (p3) or (p7).
    29. A compound or salt as claimed in claim 27, wherein NHR3 is of sub-formula (d), (e), (9), (h), (i), G0), (k), (m), (m1), (n), (0), (01) or (p). AMENDED SHEET
    PCT/EP2003/011814 ® 30. A compound or salt as claimed in claim 28 or 29, wherein NHR3 is of sub- formula (h), (i), (4), (k), (m1), (m2), (n), (0), (02), (03) or (p2).
    31. A compound or salt as claimed in claim 28 or 29, wherein NHR3 is of sub- formula (h), (k), (n), (0) or (02).
    32. A compound or salt as claimed in claim 27, wherein R3 is tetrahydro-2H- pyran-4-yl; that is NHR3 is of sub-formula (h).
    33. A compound or salt as claimed in any of claims 27 to 31, wherein, when NHR3 is of sub-formula (n), then it is a cis-(3-hydroxycyclohex-1-yl)amino group.
    34. A compound or salt as claimed in any preceding claim, wherein X is NR4RS. AMENDED SHEET
    PCT/EP2003/011814 ® 35. A compound or salt as claimed in any preceding claim, wherein RS is:
    Ci.-galkyl; Cj-3fluoroalkyl;
    C3.gcycloalkyl (unsubstituted); unsubstituted -(CHp)4-Cs_gcycloalkyl wherein n# is 1 or 2; -(CHp)p2-R11 wherein nd is 2 or 3, and each substituent R11, independently of any other R11 substituent present, is Cj._galkoxy, ‘NR! 5.C(0)-NH-R15, or -NR15.50,R16; or (CH)! 1-C(O)R 16; (CHy),12-C(O)NR12R13; -(CHy),12-C(O)OR 16; (CH) 12-S07-NR12R13; -(CH3),12-S09R 16; or -(CHy),, 12-CN wherein nll is 1 or2 and nl2is 1 or 2.
    36. A compound or salt as claimed in any of claims 1 to 34, wherein RS is -(CHp),! 3_Het, n13 is 0, 1 or 2, and Het is a 5- or 6-membered saturated heterocyclic ring containing one ring-hetero-atom selected from O, S and N, wherein the carbon ring-atoms in Het are not substituted.
    37. A compound or salt as claimed in claim 36, wherein RS is (CH) 13-Het, nl3 is —( wr | —( Oorl, and Het is one of: , : or
    38. A compound or salt as claimed in any of claims 1 to 34, wherein R3 is phenyl optionally substituted with, independently, one or two of: a halogen atom; C_palkyl; Cj_pfluoroalkyl; Cj _palkoxys; trifluoromethoxy; Cj_palkylsulphonyl
    (C1.9alkyl-SO5-); Cj _palkyl-SO7-NH-; R7R8N-S05-; R7REN-CO-; NR!5-C(O)R16; R7R8N; OH; Cj_jalkoxymethyl; Cj _oalkyl-SO,-CH»-; cyano (CN); or phenyl optionally substituted by one of fluoro, C|_palkyl, C{luoroalkyl,
    Cj .palkoxy or Cj fluoroalkoxy.
    39. A compound or salt as claimed in claim 38, wherein R> is phenyl optionally substituted with one or two of: a halogen atom, Cy_palkyl, trifluoromethyl,
    C1.oalkoxy, trifluoromethoxy, R7R8N-SO;-, R7TR8N-CO-, or C}.palkyl-SO2-CH-.
    40. A compound or salt as claimed in any of claims 1 to 34, wherein RS has the sub-formula (x) or (y) or (yl) or (2). AMENDED SHEET
    PCT/EP2003/011814 ® 41. A compound or salt as claimed in any of claims 1 to 34, wherein R3 has the sub-formula (x). 42, A compound or salt as claimed in any preceding claim, whereinn=1, m= 1, S andr= 1.
    43. A compound or salt as claimed in any preceding claim, wherein, in sub- formula (x), (y) and (y1): none, one or two of A, B, D, E and F are nitrogen; none, one, two or three of A, B, D, E and F are CRO; and the remaining of A, B, D, E and F are CH. 44, A compound or salt as claimed in claim 43, wherein, in sub-formula (x), (y) and (y1), none or one of A, B, D, E and F are nitrogen.
    45. A compound or salt as claimed in any preceding claim, wherein in sub- formula (x), (y), (yl) and (z), each RO, independently of any other RO present, isa fluorine, chlorine, bromine or iodine atom, or methyl, ethyl, n-propyl, isopropyl, Cgalkyl, trifluoromethyl, -CH>OH, methoxy, ethoxy, C1fluoroalkoxy, OH, C1-3alkylS(0)y-, C1.3alkylS(O)p-NH-, MepN-5(0)2-, HpN-5(0)7-, -CONH3, -CONHMe, -CO5H, cyano (CN), NMe», t-butoxymethyl, or C;_3alkylS(O),-CHj-.
    46. A compound or salt as claimed in claim 45, wherein in sub-formula (x), (y), (v1) and (z), each RO, independently of any other RO present, is a fluorine, chlorine or bromine atom, or methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, -CHpOH, methoxy, difluoromethoxy, methylsulphonyl, methyl-SO2-NH- or methyl-SO2-CH»-.
    47. A compound or salt as claimed in any preceding claim, wherein R3 is of sub- formula (x) and is: benzyl, (monoalkyl-phenyl)methyl, [mono(fluoroalkyl)-phenyl]methyl, (monohalo-phenyl)methyl, (monoalkoxy- phenyl)methyl, [mono(fluoroalkoxy)-phenyljmethyl, [mono(N,N- dimethylamino)-phenyl]methyl, [mono(methyl-SO»-NH-)-phenyl}methyl, [mono(methyl-SO>-)-phenyl]methyl, (dialkyl-phenyl)methyl, (monoalkyl- monohalo-phenyl)methyl, [mono(fluoroalkyl)-monohalo-phenyljmethyl, (dihalo- phenyl)methyl, (dihalo-monoalkyl-phenyl)methyl, [dihalo-mono(hydroxymethyl)- phenyl]methyl, or (dialkoxy-phenyl)methyl.
    48. A compound or salt as claimed in claim 47, wherein RO is: (monoC1_3alkyl-phenyl)methyl; (monoCfluoroalkyl-phenyl)methyl; (monoC 1 _palkoxy-phenyl)methyl; [mono(Cfluoroalkoxy)-phenyl]jmethyl; 40 (diC1.palkyl-phenyl)methyl; (monoC1_palkyl-monohalo-phenyl)methyl; (dihalo- phenyl)methyl; (dihalo-monoCj_jalkyl-phenyl)methyl; or [dihalo- mono(hydroxymethyl)-phenyl]methyl.
    49. A compound or salt as claimed in claim 48, wherein R3 is: AMENDED SHEET
    PCT/EP2003/011814 ® (4-Cj_3alkyl-phenyl)methyl; (4-Cqfluoroalkyl-phenyl)methyl; (4-Cj_oalkoxy- phenyl)methyl; (4-C1fluoroalkoxy-phenyl)methyl; (3,4-dimethyl-phenyl)methyl; (2,4- dimethyli-phenyl)methyl; (3,5-dimethyl-phenyl)methyl; (2,3-dimethyl-phenyl)methyl; (2,5-dimethyl-phenyl)methyl; (4-methyl-3-chloro-phenyl)methyl; (3-methyl-4-chloro-phenyl)methyl; (2-methyl-4-chloro-phenyl)methyl; (2-chloro- 4-fluorophenyl)methyl; (2,4-difluoro-phenyl)methyl, (4-bromo- 2-fluorophenyl)methyl; (4-chloro-2-fluorophenyl)methyl; (3,4-dichloro- phenyl)methyl; (2,4-dichloro-phenyl)methyl; (2,6-dichloro-phenyl)methyl; (2,3-dichloro-phenyl)methyl; (2,4-dichioro-6-methyl-phenyl)methyl; or [2,3-dichloro- 6-(hydroxymethyl)-phenyl]methyl.
    50. A compound or salt as claimed in claim 47, 48 or 49, wherein: Xis NR4R5: and in sub-formula (x), each RY, independently of any other RO present, is a fluorine, chlorine or bromine atom, or methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, -CH>OH, methoxy, difluoromethoxy, methylsulphonyl, or methyl-SO>-NH-.
    ST. A compound or salt as claimed in any of claims 1 to 46, wherein RS has the sub-formula (z), ris 1, none orone of J, L, M or Q is CRS, and if one of J, L, Mor Q is CR then RO is methyl or Cj fluoroalkyl, and RY is a hydrogen atom (H) or methyl.
    52. A compound or salt as claimed in any preceding claim, wherein: R32 is ethyl; R7 and R8 are independently a hydrogen atom (H); C1-palkyl; C3_gcycloalkyl; or phenyl optionally substituted by one of: fluoro, chloro, Cj _palkyl, Cfluoroalkyl,
    Cj.palkoxy or Cyfluoroalkoxy; and when R7 is cycloalkyl or optionally substituted phenyl then R38 is neither cycloalkyl nor optionally substituted phenyl; or R7 and R8 together are ~(CHy),5- or «(CH)8-X7-(CH»),- wherein X7 is NR14 or 0; nb is 4 or 5; n’ is 2,3 or 4; and nd, n? and n10 are independently 2; each substituent R11, independently of any other RI! substituent present, is: Cj_galkoxy, -NRI 5.C(0)-NH-R15, or -NR15.50,R 16; wherein any R11 alkoxy substituent is not substituted at any carbon atom, of any R> substituted alkyl, which is bonded to the nitrogen of NR4R3; R!2 and R13 independently are H; Cj.3alkyl; C3_gcycloalkyl; or phenyl optionally 40 substituted by one of: a halogen atom, Cj_palkyl, C|fluoroalkyl, Cj_palkoxy or AMENDED SHEET
    PCT/EP2003/011814 ® EN Ox—NR™ A) =) aD a C1 fluoroalkoxy; or NRIZR13 is or or or ° , —N NR'™ *—N O or \—/ , or __/ : R15 is a hydrogen atom (H) or Cy-palkyl; R15a independent of other R152 is a hydrogen atom (H) or Cq-palkyl; R16 and R162 independently are:
    Cj.galkyl;
    Cs.gcycloalkyl (unsubstituted); Cs_geycloalkyl-CHo-; pyridin-2-yl optionally substituted on a ring carbon atom by one of: a halogen atom, Cy _palkyl, Cfluoroalkyl, Cj_palkoxy or Cjfluoroalkoxy; ArC; phenyl optionally substituted by one of: a halogen atom, C1.palkyl, C1fluoroalkyl, Cy_oalkoxy or Cjfluoroalkoxy; benzyl optionally substituted at an aromatic carbon atom by one of: a halogen atom, Cy _palkyl, Cjfluoroalkyl, C{_palkoxy or Cfluoroalkoxy; or a 5- or 6- membered saturated heterocyclic ring connected at a ring-carbon and containing one ring-hetero-atom selected from O, S, and N; wherein any ring- nitrogens which are present are present as NR27 where R27 is H, Ci-oalkyl or -C(O)Me; and wherein the ring is optionally substituted at carbon by one oxo (=O) substituent, provided that any oxo (=O) substituent is substituted at a ring-carbon atom bonded to a ring-nitrogen; R17 is a hydrogen atom (H); Cj _4alkyl; C3_geycloalkyl; -(CH)p8-C(O)R16, or the optionally substituted phenyl or benzyl; and R19 is isobutyl, sec-butyl, methyl, isopropyl; -(CH»)n20-0R20 wherein n20 is 1 and R20 isa hydrogen atom (H); -CH(Me)-OH; -CH»-SH; -CH»-CH2-S-Me; benzyl; or (4-hydroxyphenyl)methyl (i.e. 4-hydroxy-benzyl).
    53. A compound or salt as claimed in claim 1, which is: Ethyl 1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, Ethyl 4-[(1-acetylpiperidin-4-yl)amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, AMENDED SHEET
    PCT/EP2003/011814
    ® Ethyl 1-methyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5- carboxylate, Ethyl 1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, Ethyl 1-ethyl-4-[(3R)-tetrahydrofuran-3-ylamino}-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, Ethyl l-ethyl-4-(tetrahydro-2H-thiopyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxylate, Ethyl 1-ethyl-4-(tetrahydrothien-3-ylamino)-1H-pyrazolo(3,4-b]pyridine-5-carboxylate, Ethyl 4-(cyclopropylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5S-carboxylate, Ethyl 4-[(1,1-dioxidotetrahydrothien-3-yl)amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-
    carboxylate,
    Ethyl 4-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino]-1-ethyl- 1 H-pyrazolo[3,4- blpyridine-5-carboxylate,
    N-Benzyl-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    1-Ethyl-N-(4-fluorophenyl)-4-(tetrahydro-2H-pyran-4-ylamino)- | H-pyrazolo[3,4-b]pyridine- S-carboxamide,
    N-Cyclopentyl-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxamide, 4-[(1-Acetylpiperidin-4-yl)amino]-N-cyclopentyl-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-
    carboxamide, 1-Ethyl-N-(pyridin-4-ylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetylpiperidin-4-yl)amino]-N-benzyl-1 -cthyl-1 H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    1-Ethyl-N-(2-ethylbutyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo(3,4-b]pyridine-5- carboxamide, 1-Ethyl-N-(2-ethylbutyl)-4-[(1-methylpiperidin-4-yl)amino}- 1H-pyrazolo[3,4-b]pyridine-5- carboxamide, 4-[(1-Acetylpiperidin-4-yl)amino]-1-ethyl-N-(2-ethylbutyl)-1H-pyrazolo[3,4-b]pyridine-5-
    carboxamide, 1-Ethyl-N-(4-fluorophenyl)-4-| (1-methylpiperidin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine- S-carboxamide, 4-[(1-Acetylpiperidin-4-yl)amino]-1-ethyl-N-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    1-Ethyl-N-n-propyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3.4-b]pyridine-5- carboxamide, 4-[(1-Acetylpiperidin-4-yl)amino]- | -ethyl-N-n-propyl- 1H-pyrazolo[3,4-b]pyridine-5- carboxamide, 4-[(1-Acetylpiperidin-4-yl)amino}]-1-ethyl-N-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-
    40 b]pyridine-5-carboxamide, N-Benzyl-1-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® N-(2-Ethylbutyl)-1-methyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-
    5-carboxamide, N-(4-Fluorophenyl)-1-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    4-[(1-Acetylpiperidin-4-yl)amino}-N-benzyl-1-methyl-1H-pyrazolo[3,4-b]pyridine-5- carboxamide, 1-Ethyl-N-methyl-4-(tetrahydro-2H-pyran-4-ylamino)- | H-pyrazolo[3,4-b]pyridine-5- carboxamide, 1-Ethyl-N-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-pyrazolo[3,4-b]pyridine-5-
    carboxamide, 1-Ethyl-N-isopropyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    N-Benzyl-1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino}- | H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    N-Benzyl-1-cthyl-4-[(3R)-tetrahydrofuran-3-ylamino]- 1 H-pyrazolo|3,4-b]pyridine-5- carboxamide, N-Benzyl-1-ethyl-4-(tetrahydrothien-3-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-Benzyl-4-[(1,1-dioxidotetrahydrothien-3-yl)amino]- 1 -ethyl-1H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    N-Benzyl-4-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino]-1-ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    N-Benzyl-1-ethyl-4-(tetrahydro-211-thiopyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridinc-5- carboxamide, 1-Ethyl-N-(4-fluorophenyl)-4-[(3S)-tetrahydrofuran-3-ylamino]- 1 H-pyrazolo[3,4-b]pyridine-
    5-carboxamide, 1-Ethyl-N-(4-fluorophenyl)-4-[(3R)-tetrahydrofuran-3-ylamino]- 1 H-pyrazolo[3,4-b] pyridine- 5-carboxamide, 1-Ethyl-N-(4-fluorophenyl)-4-(tetrahydro-2H-thiopyran-4-ylamino)-1 H-pyrazolo(3,4- b]pyridine-5-carboxamide,
    1-Ethyl-N-(4-fluorophenyl)-4-(tetrahydrothien-3-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxamide, 4-[(1,1-Dioxidotetrahydrothien-3-yl)amino]-1-ethyl-N-(4-fluorophenyl)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)amino]-1-ethyl-N-(4-fluorophenyl)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[4-(methylsulfonyl)benzyl}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo(3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[3-(methylsulfonyl)benzyl}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-
    40 pyrazolo{3,4-b]pyridine-5-carboxamide, N-[(5-Chloropyridin-2-yl)methyl}-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo(3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(5-methyl-3-phenylisoxazol-4-yl)methyl]-4-(tetrahydro-2 /-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    [ N-(2-tert-Butoxyethyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-N-(1,3-thiazol-2-ylmethyl)-1 H- pyrazolo[3,4-b]pyridine-S-carboxamide,
    1-Ethyl-N-(pyrimidin-4-ylmethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(2-methyl-1,3-thiazol-4-yl)methyl}-4-(tetrahydro-2 H-pyran-4-ylamino)-
    1 H-pyrazolo|3,4-b]pyridine-5-carboxamide, N-[3-(tert-Butoxymethyl)benzyl]-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{2-[methyl(methylsulfonyl)amino]ethyl}-4-(tetrahydro-2 H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(pyrazin-2-ylmethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo|3,4- b]pyridine-5-carboxamide,
    N-(2-Chloro-6-fluorobenzyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(6-0x0-1,6-dihydropyridin-3-yl)methyl]-4-(tetrahydro-2 H-pyran-4- ylamino)-1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[3-(Aminocarbonyl)benzyl]-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-
    pyrazolo|3.,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{4-[(methylamino)carbonyl]phenyl}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo|3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[2-(1-methyl-1 H-imidazol-4-yl)ethyl]-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-{2-[(Anilinocarbonyl)amino]ethyl}-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-
    1 H-pyrazolo|3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-(1 H-tetraazol-5-ylmethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-N-[2-(1 H-1,2 4-triazol- 1 -yl)ethyl]-1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-N-[4-(trifluoromethyl)phenyl}-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, tert-Butyl 4-({[1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo(3,4- b]pyridin-5-yljcarbonyl}amino)piperidine-1-carboxylate,
    1-Ethyl-N-{3-[(methylsulfonyl)amino]propy!}-4-(tetrahydro-2 H-pyran-4-ylamino)-
    1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[2-(Dimethylamino)benzyl]-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(1-ethylpyrrolidin-2-yl)methyl]-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-
    40 pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(tetrahydrofuran-2-ylmethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-tetrahydro-2 H-pyran-4-yl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 N-{4-[(Dimethylamino)sulfonyl]benzyl}-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo|3,4-b}pyridine-5-carboxamide, 1-Ethyl-N-{3-[(methylsulfonyl)amino]benzyl}-4-(tetrahydro-2/{-pyran-4-ylamino)-
    1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(4-methoxyphenyl)-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- )
    50 b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® 1-Ethyl-N-[3-(2-oxopyrrolidin-1-yl)propyl]-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo|3,4-b}pyridine-5-carboxamide, 1-Ethyl-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo|[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-(pyridin-3-ylmethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4- blpyridine-5-carboxamide, 1-Ethyl-N-(1-methylpiperidin-4-yl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(1-ethylpropyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, 1-Ethyl-N-(2-piperidin-1-ylethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(3-morpholin-4-ylpropyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-(3-Ethoxypropyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- blpyridine-5-carboxamide,
    N-(Cyclohexylmethyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo|3,4- b]pyridine-5-carboxamide, N-[3-(Dimethylamino)propyl]-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-neopentyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3.4-b]pyridine- 5-carboxamide, 1-ethyl-N-(4-methoxybenzyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4- blpyridine-5-carboxamide,
    1-Ethyl-N-{2-[(phenylsulfonyl)amino]ethyl}-4-(tetrahydro-2 H-pyran-4-ylamino)-1H- pyrazolo|3,4-b]pyridine-5-carboxamide, N-[2-(Acetylamino)ethyl]-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo|3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{2-[(methylsulfonyl)amino]ethyl}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{2-[(2-methoxyphenyl)(methyl)amino]ethyl}-4-(tetrahydro-2 H-pyran-4- ylamino)-1H-pyrazolo|[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(2-0x0-2-phenylethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-(2,5-Difluorobenzyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2/H-pyran-4-ylamino)-N-[4-(trifluoromethyl)benzyl]-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-Cyclopropyl-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-
    40 b]pyridine-5-carboxamide,
    N-(2-amino-2-oxoethyl)- 1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(3-methoxyphenyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3.,4- b]pyridine-5-carboxamide,
    45 N-(3,4-Difluorobenzyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, Ethyl 3-({[1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridin-5- yl]carbonyl}amino)propanoate, N-(1-Benzylpiperidin-4-yl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    50 pyrazolo{3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® 1-Ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-N-(1,3,4-thiadiazol-2-yl)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(2,3-Dihydro-1 H-inden-2-yl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[2-(2-oxoimidazolidin-1-yl)ethyl}-4-(tetrahydro-2 H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3,4-Dimethoxybenzyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3-Chlorobenzyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, 1-Ethyl-N-(2-hydroxyethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4- blpyridine-5-carboxamide, 1-Ethyl-N-{4-[(methylsulfonyl)methyl]phenyl}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[3-(dimethylamino)-3-oxopropyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(1-methyl-1H-imidazol-5-yl)methyl}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{4-[(methylamino)sulfonyl]phenyl}-4-(tetrahydro-2 H-pyran-4-ylamino)-
    1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-(2-Cyanoethyl)-1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo{3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-[(1-methyl-1 H-pyrazol-4-yl)methyl]-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo{3,4-b]pyridine-5-carboxamide,
    1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-(2-thien-2-ylethyl)-1 H-pyrazolo|3,4- b]pyridine-5-carboxamide,
    N-[2-(4-Chlorophenyl)ethyl]- 1 -ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1/1- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[2-(2-methoxyphenyl)ethyl}-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-
    pyrazolo[3,4-b]pyridine-S-carboxamide,
    Ethyl 1-n-propyl-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxylate,
    Ethyl 1-(2-hydroxyethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-pyrazolo[3,4- b]pyridine-5-carboxylate,
    N-[4-(Methylsulfonyl)benzyl]-1-n-propyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(4-Fluorophenyl)-1-n-propyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1H-pyrazolo(3,4- b]pyridine-5-carboxamide,
    Ethyl 1-ethyl-6-methyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo(3,4-
    40 b]pyridine-S-carboxylate,
    N-Benzyl-1-ethyl-6-methyl-4-(tctrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo|[3,4- b]pyridine-5-carboxamide,
    N-Benzyl-1-ethyl-4-[(2-0xoazepan-3-yl)amino]-1 /-pyrazolo[3,4-b]pyridine-5- carboxamide,
    45 N-Benzyl-1-ethyl-4-[(3-hydroxycyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine-5- carboxamide, N-Benzyl-1-ethyl-4-[(4-hydroxycyclohexyl)amino]-1/H-pyrazolo[3,4-b]pyridine-5- carboxamide, N-Benzyl-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine-5-
    50 carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814 ® -273 - 1-Ethyl-N-(2-hydroxy-1-methylethyl)-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, Methyl (25)-2-({[1-ethyl-4-(tetrahydro-2 H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridin-S-yl]carbonyl }amino)-3-hydroxypropanoate, Ethyl 1-ethyl-4-[(4-hydroxycyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, Ethyl 1-ethyl-4-[(4-oxocyclohexyl)amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, Ethyl 4-[(1-acetyl-4-piperidinyl)amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate,
    Ethyl 4-[(4-aminocyclohexyl)amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, Ethyl-N-[(1-oxido-3-pyridinyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-[(1-oxido-2-pyridinyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[(1-oxido-4-pyridinyl)methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(cis-4-Aminocyclohexyl)amino]- 1 -ethyl-N-(phenylmethyl)- 1 H-pyrazolo{3,4-b]pyridine-5- carboxamide, 1-Ethyl-4-{[(3S)-2-0x0-3-pyrrolidinyl]amino}-N-(phenylmethyl)-1H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, 4-[(2,5-Dioxo-3-pyrrolidinyl)amino]-1-ethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]pyridine- 5-carboxamide, 4-[(cis-4-Aminocyclohexyl)amino]-1-ethyl-N-{[4-(methyloxy)phenyl]methyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    4-[(cis-4-Aminocyclohexyl)amino]-1-ethyl-N-({4-[(methylsulfonyl)amino]phenyl} methyl)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(cis-4-Aminocyclohexyl)amino]-N-(2,3-dihydro-1H-inden-2-yl)-1-ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-{4-[(methylsulfonyl)methyl]phenyl}-4-[(4-oxocyclohexyl)amino]-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-{(2,4-Dimethylphenyl)methyl]-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-[(3,4-Dimethylphenyl)methyl]-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    N-[(3,4-Dichlorophenyl)methyl]-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4- bipyridine-5-carboxamide, 1-Ethyl-N-{[4-(methyloxy)phenyl]methyl}-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-({4-[(methylsulfonyl)amino]phenyl} methyl)-4-[(4-oxocyclohexyl)amino}-1H-
    40 pyrazolo(3,4-b]pyridine-5-carboxamide, N-{[4-(Dimethylamino)phenyl]methyl}-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-({4-[(Difluoromethyl)oxy]pheny!} methyl)-1-ethyi-4-[(4-oxocyclohexyl)amino}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 1-Ethyl-4-[(4-oxocyclohexyl)amino]-N-{[4-(trifluoromethyl)phenyl]methyl}-1H- pyrazolo{3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-(methylsulfonyl)phenyl]methyl}-4-[(4-oxocyclohexyl)amino]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(4-fluorophenyl)-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine-5-
    50 carboxamide, 1-Ethyl-4-[(4-oxocyclohexyl)amino]-N-(2-pyridinylmethyl)-1H-pyrazolo[3,4-b]pyridine-5- carboxamide trifluoroacetate, N-(2,3-Dihydro-1H-inden-2-yl)-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® N-(1-Acetyl-4-piperidinyl)-1-ethyl-4-[(4-oxocyclohexyl)amino]- 1 H-pyrazolo[3,4-b]pyridine- 5-carboxamide, 1-Ethyl-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-{(4-oxocyclohexyl)amino]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N,I1-Diethyl-4-[(4-oxocyclohexyl)amino}- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide 1-Ethyl-4-[(4-oxocyclohexyl)amino]-N-(1,3-thiazol-2-ylmethyl)- 1 H-pyrazolo[3,4-b]pyridine- 5-carboxamide, 1-Ethyl-N-(phenylmethyl)-4-(tetrahydro-2H-pyran-3-ylamino)-1 H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    N-({4-[(Difluoromethyl)oxy]phenyl} methyl)-1-ethyl-4-(tetrahydro-2H-pyran-3-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-4-(tetrahydro-2H-pyran-3-ylamino)-N-{[4-(trifluoromethyl)phenyl]methyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-(methylsulfonyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-3-ylamino)-1H-
    pyrazolo[3,4-b)pyridine-5-carboxamide, 1-Ethyl-N-{4-[(methylsulfonyl)methyl]phenyl}-4-(tetrahydro-2H-pyran-3-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(4-fluoropheny!)-4-(tetrahydro-2H-pyran-3-ylamino)- | H-pyrazolo[3,4-b]pyridine- S-carboxamide,
    1-Ethyl-N-(2-pyridinylmethyl)-4-(tetrahydro-2H-pyran-3-ylamino)- 1H-pyrazolo[3,4- b]pyridine-5-carboxamide trifluoroacetate, N-(2,3-Dihydro-1H-inden-2-yl)-1-ethyl-4-(tetrahydro-2H-pyran-3-ylamino)- | H-pyrazolo(3,4- b]pyridine-5-carboxamide, N-(1-Acetyl-4-piperidinyl)-1-ethyl-4-(tetrahydro-2H-pyran-3-ylamino)-1H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, 1-Ethyl-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-(tetrahydro-2H-pyran-3-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N, |-Diethyl-4-(tetrahydro-2H-pyran-3-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2H-pyran-3-ylamino)}-N-(1,3-thiazol-2-ylmethyl)- 1 H-pyrazolo[3,4-
    blpyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-(2,3-dihydro- 1H-inden-2-yl)- 1 -ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-[(3,4-dichlorophenyl)methyl]-1-ethyl-1H-pyrazolo{3,4- b]pyridine-5-carboxamide,
    4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-[(3-fluorophenyl)methyl]-1H-pyrazolo[3,4- bipyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-[(3,4-difluorophenyl)methyl]-1-ethyl-1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-[(2,5-difluorophenyl)methyl]-1-ethyl- 1 H-pyrazolo[3,4-
    40 b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-{ [3-(trifluoromethyl)phenyl]methyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-{[4-(trifluoromethyl)phenyl]methyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 4-[(1-Acetyl-4-piperidinyl)amino]-N-[(2,6-difluorophenyl)methyl}-1-ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-[(3-chlorophenyl)methyl]-1-ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-1 -ethyl-N-{[4-(methyloxy)phenyl]methyl}-1H-
    50 pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-[4-(methyloxy)phenyl}-1H-pyrazolo|[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino}-N-( {4-[(dimethylamino)sulfonyl]phenyl}methyl)-1-ethyl- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® 4-[(1-Acetyl-4-piperidinyl)amino]- 1-ethyl-N-(1,2,3,4-tetrahydro- 1-naphthalenyl)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N- {[2-(dimethylamino)phenyl]methyl}-1-ethyl-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    4-[(1-Acetyl-4-piperidinyl)amino]-N-{(2,4-dichlorophenyl)methyl]-1-ethyl-1H-pyrazolo[3,4- blpyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-[(2-chloro-6-fluorophenyl)methyl]-1-ethyl-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-( {4-[(difluoromethyl)oxy]phenyl} methyl)-1-ethyl-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N- {[3-chloro-4-(methyloxy)pheny!]methy!}-1-ethyl-1H- pyrazolo[3,4-blpyridine-5-carboxamide,
    4-[(1-Acetyl-4-piperidinyl)amino]-N-[(5-chloro-2-pyridinyl)methyl}-1-ethyl-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-1-ethyl-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]- 1-ethyl-N-(1,3-thiazol-2-ylmethyl)- 1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]- 1 -ethyl-N-{[4-(methylsulfonyl)phenyl]Jmethyl}- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-(2,2-diphenylethyl)-1-ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-({4-[(methylsulfonyl)amino]phenyl} methyl)- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]- 1 -ethy}-N-({4-[(methylamino)carbonyl]phenyl} methyl)- 1H-pyrazolo|3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N- {{4-(aminosulfonyl)phenyljmethyl}-1 -cthyl-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]- 1 -ethyl-N-({3-[(methylamino)carbonyl]phenyl} methyl)- 1H-pyrazolo{3,4-b]pyridine-5-carboxamide, 4-[(1-Acetyl-4-piperidinyl)amino]-N-{[4-(aminocarbonyl)phenyl]methyl}-1-ethyl- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    4-[(1-Acetyl-4-piperidinyl)amino]-1-ethyl-N-{[6-(methyloxy)-3-pyridinylJmethyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-4-piperidinyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5- carboxamide, 1-Ethyl-N-(4-piperidinylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo(3,4-
    40 b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(ethylsulfonyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{1-[(1-methylethyl)sulfonyl]-4-piperidinyl} -4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 N-[1-(Cyclopentylsulfonyl)-4-piperidinyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(methylsulfonyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{1-[(phenylmethyl)sulfonyl]-4-piperidinyl} -4-(tetrahydro-2H-pyran-4-ylamino)-
    50 1H-pyrazolof3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(phenylsulfonyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(propylsulfonyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    @ N-[1-(Cyclopropylcarbonyl)-4-piperidinyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(3-furanylcarbonyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[1-+(3,3-Dimethylbutanoyl)-4-piperidinyl]- 1 -ethyl-4~(tetrahydro-2H-pyran-4-ylamino)- | H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(2-ethylbutanoyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[1-(Cyclopentylacetyl)-4-piperidinyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(2-methylpropanoyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-{ 1 -(tetrahydro-2H-pyran-4-ylcarbony1)-4- piperidinyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-(1-propanoyl-4-piperidinyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-[1-(N-Acetylglycyl)-4-piperidinyl]-1-ethyl-4-(tctrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(4-morpholinylacetyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{1-[(4-oxocyclohexyl)carbonyl]-4-piperidinyl}-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[1-(1-piperidinylacetyl)-4-piperidinyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-{1-[(1-methyl-5-0x0-3-pyrrolidinyl)carbonyl]-4-piperidinyl}-4-(tetrahydro-2H- pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{1-[(3-methyl-3-oxetanyl)carbonyl]-4-piperidinyl}-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{1-[(4-fluorophenyl)acetyl]-4-piperidinyl}-4-(tetrahydro-2H-pyran-4-ylamino)-
    1H-pyrazolo[3,4-b]pyridine-S-carboxamide, N-{[1-(3,3-Dimethylbutanoyl)-4-piperidinylJmethyl}- 1 -ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[1-(Cyclopentylacetyl)-4-piperidinyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-{[1-(Cyclopropylcarbonyl)-4-piperidinyl]methyl}-1 -ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-({1-[(4-oxocyclohexyl)carbonyl}-4-piperidinyl} methyl)-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-({1-[(4-fluorophenyl)acetyl]-4-piperidinyl} methyl)-4-(tetrahydro-2H-pyran-4-
    40 ylamino)-1H-pyrazolo(3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-({1-[(1-methyl-5-0x0-3-pyrrolidinyl)carbonylj-4-piperidinyl } methy!)-4- (tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    Methyl 3-[(1-ethyl-5-{{(phenylmethyl)amino]carbonyl}-1H-pyrazolo[3,4-b]pyridin-4- yl)amino]cyclohexanecarboxylate,
    45 3-[(1-Ethyl-5-{[(phenylmethyl)amino]carbonyl}-1H-pyrazolo[3,4-b]pyridin-4- ylamino]cyclohexanecarboxylic acid, 1-Ethyl-N-(phenylmethyl)-4-(4-piperidinylamino)-1H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    Ethyl 1-ethyl-4-({1-[(methyloxy)acetyl]-4-piperidinyl}amino)-1H-pyrazolo[3,4-b]pyridine-5-
    50 carboxylate,
    Ethyl 1-(1-methylethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5- carboxylate, 1-Ethyl-N-(4-fluorophenyl)-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- blpyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    @® 1-Ethyl-6-methyl-N- {[4-(methylsulfonyl)pheny!]methyl}-4-(tetrahydro-2H-pyran-4- ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-(2,3-Dihydro-1H-inden-2-yl)-1-ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[3-(1-piperidinylcarbonyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[4-(1-methylethyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-(2-fluorophenyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-
    5-carboxamide, N-{3-[(Dimethylamino)carbonyl]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{4-[(Difluoromethyl)oxy]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-{4-[Acetyl(methyl)amino]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(4-hydroxyphenyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo|3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-{4-(4-morpholinyl)-2-(trifluoromethyl)phenyl}-4-(tetrahydro-2H-pyran-4-
    ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-4-pyridinyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxamide, 1-Ethyl-N-{4-[(4-methyl-1-piperazinyl)carbonyl]phenyl}-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo{3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[2-(2-0x0-1-pyrrolidinyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[3-(methylsulfonyl)phenyl]-4-(tetrahydro-2 H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-{3-[Acetyl(methyl)amino]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{3-[(methylsulfonyl)amino]phenyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-(4-fluoro-2-hydroxyphenyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-S-carboxamide,
    N-(4-Chloropheny!)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine- S-carboxamide,
    N-(3-Chloro-2-cyanophenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-[3-(1-piperidinylsulfonyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-
    40 pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[2-(methylsulfonyl)phenyl]-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-{2-[Acetyl(methyl)amino]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-blpyridine-5-carboxamide,
    45 1-Ethyl-N-[3-(4-morpholinylcarbonyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(4-Chloro-3-cyanophenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-(3-hydroxyphenyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-
    50 b]pyridine-5-carboxamide, N-(3-Chlorophenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine- 5-carboxamide, N-[3-[(Acetylamino)methyl]-4-(methyloxy)phenyl]-1-ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    @ 1-Ethyl-N-[4-(1-piperidinylsulfonyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3-{[Cyclohexyl(methyl)aminojcarbonyl} phenyl)-1-ethy!-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[2-(4-morpholinyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-{3-[(Acetylamino)sulfonyl]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3-Chloro-4-hydroxyphenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo([3,4-
    b]pyridine-5-carboxamide, 1-Ethyl-N-{4-[(methylsulfonyl)amino]pheny!}-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{3-[(methylamino)carbonyl]phenyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-[3-(trifluoromethyl)phenyl]-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethy}-N-3-pyridinyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5- carboxamide,
    N-(3,4-Dichlorophenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, N-[3-(Aminosulfonyl)-4-chlorophenyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo|3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[3-(4-morpholinyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    1-Ethyl-N-[4-(4-morpholinylsulfonyl)phenyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{2-[(4-methyl-1-piperazinyl)carbonyl]phenyl}-4-(tetrahydro-2H-pyran-4- ylamino)- | H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2-[(Dimethylamino)carbonyl]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-[2-Chloro-4-(trifluoromethyl)phenyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2-[(Acetylamino)methyl]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-(2-Chloropheny!)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine- 5-carboxamide,
    N-(3-Chloro-2-fluorophenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-(3-fluorophenyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-
    40 5-carboxamide,
    N-(2-Cyano-3-fluorophenyl)- 1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo(3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-[4-(propylsulfonyl)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3.4- b]pyridine-5-carboxamide,
    45 N-{4-[(Dimethylamino)carbonyl]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[4-(methylsulfonyl)phenyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-{4-[(Acetylamino)methyl]phenyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-
    50 pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-({2-[(1,1-Dimethylethyl)oxy]-3-pyridinyl} methyl)- 1 -ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate, N-[(3-Chloro-4-methylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    @® N-[(4-Chloro-2-methylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-({2-[(Difluoromethyl)oxy]phenyl} methyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-({2-[(1-methylethyl)oxy]phenyl} methyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo{3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-({3-[(1-methylethyl)oxy]phenyl}methyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-({3-[(Difluoromethyl)oxy]phenyl} methyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-hydroxy-3-(methyloxy)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(5-Acetyl-2-hydroxyphenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N- {2-[3-(trifluoromethyl)phenyl]ethyl}- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[4-(Acetylamino)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 11- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{2-(3-hydroxyphenyl)ethyl]-4-(tetrahydro-2 H-pyran-4-ylamino)-1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, N-[2-(3-Chlorophenyl)ethyl]}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-(2- {4-[(trifluoromethyl)oxy]phenyl} ethyl)- 1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-{2-[3-(methyloxy)phenyl]ethyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[2-(4-Acetylphenyl)ethyl]-1-ethyi-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-[2-(3,4-Dichlorophenyl)ethyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2-[3-(Aminosulfonyl)phenyl]ethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H- pyrazolo{3,4-b]pyridine-5-carboxamide, N-{2-[3,4-Bis(methyloxy)phenyl]ethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[2-(2,3-Dichlorophenyl)ethyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2-[3,5-Bis(methyloxy)phenyljethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{2-[3-methyl-4-(methyloxy)phenyl]ethyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    40 pyrazolo[3,4-b]pyridine-5-carboxamide, N-[2-(2,6-Difluorophenyl)ethyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2-[2,6-Bis(methyloxy)phenyl]ethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 1-Ethyl-N-[2-(2-methylphenyl)ethyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-[(3,4-Dimethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[4,5-Bis(methyloxy)-2,3-dihydro-1H-inden-2-yl]-1-ethyl-4-(tetrahydro-2H-pyran-4-
    50 ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2-[4-(Aminosulfonyl)phenyl]ethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[2-(methylsulfinyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    LJ 1-Ethyl-N-(2-phenylethyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5- carboxamide, N-{[4-(Dimethylamino)phenyi]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[2-(4-fluorophenyl)ethyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-[2-(4-methylphenyl)ethyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-{[3-(Aminosulfonyl)phenyljmethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b)pyridine-5-carboxamide, 1-Ethyl-N-[(4-methylphenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- blpyridine-5-carboxamide, 1-Ethyl-N-{[4-fluoro-3-(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    Methyl 2-[({[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5- yl]carbonyl}amino)methyl]benzoate, N-[(6-Chloro-2-pyridinyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate, N-(2,3-Dihydro-1H-inden-1-yl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide,
    N-({2-| Acetyl(methyl)amino]phenyl} methyl)- 1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- I H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(1S)-2,3-Dihydro-1H-inden-1-yl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3.4-b]pyridine-5-carboxamide,
    N-[(1R)-2,3-Dihydro-1H-inden-1-yl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b}pyridine-5-carboxamide, 1-Ethyl-N-({3-[(methylsulfonyl)amino]phenyl} methyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo|3,4-b|pyridine-5-carboxamide, 1-Ethyl-N-(1-phenyl-4-piperidinyl)-4-(tctrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo(3,4-
    b]pyridine-5-carboxamide, 1-ethyl-N-{1-[(ethylamino)carbonyl]-4-piperidinyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    Formic acid - 1-ethyl-N-[1-methyl-2-(4-methyl-1-piperazinyl)ethyl}-4-(tetrahydro-2H-pyran- 4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide (1:1),
    Methyl [4-({[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5- yl]carbonyl}amino)-1-piperidinyl]acetate, 1-Ethyl-N-{[4-(4-morpholinylmethyl)phenyljmethyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate, 1-Ethyl-N-({3-[(4-methyl-1-piperazinyl)methyl]phenyl} methyl)-4-(tetrahydro-2H-pyran-4-
    40 ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate, N-{[5-(Aminocarbonyl)-3-pyridinyljmethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-S-carboxamide trifluoroacetate, 1-Ethyl-N-{[4-(1-methylethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 N-{[3-(Cyclopentyloxy)-4-(methyloxy)phenyl]methy!}-1-ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo{3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-({4-[(4-methyl-1-piperazinyl)methyl]phenyl}methyl)-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate, N-[(2,4-Dichlorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    50 pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4-Difluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2-Chloro-4-fluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    @ N-{2-[2-Chioro-3-(methyloxy)phenyl]ethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo{3,4-b]pyridine-5-carboxamide, Methyl 3-[({[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5- yljcarbonyl}amino)methyl]benzoate,
    S 1-Ethyl-N-{[3-(1-pyrrolidinylmethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-
    1H-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate, 1-Ethyl-N-(2- {4-[(methylsulfonyl)amino]phenyl}ethyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo(3,4-b]pyridine-5-carboxamide, N-{[2,5-Bis(methyloxy)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[2,6-Bis(methyloxy)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(2-fluorophenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b}pyridine-5-carboxamide,
    N-[(3,5-Difluorophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(4-Chlorophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- bjpyridine-5-carboxamide,
    N-Cyclohexyl-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridine-5-
    carboxamide, 1-Ethyl-N-{2-[4-(methylsulfonyl)phenyl]jethyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[2-fluoro-3-(trifluoromcthyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, :
    N-({4-[(Cyclopropylamino)carbonyl]phenyl} methyl)- 1-ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-(4-methyl-1-piperazinyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo|3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-(]1-pyrrolidinylmethyl)phenyl}methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-
    1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[6-(methyloxy)-1-0x0-2,3-dihydro-1H-inden-2-y}]-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,5-Dichlorophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[(3,5-Diethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-pyrazolo(3,4- b]pyridine-5-carboxamide, N-[(2,3-Difluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[2-(methylsulfonyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    40 pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(3-hydroxyphenyl)methyi}-4-(tetrahydro-2 H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-{[3,5-Bis(methyloxy)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 1-Ethyl-N-[2-(4-hydroxyphenyl)ethyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo{3,4- b]pyridine-5-carboxamide, N-[(3,5-Dichlorophenyl)methyl}-1-ethyl-4-(tctrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[2,4-Bis(methyloxy)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    50 pyrazolo[3.4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[2-(methyloxy)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4-Dimethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® 1-Ethyl-N-({2-[(methylamino)carbonyl]phenyl} methyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-S-carboxamide, 1-Ethyl-N-{2-[4-(methyloxy)phenyljethyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[(2-Chlorophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b}pyridine-5-carboxamide, 1-Ethyl-N-[(2-hydroxyphenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-(1,3-Benzodioxol-5-ylmethyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[3-(methyloxy)phenyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- blpyridine-5-carboxamide, N-(Cyclohexylmethyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    1-Ethyl-N-(1,2,3,4-tetrahydro- 1 -naphthalenyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    Methyl 4-[({[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo{3,4-b]pyridin-5- yl]carbonyl}amino)methyl]benzoate, N-[(3,4-Dichlorophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[4-(Aminocarbony])phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,6-Difluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazoio[3,4-b]pyridine-5-carboxamide,
    N-{[3-(Aminocarbonyl)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(4-hydroxyphenyl)methyl]-4-(tetrahydro-2 H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-{[6-(mcthyloxy)-3-pyridinyl]methyl} -4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    pyrazolo[3,4-b]pyridine-S-carboxamide, 1-Ethyl-N-(2-pyridinylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo{3,4- blpyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-{[3-(trifluoromethyl)phenyl]methyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[4-(2-Amino-2-oxoethyl)phenyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-({4-[(methylamino)carbonyl]phenyl} methyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{4-[2-(methylamino)-2-oxoethyl]phenyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    40 pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(3-fluorophenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)- | H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-({4-[(methylsulfony})amino]phenyl} methyl)-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo(3,4-b]pyridine-5-carboxamide,
    45 N-{[4-(Aminosulfonyl)phenyl}methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[2-(Aminocarbonyl)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-({4-[(Difluoromethyl)oxy]phenyl} methyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-
    50 pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-({3-[(Dimethylamino)methyl]phenyl} methyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo(3,4-b]pyridine-5-carboxamide, N-{[3-Chloro-4-(methyloxy)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo{3,4-b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® N-(1-Acetyl-4-piperidinyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N- {[2-(trifluoromethyl)phenyljmethyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-(5-Chloro-2,3-dihydro-1H-inden-2-yl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-({3-[(Acetylamino)methyl]phenyl} methyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{(4-fluorophenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-fluoro-2-(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(2-cthylphenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    1-Ethyl-N-{[2-fluoro-5-(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-[(2,3,4-trifluorophenyl)methyl]- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(4-Chloro-2-fluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(4-Bromo-2-fluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(3,5-Dimethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    N-[(2,3-Dimethylphenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,3-Dichlorophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo|3,4-b]pyridine-5-carboxamide, N-[(4-Cyanophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-
    b]pyridine-5-carboxamide, N-[(4-Bromophenyl)methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-{[5-fluoro-2-(trifluoromethyl)phenyl}jmethyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-[(4-iodophenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- blpyridine-5-carboxamide, N-{[4~(1,1-Dimethylethyl)phenyljmethyl}-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(3-Cyanophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo([3,4-
    40 b]pyridine-5-carboxamide, N-[(2,6-Dichlorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(5-Chloro-2-methylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    45 N-[(3,5-Dibromophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(4-ethylphenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-Ethyl-N-{[3-fluoro-4-(trifluoromethyl)phenyljmethyl}-4-(tetrahydro-2H-pyran-4-ylamino)-
    50 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-[(2-iodophenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide, N-[(2-Bromophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814
    ® 1-Ethyl-N-{[4-(hydroxymethyl)phenyljmethyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{{3-(hydroxymethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    1-Ethyl-N-{[3-(hydroxymethyl)-2-methylphenyl]methyl}-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[2,3-Dichloro-6-(hydroxymethyl)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H-pyran-4- ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{(2,4-Dichloro-6-methylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-
    pyrazolo[3,4-b)pyridine-5-carboxamide, 1-Ethyl-N-{[4~(2-methylpropyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,5-dimethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H- pyrazolo(3,4-b]pyridine-5-carboxamide,
    1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-N-{(2,4,5-trifluorophenyl)methyl]-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[2-fluoro-4-(trifluoromethyl)phenyl)methyl}-4-(tetrahydro-2H-pyran-4-ylamino)- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2-Chloro-6-methylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-
    pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[({[1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)- 1 H-pyrazolo[3,4-b]pyridin-5- yl]carbonyl}amino)methyl]benzoic acid sodium salt, 3-[({[1-Ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H-pyrazolo[3,4-b]pyridin-5- yl]Jcarbonyl}amino)methyl]benzoic acid,
    Ethyl l-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5- carboxylate, 1-Ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}-N-{[4-(methyloxy)phenyl]methyl}-1H- pyrazolo|3,4-b]pyridine-5-carboxamide, N-{[4-(Dimecthylamino)phenyl]methyl}-1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}-
    1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-({4-[(ethyloxy)imino]cyclohexyl}amino)-N- {[4-(methyloxy)phenyl]methyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-({4-[(methyloxy)imino]cyclohexyl}amino)-N-{[4-(methyloxy)phenylJmethyl}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    4-[(4-{[(1,1-Dimethylethyl)oxy]imino}cyclohexyl)amino]-1-ethyl-N-{[4- (methyloxy)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-N-{[4-(methyloxy)phenyl]methyl}-4-[(7-oxohexahydro-1H-azepin-4-yl)amino]- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide,
    Ethyl 1-ethyl-4-[(7-oxohexahydro-1H-azepin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-
    40 carboxylate, 4-{[cis-4-(Butylamino)cyclohexyl]amino}-N-(2,3-dihydro-1H-inden-2-yl)-1-ethyl-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(trans-4-Aminocyclohexyl)amino]-1-ethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]pyridine- 5-carboxamide,
    45 4-[(trans-2-Aminocyclohexyl)amino]-1-ethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]pyridine- 5-carboxamide, 4-[(cis-2-Aminocyclohexyl)amino]-1-ethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]pyridine-5- carboxamide, 4-[(3-Aminocyclohexyl)amino]-1-ethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]pyridine-5-
    50 carboxamide,
    Ethyl 1-ethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyl]Jamino}-1H-pyrazolo[3,4- b)pyridine-5-carboxylate, N,1-Diethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyl]amino}-1H-pyrazolo[3,4- b]pyridine-5-carboxamide,
    AMENDED SHEET
    PCT/EP2003/011814 ® 1-Ethyl-N-(4-fluorophenyl)-4-{[(1SR,3RS)-3-hydroxycyclohexyl]amino }-1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-Ethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyljamino}-N-(1,3-thiazol-2-ylmethyl)- 1 H- pyrazolo[3,4-b]pyridine-5-carboxamide, l-ethyl-N-[(4-fluorophenyl)methyl]-4-{[(1SR,3RS)-3-hydroxycyclohexyl}lamino}-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyl]amino}-N-{[4- (methylsulfonyl)phenyljmethyl}-1H-pyrazolo(3,4-b]pyridine-5-carboxamide, N-{[3,4-bis(methyloxy)phenyl]methyl}-1-ethyl-4- {[(1SR,3RS)-3- hydroxycyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, I-ethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyl]amino}-N-(2-pyridinylmethyl)-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyl]amino}-N-[(1-methyl-1 H-pyrazol-4- yDmethyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(3,4-dimethylphenyl)methyl]-1-ethyl-4-{[(1SR,3RS)-3- hydroxycyclohexyl]amino}-1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-{[(1SR,3RS)-3-hydroxycyclohexyl]amino}-N-{[4- (methyloxy)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4-dimethylphenyl)methyl]-1-ethyl-4-{[(1SR,3RS)-3- : hydroxycyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,3-Dichlorophenyl)methyl]-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H- pyrazolo{3,4-b]pyridine-5-carboxamide, N-[(3-Chloro-4-methylphenyl)methyl]-1-ethyl-4-[ (4-oxocyclohexyl)amino]-1 H- pyrazolo[3,4-b]pyridine-5S-carboxamide, N-[(4-Chloro-2-methylphenyl)methyl]-1-ethyl-4-[(4-oxocyclohexyl)amino]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4-Dimethylphenyl)methyl]-1-ethyl-4-{|4-(hydroxyimino)cyclohexyl]amino}- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(3,4-Dimethylphenyl)methyl]-1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}- 1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,3-Dichlorophenyl)methyl}-1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}- 1 H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(3-Chloro-4-methylphenyl)methyl]-1-ethyl-4-{[4- (hydroxyimino)cyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(4-Chloro-2-methylphenyl)methyl]-1-ethyl-4-{[4- (hydroxyimino)cyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-({4-[(Difluoromethyl)oxy]phenyl}methyl)-1-ethyl-4-{[4- (hydroxyimino)cyclohexyl]amino}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, or 1-Ethyl-4-{[4-(hydroxyimino)cyclohexyljamino}-N-{[4- 40 (trifluoromethyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide; or a salt thereof.
    54. A compound or salt as claimed in claim 1, which is a compound of Example 45 260,261, 263, 266, 493, 494, 518, 528, 584, 626, 643, 653, 679, 680, 681, 682, 683, 684, 685 or 686, as defined by the structures and/or names described herein, or a salt thereof. AMENDED SHEET
    PCT/EP2003/011814 ® 55. A compound or salt as claimed in claim 1, which is a compound of Example 21,22, 83,100, 109, 167, 172, 178 or 600, as defined by the structures and/or names described herein, or a salt thereof.
    56. A compound or salt as claimed any preceding claim, which is the compound or a pharmaceutically acceptable salt thereof.
    57. A compound or salt as claimed in any preceding claim, which is in a particle- size-reduced form, wherein the particle size (D50 value) of the size-reduced compound or salt is about 0.5 to about 10 microns.
    58. A compound or a pharmaceutically acceptable salt as claimed in any preceding claim, for use as an active therapeutic substance in a mammal such as a human.
    59. A compound or a pharmaceutically acceptable salt as claimed in any preceding claim, for use in the treatment and/or prophylaxis of asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, urticaria, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, eosinophilic granuloma, psoriasis, rheumatoid arthritis, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, chronic glomerulonephritis, endotoxic shock, adult respiratory distress syndrome, multiple sclerosis, cognitive impairment in a neurological disorder, depression, or pain, in a mammal such as a human.
    60. A compound or a pharmaceutically acceptable salt as claimed in claim 59, for use in the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis or atopic dermatitis in a mammal such as a human.
    61. A compound or a pharmaceutically acceptable salt as claimed in claim 59, for use in the treatment and/or prophylaxis of atopic dermatitis in a human.
    62. A pharmaceutical composition comprising a compound of formula (I) or (1A) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers and/or excipients.
    63. A pharmaceutical composition as claimed in claim 62 which is suitable for and/or adapted for inhaled administration, in which the compound or salt isin a particle-size-reduced form, wherein the particle size (D50 value) of the size-reduced compound or salt is about 0.5 to about 10 microns. 40
    64. A composition as claimed in claim 62, for the treatment and/or prophylaxis of an inflammatory and/or allergic disease, or cognitive impairment in a neurological disorder, in a mammal such as a human. AMENDED SHEET
    PCT/EP2003/011814 ® 65. A composition as claimed in claim 62, for use in the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis or atopic dermatitis in a mammal such as a human.
    66. The use of a compound of formula (I) or (IA) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease, or cognitive impairment in a neurological disorder, in a mammal such as a human.
    67. The use of a compound of formula (I) or (IA) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, urticaria, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, eosinophilic granuloma, psoriasis, rheumatoid arthritis, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, chronic glomerulonephritis, endotoxic shock, adult respiratory distress syndrome, multiple sclerosis, cognitive impairment in a neurological disorder, depression, or pain, in a mammal such as a human.
    68. The use as claimed in claim 66 or 67, wherein the medicament is for the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis or atopic dermatitis in a mammal such as a human.
    69. The use as claimed in claim 66 or 67, wherein the medicament is for the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD) in a human.
    70. The use as claimed in claim 67, wherein the medicament is for the treatment and/or prophylaxis of atopic dermatitis in a human.
    71. The use as claimed in any of claims 66 to 69, wherein the medicament is for oral or inhaled administration and is a pharmaceutical composition as defined in claim
    62.
    72. A combination comprising a compound of formula (I) or (IA) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof , together with a B,-adrenoreceptor agonist, an anti-histamine, an anti-allergic, or an 40 anti-inflammatory agent.
    73. A combination comprising a compound of formula (I) or (IA) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof, together with a muscarinic (M) receptor antagonist. AMENDED SHEET
    PCT/EP2003/011814 PY - 288 -
    74. A combination as claimed in claim 73, wherein the muscarinic (M) receptor antagonist is a M3 receptor antagonist.
    75. A pharmaceutical composition comprising a combination as defined in any of claims 72 to 74, together with one or more pharmaceutically acceptable carriers and/or excipients, the composition being a separate or combined pharmaceutical composition for administration of the individual compounds of the combination either sequentially or simultaneously.
    76. A pharmaceutical composition as claimed in claim 75 for inhaled administration, and wherein the combination comprises the compound or salt together with a B3,-adrenoreceptor agonist or a muscarinic (M) receptor antagonist, and wherein the pharmaceutical composition is for the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD) in a human.
    77. A substance or composition for use in a method for the treatment and/or prophylaxis of an inflammatory and/or allergic disease or cognitive impairment in a mammal such as a human, said substance or composition comprising a compound of formula (I) or (1A) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof, and said method comprising administering said substance or composition.
    78. A substance or composition for use in a method for the treatment and/or prophylaxis of asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, urticaria, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, eosinophilic granuloma, psoriasis, rheumatoid arthritis, septic shock, ulcerative colitis, Crohn’s disease, reperfusion injury of the myocardium and brain, chronic glomerulonephritis, endotoxic shock, adult respiratory distress syndrome, multiple sclerosis, cognitive impairment in a neurological disorder, depression, or pain, in a mammal such as a human, said substance or composition comprising a compound of formula (I) or (1A) or (IB), as defined in any of claims 1 to 57, or a pharmaceutically acceptable salt thereof, and said method comprising administering said substance or composition.
    79. A substance or composition for use in a method of treatment and/or prophylaxis as claimed in claim 77 or 78, wherein said substance or composition is for the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis or atopic dermatitis in a mammal such as 40 ahuman.
    80. A substance or composition for use in a method of treatment and/or prophylaxis as claimed in claim 77 or 78, wherein said substance or composition is for the treatment and/or prophylaxis of chronic obstructive pulmonary disease (COPD) in 45 ahuman. AMENDED SHEET
    J J PCT/EP2003/011814 / -289 - J ® 81. A substance or composition for use in a method of treatment and/or prophylaxis as claimed in claim 78, wherein said substance or composition is for the treatment and/or prophylaxis of atopic dermatitis in a human.
    82. A substance or composition for use in a method of treatment and/or prophylaxis as claimed in any of claims 77 to 80, wherein said substance or composition is for oral or inhaled administration and is a pharmaceutical composition as defined in claim 62.
    83. A compound as claimed in any one of claims 1 to 61, substantially as herein described with reference to and as illustrated in any of the examples.
    84. A composition as claimed in any one of claims 62 to 65, 75 or 76, substantially as herein described with reference to and as illustrated in any of the examples.
    85. Use as claimed in any one of claims 66 to 71, substantially as herein described with reference to and as illustrated in any of the examples.
    86. A combination as claimed in any one of claims 72 to 74, substantially as herein described with reference to and as illustrated in any of the examples.
    87. A substance or composition for use in a method of treatment and/or prophylaxis as claimed in any one of claims 77 to 82, substantially as herein described with reference to and as illustrated in any of the examples. AMENDED SHEET
ZA200502185A 2002-09-16 2005-03-15 Pyrazolo[3,4-b]pyridine compounds, and their use as phosphodiesterase inhibitors ZA200502185B (en)

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