# US 7,465,743 B2 · Pyrazolo[3,4-b]pyridine compounds, and their use as PDE4 inhibitors

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- Number: US 7,465,743 B2
- Document ID: US7465743B2
- Status: Granted
- Kind: B2
- Application number: 10/598,944
- Filed: 2005-03-15
- Published: 2007-07-19
- Granted: 2008-12-16
- Earliest claimed: 2004-03-16
- Assignees: Glaxo Group Limited
- Inventors: Diane Mary Coe; Caroline Mary Cook; Anthony William James Cooper; Christopher David Edlin; Julie Nicole Hamblin; Martin Redpath Johnson; Paul Spencer Jones; Mika Kristian Lindvall; Charlotte Jane Mitchell; Alison Judith Redgrave; John Edward Robinson
- Web page: https://patentgrep.com/patent/US7465743B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/12: Antidiarrhoeals
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/14: Decongestants or antiallergics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is Et, n-Pr, i-Pr, C2fluoroalkyl, or —CH2CH2OH; R2 is H, Me, Et, n-Pr, i-Pr, C1-2fluoroalkyl, cyclopropyl or (cyclopropyl)methyl-; and NHR3 has the sub-formula (nhr3): wherein R3a is methyl or ethyl; R3b is H, methyl or ethyl; R3c is H, methyl or ethyl, R3d is H, methyl or ethyl, and R3e is H or methyl, provided that: (a) R3b is methyl or ethyl; and/or (b) R3c and R3d are independently methyl or ethyl; and provided that: (c) when R3c is ethyl and/or when R3d is ethyl and/or when R3e is methyl, then: R3a is methyl and/or R3b is hydrogen or methyl. These compounds are PDE4 inhibitors.

## Claims

### Claim 1

A compound of formula (I) or a salt thereof:
wherein:
R1 is ethyl, n-propyl, isopropyl, C1-2fluoroalkyl, or —CH2CH2OH;
R2 is hydrogen, methyl, ethyl, n-propyl, isopropyl, C1-2fluoroalkyl, cyclopropyl or (cyclopropyl)methyl-;
NHR3 has the sub-formula (nhr3):
wherein, in sub-formula (nhr3), the —NH— connection point of the NHR3 group to the bicyclic ring system of formula (I) is underlined, and wherein
R3a is methyl or ethyl;
R3b is hydrogen, methyl or ethyl,
R3c is hydrogen, methyl or ethyl,
R3d is hydrogen, methyl or ethyl, and
R3e is hydrogen or methyl,
provided that:
(a) R3b is methyl or ethyl; and (b) R3c and R3d are independently methyl or ethyl;
and provided that:
(c) when R3c is ethyl and when R3d is ethyl and when R3e is methyl, then: R3a is methyl and R3b is hydrogen or methyl;
and wherein:
R5 is C3-8alkyl; C3-8cycloalkyl optionally substituted by a C1-2alkyl group; or —(CH2)n4—C3-8cycloalkyl optionally substituted, in the —(CH2)n4- moiety or in the C3-8cycloalkyl moiety, by a C1-2alkyl group, wherein n4 is 1, 2 or 3;
or R5 is C2-6alkyl substituted by one or two independent substituents R11; wherein each substituent R11, independently of any other R11 substituent present, is: hydroxy; C1-6alkoxy; phenyloxy; benzyloxy; —NR12R13; —NR15—C(O)R16; —NR15—C(O)—NH—R15; or —NR15—SO2R16; and wherein any R11 substituent which is OH, alkoxy or —NR12R13 is not substituted at the carbon atom, of any R5 substituted alkyl, which is bonded to the nitrogen of NHR5;
or R5 is —(CH2)n12—SO2—NR12R13 or —(CH2)n12—SO2R16; wherein n12 is 2, 3 or 4;
or R5 is —(CH2)n13-Het wherein n13 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 —(CH2)n13- moiety when n13 is 1 and are not bound to the nitrogen of NHR5 when n13 is 0; wherein any ring-nitrogens which are present and which are saturated are present as NR17; and wherein one or two of the carbon ring-atoms independently are optionally substituted by C1-2alkyl;
or R5 has the sub-formula (x), (xa), (y), (y1), (z) or (za):
wherein in sub-formula (x), n=0, 1 or 2; in sub-formula (y) and (y1), m=1 or 2; and in sub-formula (z), r=0, 1 or 2;
wherein sub-formula (y) and (y1), independently, are optionally substituted by oxo at a ring carbon adjacent the 6-membered aromatic ring;
and wherein, in sub-formula (xa) and (za):
R4a is hydrogen; methyl, ethyl, n-propyl, isopropyl, C1-2fluoroalkyl, cyclopropyl, —CH2OR4aa, —CH(Me)OR4aa, or —CH2CH2OR4aa, wherein R4aa is hydrogen, methyl, or C1fluoroalkyl; and
R5a is-hydrogen; C1-8alkyl; C1-3fluoroalkyl; C3-8cycloalkyl optionally substituted by a C1-2alkyl group; or —(CH2)n4a—C3-8cycloalkyl optionally substituted, in the —(CH2)n4a- moiety or in the C3-8-cycloalkyl moiety, by a C1-2alkyl group, wherein n4a is 1 or 2;
or R5a is C1-4alkyl substituted by one substituent R11a; wherein R11a is: hydroxy (OH); C1-6alkoxy; C1-2fluoroalkoxy; phenyloxy; (monofluoro- or difluoro-phenyl)oxy; (monomethyl- or dimethyl-phenyl)oxy; benzyloxy; —NR12R13; —NR15—C(O)R16; —NR15—C(O)—NH—R15; or —NR15—S(O)2R16;
or R5a is C2-4alkyl substituted on different carbon atoms by two hydroxy substituents;
or R5a is —(CH2)n11a—C(O)R16; —(CH2)n11a—C(O)NR12R13; —CHR19a—C(O)NR12R13; —(CH2)n11a—C(O)OR16; —(CH2)n11a—C(O)OH; —CHR19a—C(O)OR16; —CHR19a—C(O)OH; —(CH2)n11a—S(O)2—NR12R13; —(CH2)n11a—S(O)2R16; or —(CH2)n11a—CN; wherein n11a is 0, 1, 2 or 3 wherein for each R5a group n11a is independent of the value of n11a in other R5a groups; and wherein R19a is C1-2alkyl;
or R5a is —(CH2)n13a-HetA, wherein n13a is 0, 1 or 2 and HetA is a 4-, 5-, 6- or 7-membered saturated or unsaturated heterocyclic ring, other than —NR12R13, 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 —(CH2)n13a moiety when n13a is 0; wherein any ring-nitrogens which are present and which are saturated and which are not connecting nitrogens are present as NR17a; and wherein one or two of the carbon ring-atoms are independently optionally substituted by C1-2alkyl;
or R5a is phenyl, —CH2-Ph, —CHMe-Ph, —CHEt-Ph, CMe2Ph, or —CH2CH2-Ph, wherein the phenyl ring is optionally substituted with one or two substituents independently selected from the group consisting of a halogen atom; C1-4alkyl; C1-2fluoroalkyl; C1-4alkoxy; C1-2fluoroalkoxy; cyclopropyl; cyclopropyloxy; —C(O)—C1-4alkyl; —C(O)OH; —C(O)—OC1-4alkyl; C1-4alkyl-S(O)2—; C1-4alkyl-S(O)2—NR8a—; R7aR8aN—S(O)2—; R7aR8aN—C(O)—; —NR8a—C(O)—C1-4alkyl; R7aR8aN; OH; nitro (—NO2); and cyano (—CN);
or R4a and R5a taken together are —(CH2)p1— or —(CH2)p3—X5—(CH2)p4—, in which: X5 is O or NR17a; p1=2, 3, 4, 5 or 6, and p3 and p4 independently are 1, 2 or 3 provided that if p3 is 3 then p4 is 1 or 2 and if p4 is 3 then p3 is 1 or 2;
provided that at least one of R4a and R5a is not hydrogen;
and wherein, in sub-formula (x) and in sub-formula (xa):
A is C—R6A, nitrogen or nitrogen-oxide,
B is C—R6B, nitrogen or nitrogen-oxide,
D is C—R6D, nitrogen or nitrogen-oxide,
E is C—R6E, nitrogen or nitrogen-oxide,
F is C—R6F, nitrogen or nitrogen-oxide,
wherein, R6A, R6B, R6D, R6E and R6F independently are: hydrogen, a halogen atom; C1-6alkyl; C1-4fluoroalkyl; C3-6cycloalkyl; C1-4alkoxy; C1-2fluoroalkoxy; C3-6cycloalkyloxy; —C(O)R16a; —C(O)OR30; —S(O)2—R16a; R16a—S(O)2—NR15a—; R7R8N—S(O)2—; C1-2alkyl-C(O)—R15aN—S(O)2—; C1-4alkyl-S(O)—, Ph-S(O)—, R7R8N—CO—; —NR15a—C(O)R16a; R7R8N; nitro; OH; C1-4alkoxymethyl; C1-4alkoxyethyl; C1-2alkyl-S(O)2—CH2—; R7R8N—S(O)2—CH2—; C1-2alkyl-S(O)2—NR15a—CH2—; —CH2—OH; —CH2CH2—OH; —CH2—NR7R8; —CH2—CH2—NR7R8; —CH2—C(O)OR30; —CH2—C(O)—NR7R8; —CH2—NR15a—C(O)—C1-3alkyl; —(CH2)n14-Het1 where n14 is 0 or 1; cyano; Ar5b; or phenyl, pyridinyl or pyrimidinyl wherein the phenyl, pyridinyl or pyrimidinyl independently are optionally substituted by one or two substituents selected from the group consisting of fluoro, chloro, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy;
and two adjacent groups are selected from the group consisting of R6A, R6B, R6D, R6E and R6F, and are: —CH═CH—CH═CH2—, —(CH2)n14a— where n14a is 3, 4 or 5, —O—(CMe2)—O—, —O—(CH2)n14b—O— where n14b is 1 or 2; —CH═CH—NR15b—; —N═CH—NR15b—; —CH═N—NR15b—; —N═N—NR15b—; —CH═CH—O—; —N═CH—O—; —CH═CH—S—; or —N═CH—S—; wherein R15b is H or C1-2alkyl;
provided that:
at least two of A, B, D, E and F are independently C—H, C—F, nitrogen, or nitrogen-oxide;
and no more than two of A, B, D, E and F are independently nitrogen or nitrogen-oxide,
and no more than one of A, B, D, E and F is nitrogen-oxide;
and wherein, in sub-formula (z) and in sub-formula (za):
G is O or S or NR9 wherein R9 is hydrogen, C1-4alkyl, or C1-2fluoroalkyl;
J is C—R6J, C-[connection point to formula (I)], or nitrogen,
L is C—R6L, C-[connection point to formula (I)], or nitrogen,
M is C—R6M, C-[connection point to formula (I)], or nitrogen,
Q is C—R6Q, C-[connection point to formula (I)], or nitrogen,
wherein, R6J, R6L, R6M and R6Q independently are:-hydrogen, a halogen atom; C1-4alkyl; C1-3fluoroalkyl; C3-6cycloalkyl; C1-4alkoxy; C1-2fluoroalkoxy; C3-6cycloalkyloxy; OH (including any tautomer thereof); or phenyl optionally substituted by one or two substituents independently selected from the group consisting of fluoro, chloro, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy;
provided that:
at least two of J, L, M and Q are independently C—H, C—F, C—C1-2alkyl, C-[connection point to formula (I)], or nitrogen;
and no more than three of J, L, M and Q are nitrogen;
and wherein:
R7 and R8 are independently hydrogen; C1-4alkyl; C3-6cycloalkyl; or phenyl optionally substituted by one or two substituents independently selected from the group consisting of: fluoro, chloro, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy;
or R7 and R8 together are —(CH2)n6— or —C(O)—(CH2)n7— or —C(O)—(CH2)n10—C(O)— or —(CH2)n8—X7—(CH2)n9— or —C(O)—X7—(CH2)n10 in which: n6 is 3, 4, 5 or 6, n7 is 2, 3, 4, or 5, n8 and n9 and n10 independently are 2 or 3, and X7 is O or NR14;
R7a is hydrogen or C1-4alkyl;
R8a is hydrogen or methyl;
R12 and R13, independent of any other R12 or R13 independently are H; C1-4alkyl; C3-6cycloalkyl; or phenyl optionally substituted by one or two substituents independently selected from the group consisting of fluoro, chloro, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy;
or R12 and R13, independent of any other R12 or R13, together are —(CH2)n6a— or —C(O)—(CH2)n7a— or —C(O)—(CH2)n10a—C(O)— or —(CH2)n8a—X12—(CH2)n9a— or —C(O)—X12—(CH2)n10a— in which: n6a is 3, 4, 5 or 6, n7a is 2, 3, 4, or 5, n8a and n9a and n10a independently are 2 or 3 and X12 is O or NR14a;
R14, R14a and R17a, independent of any other R14, R14a or R17a, independently are: hydrogen; C1-4alkyl; C1-2fluoroalkyl; cyclopropyl; —C(O)—C1-14alkyl; —C(O)NR7aR8a; or —S(O)2—C1-4alkyl;
R15, independent of any other R15, is hydrogen; C1-4alkyl; C3-6cycloalkyl; or phenyl optionally substituted by one or two substituents independently selected from the group consisting of: a halogen atom, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy;
R15a, independent of any other R15a, is hydrogen or C1-4alkyl;
R16, independent of any other R16, is: C1-4alkyl; C3-6cycloalkyl; C3-6cycloalkyl-CH2—; or phenyl or benzyl, wherein the phenyl and benzyl are independently optionally substituted by one or two substituents independently selected from the group consisting of fluoro, chloro, methyl, C1fluoroalkyl, methoxy and C1fluoroalkoxy;
R16a, independent of any other R16a, is: C1-6alkyl; C3-6cycloalkyl optionally substituted by one oxo, OH or C1-2alkyl substituent; C3-6cycloalkyl-CH2—; pyridinyl optionally substituted on a ring carbon atom by one of: a halogen atom, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy or C1fluoroalkoxy; Ar5c; phenyl optionally substituted by one or two substituents independently selected from the group consisting of: a halogen atom, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy; benzyl optionally substituted on its ring by one or two substituents independently selected from the group consisting of: a halogen atom, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy, 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 the group consisting of 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 C1-2alkyl or oxo substituent, provided that any oxo substituent is substituted at a ring-carbon atom bonded to a ring-nitrogen;
R17, independent of any other R17, is hydrogen; C1-4alkyl; C1-2fluoroalkyl; C3-6cycloalkyl; —(CH2)p6—C(O)R16 wherein p6 is 0, 1, 2 or 3; —(CH2)p6—C(O)NR12R13; —(CH2)p6—C(O)OR16; —(CH2)p6—C(O)OH; —SO2R16; —C(O)—CH2—NR12R13; —C(O)—CH2—NR15a—C(O)—C1-3 alkyl; —C(O)—CH2—O—C1-3alkyl; or phenyl or benzyl wherein the phenyl or benzyl is optionally substituted on their ring by one or two substituents independently selected from the group consisting of: a halogen atom, C1-2alkyl, C1fluoroalkyl, C1-2alkoxy and C1fluoroalkoxy;
R30, independent of any other R30, is hydrogen, C1-4alkyl or C3-6cycloalkyl;
Ar5b and Ar5c independently are a 5-membered aromatic heterocyclic ring containing one O, S or NR15a, the ring can optionally additionally contain one or two N atoms, and wherein the heterocyclic ring is optionally substituted on a ring carbon atom by a substituent selected from the group consisting of: halo, C1-2alkyl, C1fluoroalkyl, —CH2OH, —CH2—OC1-2alkyl, OH, and —CH2—NR28R29 wherein R28 and R29 independently are H or methyl; and
Het1, independent of any other Het1, 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 the group consisting of 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 C1-2alkyl or oxo substituent, provided that any oxo substituent is substituted at a ring-carbon atom bonded to a ring-nitrogen.

### Claim 2 (depends on 1)

A compound or salt as claimed in claim 1, wherein R1 is ethyl or C2fluoroalkyl.

### Claim 3 (depends on 1)

A compound or salt as claimed in claim 1, wherein R1 is ethyl.

### Claim 4 (depends on 1)

A compound or salt as claimed in claim 1 wherein R2 is hydrogen or methyl.

### Claim 5 (depends on 1)

A compound or salt as claimed in claim 1 wherein R3a is methyl, R3b is hydrogen or methyl, and R3e is hydrogen.

### Claim 6 (depends on 1)

A compound or salt as claimed in claim 1 wherein R3b is methyl or ethyl, R3c and R3d independently are-hydrogen or methyl, and R3e is-hydrogen.

### Claim 7 (depends on 6)

A compound or salt as claimed in claim 6, wherein R3 is t-butyl.

### Claim 8 (depends on 1)

A compound or salt as claimed in claim 1 wherein R3c and R3d are independently methyl or ethyl, R3a is methyl, and R3b is hydrogen or methyl.

### Claim 9 (depends on 8)

A compound or salt as claimed in claim 8, wherein R3 is 1,2-dimethyl-propyl.

### Claim 10 (depends on 1)

A compound or salt as claimed in claim 1 wherein R3c and R3d are independently methyl or ethyl, R3b is hydrogen and NHR3 has the sub-formula (nhr3a):
wherein sub-formula (nhr3a) means that more than 50% of the compound or salt present has the stereochemistry shown at the carbon atom bearing the R3a and R3b groups.

### Claim 11 (depends on 10)

A compound or salt as claimed in claim 10 wherein NHR3 has the sub-formula:

### Claim 12 (depends on 1)

A compound or salt as claimed in claim 1 wherein R5 is C3-8alkyl; C5-6cycloalkyl; (C5-6cycloalkyl)methyl-; —(CH2)n5—R11 wherein n5 is 2 or 3 or R11 is —NR15—SO2R16; or R5 has the sub-formula (x), (xa), (y), (y1), (z) or (za).

### Claim 13 (depends on 12)

A compound or salt as claimed in claim 12 wherein R5 has the sub-formula (x), (xa), (y), (y1), (z) or (za).

### Claim 14 (depends on 13)

A compound or salt as claimed in claim 13 wherein R5 has the sub-formula (x), (xa), (y), or (z).

### Claim 15 (depends on 14)

A compound or salt as claimed in claim 14 wherein R5 has the sub-formula (x) or (xa).

### Claim 16 (depends on 1)

A compound or salt as claimed in claim 1 wherein n=1, m=1 and r=1.

### Claim 17 (depends on 15)

A compound or salt as claimed in claim 15 wherein:
R5 is sub-formula (x) which is —(CH2)n—ArX, or sub-formula (xa) which is —(CR4aR5a)—ArX,
and ArX is sub-formula (x1), (x2), (x3), (x4), (x5), (x6), (x7), (x8), (x9), (x10), (x11), (x12), (x13), (x14), (x15) or (x16):

### Claim 18 (depends on 17)

A compound or salt as claimed in claim 17 wherein ArX has the sub-formula (x1).

### Claim 19 (depends on 1)

A compound or salt as claimed in claim 1 wherein, in sub-formula (x) and in sub-formula (xa), R6A, R6B, R6D, R6E and R6F, independently of each other, are hydrogen, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, isobutyl, trifluoromethyl, —CH2OH, methoxy, ethoxy, n-propoxy, isopropoxy, C1fluoroalkoxy, nitro (—NO2), OH, C1-3alkylS(O)2—, C1-2alkylS(O)2—NH—, —CONH2, cyano (—CN), or C1-2alkylS(O)2—CH2—.

### Claim 20 (depends on 19)

A compound or salt as claimed in claim 19 wherein R6A, R6B, R6D, R6E and R6F, independently of each other, are: hydrogen, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, —CH2OH, methoxy, ethoxy, n-propoxy, difluoromethoxy, nitro (—NO2), OH, MeS(O)2—, Me-S(O)2—NH— or Me-S(O)2—CH2—.

### Claim 21 (depends on 1)

A compound or salt as claimed in claim 1 wherein R5 is: benzyl, (monoalkyl-phenyl)methyl, [mono(fluoroalkyl)-phenyl]methyl, (monohalo-phenyl)methyl, (monoalkoxy-phenyl)methyl, [mono(fluoroalkoxy)-phenyl]methyl, [mono(N,N-dimethylamino)-phenyl]methyl, [mono(methyl-SO2—NH-)-phenyl]methyl, [mono(methyl-SO2-)-phenyl]methyl, (dialkyl-phenyl)methyl, (monoalkyl-monohalo-phenyl)methyl, [mono(fluoroalkyl)-monohalo-phenyl]methyl, (dihalo-phenyl)methyl, (dihalo-monoalkyl-phenyl)methyl, [dihalo-mono(hydroxymethyl)-phenyl]methyl, or (dialkoxy-phenyl)methyl.

### Claim 22 (depends on 21)

A compound or salt as claimed in claim 21 wherein R5 is:
(monoC1-4alkyl-phenyl)methyl;
(monoC1fluoroalkyl-phenyl)methyl;
(monoC1-3alkoxy-phenyl)methyl;
[mono(C1fluoroalkoxy)-phenyl]methyl;
(diC1-2alkyl-phenyl)methyl;
(monoC1-4alkyl-monohalo-phenyl)methyl;
(dihalo-phenyl)methyl;
(dihalo-monoC1-2alkyl-phenyl)methyl; or
[dihalo-mono(hydroxymethyl)-phenyl]methyl.

### Claim 23 (depends on 1)

A compound or salt as claimed in claim 1 which is:
N-benzyl-4-{[(1R)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1R)-1,2-dimethylpropyl]amino}-1-ethyl-N-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1R)-1,2-dimethylpropyl]amino}-1-ethyl-N-[4-(trifluoromethyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(2,3-dihydro-1H-inden-2-yl)-4-{[(1R)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1R)-1,2-dimethylpropyl]amino}-1-ethyl-N-[4-(methylsulfonyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-[4-(difluoromethoxy)benzyl]-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[(2-methyl-1,3-thiazol-4-yl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-[(5-chloropyridin-2-yl)methyl]-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(2-chloro-6-fluorobenzyl)-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-{1-[4-(methylsulfonyl)phenyl]ethyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[(6-methoxypyridin-3-yl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-{3-[(methylamino)carbonyl]benzyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[(1R)-1-phenylpropyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-N-(2,2-diphenylethyl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-[2-(dimethylamino)benzyl]-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(4-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-N-(diphenylmethyl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-{4-[(methylamino)carbonyl]benzyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
methyl 4-({[(4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridin-5-yl)carbonyl]amino}methyl)benzoate,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(4-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(4-hydroxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[3-(trifluoromethyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(3,4-difluorobenzyl)-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(2,6-difluorobenzyl)-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[(1R)-1-phenylethyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(2,5-difluorobenzyl)-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(3-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[2-(trifluoromethyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
methyl 3-({[(4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridin-5-yl)carbonyl]amino}methyl)benzoate,
N-[2-(aminocarbonyl)benzyl]-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-{4-[(methylsulfonyl)amino]benzyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-{3-[(methylsulfonyl)amino]benzyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[4-(trifluoromethyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-(2,3-dihydro-1H-inden-2-yl)-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[4-(methylsulfonyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-benzyl-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-[2-(aminosulfonyl)ethyl]-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[(6-oxo-1,6-dihydropyridin-3-yl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-{2-[(methylsulfonyl)amino]ethyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-[3-(methylsulfonyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(pyridin-3-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-[3-(aminocarbonyl)benzyl]-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
N-{4-[(dimethylamino)sulfonyl]benzyl}-4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-{[(1S)-1,2-dimethylpropyl]amino}-1-ethyl-N-(2-ethylbutyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-(tert-butylamino)-1-ethyl-N-benzyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-(tert-butylamino)-1-ethyl-N-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-(tert-butylamino)-1-ethyl-N-[4-(trifluoromethyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide,
4-(tert-butylamino)-N-(2,3-dihydro-1H-inden-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, or
4-(tert-butylamino)-1-ethyl-N-[4-(methylsulfonyl)benzyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide.

### Claim 24 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in claim 1 and one or more pharmaceutically acceptable carriers and/or excipients.