# US 9,433,622 B2 · Pyrimidine compounds useful in the treatment of diseases mediated by IKKE and/or TBK1 mechanisms

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- Number: US 9,433,622 B2
- Document ID: US9433622B2
- Status: Granted
- Kind: B2
- Application number: 14/769,421
- Filed: 2014-02-21
- Published: 2016-01-07
- Granted: 2016-09-06
- Earliest claimed: 2013-02-21
- Assignees: Case Western Reserve University
- Applicants: Domainex Limited
- Inventors: Gary Karl Newton; Mark Richard Stewart; Trevor Robert Perrior; Stuart Richard Crosby; Anna Hopkins; Gabriel Negoita-Giras; Kerry Jenkins
- Web page: https://patentgrep.com/patent/US9433622B2

## CPC

- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/551: having two nitrogen atoms, e.g. dilazep
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- 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 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 451/06: Oxygen atoms
- C07D 471/04: Ortho-condensed systems
- C07D 491/10: Spiro-condensed systems
- C07D 491/107: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D 498/08: Bridged systems
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds of the general formula (I) and salts thereof are useful in the treatment of diseases associated with aberrant activity of the protein kinases IKKε and/or TBK-1 in which one of V and W is N, and the other of V and W is C—H; and R1, R2, R3 and R4 are as defined in the specification. The invention also provides uses of the compounds and compositions containing them.

## Claims

### Claim 1

A compound of the general formula I:
in which:
one of V and W is N, and the other of V and W is C—H;
R1 represents an aliphatic heterocyclyl group having 4, 5, 6, 7, 8 or 9 ring atoms, bonded to the pyridyl group shown in formula I through a ring nitrogen atom, and optionally substituted by one or more substituents selected from halogen; OH; ═O; NO2; CN; NRaRb; (CHRa)xCORc; O.CO.Rc; CO2Ra; CONHRd; (CHRa)xNRa.CORc; NRaCO2Rb; C(═NH)NH2; SO2Rc; NRaSO2Rc; CH(CF3)NH2; and C1-4alkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C2-4alkenyl and C2-4alkynyl groups, each optionally substituted by one or more substituents independently selected from halogen atoms, OH, S-alkyl, CONHRa and NRaRb groups; or
R1 represents a NRa—(CHRa)x—C3-6cycloalkyl group or a NRa—(CHRa)x—C3-6heterocycloalkyl group, said heterocycloalkyl group containing one heteroatom, wherein the heteroatom is oxygen or nitrogen, and said cycloalkyl or heterocycloalkyl being optionally substituted by one or more substituents selected from halogen; OH; ═O; NO2; CN; NRaRb; (CHRa)xCORc; O.CO.Rc; CO2Ra; CONHRd; (CHRa)xNRa.CORc; NRaCO2Rb; C(═NH)NH2; SO2Rc; NRaSO2Rc; CH(CF3)NH2; and C1-4alkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C2-4alkenyl and C2-4alkynyl groups, each optionally substituted by one or more substituents independently selected from halogen atoms, OH, S-alkyl, CONHRa and NRaRb groups; or
R1 represents NRa—C1-6alkyl optionally substituted by one or more substituents independently selected from halogen; OH; ═O; NO2; CN; NRaRb; (CHRa)xCORc; O.CO.Rc; CO2Ra; CONHRd; (CHRa)xNRa.CORc; NRaCO2Rb; C(═NH)NH2; SO2Rc; NRaSO2Rc; CH(CF3)NH2; and C1-4alkyl, C1-4alkoxy, C1-4alkoxyC1-4 alkyl, C2-4alkenyl and C2-4alkynyl groups, each optionally substituted by one or more substituents independently selected from halogen atoms, OH, S-alkyl, CONHRa and a NRaRb group;
x is 0, 1 or 2;
R2 represents
wherein A is a phenyl or 5 to 10 membered heteroaryl ring containing 1, 2 or 3 heteroatoms;
n is 0, 1, 2 or 3;
each Z is a group independently selected from —(CHRa)p—, —(CHRa)p—O—(CHRa)r—, —(CHRa)p—NRa—(CHRa)r—, —C(═O)—, C(═O)NRa— and —NRaC(═O)(CHRa)p—, in which p is 0, 1 or 2; and r is 0, 1, 2 or 3;
and each R5 is a group independently selected from:
H, halogen, ORb, or NRaRb;
a 4 to 8 membered heterocyclyl ring containing 1, 2, or 3 heteroatoms, optionally substituted by one or more substituents independently selected from halogen atoms, OH, ═O, NRaRb, O—C1-4alkyl and C1-4alkyl groups, optionally substituted with one or more halogen atoms, O—C1-4alkyl, OH and NRaRb;
C1-4alkyl, C3-7cycloalkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C2-4alkenyl or C2-4alkynyl groups, each optionally substituted by one or more substituents independently selected from halogen, O—C1-4alkyl, OH and NRaRb;
NO2; CN; O.CO.Rc; NRa.CORc; NRaCO2Rb; C(═NH)NH2; SO2Rc; NRaSO2Rc; and CH(CF3)NH2;
or two Z—R5 groups on adjacent ring atoms together with the two adjacent ring atoms form a 5-7 membered fused ring composed of the two adjacent ring atoms and —(CHRa)r—(CHR5)—(CHRa)r—, wherein the —CHR5— moiety can be replaced with —O— or —NR5— and each r is independently 0, 1, 2, 3 or 4; or a 5-7 membered fused ring composed of the two adjacent ring atoms and —NRa.CO.(CH2)q—, wherein one —CH2— moiety can be replaced with —O— or —NRa—; and
each Ra independently represents a hydrogen atom or a C1-4alkyl group;
each Rb independently represents a hydrogen atom; a C1-4alkyl group optionally substituted by one or more groups selected from OH, O—C1-4alkyl, halogen, SO2Rc, CONHRc, NRa.CORc, CORc, N(Ra)2 and phenyl; or a C3-8cycloalkyl group in which a CH2 moiety may be replaced by an oxygen atom or an NRa group;
Rc represents a hydrogen atom; a —NRaRb group; a C3-8cycloalkyl group, in which CH2 moiety may optionally be replaced by an oxygen atom or an NRb group; or a C1-4alkyl group optionally substituted by a OH, O—C1-4alkyl or a NRaRb group;
Rd represents a 5- or 6-membered heteroaryl group containing 1 or 2 heteroatoms, optionally substituted with one or more C1-4alkyl groups;
q represents 1, 2 or 3;
R3 represents a hydrogen atom, a C1-4alkyl group or a halogen atom; and
R4 represents a hydrogen atom, a C1-4alkyl group or a halogen atom;
or a salt thereof.

### Claim 2 (depends on 1)

A compound as claimed in claim 1, in which R1 represents a pyrrolidine, morpholine, piperazine, piperidine, azetidine, 2-oxa-6-azaspiro[3.4]octane, thiomorpholine, homopiperazine, homomorpholine, 8-aza-bicyclo[3.2.1]oct-8-yl group or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl group, optionally substituted with one or two fluorine atoms; OH; CN; CORc; CO2Ra; CONHRd; methoxy and C1-4alkyl substituted with CONH2 or NHCOMe.

### Claim 3 (depends on 2)

A compound as claimed in claim 2, in which R1 represents a pyrrolidine ring or an 8-aza-bicyclo[3.2.1]oct-8-yl group, optionally substituted with one hydroxy group or one fluorine atom.

### Claim 4 (depends on 3)

A compound as claimed in claim 3, in which R2 represents
wherein A is a phenyl or 5 or 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms;
n is 1 or 2;
each Z is a group independently selected from —(CHRa)p—, —O—(CHRa)r—, —NRa—(CHRa)r—, —C(═O)— and —NRaC(═O)(CHRa)p—, in which p is 0, 1 or 2;
and each R5 is a group independently selected from:
H, halogen, ORb or NRaRb;
a 4- to 6-membered heterocyclyl ring containing 1 or 2 heteroatoms, optionally substituted by one or more substituents independently selected from halogen atoms, OH, ═O, NRaRb, O—C1-4alkyl and C1-4alkyl groups, optionally substituted with halogen, OMe or OH;
C1-4alkyl or C3-7cycloalkyl groups, each optionally substituted by one or more substituents independently selected from halogen, OMe, OH and NRaRb;
CN, SO2Rc and NRaSO2Rc; or
or n=2 and two Z—R5 groups on adjacent ring atoms together with the two adjacent ring atoms form a 5-7 membered fused ring composed of the two adjacent ring atoms and —(CHRa)r—(CHR5)—(CHRa)r—, wherein the —CHR5— moiety can be replaced with —NR5— and each r is independently 1 or 2; and
each Ra independently represents a hydrogen atom or a C1-4alkyl group; and
each Rb independently represents a hydrogen atom; a C1-4alkyl group optionally substituted by one or more groups selected from OH, O—C1-4alkyl, halogen and SO2Rc; or a C3-8cycloalkyl group in which a CH2 moiety may be replaced by an oxygen atom or an NRa group; and
each Rc represents —NRaRb or a methyl group.

### Claim 5 (depends on 4)

A compound as claimed in claim 4, in which A is phenyl, pyridine or pyrazole.

### Claim 6 (depends on 5)

A compound as claimed in claim 5, in which n is 1.

### Claim 7 (depends on 6)

A compound as claimed in claim 6, in which R5 is a group independently selected from:
H, OH, NRaRb or cyclopropyl;
a 4- to 6-membered heterocyclyl ring containing 1 or 2 heteroatoms, optionally substituted by one substituent selected from F, OH, ═O, O—C1-4alkyl and C1-4alkyl groups, optionally substituted with halogen, OMe or OH; and
C1-4alkyl optionally substituted by one or two OH groups.

### Claim 8 (depends on 7)

A compound as claimed in claim 7, in which R5 is a group independently selected from:
H, OH, or NRaRb; and
a 6-membered heterocyclyl ring containing 1 or 2 heteroatoms or 5-membered heterocyclyl ring containing 1 heteroatom or 4-membered heterocycloalkyl ring containing 1 nitrogen atom, optionally substituted by one substituent selected from F, ═O, C1-4alkyl, OMe and OH groups;
C1-4alkyl optionally substituted by one or two OH groups.

### Claim 9 (depends on 8)

A compound as claimed in claim 8, in which each of R3 and R4 independently represents a methyl group, a hydrogen atom or a fluorine atom.

### Claim 10 (depends on 1)

A compound as claimed in claim 1, selected from:
3-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-N-(1-methyl-piperidin-4-yl)-benzamide;
3-[4-(5-Cyano-6-pyrrolidin-1-yl-pyridin-3-yl)-pyrimidin-2-ylamino]-benzamide;
5-{2-[6-(4-Methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyrimidin-4-yl}-2-pyrrolidin-1-yl-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[3-(piperazine-1-carbonyl)-phenylamino]-pyrimidin-4-yl}-nicotinonitrile;
5-[2-(4-Morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-2-pyrrolidin-1-yl-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[3-(4-methyl-piperazine-1-carbonyl)-phenylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(1-methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
3-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-N-piperidin-4-yl-benzamide;
3-{4-[5-Cyano-6-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-N-(1-methyl-piperidin-4-yl)-benzamide;
2-((S)-3-Hydroxy-pyrrolidin-1-yl)-5-{2-[6-(1-methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
3-{4-[5-Cyano-6-(3,3-difluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-N-(1-methyl-piperidin-4-yl)-benzamide;
2-(3,3-Difluoro-pyrrolidin-1-yl)-5-{2-[6-(1-methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Hydroxy-pyrrolidin-1-yl)-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-dimethylamino-propionamide;
Cyclopropanecarboxylic acid (5-{4-[5-cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-amide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(2-morpholin-4-yl-pyrimidin-5-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-[(2-methoxy-ethyl)-methyl-amino]-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(2-hydroxy-2-methyl-propylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-(4-isopropyl-piperazin-1-yl)-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(4-methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(6-piperazin-1-yl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Hydroxy-pyrrolidin-1-yl)-5-{2-[6-((R)-3-methyl-piperazin-1-yl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(2-hydroxy-ethylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
4-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-5-fluoro-pyrimidin-2-ylamino}-N-(1-methyl-piperidin-4-yl)-benzamide;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-(4-hydroxy-piperidin-1-yl)-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(4-morpholin-4-ylmethyl-phenylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-piperazin-1-yl-acetamide;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-propionamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[1-(tetrahydro-pyran-4-yl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
N-(4-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-((S)-3-hydroxy-pyrrolidin-1-yl)-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(2-morpholin-4-yl-pyridin-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-Amino-N-(5-{4-[5-cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-methyl-propionamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(2H-pyrazol-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
(S)-Pyrrolidine-2-carboxylic acid (5-{4-[5-cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-amide;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-pyrrolidin-1-yl-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(2-morpholin-4-yl-ethylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(2-{6-[2-((S)-3-fluoro-pyrrolidin-1-yl)-ethoxy]-pyridin-3-ylamino}-pyrimidin-4-yl)-nicotinonitrile;
2-((S)-3-Hydroxy-pyrrolidin-1-yl)-5-[2-(2-morpholin-4-yl-pyridin-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[2-(2-methoxy-ethylamino)-pyridin-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(6-oxo-1,6-dihydro-pyridin-2-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-N-methyl-2-morpholin-4-yl-acetamide;
N-(5-{4-[5-Cyano-6-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-N-methyl-2-morpholin-4-yl-acetamide;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(2-methyl-2,3-dihydro-1H-isoindol-5-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(2-{6-[(2-methoxy-ethylamino)-methyl]-pyridin-3-ylamino}-pyrimidin-4-yl)-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[2-((S)-3-methyl-morpholin-4-ylmethyl)-pyridin-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-((S)-3-methyl-morpholin-4-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-((S)-3-fluoro-pyrrolidin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(2-methyl-imidazol-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(6-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(3-methoxy-azetidin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
5-[2-(6-Morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-2-[1,4]oxazepan-4-yl-nicotinonitrile;
N-{5-[4-(5-Cyano-6-[1,4]oxazepan-4-yl-pyridin-3-yl)-pyrimidin-2-ylamino]-pyridin-2-yl}-2-morpholin-4-yl-acetamide;
N-{5-[4-(5-Cyano-6-[1,4]oxazepan-4-yl-pyridin-3-yl)-5-fluoro-pyrimidin-2-ylamino]-pyridin-2-yl}-2-morpholin-4-yl-acetamide;
5-[5-Fluoro-2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-2-[1,4]oxazepan-4-yl-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-5-fluoro-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
5-[5-Fluoro-2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile;
N-(4-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-5-fluoro-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
5-[2-(6-Morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-2-(2-oxa-6-aza-spiro[3.4]oct-6-yl)-nicotinonitrile;
N-(4-{4-[5-Cyano-6-(2-oxa-6-aza-spiro[3.4]oct-6-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
N-{4-[4-(5-Cyano-6-[1,4]oxazepan-4-yl-pyridin-3-yl)-5-fluoro-pyrimidin-2-ylamino]-pyridin-2-yl}-2-morpholin-4-yl-acetamide;
5-{5-Fluoro-2-[2-(2-methoxy-ethylamino)-pyridin-4-ylamino]-pyrimidin-4-yl}-2-[1,4]oxazepan-4-yl-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-((S)-3-methoxy-pyrrolidin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(2-{6-[(2-methanesulfonyl-ethylamino)-methyl]-pyridin-3-ylamino}-pyrimidin-4-yl)-nicotinonitrile
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(2-morpholin-4-ylmethyl-pyridin-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(5-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(2-{2-[(2-hydroxy-ethyl)-methyl-amino]-pyridin-4-ylamino}-pyrimidin-4-yl)-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(3-oxo-piperazin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(6-[1,4]oxazepan-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-[2-(6-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(4-hydroxymethyl-2-oxo-oxazolidin-3-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(2-{5-[(2-methoxy-ethylamino)-methyl]-pyridin-3-ylamino}-pyrimidin-4-yl)-nicotinonitrile;
5-{2-[6-(1-Amino-1-ethyl-ethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-3-yl)-2-morpholin-4-yl-acetamide;
5-[2-(6,7-Dihydro-5H-pyrrolo[3,4-b]pyridin-3-ylamino)-pyrimidin-4-yl]-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[6-(3-hydroxy-3-methyl-azetidin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
N-(4-{4-[5-Cyano-6-((R)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
N-(5-{4-[5-Cyano-6-((R)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
N-[5-(4-{5-Cyano-6-[(R)-(tetrahydro-furan-3-yl)amino]-pyridin-3-yl}-pyrimidin-2-ylamino)-pyridin-2-yl]-acetamide;
5-{2-[6-(1-Methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-2-[(R)-(tetrahydro-furan-3-yl)amino]-nicotinonitrile;
3-(4-{5-Cyano-6-[(R)-(tetrahydro-furan-3-yl)amino]-pyridin-3-yl}-pyrimidin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide;
5-[2-(1-Methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-2-[(R)-(tetrahydro-furan-3-yl)amino]-nicotinonitrile;
3-(4-{5-Cyano-6-[(R)-(tetrahydro-furan-3-yl)amino]-pyridin-3-yl}-pyrimidin-2-ylamino)-N-piperidin-4-yl-benzamide;
2-(2-Methoxy-ethylamino)-5-{2-[6-(1-methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-Methylamino-5-{2-[6-(1-methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-(2-Hydroxy-ethylamino)-5-{2-[6-(1-methyl-piperidin-4-ylamino)-pyridin-3-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
3-[4-(6-Amino-5-cyano-pyridin-3-yl)-pyrimidin-2-ylamino]-N-(1-methyl-iperidin-4-yl)-benzamide;
2-Cyclopropylamino-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-Cyclopropylamino-5-[5-fluoro-2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
N-{4-[4-(5-Cyano-6-cyclopropylamino-pyridin-3-yl)-5-fluoro-pyrimidin-2-ylamino]-pyridin-2-yl}-2-morpholin-4-yl-acetamide;
2-Cyclopropylamino-5-{5-fluoro-2-[2-(2-methoxy-ethylamino)-pyridin-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
5-[2-(2,3-Dihydro-1H-isoindol-5-ylamino)-pyrimidin-4-yl]-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[2-(2-methoxy-ethyl)-2,3-dihydro-1H-isoindol-5-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
5-{2-[1-(2-Hydroxy-ethyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-2-pyrrolidin-1-yl-nicotinonitrile;
4-[4-(5-Cyano-6-pyrrolidin-1-yl-pyridin-3-yl)-pyrimidin-2-ylamino]-benzamide;
5-{2-[1-((S)-2,3-Dihydroxy-propyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-2-pyrrolidin-1-yl-nicotinonitrile;
5-{2-[1-((R)-2,3-Dihydroxy-propyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-2-pyrrolidin-1-yl-nicotinonitrile;
(R)-1-{3-Cyano-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidine-2-carboxylic acid;
(R)-1-{3-Cyano-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidine-2-carboxylic acid (1-methyl-1H-pyrazol-4-yl)-amide;
2-((S)-2-Cyano-pyrrolidin-1-yl)-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
(R)-1-{3-Cyano-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidine-2-carboxylic acid amide;
2-(3-Hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-5-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
5-[2-(1-Methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-2-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)-nicotinonitrile;
5-{2-[1-(2-Hydroxy-ethyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-2-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)-nicotinonitrile
5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridine-2-carboxylic acid amide;
4-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-N-(2-hydroxy-ethyl)-benzamide;
2-((S)-3-Hydroxy-pyrrolidin-1-yl)-5-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Hydroxy-pyrrolidin-1-yl)-5-[2-(6-morpholin-4-yl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[1-(2-hydroxy-ethyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[1-(3-hydroxy-propyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-{2-[1-(2-morpholin-4-yl-ethyl)-1H-pyrazol-4-ylamino]-pyrimidin-4-yl}-nicotinonitrile;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-(2-methoxy-ethylamino)-acetamide;
2-Benzylamino-N-(5-{4-[5-cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-propionamide;
2-Amino-N-(5-{4-[5-cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-propionamide;
N-(5-{4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-(2-methyl-imidazol-1-yl)-acetamide;
5-[2-(6-Amino-pyridin-3-ylamino)-pyrimidin-4-yl]-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile;
N-(1-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidin-2-ylmethyl)-acetamide;
2-(1-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidin-2-yl)-acetamide;
N-(1-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidin-3-yl)-acetamide;
5-[2-(6-Morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-2-(5-oxo-[1,4]diazepan-1-yl)-nicotinonitrile;
2-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-ylamino}-propionamide;
2-({3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-methyl-amino)-propionamide;
2-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-ylamino}-3-methyl-butyramide;
2-[Methyl-(tetrahydro-furan-3-ylmethyl)-amino]-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
5-[2-(6-Morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-2-[(tetrahydro-furan-3-ylmethyl)-amino]-nicotinonitrile;
2-Cyclopentylamino-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-[(2-Methoxy-ethyl)-methyl-amino]-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
3-((S)-3-Hydroxy-pyrrolidin-1-yl)-6-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
6-[2-(4-Morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-3-pyrrolidin-1-yl-pyridine-2-carbonitrile;
3-((S)-3-Hydroxy-pyrrolidin-1-yl)-6-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
2′-Cyano-6′-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-3,4,5,6-tetrahydro-2H-[1,3′]bipyridinyl-4-carboxylic acid amide;
N-(5-{4-[6-Cyano-5-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridin-2-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
N-(5-{4-[6-Cyano-5-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-2-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
3-((S)-3-Hydroxy-pyrrolidin-1-yl)-6-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
N-(5-{4-[6-Cyano-5-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-2-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-acetamide;
N-(5-{4-[6-Cyano-5-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridin-2-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-acetamide;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-(2-{6-[2-((S)-3-fluoro-pyrrolidin-1-yl)-ethoxy]-pyridin-3-ylamino}-pyrimidin-4-yl)-pyridine-2-carbonitrile;
6-(2-{6-[2-((S)-3-Fluoro-pyrrolidin-1-yl)-ethoxy]-pyridin-3-ylamino}-pyrimidin-4-yl)-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-{2-[6-((S)-3-methyl-morpholin-4-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-pyridine-2-carbonitrile;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-{2-[6-((S)-3-fluoro-pyrrolidin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-pyridine-2-carbonitrile;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-{2-[6-(2-methyl-imidazol-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-pyridine-2-carbonitrile;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-[2-(6-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
6-[5-Fluoro-2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-3-((S)-3-fluoro-pyrrolidin-1-yl)-pyridine-2-carbonitrile;
3-[(2-Methoxy-ethyl)-methyl-amino]-6-[2-(1-methyl-1H-pyrazol-4-ylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
3-Dimethylamino-6-[2-(4-morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-{2-[6-(3-oxo-piperazin-1-ylmethyl)-pyridin-3-ylamino]-pyrimidin-4-yl}-pyridine-2-carbonitrile;
3-((S)-3-Fluoro-pyrrolidin-1-yl)-6-(2-{6-[(2-methoxy-ethylamino)-methyl]-pyridin-3-ylamino}-pyrimidin-4-yl)-pyridine-2-carbonitrile;
2-(1-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidin-3-yl)-acetamide;
2-(2-Methyl-morpholin-4-yl)-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-(3-Methoxymethyl-pyrrolidin-1-yl)-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
2-(3-Difluoromethoxy-pyrrolidin-1-yl)-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
3-(1-{3-Cyano-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridin-2-yl}-pyrrolidin-3-yl)-propionamide;
2-[Methyl-(tetrahydro-furan-3-yl)-amino]-5-[2-(6-morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-nicotinonitrile;
6-[2-(6-Morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-3-[1,4]oxazepan-4-yl-pyridine-2-carbonitrile;
6-[2-(6-Morpholin-4-ylmethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-3-(2-oxa-6-aza-spiro[3.4]oct-6-yl)-pyridine-2-carbonitrile
N-{5-[4-(6-Cyano-5-[1,4]oxazepan-4-yl-pyridin-2-yl)-pyrimidin-2-ylamino]-pyridin-2-yl}-2-morpholin-4-yl-acetamide;
N-(5-{4-[6-Cyano-5-(2-oxa-6-aza-spiro[3.4]oct-6-yl)-pyridin-2-yl]-pyrimidin-2-ylamino}-pyridin-2-yl)-2-morpholin-4-yl-acetamide
Or a salt thereof.

### Claim 11 (depends on 1)

A pharmaceutical composition which comprises a compound as claimed in claim 1, together with a pharmaceutically suitable carrier.

### Claim 12 (depends on 11)

A composition as claimed in claim 11, which also contains an additional active ingredient.

### Claim 13 (depends on 1)

A method of treating inflammation, inflammatory bowel disease, asthma, chronic obstructive pulmonary disorder (COPD), rheumatoid arthritis, osteoarthritis, psoriatic arthritis, osteoporosis, fibrotic diseases, dermatosis, psoriasis, systemic lupus erythematosus, tissue or organ rejection, Alzheimer's disease, atherosclerosis, obesity, diabetes, cancer, adult respiratory syndrome, or septic shock in a patient, the method comprising, administering to the patient a therapeutically effective amount of the compound as claimed in claim 1.

### Claim 14 (depends on 13)

The method of claim 13, wherein the inflammation is associated with infection.

### Claim 15 (depends on 13)

The method of claim 13, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, prostate cancer, myeloma, and leukemia.

### Claim 16 (depends on 1)

A compound as claimed in claim 1, in which R2 represents
wherein A is a phenyl or 5 or 6 membered heteroaryl ring containing 1, 2 or 3 heteroatoms;
n is 1 or 2;
each Z is a group independently selected from —(CHRa)p—, —O—(CHRa)r—, —NRa—(CHRa)r—, —C(═O)— and —NRaC(═O)(CHRa)p—, in which p is 0, 1 or 2;
and each R5 is a group independently selected from:
H, halogen, ORb or NRaRb;
a 4- to 6-membered heterocyclyl ring containing 1 or 2 heteroatoms, optionally substituted by one or more substituents independently selected from halogen atoms, OH, ═O, NRaRb, O—C1-4alkyl and C1-4alkyl groups, optionally substituted with halogen, OMe or OH;
C1-4alkyl or C3-7cycloalkyl groups, each optionally substituted by one or more substituents independently selected from halogen, OMe, OH and NRaRb;
CN, SO2Rc and NRaSO2Rc; or
or n=2 and two Z—R5 groups on adjacent ring atoms together with the two adjacent ring atoms form a 5-7 membered fused ring composed of the two adjacent ring atoms and —(CHRa)r—(CHR5)—(CHRa)r—, wherein the —CHR5— moiety can be replaced with —NR5— and each r is independently 1 or 2; and
each Ra independently represents a hydrogen atom or a C1-4alkyl group; and
each Rb independently represents a hydrogen atom; a C1-4alkyl group optionally substituted by one or more groups selected from OH, O—C1-4alkyl, halogen and SO2Rc; or a C3-8cycloalkyl group in which a CH2 moiety may be replaced by an oxygen atom or an NRa group; and
each Rc represents —NRaRb or a methyl group.

### Claim 17 (depends on 1)

A compound as claimed in claim 1, in which A is phenyl, pyridine or pyrazole.

### Claim 18 (depends on 1)

A compound as claimed in claim 1, in which n is 1.

### Claim 19 (depends on 1)

A compound as claimed in claim 1, in which R5 is a group independently selected from:
H, OH, or NRaRb; and
a 6-membered heterocyclyl ring containing 1 or 2 heteroatoms or 5-membered heterocyclyl ring containing 1 heteroatom or 4-membered heterocycloalkyl ring containing 1 nitrogen atom, optionally substituted by one substituent selected from F, ═O, C1-4alkyl, OMe and OH groups;
C1-4alkyl optionally substituted by one or two OH groups.

### Claim 20 (depends on 1)

A compound as claimed in claim 1, in which each of R3 and R4 independently represents a methyl group, a hydrogen atom or a fluorine atom.

### Claim 21 (depends on 10)

A pharmaceutical composition which comprises a compound as claimed in claim 10, together with a pharmaceutically suitable carrier.

### Claim 22 (depends on 21)

A composition as claimed in claim 21, which also contains an additional active ingredient.