# US 8,785,628 B2 · Triazine derivatives as kinase inhibitors

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- Number: US 8,785,628 B2
- Document ID: US8785628B2
- Status: Granted
- Kind: B2
- Application number: 13/254,964
- Filed: 2010-03-02
- Published: 2012-03-01
- Granted: 2014-07-22
- Earliest claimed: 2009-03-06
- Assignees: UCB Pharma S.A.
- Applicants: Daniel Rees Allen; Roland Bürli; Alan Findlay Haughan; Jonathan David MacDonald; Mizio Matteucci; David John Nash; Andrew Pate Owens; Gilles Raphy; Elizabeth Anne Saville-Stones; Andrew Sharpe
- Inventors: Daniel Rees Allen; Roland Bürli; Alan Findlay Haughan; Jonathan David MacDonald; Mizio Matteucci; David John Nash; Andrew Pate Owens; Gilles Raphy; Elizabeth Anne Saville-Stones; Andrew Sharpe
- Web page: https://patentgrep.com/patent/US8785628B2

## CPC

- A61K 31/47: Quinolines; Isoquinolines
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 11/06: Antiasthmatics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/16: Anti-Parkinson drugs
- 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 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07D 401/14: containing three or more hetero rings
- 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

A series of substituted [1,3,5]triazin-2-yl derivatives, being selective inhibitors of PI3 kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.

## Claims

### Claim 1

A compound of formula (I) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:
wherein
E represents an optionally substituted straight or branched C1-3 alkylene chain;
Q represents oxygen, sulfur, N—R6 or a covalent bond;
the ring comprising M represents an optionally substituted saturated five-, six- or seven-membered monocyclic ring containing one nitrogen atom and 0, 1, 2 or 3 additional heteroatoms independently selected from N, O and S, but containing no more than one O or S atom;
W represents C—R7 or N;
R1, R2 and R3 independently represent hydrogen, halogen, cyano, nitro, C1-6 alkyl, trifluoromethyl, aryl(C1-6)alkyl, hydroxy, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, amino, C1-6 alkylamino, di(C1-6)alkyl-amino, C2-6 alkylcarbonylamino, C2-6alkoxycarbonylamino, C1-6alkylsulfonylamino, formyl, C2-6 alkylcarbonyl, carboxy, C2-6 alkoxycarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di(C1-6)alkylaminocarbonyl, aminosulfonyl, C1-6 alkylaminosulfonyl or di(C1-6)alkylaminosulfonyl;
R4 and R5 independently represent C1-6 alkyl, aryl, aryl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents; or hydrogen, halogen, trifluoromethyl, —ORa, —SRa, —SORa, —SO2Ra, —NRbRc, —NRcCORd, —NRcCO2Rd, —NRcSO2Re, —CORd, —CO2Rd, —CONRbRc or —SO2NRbRc;
R6 represents hydrogen or C1-6 alkyl;
R7 represents hydrogen, halogen, C1-6 alkyl or C1-6 alkoxy;
Ra represents C1-6 alkyl, difluoromethyl or trifluoromethyl;
Rb represents hydrogen or trifluoromethyl; or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl-(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;
Rc represents hydrogen, C1-6 alkyl or C3-7 cycloalkyl;
Rd represents hydrogen or C1-6 alkyl; and
Re represents C1-6 alkyl.

### Claim 2 (depends on 1)

A compound as claimed in claim 1 represented by formula (IIA) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:
wherein E, Q, M, R1, R2, R4 and R5 are as defined in claim 1.

### Claim 3 (depends on 1)

A compound as claimed in claim 1 wherein the ring comprising M represents a monocyclic ring selected from pyrrolidin-1-yl, imidazolidin-1-yl, piperidin-1-yl, morpholin-4-yl, [1,4]oxazepan-4-yl, thiomorpholin-4-yl, piperazin-l-yl and [1,4]diazepan-1-yl, any of which rings may be optionally substituted by one or more substituents independently selected from halogen, C1-6 alkyl, C1-6 alkoxy(C1-6)alkyl, C1-6 alkylsulphonyl, hydroxy, hydroxy(C1-6)alkyl, trifluoroethyl, oxo, C2-6 alkylcarbonyl, hydroxy(C2-6)alkylcarbonyl, (C3-7)cycloalkylcarbonyl, carboxy(C1-6)alkyl, C2-6 alkoxycarbonyl, C2-6alkoxycarbonyl(C1-6)alkyl, C2-6alkylcarbonylamino, (C2-6)alkylcarbonylamino(C1-6)alkyl, C1-6 alkylsulphonylamino, aminocarbonyl, di(C1-6)alkylaminocarbonyl, di(C1-6)alkylaminocarbonyl(C1-6)alkyl and (C3-7)heterocycloalkylcarbonyl(C1-6)alkyl.

### Claim 4 (depends on 1)

A compound as claimed in claim 1 wherein R5 represents —NRbRc, in which Rb and Rc are as defined in claim 1.

### Claim 5 (depends on 2)

A compound as claimed in claim 2 represented by formula (IIB) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:

### Claim 6 (depends on 1)

A compound as claimed in claim 1 wherein E represents methylene or (methyl)methylene.

### Claim 7 (depends on 1)

A compound as claimed in claim 1 wherein Q represents oxygen or N—R6, in which R6 is as defined in claim 1.

### Claim 8 (depends on 1)

A compound as claimed in claim 1 wherein R1 represents hydrogen, halogen or C1-6 alkyl.

### Claim 9 (depends on 1)

A compound as claimed in claim 1 wherein R2 represents hydrogen or halogen.

### Claim 10 (depends on 1)

A compound as claimed in claim 1 wherein R4 represents hydrogen or C1-6 alkyl.

### Claim 11

A compound selected from the group consisting of
6-Methyl-N-{(S)-1-[8-methyl-2-(morpholin-4-yl)quinolin-3-yl]ethyl}1-[1,3,5]triazine-2,4-diamine,
6-Methyl-N-{(S)-1-[8-methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}1-[1,3,5]triazine-2,4-diamine,
4-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}-piperazin-2-one,
N2-[(S)-1-{8-Chloro-2-[(S)-3-methylmorpholin-4-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(S)-3-methylmorpholin-4-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,
N-[(S)-1-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}pyrrolidin-3-yl]acetamide,
(S)-6-Methyl-N2-{1[-8-methyl-2-(thiomorpholin-4-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,
(S)-6-Methyl-N2-{1-1-[8-chloro-2-(1,1-dioxothiomorpholin-4-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,
(S)-N-(1-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperidin-4-yl)methanesulfonamide,
(S)-N-(1-{3-[1-(4Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-piperidin-4-yl)methanesulfonamide,
(S)-1(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanone,
(S)-1-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanone,
(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-2-one,
(S)-4-{3-[1-(4-Amino[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-2-one,
(S)-4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-2-one,
(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazin-2-one,
(S)-4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methyl-quinolin-2-yl}piperazin-2-one,
N-{(1S)-1-[8-Chloro-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,
N-{(1S)-1-[8-Chloro-2-(morpholin-4-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,
(3R)-1-(3-{(1S)-1-[(4-Amino-[1,3,5 ]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)pyrrolidin-3-ol,
(3R)-1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)aminol]ethyl}-8-chloro-quinolin-2-yl)pyrrolidin-3-ol,
(3S)-1-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)pyrrolidin-3-ol,
(3S)-1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)pyrrolidin-3-ol,
1-(3-{(1S)-1-1-[(4-Amino-[1,3,5]triazin-2-yl)aminol]ethyl}-8-chloroquinolin-2-yl)-[1,4]-diazepan-5-one,
1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-[1,4]diazepan-5-one,
4-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-1-methylpiperazin-2-one,
4-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-1-methylpiperazin-2-one,
1-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-imidazolidin-2-one,
(S)-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-1-yl)(cyclopropyl)methanone,
(S)-4-(8-Chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-2-one,
1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-methylquinolin-2-yl)-[1,4]diazepan-5-one,
1-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-methylquinolin-2-yl)-[1,4]-diazepan-5-one,
6-Methyl-N-{(1S)-1-[8-methyl-2-(piperazin-1-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,
(S)-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)(cyclopropyl)methanone,
(S)-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)(cyclopropyl)methanone,
(S)-2-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-1-yl)-N,N-dimethylacetamide,
(S)-2(4-{3-[1-(4Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-1-yl)-1-(morpholin-4-yl)ethanone,
(S)-N2-(1-{8-Chloro-2-[4-(methylsulfonyl)piperazin-1-yl]quinolin-3-yl}ethyl)-6-methyl-[1,3,5]triazine-2,4-diamine,
(S)-Ethyl 2-(4-{3-[1-(4-amino-6-methyl-[1,3 ,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)acetate,
(S)-2(4-{3-[1-(4Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)-N,N-dimethylacetamide,
(S)-N2-(4-Methoxybenzyl)-6-methyl-N4-{1-[8-methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]-ethyl}-[1,3,5]triazine-2,4-diamine,
(S)-4-(3-{1-[4-(4-Methoxybenzylamino)-6-methyl-[1,3,5]triazin-2-ylamino]ethyl}-8-methylquinolin-2-yl)piperazin-2-one,
N-{(1S)-1-[7-Fluoro-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine
N-[1-(3-{(1S)-1-[-(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl)-piperidin-4-yl]-acetamide,
N-{(1S)-1-[7-Fluoro-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,
N-[-1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl)piperidin-4-yl]acetamide,
1-[4-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl)piperazin-1-yl]ethanone,
1-[4-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl-piperazin-l-yl-]ethanone,
4-{[8-Methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]methoxy}-[1,3,5]triazin-2-amine,
4-{[8-Methyl-2-(morpholin-4-yl)quinolin-3-yl]methoxy}-[1,3,5]triazin-2-amine,
4-{3-[(4-Amino-[1,3,5]triazin-2-ylamino)methyl]-8-methylquinolin-2-yl}piperazin-2-one,
4-{3-[(4-Amino-6-methyl-[-1,3,5]triazin-2-ylamino)methyl]-8-methylquinolin-2-yl}-piperazin-2-one,
(S)-1-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}-piperazin-1-yl)ethanone,
4-{3-[(4-Amino-[1,3,5]triazin-2-yloxy)methyl]-8-methylquinolin-2yl}piperazin-2-one
4-{3-[(4-Amino-6-methyl-[1,3,5]-triazin-2-yloxy)methyl]-8-methylquinolin-2-yl}-piperazin-2-one,
(S)-4-(8-Chloro-3-{1-[4-(dimethylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-2-one,
(S)-N2-{1-[8-Chloro-2-(3,3-difluoropyrrolidin-1-yl)quinolin-3-yl]-lethyl}-[1,3,5]-1triazine-2,4-diamine,
(S)-N2-{1-[8-Chloro-2-(3 ,3-difluoropyrrolidin-1-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(R)-3-fluoropyrrolidin-1-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(R)-3-fluoropyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]1triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(S)-3-fluoropyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,
(S)-Ethyl 2(4-{3-[-1-(4amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)acetate,
(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-N,N-dimethylpiperazine-1-carboxamide,
(S)-1-(4-{3-[1-(4Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-[1,4]diazepan-1-yl)ethanone,
(S)-4-(7-Fluoro-8-methyl-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}-quinolin-2-yl)piperazin-2-one,
(S)-N2-{1-[7-Fluoro-8-methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,
(S)-2-[4-(8-Chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-1-yl]ethanol,
(S)-2-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanol,
(S)-2-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanol,
(S)-1-(4-{3-[1-(4Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazin-1-yl)-2-hydroxyethanone,
(S)-Ethyl 2-[4-(8-chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-1-yl]acetate,
(S)-2-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)acetic acid,
(S)-2-[4-(8-Chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-1-yl]acetic acid,
N-{[(R)-1-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloro-quinolin-2-yl}pyrrolidin-3-yl]methyl}acetamide,
(S)-1-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methyl-quinolin-2-yl}piperidine-4-carboxamide,
(S)-1-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperidine-4-carboxamide,
(S)-N2-(1-{7-Fluoro-8-methyl-2-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]quinolin-3-yl}ethyl)-6-methyl-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{2-[(3S,5R)-3,5-Dimethylpiperazin-1-yl]-7-fluoro-8-methylquinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,
(S)-N2-{1-[7-Fluoro-2-(4-isopropylpiperazin-1-yl)-8-methylquinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,
(S)-1-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazin-1-yl)-2,2-dimethylpropan-1-one,
(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-bromoquinolin-2-yl}piperazin-2-one,
(S)-4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-5-fluoro-8-methyl-quinolin-2-yl}piperazin-2-one,
N-[(R)-1-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}pyrrolidin-3-yl]acetamide,
N-[(R)-1-{3-[(S)-1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}pyrrolidin-3-yl]acetamide,
(S)-N -(1-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperidin-4-yl)acetamide,
(S)-N-(1-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-piperidin-4-yl)acetamide,
(S)-N2-{1-[8-chloro-2-([1,4]oxazepan-4-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,
(S)-Methyl 4-{3-[1-(4-amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazine-1-carboxylate,
N2-[(S)-1-{8-chloro-2-[(R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(S)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,
N2-[(S)-1-{8-Chloro-2-[(S)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,
4-{3-[(4-Amino-[1,3,5]triazin-2-ylamino)methyl]-8-chloroquinolin-2-yl}piperazin-2-one,
and N-oxides, and pharmaceutically acceptable salts and solvates of any of the above compounds.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable carrier.