IP Library › Granted Patent US 9,216,991

Granted Patent B2

US 9,216,991 · App. 14/406,389 · Granted Dec 22, 2015

Pyrimidine pyrazolyl derivatives

Inventors: Stefano Crosignani (Nivelles, BE); Catherine Jorand-Lebrun (Arlington, MA); Patrick Gerber (Etoy, CH); Mathilde Muzerelle (Gaillard, FR)

Assignee: Ares Trading S.A.

C07D493/10 A61K31/506 A61K31/5377 A61K31/5386 A61K31/553 A61K45/06 C07D401/14 C07D403/04 C07D403/14 C07D405/14 C07D407/14 C07D413/14 C07D417/14 C07D487/08 C07D491/08 C07D491/10 C07D491/107 C07D498/08

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Quick Facts

Patent No.: US 9,216,991
App. No.: 14/406,389
Granted: Dec 22, 2015
Kind: B2

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USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention provides compounds of Formula (I) for the treatment of cancer, rheumatoid arthritis and other diseases.

Claims (948)

1. A compound of Formula (I)

wherein

R 1 denotes absent, A, or Q-Het,

Z is

wherein

X denotes O, S or N,

Y denotes C or N,

T denotes C or N, or

Z denotes a pyridine or a pyridazine group,

R a is absent, OR 3 , CF 3 , Hal, or NO 2 ,

R b is absent, A, or COHet,

R 2 denotes H, Het, Q-Het, Cyc, A or OA, each Het is independently a 4-9 membered monocyclic ring or a fused, spiro or bridged bicyclic ring, which is saturated, unsaturated, or aromatic, which contains 1 to 3 heteroatoms independently selected from N, O, and S, and a group CO, SO or SO 2 , and wherein 1 or 2 H atoms may be replaced by A, OA, COA, CN, Hal, NO 2 , OR 3 , SOA and/or SO 2 A,

Cyc denotes a 4-8 saturated carbocyclic ring optionally containing a group SO, SO 2 , or CO, and optionally substituted once or twice by a group selected from CO(NR 3 ) 2 , COHet, OR 3 , Het 1 , A, CH 2 Het 1 , NH 2 , NHCOA, OCH 2 Cyc 1 , SO 2 A and -SA(═NH)(═O),

each Q is independent a linear or branched alkylene, having 1 to 6 carbon atoms wherein 1-5 H atoms may be replaced by a group independently selected from OR 3 , Hal, and N(R 3 ) 2 , and wherein 1 or 2 CH 2 groups may be replaced by a group independently selected from CO, SO, SO 2 and NR 3 , or Q denotes a 4-8-membered bivalent heterocyclic ring, which is saturated, unsaturated or aromatic and which contains 1 to 3 heteroatoms independently selected from N, O and S,

each A is independently a linear or branched alkyl having 1 to 10 carbon atoms wherein 1 to 7 H atoms may be replaced by a group independently selected from —OR 3 , Hal, NHSO 2 A, SO 2 A, SOA, and N(R 3 ) 2 , and wherein 1, 2 or 3 non-adjacent —CH 2 —groups may be replaced by a group independently selected from —CO—, NR 3 and —O—,

each Hal is independently F, CI, Br or I,

each R 3 is independently H or C 1 -C 6 -alkyl wherein 1 H atom may be replaced by a group selected from OH, O—C 1 -C 6 -alkyl, and Hal,

each Het 1 is independently a five- or six membered saturated monocyclic heterocycle which contains 1-3 N—and/or O-atoms, which optionally is monosubstituted by A,

Cyc 1 denotes cycloalkyl with 3-7 atoms, and pharmaceutically acceptable, solvates, tautomers, salts, hydrates and stereoisomers thereof, including mixtures thereof in all ratios.

2. The compound of claim 1 wherein Z denotes one of the following groups:

3. The compound of claim 1 wherein the group Z—R 1 denotes one of the following groups:

4. The compound of claim 1 wherein R 2 denotes one of the following groups:

5. The compound of claim 1 wherein R b is selected from one of the following groups:

6. The compound of claim 1 , selected from the following group;

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-

pyrimidine hydrochloride

5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-2-(3-(pyridin-3-

yl)phenyl)pyrimidine_hydrochloride

2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

2,2,2-Trifluoro-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-

piperidin-1-yl]-ethanone

5-[1-(1-Methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidine

2-(3-Furan-3-yl-phenyl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyrimidine

Hydrochloride

4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-

yl)-acetic acid

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-pyrrolidin-1-yl-ethanone

4-[2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-ethyl]-morpholine

Dimethyl-[2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-ethyl]-amine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(tetrahydro-furan-3-yl)-

1H-pyrazol-4-yl]-pyrimidine

2-(3-Isoxazol-4-yl-phenyl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-

pyrimidine hydrochloride

2-[3-(1,3-Dimethyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

2-[3-(1,5-Dimethyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

2-{3-[1-(2-Fluoro-1-fluoromethyl-ethyl)-1H-pyrazol-4-yl]-phenyl}-5-(1-

piperidin-4-yl-1H-pyrazol-4-yl)-pyrimidine hydrochloride

2-(4-{3-[5-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-phenyl}-

pyrazol-1-yl)-1-pyrrolidin-1-yl-ethanone hydrochloride

5-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-2-[3-(1H-pyrazol-4-yl)-phenyl]-

pyrimidine hydrochloride

5-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-2-[3-(1-propyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidine hydrochloride

2-[3-(1-Isopropyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

2-[3-(1-Benzyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-pyridin-3-ylmethyl-1H-

pyrazol-4-yl)-pyrimidine

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-ethanol

2-[3-Fluoro-5-(1-methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-

1H-pyrazol-4-yl)-pyrimidine hydrochloride

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-piperidin-1-yl-ethanone

5-(1-Azetidin-3-yl-1H-pyrazol-4-yl)-2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidine hydrochloride

5-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-

4-yl)-phenyl]-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(1-oxetan-3-yl-piperidin-

4-yl)-1H-pyrazol-4-yl]-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-ylmethyl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

trans-5-[1-(3-Fluoro-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-

1H-pyrazol-4-yl)-phenyl]-pyrimidine hydrochloride

1,1,1-Trifluoro-3-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-propan-2-ol

5-(1-Methyl-1H-pyrazol-4-yl)-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidine

5-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-2-(3-pyridin-4-yl-phenyl)-

pyrimidine hydrochloride

3-(1-Methyl-1H-pyrazol-4-yl)-5-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-

pyrimidin-2-yl]-phenol Formate

1-Methoxy-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-propan-2-ol

1-Methoxy-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-propan-2-ol

2-(4-{2-[3-(3-Methyl-3H-imidazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-1-pyrrolidin-1-yl-ethanone

N,N-Dimethyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-acetamide

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[1-(tetrahydro-pyran-4-

yl)-piperidin-4-yl]-1H-pyrazol-4-yl}-pyrimidine

1-(3-Methoxy-azetidin-1-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

2-(4-{2-[3-(1-Methyl-1H-yrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-

ylmethyl)-morpholine hydrochloride

2-[4-(2-{3-[1-(3-Amino-propyl)-1H-pyrazol-4-yl]-phenyl}-pyrimidin-5-

yl)-pyrazol-1-yl]-1-pyrrolidin-1-yl-ethanone hydrochloride

2-{4-[2-(3-Pyridin-4-yl-phenyl)-pyrimidin-5-yl]-pyrazol-1-yl}-1-

pyrrolidin-1-yl-ethanone

1-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-propan-2-one

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(tetrahydro-furan-3-

ylmethyl)-1H-pyrazol-4-yl]-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-oxazol-2-ylmethyl-1H-

pyrazol-4-yl)-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(2-pyridin-2-yl-ethyl)-1H-

pyrazol-4-yl]-pyrimidine

2-[2-Fluoro-3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-

1H-pyrazol-4-yl)-pyrimidine Formate

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-acetamide

2-[4-(2-{3-[1-(2-Amino-ethyl)-1H-pyrazol-4-yl]-phenyl}-pyrimidin-5-yl)-

pyrazol-1-yl]-1-pyrrolidin-1-yl-ethanone hydrochloride

1-(4-Methyl-piperazin-1-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone hydrochloride

1-(3-Hydroxy-piperidin-1-l)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(2-pyridin-4-yl-ethyl)-1H-

pyrazol-4-yl]-pyrimidine

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-N-(tetrahydro-pyran-4-yl)-acetamide

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-ethanone

2-(4-{2-[3-(2-Methyl-thiazol-5-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-

1-pyrrolidin-1-yl-ethanone

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(2-piperidin-1-yl-ethyl)-

1H-pyrazol-4-yl]-pyrimidne

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(2-pyrrolidin-1-yl-ethyl)-

1H-pyrazol-4-yl]-pyrimidine

2-[4-(2-{3-[1-(2-Hydroxy-ethyl)-1H-pyrazol-4-yl]-phenyl}-pyrimidin-5-

yl)-pyrazol-1-yl]-1-pyrrolidin-1-yl-ethanone

N-(1-Hydroxymethyl-propyl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-acetamide

(3-exo)-8-Methyl-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-8-aza-bicyclo[3.2.1]octane

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanecarboxylic acid

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1H-pyrazol-4-yl)-

pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[2-(1-methyl-pyrrolidin-

2-yl)-ethyl]-1H-pyrazol-4-yl}-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-pyrrolidin-3-ylmethyl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

5-(1-Azetidin-3-ylmethyl-1H-pyrazol-4-yl)-2-[3-(1-methyl-1H-pyrazol-

4-yl)-phenyl]-pyrimidine hydrochloride

5-[1-(2,2-Difluoro-ethyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-

4-yl)-phenyl]-pyrimidine

1-Morpholin-4-yl-2-{4-[2-(3-pyridin-4-yl-phenyl)-pyrimidin-5-yl]-

pyrazol-1-yl}-ethanone

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[2-(tetrahydro-pyran-4-

yl)-ethyl]-1H-pyrazol-4-yl}-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-(S)-1-pyrrolidin-2-

ylmethyl-1H-pyrazol-4-yl)-pyrimidine hydrochloride

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-(R)-1-pyrrolidin-2-

ylmethyl-1H-pyrazol-4-yl)-pyrimidine hydrochloride

2-[3-(1-Methyl-1H-[1,2,3]triazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-

pyrazol-4-yl)-pyrimidine hydrochloride

1-(3-Hydroxy-azetidin-1-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

1-(3-Hydroxy-pyrrolidin-1-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

1-[2-(2-Hydroxy-ethyl)-morpholin-4-yl]-2-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

5-[1-(1-Methanesulfonyl-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

1-Azetidin-1-yl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

1-Morpholin-4-yl-2-{4-[2-(3-oxazol-5-yl-phenyl)-pyrimidin-5-yl]-

pyrazol-1-yl}-ethanone

1-Morpholin-4-yl-2-(4-{2-[3-(1H-[1,2,3]triazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-ethanone

1-(2-Methyl-morpholin-4-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

1-((S)-2-Hydroxymethyl-pyrrolidin-1-yl)-2-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

1-(4,4-dimethyloxazolidin-3-yl)-2-[4-[2-[3-(1-methylpyrazol-4-

yl)phenyl]pyrimidin-5-yl]pyrazol-1-yl]ethanone

82a

N-(2-Hydroxy-1,1-dimethyl-ethyl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-

yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-acetamide

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-morpholin-4-yl-propan-1-one

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-pyrrolidin-1-yl-propan-1-one

N,N-Dimethyl-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-propionamide

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-(2-oxa-7-aza-spiro[3.5]non-7-yl)-ethanone

1-[2-(2-Methoxy-ethyl)-morpholin-4-yl]-2-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

1-(3-Methoxymethyl-piperidin-1-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-

4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[2-(2-methyl-pyridin-3-

yl)-ethyl]-1H-pyrazol-4-yl}-pyrimidine

1-(3-Methoxy-pyrrolidin-1-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

N-Methyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-N-(tetrahydro-pyran-4-yl)-acetamide

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-(1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl-ethanone

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-[1,4]oxazepan-4-yl-ethanone

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-ethanone

Cis-5-{1-[1-(3-Fluoro-tetrahydro-pyran-4-yl)-piperidin-4-yl]-1H-

pyrazol-4-yl}-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

5-{1-[2-(3,4-Dimethoxy-phenyl)-ethyl]-1H-pyrazol-4-yl}-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(tetrahydro-pyran-4-yl)-

1H-pyrazol-4-yl]-pyrimidine

5-[1-(2-Methoxy-ethyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-

yl)-phenyl]-pyrimidine

N,N-Dimethyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-propionamide

100

1-(3-Methoxy-azetidin-1-yl)-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-propan-1-one

101

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-propan-1-one

102

1-(4-Methyl-piperazin-1-yl)-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-propan-1-one

103

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-morpholin-4-yl-propan-1-one

104

[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-piperidin-1-yl]-(tetrahydro-furan-3-yl)-methanone

105

2-Methoxy-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

106

2-Hydroxy-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

107

[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-piperidin-1-yl]-(tetrahydro-pyran-4-yl)-methanone

108

[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-piperidin-1-yl]-(tetrahydro-pyran-2-yl)-methanone

109

3-Methoxy-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-piperidin-1-yl]-propan-1-one

110

(1R,5S)-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-8-aza-bicyclo[3.2.1]octane

111

2-Ethoxy-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

112

5-{1-[1-(3-Ethoxy-2,2-dimethyl-cyclobutyl)-piperidin-4-yl]-1H-pyrazol-

4-yl}-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

113

1-Methyl-4-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-piperidine-1-carbonyl]-pyrrolidin-2-one

114

3,3,3-Trifluoro-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-propan-1-one

115

3,3,3-Trifluoro-2-hydroxy-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-propan-1-one

116

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-((R)-1-pyrrolidin-3-yl-1H-

pyrazol-4-yl)-pyrimidine

117

3-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-piperidine-1-carbonyl]-cyclobutanone

118

1,1,1-Trifluoro-3-[(1R,5S)-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-

propan-2-ol

119

1-[(1R,5S)-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethanone

120

(3-Hydroxy-cyclobutyl)-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-methanone

121

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanecarboxylic acid dimethylamide

122

5-{1-[1-((S)-3-Methoxy-tetrahydro-pyran-4-yl)-piperidin-4-yl]-1H-

pyrazol-4-yl}-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

123

[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-piperidin-1-yl]-((S)-1-methyl-pyrrolidin-2-yl)-methanone

124

(S)-2-Amino-3-methyl-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-butan-1-one

125

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-((S)-1-pyrrolidin-3-yl-1H-

pyrazol-4-yl)-pyrimidine

126

1-[(S)-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-pyrrolidin-1-yl]ethanone

127

1-(3-Hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-2-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

128

1-(3-Hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-2-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

129

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-dihydro-furan-2-one

130

1-[(R)-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-pyrrolidin-1-yl]ethanone

131

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[2-(tetrahydro-furan-3-

yl)-ethyl]-1H-pyrazol-4-yl}-pyrimidine

132

3-[2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-ethyl]dihydro-furan-2-one

133

9-Isopropyl-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-9-aza-bicyclo[3.3.1]nonane

134

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

135

Cis-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

136

4-(3-{5-[1-(Tetrahydro-pyran-4-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-

phenyl)-pyridin-2-ylamine

137

4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-1-

(tetrahydro-pyran-4-yl)-1H-pyrazole-3-carboxylic acid amide

138

3-Methyl-5-(3-{5-[1-(tetrahydro-pyran-4-yl)-1H-pyrazol-4-yl]-

pyrimidin-2-yl}-phenyl)-pyridazine

139

2-[3-(2-Methyl-pyridin-4-yl)-phenyl]-5-[1-(tetrahydro-pyran-4-yl)-1H-

pyrazol-4-yl]-pyrimidine

140

4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-1-

(tetrahydro-pyran-4-yl)-1H-pyrazole-3-carboxylic acid

141

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-oxetan-3-yl-1H-pyrazol-

4-yl)-pyrimidine

142

Exo-9-Methyl-3-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-9-aza-bicyclo[3.3.1]nonane

143

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid methylamide

144

1-Methyl-4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

1H-pyrazole-3-carboxylic acid methylamide

145

N-Methyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-N-oxetan-3-yl-acetamide

146

1-(3-Methoxymethyl-morpholin-4-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-

4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

147

1-(3-Methyl-morpholin-4-yl)-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-ethanone

148

1-((1R,4R)-5-Methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-2-(4-{2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-

ethanone

149

N,N-Dimethyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-isobutyramide

150

2-Methyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-1-morpholin-4-yl-propan-1-one

151

[4-(3-{5-[1-(Tetrahydro-pyran-4-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-

phenyl)-pyridin-2-yl]-methanol

152

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-methoxy-ethyl)-methyl-

amide

153

(3-Hydroxy-azetidin-1-yl)-[4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-1-(tetrahydro-pyran-4-yl)-1H-pyrazol-3-yl]-methanone

154

4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-1-

(tetrahydro-pyran-4-yl)-1H-pyrazole-3-carboxylic acid (2-hydroxy-

ethyl)-amide

155

(1-Methyl-4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

1H-pyrazol-3-yl)-methanol

156

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexylamine

157

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclobutanecarboxylic acid methylamide

158

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclobutanecarboxylic acid dimethylamide

159

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-methoxy-ethyl)-amide

160

Trans-(4-Methyl-piperazin-1-yl)-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-

yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-methanone

161

Cis-N-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-acetamide

162

Trans-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-morpholin-4-yl-methanone

163

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid ((R)-1-hydroxymethyl-2-

methyl-propyl)-amide

164

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid((R)-1-hydroxymethyl-2-

methyl-propyl)-amide

165

[4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-1-

(tetrahydro-pyran-4-yl)-1H-pyrazol-3-yl]-methanol

166

Cis-3-Methoxy-N-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-propionamide

167

5-{1-[1-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-yl)-piperidin-4-yl]-1H-

pyrazol-4-yl}-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

168

((R)-3-Methoxy-pyrrolidin-1-yl)-trans-[4-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-

methanone

169

4-Hydroxy-N-methyl-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-butyramide

170

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid cyclopropylamide

171

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanecarboxylic acid (2-dimethylamino-ethyl)-amide

172

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-azepane

173

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid isobutyl-amide

174

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanecarboxylic acid isopropylamide

175

5-{1-[1-(2-Fluoro-phenyl)-piperidin-4-yl]-1H-pyrazol-4-yl}-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

176

5-[1-(1,1-Dioxo-hexahydro-1l6-thiopyran-4-yl)-1H-pyrazol-4-yl]-2-[3-

(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

177

5-[1-(1,1-Dioxo-hexahydro-1l6-thiopyran-3-yl)-1H-pyrazol-4-yl]-2-[3-

(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin

178

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanecarboxylic acid (2-methoxy-1-methyl-ethyl)-amide

179

7-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-3-oxa-9-aza-bicyclo[3.3.1]nonane

180

cis-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid methylamide

181

trans-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid methylamide

182

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanol

183

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-((R)-1-piperidin-3-yl-1H-

pyrazol-4-yl)-pyrimidine

184

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-hydroxy-ethyl)-amide

185

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-hydroxy-ethyl)-methyl-

amide

186

((R)-3-Hydroxy-pyrrolidin-1-yl)-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-

phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-methanone

187

trans-4-(4-{2-[3-(6-Methyl-pyridazin-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

188

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-hydroxy-1-methyl-ethyl)-

amide

189

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanone

190

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (3-hydroxy-propyl)-amide

191

Trans-((S)-3-Methoxy-pyrrolidin-1-yl)-[4-(4-{2-[3-(1-methyl-

1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-

methanone

192

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid tert-butylamide

193

exo-1-[7-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-3-oxa-9-aza-bicyclo[3.3.1]non-9-yl]-ethanone

194

cis-cis-9-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-3-oxa-bicyclo[3.3.1]nonane-7-carboxylic acid

dimethylamide

195

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanone

196

Cis-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanol

197

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid ethylamide

198

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid ((S)-2-hydroxy-1-methyl-

ethyl)-amide

199

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid ((R)-2-hydroxy-1-methyl-

ethyl)-amide

200

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid isopropyl-methyl-amide

201

1-[(3R,4R)-3-Hydroxy-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

(stereochemistry attributed arbitrarely)

202

1-[(3S,4S)-3-Hydroxy-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

(stereochemistry attributed arbitrarely)

203

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-hydroxy-butyl)-amide

204

4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclohexanecarboxylic acid ethyl-methyl-amide

205

trans-((S)-3-Hydroxy-pyrrolidin-1-yl)-[4-(4-{2-[3-(1-methyl-1H-pyrazol-

4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-methanone

206

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid amide

207

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(tetrahydro-thiopyran-3-

yl)-1H-pyrazol-4-yl]-pyrimidine

208

Trans-4-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-cyclohexyl]-morpholine

209

cis-4-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-morpholine

210

N-[2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-ethyl]-methanesulfonamide

211

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-cyclopentanol

212

3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-propane-1,2-diol

213

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-hydroxy-1,1-dimethyl-

ethyl)-amide

214

3-Isopropoxy-2-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-propan-1-ol

215

2-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-1-pyridin-2-yl-ethanol

216

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(tetrahydro-thiophen-3-

yl)-1H-pyrazol-4-yl]-pyrimidine

217

trans-5-{1-[4-(2-Methoxy-ethoxy)-cyclohexyl]-1H-pyrazol-4-yl}-2-[3-

(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

218

cis-5-{1-[4-(2-Methoxy-ethoxy)-cyclohexyl]-1H-pyrazol-4-yl}-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

219

5-[1-(1,1-Dioxo-tetrahydro-1lambda6-thiophen-3-yl)-1H-pyrazol-4-yl]-

2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

220

trans-5-[1-(4-Cyclopropylmethoxy-cyclohexyl)-1H-pyrazol-4-yl]-2-[3-

(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

221

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(tetrahydro-pyran-3-yl)-

1H-pyrazol-4-yl]-pyrimidine

222

6-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-spiro[3.3]heptane-2-carboxylic acid dimethylamide

223

1-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-azepan-1-yl]-ethanone

224

trans-2-Methyl-1-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyloxy]-propan-2-ol

225

1-[(3S,4S)-3-Hydroxy-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

226

1-[(3R,4R)-3-Hydroxy-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

(Stereochemistry attributed arbitrarely)

227

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2-hydroxy-2-methyl-

propyl)-amide

228

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (3-hydroxy-butyl)-amide

229

Trans-4-(4-{2-[3-(2-Methyl-pyridin-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

230

trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid cyanomethyl-amide

231

(1S,4R)-4-[4-[2-[3-(1-methylpyrazol-4-yl)phenyl]pyrimidin-5-

yl]pyrazol-1-yl]cyclopent-2-en-1-ol

232

Trans-dimethyl-[4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexylmethyl]-amine

233

Trans-4-{4-[2-(3-Pyridazin-4-yl-phenyl)-pyrimidin-5-yl]-pyrazol-1-yl}-

cyclohexanecarboxylic acid dimethylamide

234

Trans-4-(4-{2-[3-(6-Chloro-pyridazin-3-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

235

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(Trans-1-oxo-tetrahydro-

thiopyran-3-yl)-1H-pyrazol-4-yl]-pyrimidine (racemate; isomery

attributed arbitrarely)

236

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-[1-(Cis-1-oxo-tetrahydro-

thiopyran-3-yl)-1H-pyrazol-4-yl]-pyrimidine (racemate; isomery

attributed arbitrarely)

237

Trans-4-(4-{2-[3-(6-Methyl-pyridazin-3-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

238

Trans-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-methanol

239

Trans-4-(4-{2-[3-(6-Amino-pyridazin-3-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide

240

5-(3-{5-[1-((S)-1,1-Dioxo-hexahydro-1l6-thiopyran-3-yl)-1H-pyrazol-4-

yl]-pyrimidin-2-yl}-phenyl)-3-methyl-pyridazine (stereochemistry

attributed arbitrarely)

241

5-(3-{5-[1-((R)-1,1-Dioxo-hexahydro-1l6-thiopyran-3-yl)-1H-pyrazol-

4-yl]-pyrimidin-2-yl}-phenyl)-3-methyl-pyridazine (stereochemistry

attributed arbitrarely)

242

Trans-4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanecarboxylic acid (2,3-dihydroxy-propyl)-

amide

243

5-[1-((2R,4R)-2-Methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine formic acid

244

((3S,4S)-3,4-Dihydroxy-pyrrolidin-1-yl)-[4-(4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-

methanone

245

(Trans-3-Hydroxy-4-methoxy-pyrrolidin-1-yl)-[4-Trans-(4-{2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-

cyclohexyl]-methanone

246

5-[1-((2S,4S)-2-Methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

247

trans-4-(4-{2-[3-(6-Methyl-pyridazin-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanol

248

1-[(2S,4S)-2-Methyl-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

249

1-[(2R,4R)-2-Methyl-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

250

cis-8-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-1-aza-spiro[4.5]decan-2-one (first isomer)

251

Cis-8-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-1-aza-spiro[4.5]decan-2-one (second isomer)

252

Cis-5-[1-(4-Methoxy-cyclohexyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidine

253

trans-5-[1-(4-Methoxy-cyclohexyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-

1H-pyrazol-4-yl)-phenyl]-pyrimidine

254

4-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-morpholin-3-one

255

:3-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-oxazolidin-2-one

256

Trans-[4-(4-{2-[3-(6-Methyl-pyridazin-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-methanol

257

3-[cis-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexyl]-oxazolidin-2-one

258

Cis-1-Hydroxymethyl-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanol

259

5-[1-(3,3-Difluoro-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidine

260

trans-2-Methyl-8-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-2-aza-spiro[4.5]decan-3-one

261

((S)-2-Hydroxymethyl-morpholin-4-yl)-[4-((S)-4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-

methanone

262

cis-2-Methyl-8-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-

5-yl}-pyrazol-1-yl)-2-aza-spiro[4.5]decan-3-one

263

Cis-1-[3-Fluoro-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

264

5-[1-(1,9-Dioxa-spiro[5.5]undec-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-

1H-pyrazol-4-yl)-phenyl]-pyrimidine

265

cis-3-Fluoro-piperidin-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidine

266

((R)-2-Hydroxymethyl-morpholin-4-yl)-[4-((S)-4-{2-[3-(1-methyl-1H-

pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexyl]-

methanone

267

5-[1-(1,9-Dioxa-spiro[5.5]undec-4-yl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-

1H-pyrazol-4-yl)-phenyl]-pyrimidine

268

5-[(R)-1-(1-Methanesulfonyl-piperidin-3-yl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

269

1-[3-((R)-4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-piperidin-1-yl]-ethanone

270

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[1-(tetrahydro-pyran-3-

yl)-piperidin-4-yl]-1H-pyrazol-4-yl}-pyrimidine

271

4-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-tetrahydro-pyran-3-ylmethyl]-morpholine

272

5-[(R)-1-(1-Methanesulfonyl-piperidin-3-yl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

273

trans,cis-9-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-3-oxa-bicyclo[3.3.1]nonane-7-carboxylic acid

dimethylamide

274

1-[3-((R)-4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-piperidin-1-yl]-ethanone

275

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-{1-[1-(3-methyl-tetrahydro-

pyran-4-yl)-piperidin-4-yl]-1H-pyrazol-4-yl}-pyrimidine

276

[9-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-

1-yl)-3-oxa-bicyclo[3.3.1]non-7-yl]-methanol

277

Trans-2-[4-(-4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-cyclohexyloxy]-ethanol

278

(5-Methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-trans-[4-(-4-{2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-

cyclohexyl]-methanone hydrobromide

279

5-[1-(Cis-3-Methanesulfonyl-cyclohexyl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine (isomery attributed

arbitrarely)

280

(3aS,7aS)-7a-Hydroxymethyl-5-((R)-4-{2-[3-(1-methyl-1H-pyrazol-4-

yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-hexahydro-isobenzofuran-3a-

ol (configuration attributed arbitrarily)

281

(3aR,5R,7aR)-7a-Hydroxymethyl-5-(4-{2-[3-(1-methyl-1H-pyrazol-4-

yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-hexahydro-isobenzofuran-3a-

ol (configuration attributed arbitrarily)

282

5-[1-(trans-3-Methanesulfonyl-cyclohexyl)-1H-pyrazol-4-yl]-2-[3-(1-

methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine (isomery attributed

arbitrarely)

283

2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-((S)-1-piperidin-3-yl-1H-

pyrazol-4-yl)-pyrimidine

284

1-[3,3-Difluoro-4-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-

pyrimidin-5-yl}-pyrazol-1-yl)-piperidin-1-yl]-ethanone

285

1-Methyl-8-(4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-1-aza-spiro[4.5]decan-2-one

286

trans-8-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-2-aza-spiro[4.5]decan-3-one

287

cis-8-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pyrimidin-5-yl)-1H-

pyrazol-1-yl)-2-azaspiro[4.5]decan-3-one

288

imino(methyl)(3-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pyrimidin-

5-yl)-1H-pyrazol-1-yl)cyclohexyl)-λ6-sulfanone

289

2-trans-[4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexylamino]-ethano

290

Trans-3-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-

pyrazol-1-yl)-cyclohexanol

291

4-(3-Methyl-4-{2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-cyclohexanol

292

4-(4-{2-[2-Fluoro-5-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-

yl}-pyrazol-1-yl)-cyclohexanol.

7. A method for the treatment of multiple sclerosis, rheumatoid arthritis, lupus nephritis, or systemic lupus erythematosus, comprising administering to a subject a therapeutically effective amount of a compound of claim 1 .

8. A pharmaceutical composition comprising at least one compound of claim 1 and an excipient or an adjuvant.

9. The pharmaceutical composition according to claim 8 which further comprising at least one further medicament used in the treatment of inflammatory diseases or immune disorders or immunomodulating agent.

10. A process for producing compounds of Formula (I) according to claim 1 , comprising the step of reacting a compound of Formula (II)

Wherein X denotes Hal or a triflate group and wherein R 1 , R a and Z are as defined in claim 1 , With a compound of Formula (III)

Wherein R is H or a C 1 -C 6 -alkyl group, and wherein R b and R 2 are as defined in claim 1 .

11. The compound of claim 1 , wherein Z is pyridazine, pyrazole, or 4-pyridine.

12. The compound of claim 1 , wherein R 1 is a linear or branched C 1 -C 6 alkyl group.

13. The compound of claim 1 , wherein R 2 is a piperidine or Cyc.

14. The compound of claim 1 , wherein R b is H.

15. The compound of claim 1 , wherein R b is COHet or a linear or branched C 1 -C 6 -alkyl group wherein 1 H atoms are optionally substituted by a group selected from NR 3 and OR 3 , and wherein 1 CH 2 group is optionally substituted by CO.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 6, 2015

From: CROSIGNANI, STEFANO; GERBER, PATRICK; JORAND-LEBRUN, CATHERINE; MUZERELLE, MATHILDE

To: ARES TRADING S.A.

Reel/Frame 036266/0285 →

Priority Claims (1)

EP 12175660 · Jul 10, 2012 · regional

Continuity (2)

Provisional Application 61669843 · Jul 10, 2012

Related Publication 20150141396A1 · May 21, 2015