IP Library Granted Patent US 7,855,212
Granted Patent B2
US 7,855,212 · App. 10/555,960 · Granted Dec 21, 2010

Pyridinyl acetonitriles

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Quick Facts
Patent No.
US 7,855,212
App. No.
10/555,960
Granted
Dec 21, 2010
Kind
B2
Abstract

The present invention is related to pyridinyl acetonitriles as well as to pharmaceutical formulations containing such pyridinyl acetonitriles. Said pyridinyl acetonitriles are modulators of the protein kinase signalling pathways, particularly the one involving Glycogen Kinase Synthase 3 or JNK. The present invention is furthermore related to methods of preparing pyridinyl acetonitriles. X is a substituted or unsubstituted pyridinyl. G is an unsubstituted or substituted pyrimidinyl or triazinyl.

Claims (113)

1. A compound of formula (Ib) in all tautomeric forms:

wherein

L is selected from the group consisting of sulfonyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl, heteroaryl, saturated 3-8-membered cycloalkyl, unsaturated 3-8-membered cycloalkyl, 3-8-membered heterocycloalkyl, an acyl moiety, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl cycloalkyl, C 2 -C 6 -alkenyl heterocycloalkyl, C 2 -C 6 -alkynyl cycloalkyl, C 2 -C 6 -alkynyl heterocycloalkyl, alkoxycarbonyl, aminocarbonyl, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyl, aryl acyl, heteroaryl acyl, C 3 -C 8 -(hetero)cycloalkyl acyl, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C 6 -alkyl acylamino, acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl carbamate, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl ammonium, C 1 -C 6 -alkyl sulfonyloxy, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfonylamino, C 1 -C 6 -alkyl aminosulfonyl, hydroxy, halogen, and cyano,

R 1 is a hydrogen, a sulfonyl, amino, a C 1 -C 6 -alkyl, a C 2 -C 6 -alkenyl, a C 2 -C 6 -alkynyl, an aryl or a C 1 -C 6 -alkoxy, a halogen, a cyano or a hydroxy,

R 2 is a hydrogen, a sulfonyl, amino, a C 1 -C 6 -alkyl, a C 2 -C 6 -alkenyl, a C 2 -C 6 -alkynyl or a C 1 -C 6 -alkoxy, a halogen, a cyano or a hydroxyl,

wherein heteroaryl is optionally substituted pyridyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadia-zolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,3,4-triazinyl, 1,2,3-triazinyl, benzofuryl, [2,3-dihydro]benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, isobenzothienyl, indolyl, isoindolyl, 3H-indolyl, benzimidazolyl, imidazo[1,2-a]pyridyl, benzothiazolyl, benzoxa-zolyl, quinolizinyl, quinazolinyl, pthalazinyl, quinoxalinyl, cinnolinyl, napthyridinyl, pyrido[3,4-b]pyridyl, pyrido[3,2-b]pyridyl, pyrido[4,3-b]pyridyl, quinolyl, isoquinolyl, tetrazolyl, 5,6,7,8-tetrahydroquinolyl, 5,6,7,8-tetrahydroisoquinolyl, purinyl, pteridinyl, carbazolyl, xanthenyl or benzoquinolyl;

sulfonyl is —SO 2 —R wherein R is H, aryl, heteroaryl, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl substituted with a halogen, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynylheteroaryl, C i -C 6 -alkyl cycloalkyl, or C 1 -C 6 -alkyl heterocycloalkyl;

acyl is —C(O)R where R is H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynylheteroaryl, C 1 -C 6 -alkyl cycloalkyl, or C 1 -C 6 -alkyl heterocycloalkyl; and

heterocycloalkyl is pyrrolidine, piperidine, piperazine, 1-methylpiperazine, or morpholine.

2. A compound of formula (Ic) in all tautomeric forms:

wherein

L is selected from the group consisting of sulfonyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl, heteroaryl, saturated 3-8-rnembered cycloalkyl, unsaturated 3-8-membered cycloalkyl, 3-8-membered heterocycloalkyl, an acyl moiety, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl cycloalkyl, C 2 -C 6 -alkenyl heterocycloalkyl, C 2 -C 6 -alkynyl cycloalkyl, C 2 -C 6 -alkynyl heterocycloalkyl, alkoxycarbonyl, aminocarbonyl, C 1 -C 6 -alkyl carboxy, C-C 6 -alkyl acyl, aryl acyl, heteroaryl acyl, C 3 -C 8 -(hetero)cycloalkyl acyl, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C 6 -alkyl acylamino, acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl carbamate, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl ammonium, C 1 -C 6 -alkyl sulfonyloxy, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfonylamino, C 1 -C 6 -alkyl aminosulfonyl, hydroxy, halogen, and cyano,

R 1 is a hydrogen, a sulfonyl, amino, a C 1 -C 6 -alkyl, a C 2 -C 6 -alkenyl, a C 2 -C 6 -alkynyl, an aryl or a C 1 -C 6 -alkoxy, a halogen, a cyano or a hydroxy,

R 2 is a hydrogen, a sulfonyl, amino, a C 1 -C 6 -alkyl, a C 2 -C 6 -alkenyl, a C 2 -C 6 -alkynyl or a C 1 -C 6 -alkoxy, a halogen, a cyano or a hydroxyl

wherein heteroaryl is optionally substituted pyridyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadia-zolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,3,4-triazinyl, 1,2,3-triazinyl, benzofuryl, [2,3-dihydro]benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, isobenzothienyl, indolyl, isoindolyl, 3H-indolyl, benzimidazolyl, imidazo[1,2-a]pyridyl, benzothiazolyl, benzoxa-zolyl, quinolizinyl, quinazolinyl, pthalazinyl, quinoxalinyl, cinnolinyl, napthyridinyl, pyrido[3,4-b]pyridyl, pyrido[3,2-b ]pyridyl, pyrido[4,3-b]pyridyl, quinolyl, isoquinolyl, tetrazolyl, 5,6,7,8-tetrahydroquinolyl, 5,6,7,8-tetrahydroisoquinolyl, purinyl, pteridinyl, carbazolyl, xanthenyl or benzoquinolyl;

sulfonyl is —SO 2 —R wherein R is H, aryl, heteroaryl, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl substituted with a halogen, C 2 -C 6 -alkenyl, C 2 -C o -alkynyl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynylheteroaryl, C 1 -C 6 -alkyl cycloalkyl, or C 1 -C 6 -alkyl heterocycloalkyl;

acyl is —C(O)R where R is H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynylheteroaryl, C 1 -C 6 -alkyl cycloalkyl, or C 1 -C 6 -alkyl heterocycloalkyl; and

heterocycloalkyl is pyrrolidine, piperidine, piperazine, 1-methylpiperazine, or morpholine.

3. The compound according to claim 1 , wherein R 1 and R 2 are each independently H or C 1 -C 3 alkyl.

4. The compound according to claim 1 , which -selected from the group consisting of:

2-[[1-(diphenylmethyl)-3-azetidinyl]amino]-5-methyl-alpha-2(1H)-pyridinylidene-4-pyrimidineacetonitrile,

5-methyl-2-[[2-(3-pyridinyl)ethyl]amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[[2- [6-(dimethylamino)-3-pyridinyl]ethyl]amino]-5-methyl-alpha-2(1 H) pyridinylidene-4-pyrimidineacetonitrile,

5-methyl-2-[[3-(2-oxo-1-pyrrolidinyl)propyl]amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

5-methyl-alpha-2-pyridinyl-2-[[2-(2-pyridinyl)-ethyl]amino]-4 pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-(6-phenyl-2(1H)-pyridinylidene)-4-pyrimidineacetonitrile,

2

5-methyl-2-(4-piperidinylamino)-alpha-2 (1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-(cyclohexylamino)-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-[(cyclohexylmethyl)amino]-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2- [(3-hydroxy- 1-phenylpropyl)amino]-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-(cyclobutylamino)-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha-(1-ethyl-2(1 H)-pyridinylidene)-5-methyl-4-pyrimidineacetonitrile,

2-(cyclopropylamino)-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

5-methyl-2-[[1-(phenylmethyl)-4-piperidinyl]amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[(1 ethylpropyl)amino]-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

5-methyl-alpha-2(1 H)-pyridinylidene-2- [[(tetrahydro-2H-pyran-4-yl)methyl]amino]-4-pyrimidineacetonitrile,

5-methyl-alpha-2(1 H)-pyridinylidene-2- [[(tetrahydro-2-furanyl)methyl]amino]-4-pyrimidineacetonitrile,

5-methyl-2-[(2-methylpropyl)amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

5-methyl-2-[(1 methylethyl)amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[[(1 S ,2S)-2-hydroxycyclohexyl]amino]-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[[(1 S,2S)-2-hydroxycyclopentyl]amino]-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[(trans-4-hydroxycyclohexyl)amino]-5-methyl-alpha-2(1H)-pyridinylidene-1-piperidinecarboxylic acid,

4-[[4-[(E)-cyano-2(1H)-pyridinylidenemethyl]-5-methyl-2-pyrimidinyl]amino]-1,1 dimethylethyl ester 4-pyrimidineacetonitrile,

5-methyl-2-[(1-methylbutyl)amino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-(cyclohexylamino)-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

5-methyl-alpha-2-pyridinyl-2-[4-(2-pyrimidinylamino)-1-piperidinyl]-4-pyrimidineacetonitrile,

alpha-2-pyridinyl-2-[[2-(3 pyridinyl)ethyl]amino]-4-pyrimidineacetonitrite,

2-(cyclopropylamino)-alpha-2-pyridinyl-benzoic acid,

4-[2-[[4-(cyano-2-pyridinylmethyl)-5methyl-2-pyrimidinyl]amino]ethyl]-methyl ester 4-pyrimidineacetonitrile,

2-[(1,2-dimethylpropyl)amino]-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-[(2,3-dimethylcyclohexyl)amino]-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

alpha-4-pyridinyl-2- [[2-(3-pyridinyl)ethyl]amino]-4-pyrimidineacetonitrile,

2-[(2furanylmethyl)amino]-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-[(1-methylbutypamino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

5-methyl-2-[[2-(1H-pyrazol-1yl)ethyl]amino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-[[2(4aminophenyl)ethyl]amino]-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2- [[(4-methoxyphenyl)ethyl]amino]-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

6-(cyclopentylamino)-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

alpha-2-pyridinyl-2-[[2(2pyridinyl)ethyl]amino]-4-pyrimidineacetonitrile,

2-4-ethyl-1-piperazinyl)-6-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha-4-pyridinyl-4-pyrimidineacetonitrile,

2- [[[4-(difluoromethoxy)phenyl]methyl]amino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-[(2,3dimethylcyclohexyl)amino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

6-methyl-2-[(1-methylbutypamino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-[(2-furanylmethyl)amino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-6-methyl-alpha-2-pyridinyl-1,3,5-triazine-2-acetonitrile, 4-(methylamino)-alpha-2-pyridinyl-6-[[2-(3pyridinyl)ethyl]amino]-4-pyrimidineacetonitrile,

2-[[2-[6-(dimethylamino)-3-pyridinyl]ethyl]amino]-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

2-(dipropylamino)-5-methyl-alpha-2-pyridinyl-4-pyrimidineacetonitrile,

alpha-2-pyridinyl-6-[[2-(3-pyridinyl)ethyl]amino]-4-pyrimidineacetonitrile,

alpha-(3-bromo-2(1H)-pyridinylidene)-2-(cyclopentylamino)-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1H)-pyridinylidene)-5-methyl-2-[[3-(1 H-pyrazol -1 yl)propyl]amino]-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1 H)-pyridinylidene)-5-methyl-2-[[3-(2-oxo-1 pyrrolidinyl)propyl]amino]-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1H)-pyridinylidene)-2-(cyclopentylamino)-5-methyl-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1H)-pyridinylidene)-2-(cyclopentylamino)-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1 H)-pyridinylidene)-5-methyl-2-[[3-(3-oxo-4 morpholinyl)propyl]amino]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha-[6-(cyclopropylamino)-2(1H)-pyridinylidene]-5methyl -4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1H)-pyridinylidene)-5-methyl-2-[[3-(1H-1,2,4-triazol- 1-yl)propyl]amino]-4-pyrimidineacetonitrile,

alpha-(3-bromo-2(1H)-pyridinylidene)-2-[[3-(2-oxo-1-pyrrolidinyl)propyl]amino]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-[6-(phenylamino)-2(1 H)-pyridinylidene]-4-pyrimidineacetonitrile,

5-methyl-2-[[3-(1 H-pyrazol- 1-yl)propyl]amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1 H)-pyridinylidene)-2-[[3-(1H-1 ,2,4-triazol- 1-yl)propyl]amino]-4-pyrimidineacetonitrile,

5-methyl-2-[[3-(3-oxo-4-morpholinyl)propyl]amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-(cycloheptylamino)-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1 H)-pyridinylidene)-2-[[2-(1 H-1,2,4-triazol- 1yl)ethyl]amino]-4-pyrimidineacetonitrile,

5-methyl-alpha-2(1 H)-pyridinylidene-2-[[3-(1H-1,2,4-triazol- 1-yl)propyl]amino]-4-pyrimidineacetonitrile,

alpha-(5-bromo-2(1H)-pyridinylidene)-2-(cyclopentylamino)-4-pyrimidineacetonitrile,

2- [[3-(1 H-pyrazol- 1-yl)propyl]amino]-alpha- [6-[[3-(1 H-pyrazol- 1-yl)propyl]amino]2(1 H)-pyridinylidene]-4-pyrimidineacetonitrile,

2-(cycloheptylamino)-alpha-2(1H)-pyridinylidene-4-pyrimidineacetonitrile,

alpha-(6-bromo-2(1 H)-pyridinylidene)-5-methyl-2-[[2-(1 H-1 ,2,4-triazol- 1-yl)ethyl]amino]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-[6-(4-morpholinyl)-2(1 H)-pyridinylidene]-4-pyrimidineacetonitrile,

2-[[(1 S,2S)-2-hydroxycyclopentyl]amino]-alpha-2(1H)-pyridinylidene-4-pyrimidineacetonitrile,

alpha-(3-bromo-2(1H)-pyridinylidene)-2-(cyclopentylamino)-5-methyl-4-pyrimidineacetonitrile,

2-[[3-(2-oxo-1-pyrrolidinyl)propyl]amino]-alpha-2(1H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[[2-(1 H-imidazol-4-yl)ethyl]amino]-5-methyl-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-[[(1 S,2S)-2-hydroxycyclohexyl]amino]-5-methyl-alpha-2(1H)-pyridinylidene-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-[6-[[2-(3 pyridiny)ethyl]amino]-2(1 H) -pyridinylidene]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-[6-[[3-(2-oxo- 1-pyrrolidinyl)propyl]amino]2(1 H)-pyridinylidene]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-[6-[methyl(phenylmethyl)amino]-2(1 H) -pyridinylidene]-4-pyrimidineacetonitrile,

alpha-(3-bromo-2(1H)-pyridinylidene)-5-methyl-2-[[3-(3-oxo-4-morpholinyl)propyl]amino]-4-pyrimidineacetonitrile,

2-[[(1 S,2S)-2-(phenylmethoxy)cyclopentyl]amino]-alpha-2(1 H)-pyridinylidene-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha- [6-(2-pyridinylamino)-2(1 H)-pyridinylidene]-4-pyrimidineacetonitrile,

alpha-(3-bromo-2(1 H)-pyridinylidene)-5-methyl-2-[[3-(2-oxo- 1 pyrrolidinyl)propyl]amino]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-5-methyl-alpha-[6-[(trimethylsilyl)ethynyl]-2(1H) pyridinylidene]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha-[6-(3-pyridinylamino)-2(1 H)-pyridinylidene]-4-pyrimidineacetonitrile,

2-(cyclopentylamino)-alpha- [6-(cyclopentylamino)-2(1 H)-pyridinylidene]-5-methyl-4-pyrimi dineacetonitrile,

alpha-[3-(3-hydroxy-3-methyl-1-butynyl)-2(1 H)-pyridinylidene]-5-methyl-2[[3-(3 oxo-4-morpholinyl)propyl]amino]-4-pyrimidineacetonitrile, and

alpha-(3-bromo-2(1 H)-pyridinylidene)-5-methyl-2-[[3-(1 H-1 ,2,4-triazol- 1-yl)propyl]amino]-4pyrimidineacetonitrile.

5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, a diluent or an excipient thereof.

6. A method of preparing a compound of formula (Ib) according to claim 1 , comprising the following step:

wherein X is a pyridinyl group and G is a pyrimidinyl or a triazinyl.

Assignments (3)
CHANGE OF NAME Recorded Dec 3, 2009
From: LABORATOIRES SERONO SA
To: MERCK SERONO SA
Reel/Frame 023599/0944 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 11, 2007
From: APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.
To: LABORATOIRES SERONO SA
Reel/Frame 019966/0026 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2007
From: SCHWARZ, MATTHIAS; GAILLARD, PASCALE; GOTTELAND, JEAN-PIERRE; THOMAS, RUSSELL J.; PAGE, PATRICK
To: APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.
Reel/Frame 019040/0388 →