Phenyl-[4-(3-phenyl-1h-pyrazol-4-yl)-pyrimidin-2-yI)-amine derivatives

• US 20060106027A1
• Filed: 07/08/2003
• Published: 05/18/2006
• Est. Priority Date: 07/09/2002
• Status: Active Grant

• Current Assignee: Achim Schlapbach, Dieter Scholz, Giorgio Caravatti, Pascal Furet, Patricia Imbach, Timothy Michael Ramsey
• Original Assignee: Achim Schlapbach, Dieter Scholz, Giorgio Caravatti, Pascal Furet, Patricia Imbach, Timothy Michael Ramsey
• Inventors: Furet, Pascal, Caravatti, Giorgio, Imbach, Patricia, Schlapbach, Achim, Scholz, Dieter, Ramsey, Timothy Michael
• Granted Patent: US 7,691,855 B2
• Time in Patent Office: Days
• US Class Current: 514/252.190
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond

Abstract

The invention relates to phenyl-[4-(3-phenyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine derivatives and to processes for the preparation thereof, to pharmaceutical compositions comprising such derivatives and to the use of such derivatives—alone or in combination with one or more other pharmaceutically active compounds—for the preparation of pharmaceutical compositions for the treatment especially of a proliferative disease, such as a tumour.

Claims

1. A compound of formula I

2. A compound of formula I according to claim 1, wherein

m is an integer from 1 to 5;

R₁ is unsubstituted, mono- or di-substituted amino-sulfonyl;

unsubstituted, mono- or di-substituted amino;

a heterocyclic radical;

lower alkyl substituted by a heterocyclic radical;

a radical R₄-lower alkyl-X—

, wherein R₄ is hydrogen, unsubstituted, mono- or di-substituted amino, or a heterocyclic radical, and X is —

S—

or —

O—

;

or a radical R₅—

C(═

O)—

, wherein R₅ is hydrogen, unsubstituted or substituted lower alkyl, free or etherified hydroxy, unsubstituted, mono- or di-substituted amino, or a heterocyclic radical;

wherein the R₁ substituents are selected independently of one another if m>

1;

or two vicinal R₁ substituents together with the phenyl carbon atoms to which they are attached form a heterocyclic ring;

R₂ is hydrogen, unsubstituted or substituted lower alkyl or a heterocyclic radical;

R₃ is a radical of the formula Ia, wherein n is from 1 to 5 and Z is halogen;

unsubstituted or substituted lower alkyl;

or free, etherified or esterified hydroxy;

wherein the Z substituents are selected independently of one another if n>

1;

or two vicinal Z substituents together with the phenyl carbon atoms to which they are attached form a heterocyclic ring; and

R₃′

is hydrogen;

with the proviso that R₁ is not methoxy if m and n are both 1, R₂ is hydrogen and Z is fluoro;

or a salt thereof.

3. A compound of formula I according to claim 2, wherein

m is an integer from 1 to 5;

R₁ is unsubstituted, mono- or di-substituted amino-sulfonyl;

unsubstituted, mono- or di-substituted amino;

a heterocyclic radical;

lower alkyl substituted by a heterocyclic radical;

a radical R₄-lower alkyl-X—

, wherein R₄ is hydrogen, unsubstituted, mono- or di-substituted amino, or a heterocyclic radical, and X is —

S—

or —

O—

;

or a radical R₅—

C(═

O)—

, wherein R₅ is hydrogen, unsubstituted or substituted lower alkyl, free or etherified hydroxy, unsubstituted, mono- or di-substituted amino, or a heterocyclic radical;

wherein the R₁ substituents are selected independently of one another if m>

1;

or two vicinal R₁ substituents together with the phenyl carbon atoms to which they are attached form a heterocyclic ring;

R₂ is hydrogen;

R₃ is a radical of the formula Ia, wherein n is from 1 to 5 and Z is halogen;

unsubstituted or substituted lower alkyl;

or free, etherified or esterified hydroxy;

wherein the Z substituents are selected independently of one another if n>

1;

or two vicinal Z substituents together with the phenyl carbon atoms to which they are attached form a heterocyclic ring; and

R₃′

is hydrogen;

with the proviso that R₁ is not methoxy if m and n are both 1, R₂ is hydrogen and Z is fluoro;

or a salt thereof.

4. A compound of formula I according to claim 2, wherein

m is an integer from 1 to 3;

R₁ is amino-sulfonyl;

mono- or di-substituted amino;

a heterocyclic radical;

lower alkyl substituted by a heterocyclic radical;

a radical R₄-lower alkyl-X—

, wherein R₄ is hydrogen, mono- or di-substituted amino, or a heterocyclic radical, and X is —

S—

or —

O—

;

or a radical R₅—

C(═

O)—

, wherein R₅ is lower alkyl, free or etherified hydroxy, or a heterocyclic radical;

wherein the R₁ substituents are selected independently of one another if m>

1;

or two vicinal R₁ substituents together with the phenyl carbon atoms to which they are attached form a heterocyclic ring;

R₂ is hydrogen;

R₃ is a radical of the formula Ia, wherein n is from 1 to 3 and Z is halogen;

lower alkyl;

or free or etherified hydroxy;

wherein the Z substituents are selected independently of one another if n>

1;

or two vicinal Z substituents together with the phenyl carbon atoms to which they are attached form a heterocyclic ring; and

R₃′

is hydrogen;

with the proviso that R₁ is not methoxy if m and n are both 1, R₂ is hydrogen and Z is fluoro;

or a salt thereof.

5. A compound of formula I according to claim 1, wherein

m is an integer from 1 to 3;

R₁ is lower alkyl-sulfonyl;

amino-sulfonyl;

N,N-di-lower alkylamino;

piperazinyl;

lower alkyl-piperazinyl;

tetrazolyl;

lower alkyl substituted by lower alkyl-piperazinyl, hydroxy-lower alkyl-piperazinyl, piperidyl-amino or piperidyl-oxy wherein the piperidyl moiety is substituted by 1 to 4 lower alkyl radicals;

a radical R₄-lower alkyl-X—

, wherein R₄ is hydrogen, halogen, N,N-di-lower alkylamino, morpholin-4-yl or lower alkyl-piperidyl, and X is —

S—

or —

O—

;

or a radical R₅—

C(═

O)—

, wherein R₅ is lower alkyl, hydroxy, lower alkoxy or lower alkyl-piperazinyl;

wherein the R₁ substituents are selected independently of one another if m>

1;

or two vicinal R₁ substituents together with the phenyl carbon atoms to which they are attached form a thiazol or 1-oxo-thiazol ring;

R₂ is hydrogen, lower alkyl, N,N-di-lower alkylamino-lower alkyl, lower alkyl-piperidyl or lower alkyl-piperidyl-lower alkyl;

R₃ is a radical of the formula Ia, wherein n is 0, 1 or 2 and Z is halogen, lower alkyl, tri-halogen-lower alkyl, hydroxy, lower alkoxy or phenyl-lower alkoxy;

wherein the Z substituents are selected independently of one another if n is 2;

or two Z radicals together form a dioxol ring; and

R₃′

is hydrogen;

with the proviso that R₁ is not methoxy if m and n are both 1, R₂ is hydrogen and Z is fluoro;

or a salt thereof.

6. A compound of formula I according to claim 2, wherein

m is an integer from 1 to 3;

R₁ is amino-sulfonyl;

N,N-di-lower alkylamino;

lower alkyl-piperazinyl;

lower alkyl substituted by lower alkyl-piperazinyl;

a radical R₄-lower alkyl-X—

, wherein R₄ is hydrogen, N,N-di-lower alkylamino, morpholin-4-yl or lower alkyl-piperidyl, and X is —

S—

or —

O—

;

or a radical R₅—

C(═

O)—

, wherein R₅ is lower alkyl, hydroxy, lower alkoxy or lower alkyl-piperazinyl;

wherein the R₁ substituents are selected independently of one another if m>

1;

or two vicinal R₁ substituents together with the phenyl carbon atoms to which they are attached form a thiazol or 1-oxo-thiazol ring;

R₂ is hydrogen;

R₃ is a radical of the formula Ia, wherein n is 1 or 2 and Z is halogen, lower alkyl, hydroxy, lower alkoxy or phenyl-lower alkoxy;

wherein the Z substituents are selected independently of one another if n is 2;

or two Z radicals together form a dioxol ring; and

R₃′

is hydrogen;

with the proviso that R₁ is not methoxy if m and n are both 1, R₂ is hydrogen and Z is fluoro;

or a salt thereof.

7. A compound of formula I according to claim 1,

with the proviso that R₁ is not a radical R₄-lower alkyl-X—

, or a salt thereof.

8. A compound of formula I according to claim 1, selected from the group consisting of

{4-[3-(2,3-dimethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[3-(2,3-dimethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[3-(2-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[3-(2-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[1-(2-dimethylamino-ethyl)-5-p-tolyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[1-(2-dimethylamino-ethyl)-3-p-tolyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[5-(2,4-dichloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4-dimethoxy-phenyl)-amine;

{4-[3-(2,4-dichloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4-dimethoxy-phenyl)-amine;

4-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-ylamino]-benzoic acid;

(4-Methyl-piperazin-1-yl)-{4-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-ylamino]-phenyl}-methanone;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[5-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

[4-(4-methyl-piperazin-1-yl)-phenyl]-[4-(1-methyl-5-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2yl]-amine;

[4-(4-methyl-piperazin-1-yl)-phenyl]-[4-(1-methyl-3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2yl]-amine;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[4-(1-methyl-5-p-tolyl-1 H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[4-(1-methyl-3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4-dimethoxy-phenyl)-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine;

{4-[3-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[5-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[5-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[5-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4-dimethoxy-phenyl)-amine;

{4-[3-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine;

{4-[5-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine;

{4-[3-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[5-(4-chloro-phenyl)-1-(2-dimethylamino-ethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[5-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[5-(4-chloro-phenyl)-1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[1-(2-dimethylamino-ethyl)-5-p-tolyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[1-(2-dimethylamino-ethyl)-3-p-tolyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-{4-[1-(1-methyl-piperidin-4-yl)-5-p-tolyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-{4-[1-(1-methyl-piperidin-4-yl)-3-p-tolyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

{4-[3-(4-chloro-3-methyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4-dimethoxy-phenyl)-amine;

(3-methoxy-phenyl)-{4-[3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

(3-methoxy-phenyl)-{4-[1-methyl-3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

(3-methoxy-phenyl)-{4-[1-methyl-5-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

{4-[1-(2-dimethylamino-ethyl)-3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine;

{4-[3-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[5-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1yl)-phenyl]-amine;

[4-(4-methyl-piperazin-1-yl)-phenyl]-{4-[3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-{4-[3-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl)-amine;

[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-(3-trifluoromethoxy-phenyl)-amine;

(4-methanesulfonyl-phenyl)-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

(3-{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-phenyl)-(4-methyl-piperazin-1-yl)-methanone;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(4-methane-sulfonyl-phenyl)-amine;

{(3-methoxy-phenyl)-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

(3-methoxy-phenyl)-{4-[3-(3-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

[4-(4-ethyl-piperazin-1-ylmethyl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[3-(4-methyl-piperazin-phenyl]-amine;

[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[4-(3-phenyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[5-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1-(1-methyl-piperidin-4-ylmethyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine;

{4-[5-(4-chloro-phenyl)-1-(1-methyl-piperidin-4-ylmethyl)-1H-pyrazol-4-yl]-pyrimidin-methoxy-phenyl)-amine;

[4-(4-ethyl-piperazin-1-yl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-{4-[3-(3-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

2-(4-{4-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-ylamino]-benzyl}-piperazin-1-yl)-ethanol;

{4-[3-(4-chloro-phenyl)-1-methyl-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[3-( 1-methyl-piperidin-4-ylmethoxy)-phenyl]-amine;

3-{4-[3-(3,5-dimethoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-benzenesulfonamide;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-ethyl-piperazin-1-ylmethyl)-phenyl]-amine;

[4-(4-ethyl-piperazin-1-ylmethyl)-phenyl]-[4-(3-phenyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(1H-tetrazol-5-yl)-phenyl]-amine;

[4-(4-ethyl-piperazin-1-ylmethyl)-phenyl]-[4-(1-methyl-3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[4-(4-ethyl-piperazin-1-ylmethyl)-phenyl]-[4-(1-methyl-5-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl)-{4-[(2,2,6,6-tetramethyl-piperidin-4-ylamino)-methyl]-phenyl}-amine;

[4-(3-phenyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-{4-[(2,2,6,6-tetramethyl-piperidin-4-ylamino)-methyl]-phenyl}-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-ethyl-piperazin-1-yl)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(4-piperazin-1-yl-phenyl)-amine;

[3-(1-methyl-piperidin-4-yloxymethyl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2yl]-amine;

[3-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[3-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-[4-( 1-methyl-3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

4-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-ylamino]-benzenesulfonamide and pharmaceutically acceptable salts thereof.

9. A compound of formula I according to claim 2, selected from the group consisting of

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-di methyl-amino-ethoxy)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-diethylamino-ethoxy)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl)-pyrimidin-2-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine;

{4-[3-(3-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl)-[4-(2-dimethylamino-ethoxy)-phenyl]-amine;

{4-[3-(3-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl)-[4-(2-morpholin-4-yl-ethoxy)-Phenyl]-amine;

{4-[3-(3-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-diethylamino-ethoxy)-phenyl]-amine;

{4-[3-(3-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1yl)-phenyl]-amine;

{4-[3-(4-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[3-(4-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine;

{4-[3-(4-ethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

[4-(2-diethylamino-ethoxy)-phenyl]-{4-[3-(4-ethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

[4-(2-diethylamino-ethoxy)-phenyl]-{4-[3-(4-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2yl}-amine;

[4-(2-diethylamino-ethoxy)-phenyl]-{4-[3-(3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

{4-[3-(3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine;

{4-[3-(3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

[4-(2-dimethylamino-ethoxy)-phenyl]-{4-[3-(4-ethyl-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

[4-(4-methyl-piperazin-1-yl)-phenyl]-[4-(3-m-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[4-(2-diethylamino-ethoxy)-phenyl]-[4-(3-m-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[4-(2-dimethylamino-ethoxy)-phenyl]-[4-(3-m-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(3,4-dichloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-dimethylamino-ethoxy)-phenyl]-amine;

{4-[3-(3,4-dichloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

{4-[3-(4-benzyloxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(2-dimethylamino-ethoxy)-phenyl]-amine;

4-(4-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1H-pyrazol-3-yl)-phenol;

[4-(4-methyl-piperazin-1-yl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

[4-(2-dimethylamino-ethoxy)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[3-(1-methyl-piperidin-4ylmethoxy)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-amine;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine;

4-{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-benzoic acid;

(4-{4-[3-(4-chloro-phenyl )-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-phenyl)-(4-methyl-piperazin-1-yl)-methanone;

{4-[3-(4-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amine;

{4-[3-(2,4-dichloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[3-(2,4-dichloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine;

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

,N′

-dimethyl-benzene-1,3-diamine;

{4-[3-(4-ethoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1yl)-phenyl]-amine;

{4-[3-(4-ethoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

{4-[3-(4-chloro-3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(3,4,5-trimethoxy-phenyl)-amine;

3-{4-[3-(4-chloro-3-hydroxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-benzenesulfonamide;

3-{4-[3-(4-chloro-3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino)-benzenesulfonamide;

3-{4-[3-(4-chloro-3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-benzoic acid ethyl ester;

3-{4-[3-(4-chloro-3-hydroxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-benzoic acid ester;

1-(3-{4-[3-(4-chloro-3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-phenyl)-ethanone;

benzothiazol-6-yl-{4-[3-(4-chloro-3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amine;

{4-[3-(4-chloro-3-methoxy-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-(1-oxo-benzothiazol-6-yl)-amine;

[4-(3-benzo[1,3]dioxol-5-yl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine;

3-[4-(3-benzo[1,3]dioxol-5-yl-1H-pyrazol-4-yl)-pyrimidin-2-ylamino]-benzoic acid tert-butyl ester;

3-[4-(3-benzo[1,3]dioxol-5-yl-1H-pyrazol-4-yl)-pyrimidin-2-ylamino]-benzenesulfonamide;

[4-(3-benzo[1,3]dioxol-5-yl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-(3-methylsulfanyl-phenyl)-amine; and

pharmaceutically acceptable salts thereof.

10. A compound of formula I, or a pharmaceutically acceptable salt thereof, according to claim 1 for use in a method for the treatment of the human or animal body.

11. A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, together with at least one pharmaceutically acceptable carrier.

13. A method for the treatment of a disease which responds to an inhibition of a protein tyrosine kinase comprising administering a compound of formula I according to claim 1 or a Pharmaceutically acceptable salt thereof.

14. A process for the preparation of a compound of formula I according to claim 1 or of a salt of such a compound, characterized in that

a) a compound of formula II

wherein Y is a leaving group such as halogen, —

S(═

O)—

CH₃ or —

S(O₂)—

CH₃ and R₂, R₃ and R₃′

have the meanings as defined for a compound of formula I according to claim 1, is reacted with a compound of formula III

wherein m and R₁ have the meanings as defined for a compound of formula I according to claim 1;

b) in order to prepare a compound of formula I, wherein R₁ is a radical R₅—

C(═

O)—

in which R₅ is mono- or di-substituted amino or a heterocyclic radical that is bound to the carbonyl moiety via a nitrogen ring atom, a compound of formula IV

wherein R₂, R₃ and R₃′

have the meanings as defined for a compound of formula I according to claim 1, or a reactive carboxylic acid derivative thereof, is reacted with a mono- or di-substituted amine or a heterocyclic radical containing at least one nitrogen ring atom to which a hydrogen is bound, respectively;

or

c) in order to prepare a compound of formula I, wherein R₂ is unsubstituted or substituted lower alkyl or a heterocyclic radical, a compound of formula I, wherein R₂ is hydrogen, is reacted with a compound of the formula R₂—

OH, wherein R₂ is unsubstituted or substituted lower alkyl or a heterocyclic radical wherein the substituted lower alkyl or the heterocyclic radical is attached to the hydroxy group of R₂—

OH via a carbon atom of the lower alkyl moiety or via a carbon ring atom of the heterocyclic radical, respectively;

whereby functional groups which are present in the starting compounds of processes a) to c) and are not intended to take part in the reaction, are present in protected form if necessary, and protecting groups that are present are cleaved, whereby the said starting compounds may also exist in the form of salts provided that a salt-forming group is present and a reaction in salt form is possible;

and, if so desired, a compound of formula I thus obtained is converted into another compound of formula I, a free compound of formula I is converted into a salt, an obtained salt of a compound of formula I is converted into the free compound or another salt, and/or a mixture of isomeric compounds of formula I is separated into the individual isomers.

12. (canceled)