Thiazolyl urea compounds and methods of uses

• US 20020193405A1
• Filed: 02/15/2002
• Published: 12/19/2002
• Est. Priority Date: 08/15/2000
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Santora, Vincent, Liu, Gang, Lopez, Patricia, Tegley, Christopher, Li, Aiwen, Yang, Kevin, De Morin, Frenel F., Askew, Benny C., Nomak, Rana, Laber, Ellen, Hague, Andrew
• Granted Patent: US 6,645,990 B2
• Time in Patent Office: Days
• US Class Current: 514/318
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: 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
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 : 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 453/06 : containing isoquinuclidine ring systems
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems

Abstract

Selected novel urea compounds are effective for prophylaxis and treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stoke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Claims

1. A compound of formula VI

2. A compound of claim 1 wherein R¹⁵ is selected from H, optionally substituted pyrrolidinyl, optionally substituted piperazinyl, optionally substituted piperidinyl, morpholinyl, 1,2,3,6-tetrahydro-pyridinyl, (optionally substituted pyrrolidinyl) -C₁-C₂-alkyl, (optionally substituted piperidinyl) -C₁-C₂-alkyl, (optionally substituted piperazinyl) -C₁-C₂-alkyl, morpholinyl-C₁-C₂-alkyl, C₁-C₄-alkylamino-C₁-C₄-alkyl, C₁-C₄-hydroxyalkylamino, (optionally substituted pyrrolidinyl) -C₁-C₂-alkylamino, (optionally substituted piperidinyl) -C₁-C₂-alkylamino, (optionally substituted piperazinyl) -C₁-C₂-alkylamino, morpholinyl-C₁-C₂-alkylamino, optionally substituted pyrrolidinyl-C₁-C₄-alkoxy, optionally substituted azetidinyl-C₁-C₄-alkoxy, tetrahydrofuryl-C₁-C₄-alkoxy, optionally substituted piperidinyl-C₁-C₄-alkoxy, C₁-C₄-alkylamino-C₁-C₄-alkoxy, tetrahydrofuryloxy, optionally substituted piperidinyloxy, optionally substituted phenoxy, C₁-C₄-alkylaminocarbonyl and C₁-C₄-alkylaminothiocarbonyl;

wherein R¹⁶ is selected from H, 5-6-membered nitrogen containing heterocyclylcarbonyl, C₁-C₄-alkylaminocarbonyl, C₁-C₄-alkylaminomethyl, and 5-6-membered nitrogen containing heterocyclylmethyl; and

wherein R¹⁷ is selected from halo, C₁-C₂-alkyl, optionally substituted 5-6-membered heteroarylsulfonyl-C₁-C₂-alkyl, optionally substituted phenoxy, and C₃-C₆-cycloalkyl-C₂-C₄-alkynyl; and

pharmaceutically acceptable derivatives thereof.

3. A compound of claim 2 wherein R¹⁵ is selected from H, tetrahydro-furanyloxy, l-methylpyrrolidin-2-ylmethoxy, 2-pyrrolidinylmethoxy, 3-pyrrolidinylmethoxy, 1-Boc-pyrrolidin-2-ylmethoxy, 4-piperidinylmethoxy, 1-Boc-piperidin-4-ylmethoxy, 1-Boc-piperidin-4-ylethoxy, piperidin-4-ylethoxy, 1-methyl-piperidin-4-ylmethoxy, 1-Boc-azetidin-3-ylmethoxy, 1-methyl-azetidin-3-ylmethoxy, 3-azetidinylmethoxy, l-methyl-piperidin-4-yloxy, phenyloxy, 4-(pyrrolidin-1-ylmethyl)phenoxy, dimethylaminoethoxy, 1piperidinylmethyl, 1-(piperidin-1-yl)ethyl, 3-methylpiperidin-1-ylmethyl, 1-pyrrolidinylmethyl, 2,2,6,6-tetramethylpiperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, dimethylaminomethyl, diethylaminomethyl, diethylaminothiocarbonyl, diethylaminocarbonyl, N-Boc-N-isopropylaminomethyl, isopropylaminomethyl, 2-thienylsulfonylmethyl, hydroxypropylamino, 4-ethyl-piperidin-1-yl, 4-(2-pyridyl)piperidin-1-yl, 1-methylpiperidin-4-yl, 4-(2-pyrazinyl)piperidin-1-yl, 1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl, 1,2,3,6-tetrahydro-pyridin-4-yl, and 1-Boc-1,2,3,6-tetrahydro-pyridin-4-yl;

wherein R¹⁶ is selected from H, 1-piperidinylcarbonyl, diethylaminocarbonyl, diethylaminomethyl, 1-piperidinylmethyl; and

wherein R¹⁷ is selected from chloro, bromo, methyl and cyclopropylethynyl; and

pharmaceutically acceptable derivatives thereof.

4. A compound of claim 3 wherein R¹⁷ is chloro or bromo;

and pharmaceutically acceptable derivatives thereof.

5. A compound of claim 1 wherein R¹⁵ is selected from H, optionally substituted pyrrolidinyl, optionally substituted piperazinyl, optionally substituted piperidinyl, morpholinyl, 1,2,3, 6-tetrahydro-pyridinyl, (optionally substituted pyrrolidinyl) -C₁-C₂-alkyl, (optionally substituted piperidinyl) -C₁-C₂-alkyl, (optionally substituted piperazinyl) -C₁-C₂-alkyl, morpholinyl-C₁-C₂-alkyl, (optionally substituted pyrrolidinyl) -C₁-C₂-alkylamino, (optionally substituted piperidinyl) -C₁-C₂-alkylamino, (optionally substituted piperazinyl)-C₁-C₂-alkylamino, morpholinyl-C₁-C₂-alkylamino, C₁-C₄-alkylamino-C₁-C₄-alkyl, C₁-C₄-hydroxyalkylamino, optionally substituted pyrrolidinyl-C₁-C₄-alkoxy, optionally substituted azetidinyl-C₁-C₄-alkoxy, tetrahydrofuryl-C₁-C₄-alkoxy, optionally substituted piperidinyl-C₁-C₄-alkoxy, C₁-C₄-alkylamino-C₁-C₄-alkoxy, tetrahydrofuryloxy, optionally substituted piperidinyloxy, optionally substituted phenoxy, C₁-C₄-alkylaminocarbonyl and C₁-C₄-alkylaminothiocarbonyl;

wherein R¹⁶ is selected from H, 5-6-membered nitrogen containing heterocyclylcarbonyl, C₁-C₄-alkylaminocarbonyl, C₁-C₄-alkylaminomethyl, and 5-6-membered nitrogen containing heterocyclylmethyl; and

wherein R¹⁷ is selected from C₃-C₆-cycloalkyl and phenyl optionally substituted with one or two substituents selected from halo,

C₁-C₄-alkylamino, amino, nitro, C₁-C₄-alkoxy, C₁-C₂-haloalkyl, hydroxy, C₁-C₄-alkylthio, C₁-C₄-alkylcarbonylamino, (optionally substituted phenyl)sulfonylamino, cyano, C₁-C₂-haloalkoxy, 5- or 6-membered N-containing heterocyclyl, aminosulfonyl, (6-membered N-containing heterocyclyl)sulfonyl, C₁-C₂-haloalkylcarbonylaminosulfonyl and (optionally substituted phenyl)aminosulfonyl;

and pharmaceutically acceptable derivatives thereof.

6. A compound of claim 5 wherein R¹⁵ is selected from H, tetrahydro-furanyloxy, l-methylpyrrolidin-2-ylmethoxy, 2-pyrrolidinylmethoxy, 3-pyrrolidinylmethoxy, 1-Boc-pyrrolidin-2-ylmethoxy, 4-piperidinylmethoxy, 1-Boc-piperidin-4-ylmethoxy, 1-Boc-piperidin-4-ylethoxy, piperidin-4-ylethoxy, 1-methyl-piperidin-4-ylmethoxy, 1-Boc-azetidin-3-ylmethoxy, 1-methyl-azetidin-3-ylmethoxy, 3-azetidinylmethoxy, 1-methyl-piperidin-4-yloxy, phenyloxy, 4-(pyrrolidin-1-ylmethyl)phenoxy, dimethylaminoethoxy, 1-piperidinylmethyl, 1-(piperidin-1-yl)ethyl, 3-methylpiperidin-1-ylmethyl, 1-pyrrolidinylmethyl, 2,2,6,6-tetramethylpiperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, dimethylaminomethyl, diethylaminomethyl, diethylaminothiocarbonyl, diethylaminocarbonyl, N-Boc-N-isopropylaminomethyl, isopropylaminomethyl, 2-thienylsulfonylmethyl, hydroxypropylamino, 4-ethyl-piperidin-1-yl, 4-(2-pyridyl)piperidin-1-yl, 1-methylpiperidin-4-yl, 4-(2-pyrazinyl)piperidin-1-yl, 1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl, 1,2,3,6-tetrahydro-pyridin-4-yl, and 1-Boc-1,2,3,6-tetrahydro-pyridin-4-yl;

wherein R¹⁶ is selected from H, 1-piperidinylcarbonyl, diethylaminocarbonyl, diethylaminomethyl, 1-piperidinylmethyl; and

wherein R¹⁷ is selected from cyclopropyl and phenyl optionally substituted with aminosulfonyl; and

pharmaceutically acceptable derivatives thereof.

7. A compound of claim 6 wherein R¹⁷ is unsubstituted phenyl;

and pharmaceutically acceptable derivatives thereof.

8. Compound of claim 1 wherein R¹⁵ is selected from H, optionally substituted pyrrolidinyl, optionally substituted piperazinyl, optionally substituted piperidinyl, morpholinyl, 1,2,3,6-tetrahydro-pyridinyl, (optionally substituted pyrrolidinyl)-C₁-C₂-alkyl, (optionally substituted piperidinyl)-C₁-C₂-alkyl, (optionally substituted piperazinyl)-C₁-C₂-alkyl, morpholinyl-C₁-C₂-alkyl, (optionally substituted pyrrolidinyl)-C₁-C₂-alkylamino, (optionally substituted piperidinyl)-C₁-C₂-alkylamino, (optionally substituted piperazinyl)-C₁-C₂-alkylamino, morpholinyl-C₁-C₂-alkylamino, C₁-C₄-alkylamino-C₁-C₄-alkyl, C₁-C₄-hydroxyalkylamino, optionally substituted pyrrolidinyl-C₁-C₄-alkoxy, optionally substituted azetidinyl-C₁-C₄-alkoxy, tetrahydrofuryl-C₁-C₄-alkoxy, optionally substituted piperidinyl-C₁-C₄-alkoxy, C₁-C₄-alkylamino-C₁-C₄-alkoxy, tetrahydrofuryloxy, optionally substituted piperidinyloxy, optionally substituted phenoxy, C₁-C₄-alkylaminocarbonyl and C₃-C₄-alkylaminothiocarbonyl;

wherein R¹⁶ is selected from H, 5-6-membered nitrogen containing heterocyclylcarbonyl, C₁-C₄-alkylaminocarbonyl, C₁-C₄-alkylaminomethyl, and 5-6-membered nitrogen containing heterocyclylmethyl; and

wherein R¹⁷ is selected from optionally substituted indazolyl, optionally substituted indolyl, unsubstituted 5-membered oxygen or sulfur containing heteroaryl, unsubstituted 6-membered nitrogen-containing heterocyclyl, and 6-membered nitrogen-containing heterocyclyl substituted with one or more substituents independently selected from pyridyl, phenyl,

C₁-C₄ alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy, amino, halo, piperidinyl, morpholinyl, C₁-C₂ alkylpiperazinyl, C₁-C₃ alkylaminothiocarbonyl, N,N-di-C₁-C₂-alkylamino-C₁-C₄-alkylenyl, N—

C₁-C₂-alkylamino-C₁-C₄-alkylenyl, morpholinyl-C₁-C₄-alkylenylaminocarbonyl, aminocarbonyl, C₁-C₂-haloalkylcarbonylamino, morpholinyl-C₁-C₄-alkylenylamino, N,N-di-C₁-C₂-alkylamino and N,N-di-C₁-C₂-alkylamino-C₁-C₄-alkylenylamino;

and pharmaceutically acceptable derivatives thereof.

9. Compound of claim 8 wherein R¹⁵ is selected from H, tetrahydro-furanyloxy, 1-methylpyrrolidin-2-ylmethoxy, 2-pyrrolidinylmethoxy, 3-pyrrolidinylmethoxy, 1-Boc-pyrrolidin-2-ylmethoxy, 4-piperidinylmethoxy, 1-Boc-piperidin-4-ylmethoxy, 1-Boc-piperidin-4-ylethoxy, piperidin-4-ylethoxy, 1-methyl-piperidin-4-ylmethoxy, 1-Boc-azetidin-3-ylmethoxy, 1-methyl-azetidin-3-ylmethoxy, 3-azetidinylmethoxy, 1-methyl-piperidin-4-yloxy, phenyloxy, 4-(pyrrolidin-1-ylmethyl)phenoxy, dimethylaminoethoxy, 1-piperidinylmethyl, 1-(piperidin-1-yl)ethyl, 3-methylpiperidin-1-ylmethyl, 1-pyrrolidinylmethyl, 2,2,6,6-tetramethylpiperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, dimethylaminomethyl, diethylaminomethyl, -diethylaminothiocarbonyl, diethylaminocarbonyl, N-Boc-N-isopropylaminomethyl, isopropylaminomethyl, 2-thienylsulfonylmethyl, hydroxypropylamino, 4-ethyl-piperidin-1-yl, 4-(2-pyridyl)piperidin-1-yl, 1-methylpiperidin-4-yl, 4-(2-pyrazinyl)piperidin-1-yl, 1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl, 1,2,3,6-tetrahydro-pyridin-4-yl, and 1-Boc-1,2,3,6-tetrahydro-pyridin-4-yl;

wherein R¹⁶ is selected from H, 1-piperidinylcarbonyl, diethylaminocarbonyl, diethylaminomethyl, 1-piperidinylmethyl; and

wherein R¹⁷ is selected from 5-indazolyl, l-Boc-indol-5-yl, unsubstituted thienyl, 5-tert-butyloxazol-2-yl and 4-pyridyl substituted with one or more substituents independently selected from methoxy and chloro; and

pharmaceutically acceptable derivatives thereof.

10. A compound of claim 9 wherein R¹⁷ is 4-pyridyl;

and pharmaceutically acceptable derivatives thereof.

11. Compound of claim 1 and pharmaceutically acceptable derivatives thereof selected from:

1-[6-(3-Methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[4-(Piperidine-1-carbonyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-Chloro-thiazol-4-yl)-3-[4-(piperidine-1-carbonyl)-pyridin-2-yl]-urea;

N,N-Diethyl-2-[3-(2-pyridin-4-yl-thiazol-4-yl)-ureido]-isonicotinamide;

N,N-Diethyl-2-[3-(2-phenyl-thiazol-4-yl)-ureido]-isonicotinamide;

2-[3-(2-Bromo-thiazol-4-yl)-ureido]-N,N-diethyl-isonicotinamide;

1-(4-Diethylaminomethyl-pyridin-2-yl)-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(2,6-Dimethyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Piperidin-1-yl-ethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

2-({6-[3-(2-Pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-ylamino)-methyl)-piperidine-1-carboxylic acid tert-butyl ester;

1-[6-[(Piperidin-2-ylmethyl)-amino]-pyridin-2-yl}-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

(S)-1-[6-(3-Methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

(R)-1-[6-(3-Methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-Chloro-thiazol-4-yl)-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(2-piperidin-4-yl-ethoxy)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(2-piperidin-4-yl-ethoxy)-pyridin-2-yl]-urea;

1-[6-(Azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-bromo-thiazol-4-yl)-urea;

1-[6-(Azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-chloro-thiazol-4-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(piperidin-4-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(piperidin-4-ylmethoxy)-pyridin-2-yl]-urea;

tert-Butyl 3-{6-[3-(2-pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-yloxymethyl}-pyrrolidine-1-carboxylate;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-[6-(pyrrolidin-3-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-Cyclopropyl-thiazol-4-yl)-3-[6-(2-piperidin-4-yl-ethoxy)-pyridin-2-yl]-urea;

1-[6-(Isopropylamino-methyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(Isopropylamino-methyl)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(isopropylamino-methyl)-pyridin-2-yl]-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-phenylthiazol-4-yl)-3-(6-p-pyrrolidin-1-ylmethylphenoxypyridin-2-yl)urea;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-[6-(tetrahydro-furan-3-yloxy)-pyridin-2-yl]-urea;

1-[2-(1H-Indazol-5-yl)-thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)-urea;

1-(1′

-Methyl-1′

,2′

,3′

,6′

-tetrahydro-[2,4′

]bipyridinyl-6-yl)-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-Bromo-thizol-4-yl)-3-(1′

-methyl-1′

,2′

,3′

,6′

-tetrahydro-[2,4′

]bipyridinyl-6-yl)-urea;

1-(1′

-Methyl-1′

,2′

,3′

,6′

-tetrahydro-2[2,4]bipyridinyl-6-yl)-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(3-Hydroxy-propylamino)-pyridin-2-yl]-3-(2-pyridin-4-yl-thizol-4-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6(3-hydroxy-propylamino)-pyridin-2-yl]-urea;

1-(1′

-Methyl-1′

,2′

,3′

,4′

,5′

,6′

-hexahydro-[2,4′

]bipydrinyl-6-yl)-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(1′

-Methyl-1′

,2′

,3′

,4′

,5′

,6′

-hexahydro-[2,4′

]bipyridinyl-6-yl)-3-(2-phenyl-thiazol-4-yl)-urea;

6-[3-(2-Pyridin-4-yl-thizol-4-yl)-ureido]-3′

,6′

-dihydro-2′

H-[2,4]bipyridinyl-1′

-carboxylic acid tert-butylester;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-(1′

,2′

,3′

,6′

-tetrahydro-[2,4′

]bipyridinyl-6-yl)-urea;

1-(2-Pyridin-4-yl-thizol-4-yl)-3-[6-(tetrahydro-furan-3-ylmethoxy)-pyridin-2-yl]-urea;

2-[6-[3-(2-Pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-[6-(pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

6-[3-(2-Pyridin-4-yl-thiazol-4-yl)-ureido]-pyridine-2-carbothioic acid diethylamide;

1-(2-Bromo-thiazol-4-yl)-3-[6-(3-methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(3-methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-urea;

1-(2-Phenyl-thiazol-4-yl)-3-[4-(piperidine-1-carbonyl)-pyridin-2-yl]-urea;

1-(2-Bromo-thiazol-4-yl)-3-[4-(piperidine-1-carbonyl)-pyridin-2-yl]-urea;

1-[2-(2-Methoxy-pyridin-4-yl)-thiazol-4-yl]-3-(6-phenoxy-pyridin-2-yl)-urea;

1-[2-(2-Methoxy-pyridin-4-yl)-thiazol-4-yl]-3-[6-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

1-[6-(2-Dimethylamino-ethoxy)-pyridin-2-yl]-3-[2-(2-methoxy-pyridin-4-yl)-thiazol-4-yl]-urea;

1-[6-(1-Methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-phenylthiazol-4-yl)-3-(6-pyrrolidin-1-ylmethyl-pyridin-2-yl)urea;

1-(6-Diethylaminomethylpyridin-2-yl)-3-(2-phenylthiazol-4-yl)urea;

(S)-1-[6-(1-Methylpyrrolidin-2-ylmethoxy)pyridin-2-yl]-3-(2-phenylthiazol-4-yl)urea;

1-[6-(2-Piperidin-4-yl-ethoxy)pyridin-2-yl]-3-[2-phenylthiazol-4-yl]urea;

1-[6-(4-Ethylpiperazin-1-yl)-pyridin-2-yl]-3-(2-phenylthiazol-4-yl)urea;

Diethyl 6-[3-(2-phenylthiazol-4-yl)ureido]-pyridine-2-carboxamide;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-(6-p-pyrrolidin-1-ylmethylphenoxypyridin-2-yl)urea;

1-(2-Bromothiazol-4-yl)-3-(6-p-pyrrolidin-1-ylmethylphenoxypyridin-2-yl)urea;

1-[6-(Piperidin-4-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-piperidin-4-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-piperidin-4-yloxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(Azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-(2-Phenyl-thiazol-4-yl)-3-[6-(piperidin-4-ylmethoxy)-pyridin-2-yl]-urea;

1-[6-(1-Methyl-piperidin-4-ylmethoxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-piperidin-4-yloxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(2-Piperidin-4-yl-ethoxy)-pyridin-2-yl]-3-(2-thiophen-2-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-3-[2-(thiophene-2-sulfonylmethyl)-thiazol-4-yl]-urea;

1-[2-(2-Methoxy-pyridin-4-yl)-thiazol-4-yl]-3-(6-piperdin-1-ylmethyl-pyridin-2-yl)-urea; and

[2-(2-Chloro-pyridin-4-yl)-thiazol-4-yl]-3-(6-piperdin-1-ylmethyl-pyridin-2-yl)-urea.

12. Compound of claim 1 and pharmaceutically acceptable derivatives thereof selected from:

1-[6-(3-Methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[4-(Piperidine-1-carbonyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

N,N-Diethyl-2-[3-(2-pyridin-4-yl-thiazol-4-yl)-ureido]-isonicotinamide;

1-(4-Diethylaminomethyl-pyridin-2-yl)-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(2,6-Dimethyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Piperidin-1-yl-ethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

2-({6-[3-(2-Pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-ylamino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester;

1-{6-[(Piperidin-2-ylmethyl)-amino]-pyridin-2-yl}-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

(S)-1-[6-(3-Methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

(R)-1-[6-(3-Methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-Chloro-thiazol-4-yl)-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(2-piperidin-4-yl-ethoxy)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(2-piperidin-4-yl-ethoxy)-pyridin-2-yl]-urea;

1-[6-(Azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-bromo-thiazol-4-yl)-urea;

1-[6-(Azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-chloro-thiazol-4-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(piperidin-4-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(piperidin-4-ylmethoxy)-pyridin-2-yl]-urea;

3-(4-{3-[6-(1-Methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-ureido}-thiazol-2-yl)-benzenesulfonamide;

tert-Butyl 3-{6-[3-(2-pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-yloxymethyl}-pyrrolidine-1-carboxylate;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-[6-(pyrrolidin-3-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-Cyclopropyl-thiazol-4-yl)-3-[6-(2-piperidin-4-yl-ethoxy)-pyridin-2-yl]-urea;

Isopropyl-{6-[3-(2-pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-ylmethyl}-carbamic acid tert-butyl ester;

1-[6-(Isopropylamino-methyl)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

Isopropyl-{6-[3-(2-phenyl-thiazol-4-yl)-ureido]-pyridin-2-ylmethyl}-carbamic acid tert-butyl ester;

1-[6-(Isopropylamino-methyl)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

1-(2-phenylthiazol-4-yl)-3-(6-p-pyrrolidin-1-ylmethylphenoxypyridin-2-yl)urea;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-[6-(tetrahydro-furan-3-yloxy)-pyridin-2-yl]-urea;

1-[2-(1H-Indazol-5-yl)-thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)-urea;

1-(1′

-Methyl-1′

,2′

,3′

,6′

-tetrahydro-[2,4′

]bipyridinyl-6-yl)-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-Bromo-thizol-4-yl)-3-(1′

-methyl-1′

,2′

,3′

,6′

-tetrahydro-[2,4′

]bipyridinyl-6-yl)-urea;

1-(1′

-Methyl-1′

,2′

,3′

,6′

-tetrahydro-2[2,4]bipyridinyl-6-yl)-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(3-Hydroxy-propylamino)-pyridin-2-yl]-3-(2-pyridin-4-yl-thizol-4-yl)-urea;

1-(2-Bromo-thiazol-4-yl)-3-[6(3-hydroxy-propylamino)-pyridin-2-yl]-urea;

1-(1′

-Methyl-1′

,2′

,3′

,4′

,5′

,6′

-hexahydro-[2,4′

]bipydrinyl-6-yl)-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(1′

-Methyl-1′

,2′

,3′

,4′

,5′

,6′

-hexahydro-[2,4′

]bipyridinyl-6-yl)-3-(2-phenyl-thiazol-4-yl)-urea;

6-[3-(2-Pyridin-4-yl-thizol-4-yl)-ureido]-3′

,6′

-dihydro-2′

H-[2,4]bipyridinyl-l′

-carboxylic acid tert-butylester;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-(1′

,2′

,3′

,6′

-tetrahydro-[2,4′

]bipyridinyl-6-yl)-urea;

1-(2-Pyridin-4-yl-thizol-4-yl)-3-[6-(tetrahydro-furan-3-ylmethoxy)-pyridin-2-yl]-urea;

2-[6-[3-(2-Pyridin-4-yl-thiazol-4-yl)-ureido]-pyridin-2-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-[6-(pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

6-[3-(2-Pyridin-4-yl-thiazol-4-yl)-ureido]-pyridine-2-carbothioic acid diethylamide;

1-(2-Bromo-thiazol-4-yl)-3-[6-(3-methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-urea;

1-(2-Chloro-thiazol-4-yl)-3-[6-(3-methyl-piperidin-1-ylmethyl)-pyridin-2-yl]-urea;

1-[2-(2-Methoxy-pyridin-4-yl)-thiazol-4-yl]-3-[6-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-urea;

1-[6-(2-Dimethylamino-ethoxy)-pyridin-2-yl]-3-[2-(2-methoxy-pyridin-4-yl)-thiazol-4-yl]-urea;

1-[6-(1-Methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-(2-phenylthiazol-4-yl)-3-(6-pyrrolidin-1-ylmethyl-pyridin-2-yl)urea;

1-(6-Diethylaminomethylpyridin-2-yl)-3-(2-phenylthiazol-4-yl)urea;

(S)-1-[6-(1-Methylpyrrolidin-2-ylmethoxy)pyridin-2-yl]-3-(2-phenylthiazol-4-yl)urea;

1-[6-(2-Piperidin-4-yl-ethoxy)pyridin-2-yl]-3-[2-phenylthiazol-4-yl]urea;

1-[6-(4-Ethylpiperazin-1-yl)-pyridin-2-yl]-3-(2-phenylthiazol-4-yl)urea;

1-(2-phenylthiazol-4-yl)-3-[6-(4-pyrimidin-2-yl-piperazin-1-yl)pyridin-2-yl]urea;

Diethyl 6-[3-(2-phenylthiazol-4-yl)ureido]-pyridine-2-carboxamide;

1-(2-Pyridin-4-yl-thiazol-4-yl)-3-(6-p-pyrrolidin-1-ylmethylphenoxypyridin-2-yl)urea;

1-(2-Bromothiazol-4-yl)-3-(6-p-pyrrolidin-1-ylmethylphenoxypyridin-2-yl)urea;

1-[6-(Piperidin-4-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-piperidin-4-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-piperidin-4-yloxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-pyridin-4-yl-thiazol-4-yl)-urea;

1-[6-(Azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-azetidin-3-ylmethoxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-(2-Phenyl-thiazol-4-yl)-3-[6-(piperidin-4-ylmethoxy)-pyridin-2-yl]-urea;

1-[6-(1-Methyl-piperidin-4-ylmethoxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-piperidin-4-yloxy)-pyridin-2-yl]-3-(2-phenyl-thiazol-4-yl)-urea;

1-[6-(2-Piperidin-4-yl-ethoxy)-pyridin-2-yl]-3-(2-thiophen-2-yl-thiazol-4-yl)-urea;

1-[6-(1-Methyl-pyrrolidin-2-ylmethoxy)-pyridin-2-yl]-3-[2-(thiophene-2-sulfonylmethyl)-thiazol-4-yl]-urea;

1-[2-(2-Methoxy-pyridin-4-yl)-thiazol-4-yl]-3-(6-piperdin-1-ylmethyl-pyridin-2-yl)-urea; and

[2-(2-Chloro-pyridin-4-yl)-thiazol-4-yl]-3-(6-piperdin-1-ylmethyl-pyridin-2-yl)-urea.

13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1.

14. A method of inhibiting cell proliferation which comprises administering an effective amount of a compound of claim 1.

15. A method of treating cancer which comprises administering an effective amount of a compound of claim 1.

16. A method of inhibiting a serine/threonine kinase which comprises administering an effective amount of a compound of claim 1.

17. A method of treating a neurological disorder which comprises administering an effective amount of a compound of claim 1.