US 6,645,990 B2Granted

Thiazolyl urea compounds and methods of uses

AssigneeAmgen Inc.

InventorsBenny C. Askew, Frenel F. De Morin, Andrew Hague, Ellen Laber, Aiwen Li, Gang Liu, Patricia Lopez, Rana Nomak, Vincent Santora, Christopher Tegley, Kevin Yang

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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.

Claims18

Dependent claims

A compound of formula VI

wherein R15 is one or more substituents selected from H, optionally substituted 6-membered nitrogen-containing heterocyclyl, phenyl, C1-C3-alkyl, C1-C2-haloalkyl, C1-C4-hydroxyalkyl, amino, C1-C4-azidoalkyl, C1-C4-cyanoalkyl, C1-C4-aminoalkyl, halo, hydroxy, (optionally substituted 6-membered nitrogen-containingheterocyclyl)-C1-C4-alkyl, optionally substituted phenoxy-C1-C2-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, C1-C4-hydroxyalkylamino, amino-C1-C4-alkoxy-C1-C4-alkyl, optionally substituted 6-membered nitrogen-containing heterocyclyloxy, optionally substituted 6-membered nitrogen-containing heterocyclyl-C1-C4-alkoxy, C1-C4-alkylamino-C1-C4-alkoxy, optionally substituted phenoxy, C1-C4-alkoxycarbonyl, 6-membered heterocyclyl-C1-C4-alkylaminocarbonyl, 6-membered N-containing heterocyclylcarbonyl, C1-C4-alkylaminocarbonyl, C1-C4-alkylaminothiocarbonyl, C1-C4-alkylamino-C1-C4-alkylaminocarbonyl, aminocarbonyl, 6-membered N-containing heterocyclyl-sulfonyl-C1-C4-alkyl, 6-membered N-containing heterocyclyl-C1-C4-alkylamino, C1-C4-alkylamino, C1-C4-alkylamino-C1-C4-alkylamino-C1-C4-alkyl, and C1-C4-alkylamino-C1-C4-alkylamino;
wherein R16 is selected from H, 6-membered nitrogen-containingheterocyclylcarbonyl, alkylaminocarbonyl, alkylaminomethyl, and 6-membered nitrogen-containing heterocyclylmethyl;
and
wherein R17 is selected from halo, C1-C6-alkyl, cycloalkylalkynyl, cycloalkyl, optionally substituted phenoxy, optionally substituted 6-membered nitrogen-containing heteroarylsulfonyl-C1-C4-alkyl, unsubstituted 6-membered nitrogen-containing heterocyclyl, 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 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-C2alkylamino-C1-C4-alkylenyl, N—C1-C2alkylamino-C1-C4-alkylenyl, morpholinyl-C1-C4-alkylenylaminocarbonyl, aminocarbonyl, C1-C2-haloalkylcarbonylamino, morpholinyl-C1-C4-alkylenylamino, N,N-di-C1-C2alkylamino and N,N-di-C1-C2alkylamino-C1-C4-alkylenylamino;
and pharmaceutically acceptable salts thereof;
provided only one of R15 and R16 is H.

5 more elements

A compound of Formula II

wherein X1 is CR1;
wherein X2 is CR1;
wherein X3 is CH;
wherein R1 is one or more substituents selected from H, optionally substituted piperidinyl, pyridyl, phenyl, C1-C6-alkyl, C1-C2-haloalkyl, C1-C4-hydroxyalkyl, amino, C1-C4-azidoalkyl, C1-C4-cyanoalkyl, C1-C4-aminoalkyl, halo, hydroxy, (optionally substituted piperidinyl)-C1-C2-alkyl, optionally substituted phenoxy-C1-C2-alkyl, C1-C4-alkylaminothiocarbonyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, C1-C4-hydroxyalkylamino-C1-C4-alkyl, amino-C1-C4-alkoxy-C1-C4-alkyl, optionally substituted piperidinyl-C1-C4-alkoxy, C1-C4-alkylamino-C1-C4-alkoxy, optionally substituted pyridyloxy, optionally substituted phenoxy, C1-C4-alkoxycarbonyl, (6-membered N-containing heterocyclyl)-C1-C4-alkylaminocarbonyl, (6-membered N-containing heterocyclyl)carbonyl, C1-C4-alkylaminocarbonyl, C1-C4-alkylamino-C1-C4-alkylaminocarbonyl, aminocarbonyl, (6-membered N-containing heterocyclyl)-C1-C4-alkylamino, C1-C4-alkylamino, C1-C4-alkylamino-C1-C4-alkylamino-C1-C4-alkyl, and C1-C4-alkylamino-C1-C4-alkylamino;
wherein R2 is selected from halo, C1-C4-alkyl, C1-C4-alkylamino-C2-C4-alkynyl, C3-C6-cycloalkyl, optionally substituted benzodioxolyl, optionally substituted phenoxy, unsubstituted 6-membered nitrogen-containing heterocyclyl, 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
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-C2alkylamino-C1-C4-alkylenyl, N—C1-C2alkylamino-C1-C4-alkylenyl, morpholinyl-C1-C4-alkylenylaminocarbonyl, aminocarbonyl, C1-C2-haloalkylcarbonylamino, morpholinyl-C1-C4-alkylenylamino, N,N-di-C1-C2alkylamino and N,N-di-C1-C2alkylamino-C1-C4-alkylenylamino;
and
wherein Y2 is NH;
and pharmaceutically acceptable salts thereof.

8 more elements

A compound of Formula V

wherein R7 is selected from halo, C1-C4-alkyl, C3-C6-cycloalkyl, optionally substituted benzodioxolyl, optionally substituted phenoxy, 6-membered nitrogen-containing heterocyclyl, phenyl optionally substituted with one or two substituents selected from
halo, C1-C4-alkylamino, amino, C1-C4-alkoxy, C1-C2-haloalkyl, hydroxy, C1-C4-alkylthio, cyano, C1-C2-haloalkyloxy, aminosulfonyl, (6-membered N-containing heterocyclyl)sulfonyl, C1-C2-haloalkylcarbonylaminosulfonyl, and (optionally substituted phenyl)aminosulfonyl, 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, 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, morpholinyl-C1-C4-alkylenylamino, N,N-di-C1-C2alkylamino and N,N-di-C1-C2alkylamino-C1-C4-alkylenylamino;
wherein R8 is optionally substituted with one or two substituents independently selected from H, optionally substituted piperidinyl, pyridyl, phenyl, C1-C6-alkyl, C1-C2-haloalkyl, C1-C4-hydroxyalkyl, amino, C1-C4-azidoalkyl, C1-C4-cyanoalkyl, C1-C4-aminoalkyl, halo, hydroxy, (optionally substituted piperidinyl)-C1-C2-alkyl, optionally substituted phenoxy-C1-C2-alkyl, C1-C4-alkylaminothiocarbonyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, C1-C4-hydroxyalkylamino-C1-C4-alkyl, amino-C1-C4-alkoxy-C1-C4-alkyl, optionally substituted piperidinyl-C1-C4-alkoxy, C1-C4-alkylamino-C1-C4-alkoxy, optionally substituted pyridyloxy, optionally substituted phenoxy, C1-C4-alkoxycarbonyl, (6-membered N-containing heterocyclyl)-C1-C4-alkylaminocarbonyl, (6-membered N-containing heterocyclyl)carbonyl, C1-C4-alkylaniinocarbonyl, C1-C4-alkylamino-C1-C4-alkylaminocarbonyl, aminocarbonyl, (6-membered N-containing heterocyclyl)-C1-C4-alkylamino, C1-C4-alkylamino, C1-C4-alkylamino-C1-C4-alkylamino-C1-C4-alkyl, and C1-C4-alkylamino-C1-C4-alkylamino;
and pharmaceutically acceptable salts thereof.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/077,124Filed 15 Feb 2002 · continuation in part
Priority: 15 Aug 2000
Published: US 2002/0173507 A119 Dec 2002
Granted: 11 Nov 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification31 codes

C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 7/00
Drugs for disorders of the blood or the extracellular fluid

Family

Application60/225,793Us provisional application · filed 15 Aug 2000
Application09/930,753Parent of this continuation-in-part · filed 14 Aug 2001
US 2002/0193405 A1Pre-grant publication · published 19 Dec 2002
US 2002/0173507 A1Published application
US 6,645,990 B2This patent

From the US filing history. Foreign family members aren’t listed.