US 7,598,244 B2
[1,2,4]triazolo[1,5,a]pyrimidin-2-ylurea derivative and use thereof
Akira Masuda, Saitama (Japan); Yoshitaka Satoh, Yoshikawa (Japan); Yuji Akiyama, Saitama (Japan); Kan Saiga, Tokyo (Japan); and Eriko Toyoda, Kawasaki (Japan)
Assigned to Nippon Kayaku Kabushiki Kaisha, Tokyo (Japan)
Appl. No. 10/559,198
PCT Filed Jun. 02, 2004, PCT No. PCT/JP2004/007623
§ 371(c)(1), (2), (4) Date Jan. 30, 2006,
PCT Pub. No. WO2004/108729, PCT Pub. Date Dec. 16, 2004.
Claims priority of application No. 2003-157663 (JP), filed on Jun. 03, 2003.
Prior Publication US 2007/0010515 A1, Jan. 11, 2007
Int. Cl. A61K 31/535 (2006.01); A61K 31/497 (2006.01); A01N 43/90 (2006.01); A61K 31/519 (2006.01); C07D 413/00 (2006.01); C07D 487/00 (2006.01)
U.S. Cl. 514—234.5  [514/252.16; 514/259.31; 544/114; 544/262] 5 Claims
 
1. A compound of formula (1), or a pharmacologically acceptable salt thereof:

OG Complex Work Unit Drawing
wherein Ar represents a phenyl group, which may have 1 to 4 identical or different substituents selected from the group consisting of a fluoro group, chloro group, hydroxyl group, methyl group, methoxy group, ethoxy group, isopropoxy group, isobutoxy group, benzyloxy group, methoxymethoxy group, 2-methoxyethoxy group, 2-methoxyethoxymethoxy group, 2-(2-methoxyethoxy)ethoxy group, 2-[2-(2-methoxyethoxy)ethoxy]ethoxy group, tetrahydrofuran-2-ylmethoxy group, tetrahydropyran-4-ylmethoxy group, 2-[1,3]dioxan-2-ylethoxy group, 2-dimethylaminoethoxy group, 3-dimethylaminopropoxy group, 2-diethylaminoethoxy group, 2-morpholin-4-yl-2-oxoethoxy group, 2-piperidin-1-ylethoxy group, 3-piperidin-1-ylpropoxy group, 2-morpholin-4-ylethoxy group, 3-morpholin-4-ylpropoxy group, pyridin-2-ylmethoxy group, pyridin-3-ylmethoxy group, pyridin-4-ylmethoxy group, amino group, dimethylamino group, diethylamino group, and methylenedioxy group; a 2,3-dihydrobenzofuran-5-yl group, or a thiophen-2-yl group; X represents O; and R represents a hydrogen atom or a group represented by any one of the following formulas (2) to (6):

OG Complex Work Unit Drawing
wherein R4 represents a hydrogen atom, a methyl group, an ethyl group, or an isopropyl group;
R5 represents a hydrogen atom or a methyl group; and
R6 represents a hydrogen atom, a methoxybutenyl group, or a (C1-C6) alkyl group, which may have 1 to 2 identical or different substituents selected from the group consisting of a cyclopentyl group, a cyclohexyl group, a morpholin-4-yl group, a hydroxyl group, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an isobutoxy group, a tert-butoxy group, an acetyl group, a propionyl group, a phenyl group, a halogenophenyl group, a pyridyl group, an imidazolyl group, a (C1-C6) alkyloxycarbonyl group, a phenylaminocarbonyl group, a tetrahydrofurfurylaminocarbonyl group, a morpholin-4-ylcarbonyl group, a 2-methyl[1,3]dioxolan-2-yl group, and a di(C1-C6)alkylamino group, which may be substituted with 1 to 2 identical or different substituents selected from a (C1-C6)alkyl group, a (C1-C6)acyl group, a (C1-C6)acyloxy(C1-C6)acyl group, and a (C1-C6)alkoxycarbonyl group,

OG Complex Work Unit Drawing
wherein R7 represents a hydrogen atom, a methyl group, or an ethyl group;
R8 represents a tetrahydrofuran-2-yl group or a tetrahydropyran-4-yl group; and
the sum of p and q is an integer of 4 or less,

OG Complex Work Unit Drawing
wherein R9 represents a hydrogen atom, a methyl group, or an ethyl group; and
R10 represents a phenyl group having 1 to 4 substituents selected from the group consisting of a hydroxy group, a (C1-C6)alkoxy group, a halogeno group, a (C1-C6)alkoxycarbonyl group, a nitro group, a methylenedioxy group, a benzyloxycarbonyloxy group, and a methanesulfonyloxy group; a naphthyl group, or a pyridyl group,

OG Complex Work Unit Drawing
wherein Cy represents a phenyl group, a cyclopentyl group, a cyclohexyl group, an adamantyl group, a 1,2,3,4-tetrahydronaphthalen-1-yl group, or a piperadinyl group, which may be substituted with 1 to 4 identical or different groups selected from the group consisting of a hydroxyl group, a carboxyl group, a benzyl group, a (C1-C7)-acyl group, a (C1-C6)-alkoxycarbonyl group, an N—(C1-C6)-alkylcarbamoyl group, an N,N-di(C1-C6)alkylcarbamoyl group, and

OG Complex Work Unit Drawing
wherein Y represents a single bond;
R11 represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group, or an isopropyl group; and
R12 represents a hydroxyl group, a (C1-C6) alkoxyl group, an amino group, a (C1-C6) alkylamino group, which may be substituted with 1 to 2 identical or different substituents selected from the group consisting of a(C1-C6)alkoxyl group, a (C1-C6)alkoxycarbonyl group, a phenyl group, a pyridyl group, an amino group represented by the formula NR13R14 (wherein each of R13 and R14 independently represents a hydrogen atom or a (C1-C6)alkyl group), a piperidin-1-yl group, a morpholin-4-yl group, and a piperazinyl group which may be substituted with a (C1-C6) alkyl group, a di(C1-C6) alkylamino group, which may be substituted with 1 to 2 identical or different substituents selected from said substituent group [C], a cyclohexylmethylamino group, a phenylamino group, a tetrahydrofurfurylamino group, a piperidin-1-yl group, a morpholin-4-yl group, or a piperazinyl group which may be substituted with a (C1-C6)alkyl group.