6-(Aryl-amido or aryl-amidomethyl)-naphthalen-2-yloxy-acidic derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
申请人:Wyeth
公开号:US20030045560A1
公开(公告)日:2003-03-06
This invention provides novel compounds, pharmaceutical compositions and methods of treating thrombotic disorders in mammals, the compounds having the formula:
1
Wherein: Ar is phenyl, naphthyl, furanyl, benzofuranyl, indolyl, pyrazolyl, oxazolyl, fluorenyl, phenylcycloalkane where the cycloalkane can be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl and Ar can be optionally substituted by 1 to 3 groups selected from C
1
-C
6
alkyl, C
1
-C
6
alkoxy, hydroxy, phenyl-(CH
2
)
0-6
—, phenyl-(CH
2
)
0-6
O—, C
3
-C
6
cycloalkyl, —(CH
2
)—C
3
-C
6
cycloalkyl, halogen, C
1
-C
3
perflouroalkyl and C
1
-C
3
perfluoroalkoxy where phenyl can be substituted with from 1 to 3 groups selected from C
1
-C
6
alkyl, C
1
-C
6
alkoxy, phenyl, halogen, trifluoromethyl or trifluoromethoxy; R
1
is hydrogen, C
1
-C
6
alkyl or phenyl-(CH
2
)
1-6
— where phenyl can be substituted with C
1
-C
6
alkyl, C
1
-C
6
alkoxy, halo, trifluoromethyl or trifluoromethoxy; R
2
and R
3
are H, C
1
-C
6
alkyl, phenyl-(CH
2
)
0-3
—, halo and C
1
-C
3
perfluoroalkyl where phenyl can be substituted with C
1
-C
6
alkyl, C
1
-C
6
alkoxy, halo, trifluoromethyl or trifluoromethoxy; R
4
is —CHR
5
CO
2
H or —CH
2
-tetrazole where R
5
is H or benzyl; and n=0 or 1; or a pharmaceutically acceptable salt or ester form thereof.
这项发明提供了新颖的化合物、药物组合物和治疗哺乳动物血栓性疾病的方法,这些化合物具有以下结构式:1其中:Ar为苯基、萘基、呋喃基、苯并呋喃基、吲哚基、吡唑基、噁唑基、芴基、苯基环烷烃,其中环烷烃可以是环丙基、环丁基、环戊基或环己基,Ar可以选择性地被1至3个来自C1-C6烷基、C1-C6烷氧基、羟基、苯基-(CH2)0-6—、苯基-(CH2)0-6O—、C3-C6环烷基、—(CH2)—C3-C6环烷基、卤素、C1-C3全氟烷基和C1-C3全氟烷氧基的基团取代;R1为氢、C1-C6烷基或苯基-(CH2)1-6—,其中苯基可以被C1-C6烷基、C1-C6烷氧基、卤素、三氟甲基或三氟甲氧基取代;R2和R3为H、C1-C6烷基、苯基-(CH2)0-3—、卤素和C1-C3全氟烷基,其中苯基可以被C1-C6烷基、C1-C6烷氧基、卤素、三氟甲基或三氟甲氧基取代;R4为—CHR5CO2H或—CH2-四唑基,其中R5为H或苄基;n=0或1;或其药用可接受的盐或酯形式。