申请人:Barta E. Thomas
公开号:US20060084688A1
公开(公告)日:2006-04-20
A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. The administered enzyme inhibitor corresponds in structure to formula (I), below, or a pharmaceutically acceptable salt thereof, wherein R
1
and R
2
are both hydrido or R
1
and R
2
together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two, or three heteroatoms in the ring that are oxygen, sulfur, or nitrogen. R
3
in formula (I) is an optionally substituted aryl or optionally substituted heteroaryl radical. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.
本发明揭示了一种治疗方法,包括向患有与病理性基质金属蛋白酶活性相关的病症的宿主施用一种具有出色的抑制一种或多种基质金属蛋白酶(MMP)酶活性的芳香磺酰羟肟酸有效量,例如MMP-2、MMP-9和MMP-13,同时在至少MMP-1方面表现出显著较少的抑制作用。所施用的酶抑制剂在结构上对应于下式(I)或其药学上可接受的盐,其中R1和R2均为氢基或R1和R2与它们键合的原子形成一个5到8个成员环,该环中含有一个、两个或三个杂原子,该杂原子为氧、硫或氮。式(I)中的R3为可选的取代芳基或可选的取代杂芳基基团。本发明还揭示了具有这些选择性活性的金属蛋白酶抑制剂化合物,制造这种化合物的过程以及使用抑制剂的制药组合物。