申请人:Luke P. George
公开号:US20070208048A1
公开(公告)日:2007-09-06
The invention provides Aryl substituted imidazoles, pyrazoles, pyridizines and related compounds of the Formula
where the ring system represented by
is a 5 membered heteroaryl ring system, in which x is 0, A is chosen from carbon and heteroatoms nitrogen, oxygen, and sulfur, and E and G are independently carbon or nitrogen provided that the 5 membered heteroaryl ring system does not contain more than 3 heteroatoms or more than 1 oxygen or sulfur atom, or a 6 membered heteroaryl ring system, in which x is 1, A, B, E, and G are independently chosen from carbon and nitrogen, provided that the 6 membered heteroaryl ring system does not contain more than 3 nitrogen atoms. The remaining variables, Ar
1
, Ar
2
, R, R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, y and z are defined herein
Such compounds are ligands of C5a receptors. Preferred compounds of the invention act bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of inflammatory and immune system disorders.
本发明提供了Aryl取代的咪唑、吡唑、吡啶并相关化合物的公式,其中由环系表示的是一个5元杂环芳基环系,其中x为0,A选择自碳和杂原子氮、氧和硫,而E和G独立地为碳或氮,但5元杂环芳基环系不含有超过3个杂原子或超过1个氧或硫原子,或者是一个6元杂环芳基环系,其中x为1,A、B、E和G独立地选择自碳和氮,但6元杂环芳基环系不含有超过3个氮原子。其余变量Ar1、Ar2、R、R1、R2、R3、R4、R5、R6、y和z在此定义。这些化合物是C5a受体的配体。本发明的优选化合物具有高亲和力结合到C5a受体,并在C5a受体上表现出中性拮抗剂或反向激动剂活性。本发明还涉及包含这种化合物的制药组合物。它还涉及使用这些化合物治疗各种炎症和免疫系统疾病。