Thiazole, imidazole and oxazole compounds and treatments of disorders associated with protein aging
申请人:ALTEON, INC.
公开号:EP1785134A2
公开(公告)日:2007-05-16
Use of a compound of formula I or IA below in the manufacture of a medicament for use in treating (i) diabetes, treating or ameliorating (ii) adverse sequelae of diabetes, (iii) kidney damage, (iv) damage to blood vasculature, atherosclerosis, peripheral vascular disease, coronary heart disease or heart failure, (v) hypertension, (vi) retinopathy, (vii) peripheral neuropathy, (viii) cataracts, (ix) osteoarthritis, (x) rheumatoid arthritis, (xi) Alzheimer's disease, (xii) damage to a tissue caused by contact with elevated levels of reducing sugars or (xiii) stroke, (xiv) improving the elasticity or reducing wrinkles of the skin of an animal or (xv) increasing RBC deformability:
wherein:
a. J is oxygen, sulfur or N-Rd,
b. the bond between carbons 4 and 5 is a single bond or a double bond;
c. Ra and Rb are:
1. independently selected from alkyl and cycloalkyl; or
2. together with their ring carbons form a C5-C7 fused cycloalkyl ring having up to two double bonds including a fused double bond of the containing group, which cycloalkyl ring can be substituted by one or more of alkyl and fluoro;
d. Rc is alkyl; and
e. Rd is alkyl or hydrogen;
or a pharmaceutically acceptable salt of said compound.
以下式 I 或 IA 的化合物在制造用于治疗以下疾病的药物中的用途:(i) 糖尿病,治疗或改善(ii) 糖尿病的不良后遗症,(iii) 肾损伤,(iv) 血管损伤、动脉粥样硬化、外周血管疾病、冠心病或心力衰竭,(v) 高血压,(vi) 视网膜病变,(vii) 周围神经病变,(viii) 白内障,(ix) 骨关节炎,(x) 类风湿性关节炎,(xi) 阿尔茨海默病、(vii) 周围神经病变,(viii) 白内障,(ix) 骨关节炎,(x) 类风湿性关节炎,(xi) 阿尔茨海默病,(xii) 因接触还原糖水平升高而造成的组织损伤,或 (xiii) 中风,(xiv) 改善动物皮肤的弹性或减少皱纹,或 (xv) 增加红细胞变形能力:
其中
a.J 是氧、硫或 N-Rd、
b. 碳原子 4 和 5 之间的键是单键或双键;
c.Ra 和 Rb
1. 独立选自烷基和环烷基;或
2. 与它们的环碳一起形成一个 C5-C7 融合环烷基环,该环烷基环最多有两个双键,包括一个含基的融合双键,该环烷基环可被一个或多个烷基和氟取代;
d.Rc 是烷基
e.Rd 是烷基或氢;
或所述化合物的药学上可接受的盐。