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    • 6. 发明授权
    • Aniline-derived ligands for the thyroid receptor
    • 苯胺衍生的甲状腺受体配体
    • US06800605B1
    • 2004-10-05
    • US09761050
    • 2001-01-16
    • Todd J. FriendsDenis E. RyonoMinsheng Zhang
    • Todd J. FriendsDenis E. RyonoMinsheng Zhang
    • C07C3700
    • C07C233/27A61K31/167A61K45/06C07C233/25A61K2300/00
    • New thyroid receptor ligands are provided which have the general formula in which: X is —O—, —S—, —CH2—, —CO—, or —NH—; Y is —(CH2)n— where n is an integer from 1 to 5, or cis- or trans-ethylene; R1 is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 6 carbons, at least one of R2 and R3 being other than hydrogen; R4 is hydrogen or lower alkyl; R5 is hydrogen or lower alkyl; R6 is carboxylic acid, or esters or prodrugs; R7 is hydrogen or an alkanoyl or an aroyl. In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a T3 regulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders.
    • 提供了新的甲状腺受体配体,其具有以下通式:X是-O-,-S-,-CH 2 - , - CO-或-NH-; Y是 - (CH 2)n - ,其中n是 1至5,或顺式或反式 - 亚乙基; R 1为卤素,三氟甲基,或1至6个碳原子的烷基或3至7个碳的环烷基; R 2和R 3相同或不同,为氢,卤素, 至4个碳或3至6个碳的环烷基,R2和R3中的至少一个不是氢; R4是氢或低级烷基; R5是氢或低级烷基; R6是羧酸或酯或前药; R7是氢 或烷酰基或芳酰基。此外,提供了用于预防,抑制或治疗与代谢功能障碍相关的疾病或取决于T3调节基因的表达的方法,其中如上所述的化合物以治疗 有效量。 与代谢功能障碍相关或依赖于T3调节基因的表达的这种疾病的实例包括肥胖症,高胆固醇血症,动脉粥样硬化,心律失常,抑郁症,骨质疏松症,甲状腺功能减退,甲状腺癌,青光眼,充血性心力衰竭和皮肤病 。