Benziodarone(Benziodarone) - 药物靶点：TTR_在研适应症：家族性淀粉样变性_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

TTR

作用机制

TTR调节剂(转甲状腺素蛋白调节剂)

治疗领域

遗传病与畸形内分泌与代谢疾病其他疾病

在研适应症

家族性淀粉样变性

非在研适应症-

原研机构

University of Toyama

在研机构

University of Toyama

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C17H12I2O3

InChIKeyCZCHIEJNWPNBDE-UHFFFAOYSA-N

CAS号68-90-6

关联

100 项与 Benziodarone 相关的临床结果

登录后查看更多信息

100 项与 Benziodarone 相关的转化医学

登录后查看更多信息

100 项与 Benziodarone 相关的专利（医药）

登录后查看更多信息

1

项与 Benziodarone 相关的文献（医药）

2024-05-09·Journal of Medicinal Chemistry

Development of Benziodarone Analogues with Enhanced Potency for Selective Binding to Transthyretin in Human Plasma

Article

作者: Mizuguchi, Mineyuki ; Nakagawa, Yusuke ; Toyooka, Naoki ; Ando, Yukio ; Takahashi, Kanoko ; Yamakawa, Shiori ; Kanamitsu, Kayoko ; Okada, Takuya ; Fujii, Kanako ; Yokoyama, Takeshi ; Nakagawa, Shinsaku ; Luan, Nguyen Ngoc Thanh ; Nabeshima, Yuko ; Ueda, Mitsuharu

Transthyretin amyloidosis is a fatal disorder caused by transthyretin amyloid aggregation. Stabilizing the native structure of transthyretin is an effective approach to inhibit amyloid aggregation. To develop kinetic stabilizers of transthyretin, it is crucial to explore compounds that selectively bind to transthyretin in plasma. Our recent findings demonstrated that the uricosuric agent benziodarone selectively binds to transthyretin in plasma. Here, we report the development of benziodarone analogues with enhanced potency for selective binding to transthyretin in plasma compared to benziodarone. These analogues featured substituents of chlorine, bromine, iodine, a methyl group, or a trifluoromethyl group, at the 4-position of the benzofuran ring. X-ray crystal structure analysis revealed that CH···O hydrogen bonds and a halogen bond are important for the binding of the compounds to the thyroxine-binding sites. The bioavailability of benziodarone analogues with 4-Br, 4-Cl, or 4-CH₃ was comparable to that of tafamidis, a current therapeutic agent for transthyretin amyloidosis.

100 项与 Benziodarone 相关的药物交易

登录后查看更多信息