JP-2(JP-2) - 药物靶点：JAK1 x JAK2_专利_临床

概要

基本信息

药物类型

蛋白水解靶向嵌合体（PROTAC）

别名-

靶点

JAK1 x JAK2

作用机制

JAK1抑制剂(酪氨酸蛋白激酶JAK1抑制剂)、JAK2抑制剂(酪氨酸蛋白激酶JAK2抑制剂)

治疗领域-

在研适应症-

非在研适应症-

原研机构

GSK Plc

在研机构

GSK Plc

University of Strathclyde

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/序列

分子式C51H68ClF2N11O4

InChIKeyYHXPOJGWUNGCCI-PUNCXHJESA-N

CAS号-

关联

100 项与 JP-2 相关的临床结果

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100 项与 JP-2 相关的转化医学

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100 项与 JP-2 相关的专利（医药）

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1

项与 JP-2 相关的文献（医药）

2013-01-01·Bioorganic & Medicinal Chemistry3区 · 医学

A novel, potent, and orally active VLA-4 antagonist with good aqueous solubility: trans-4-[1-[[2-(5-Fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl]acetyl]-(5S)-[methoxy(methyl)amino]methyl-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid

3区 · 医学

Article

作者: Fumihito Muro ; Nobuo Machinaga ; Tohru Takashi ; Atsushi Nakayama ; Misato Aonuma ; Masaki Setoguchi ; Yutaka Iigo ; Jun Chiba ; Gensuke Takayama ; Yoshiyuki Yoneda ; Shin Iimura ; Toshiyuki Watanabe ; Mika Yokoyama ; Yuuichi Sugimoto ; Tomoe Taira

We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F=54%) in monkeys.

100 项与 JP-2 相关的药物交易

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