更新于：2024-11-01

Etiprednol dicloacetate

更新于：2024-11-01

概要

研发状态

概要

基本信息

药物类型

小分子化药

别名

Cronaze、Ethinase、Etiprednol

+ [3]

靶点

作用机制

GR激动剂(糖皮质激素受体激动剂)

治疗领域

免疫系统疾病消化系统疾病呼吸系统疾病+ [2]

在研适应症-

非在研适应症

哮喘溃疡性结肠炎克罗恩病+ [1]

原研机构

IVAX LLC

在研机构-

非在研机构

IVAX LLC

Teva Pharmaceutical Industries Ltd.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C24H30Cl2O6

InChIKeyQAIOVDNCIZSSSF-RFAJLIJZSA-N

CAS号199331-40-3

关联

项与 Etiprednol dicloacetate 相关的临床试验

NCT00035503 / Completed临床2期

Multicenter Trial For Patients With Acute Crohn's Disease

The purpose of this study is to see if etiprednol dicloacetate is safe and effective for the treatment of acute Crohn's disease.

开始日期2002-01-31

申办/合作机构

Teva Branded Pharmaceutical Products R&D, Inc.

100 项与 Etiprednol dicloacetate 相关的临床结果

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100 项与 Etiprednol dicloacetate 相关的转化医学

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100 项与 Etiprednol dicloacetate 相关的专利（医药）

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项与 Etiprednol dicloacetate 相关的文献（医药）

2017-11-10·Journal of Pharmacy and Pharmacology3区 · 医学

Potent analogues of etiprednol dicloacetate, a second generation of soft corticosteroids*

3区 · 医学

Article

作者: Bodor, Erik ; Kurucz, István ; Zubovics, Zoltán ; Bodor, Nicholas ; Sólyom, Sandor

AbstractObjectivesLoteprednol etabonate (LE) is the first, highly successful soft corticosteroid (SC) designed using the ‘inactive metabolite’ approach, starting with ∆1-cortienic acid (d-CA). The next generation of SCs based on d-CA was etiprednol dicloacetate (ED). The 17α-dichloroacetyl function serves both as a unique pharmacophore and as the source of the molecule's softness. Highly potent SCs were designed based on a combination of ED and LE, introducing 6, 9 and 16 substituents in the molecule.MethodsThe new 6α, 9α, 16α and β 17α-dichloroacetyl 17β-esters were synthesized from the correspondingly substituted ∆1-cortienic acids. The anti-inflammatory activity was assessed using LPS-induced TNF α-release under various conditions to determine intrinsic activity vs. systemic biological stability. In vivo anti-inflammatory activity was studied in the widely used ovalbumin-sensitized and ovalbumin-challenged Brown Norway rat model.Key findingsThe 6α or 9α-fluoro substitution produced highly potent corticosteroids, but the 17α-dichloroacetyl substituent provided ‘softness’ in all cases. Local application of these steroids will significantly reduce systemic activity, due to the facile hydrolytic deactivation of these molecules.ConclusionsA 17α-dichloroacetyl derivative of fluticasone (FLU) is highly potent but much safer than the currently used propionate or furoate ester.

2017-03-01·Biochemical Pharmacology2区 · 医学

Identification of esterase involved in the metabolism of two corticosteroid soft drugs

2区 · 医学

Article

作者: Samir, Ahmed ; Bodor, Nicholas ; Imai, Teruko

The soft drug approach is successful in obtaining high local therapeutic efficacy without systemic adverse effects, because soft drugs are designed to be bioconverted to inactive form by hydrolytic enzymes in systemic circulation. However, there is little information about the exact nature of these metabolic enzymes. In this study, the human enzymes for biotransformation of soft drugs were investigated. Loteprednol etabonate (LE) and etiprednol dicloacetate (ED) were designed from Δ¹-cortienic acid (Δ¹-CA), the inactive metabolite of prednisolone, by introducing two labile ester bonds to restore the corticosteroidal activity. We found that LE and ED were mainly deactivated in human plasma rather than the liver. Inactive monoesters were produced, but the second hydrolysis to Δ¹-CA was much slower. ED was hydrolyzed 10 times faster than LE in plasma (t_1/2=1.35±0.08, 12.07±0.52h respectively). Paraoxonase 1 that attached with high density lipoprotein (HDL) was found to be the major hydrolase for LE and ED in human plasma as demonstrated by enzyme inhibition and stimulation experiments and the hydrolysis in lipoproteins-rich plasma fractions. Human serum albumin (HSA) showed slight hydrolase activity against ED but not LE. LE was slowly hydrolyzed in liver (clearance: 0.21±0.04 and 2.41±0.13ml/h/kg in liver and plasma, respectively) but ED wasn't hydrolyzed at all, so LE has superior metabolism in two sites. The difficult diffusion of HDL into tissues from blood suggests the stable presence of LE at the administration site, while ED might be deactivated by its relatively rapid chemical hydrolysis and hydrolase activity of HSA, in the interstitial fluid of the administration tissue. Moreover, deactivation in plasma and strong protein binding (around 98%) minimize the adverse effects of LE and ED in the systemic circulation.

2006-09-01·Current Pharmaceutical Design4区 · 医学

Corticosteroid Design for the Treatment of Asthma: Structural Insights and the Therapeutic Potential of Soft Corticosteroids

4区 · 医学

Review

作者: Nicholas Bodor ; Peter Buchwald

Inhaled and intranasal corticosteroids (ICSs) still are the most effective treatment available for allergic airway diseases and are likely to remain the cornerstone of managing persistent asthma/allergic rhinitis in the foreseeable future. Even if the therapeutic index of this class increased significantly with the introduction of newer corticosteroids, and even if new therapeutic potentials are beginning to emerge with our increasing understanding of the mechanisms of asthma, chronic obstructive pulmonary disease, and rhinitis, corticosteroid development still remains a very important field for drug designers. After a brief review of issues related to the structure-activity relationships of glucocorticoids and the main determinants of their receptor-binding affinity at the glucocorticoid receptor, the main focus of the present article will be on the development of soft corticosteroids, as they are particularly well suited to separate local activity from systemic side effects, which still is an important issue for ICSs. Design consideration required in the search for safe and effective soft drugs on one hand, and safe and effective ICSs on the other hand, will be briefly discussed and illustrated with a number of cases, in particular, with that of loteprednol etabonate and etiprednol dicloacetate, soft corticosteroids that are being developed for a full spectrum of therapeutic applications including asthma and allergic rhinitis.

100 项与 Etiprednol dicloacetate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04100	-	-	DB05442

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床2期	美国	IVAX LLC	-
溃疡性结肠炎	临床2期	美国	IVAX LLC	-
克罗恩病	临床2期	美国	IVAX LLC	-
过敏性鼻炎	临床前	美国	IVAX LLC	-
克罗恩病	药物发现	美国	IVAX LLC	-