118564-89-9

Usage

Uses

Used in Pharmaceutical Industry:
2-(1-HYDROXYLAMINOETHYL)-BENZOTHIOPHENE is used as a reagent for the preparation of Zileuton, an anti-asthmatic drug. It plays a significant role in the synthesis process, enabling the development of medications that help manage asthma symptoms and improve the quality of life for those affected by the condition.

Upstream product

• 147396-07-4 2-acetylbenzothiophene oxime 
• 1013036-71-9 1-[N-(tert-butoxycarbonyl)-N-(hydroxy)amino]-1-(benzothien-2-yl)ethane 
• 118564-88-8 2-[1-(hydroxyimino)ethyl]-benzo[b]thiophene 
• 1206596-72-6 O-(trimethylsilyl)-N-(1-benzo[b]thien-2-yl-ethyl)hydroxylamine 
• 22720-75-8 2-acetyl benzo[b]thiophene 
• 136386-26-0 C₇H₁₃NO₂ 
• 95-15-8 Benzo[b]thiophene 

Downstream Products

• 142606-21-1 zileuton 

Relevant academic research and scientific papers

Iridium-Catalyzed Acid-Assisted Hydrogenation of Oximes to Hydroxylamines

We found that cyclometalated cyclopentadienyl iridium(III) complexes are uniquely efficient catalysts in homogeneous hydrogenation of oximes to hydroxylamine products. A stable iridium C,N-chelation is crucial, with alkoxy-substituted aryl ketimine ligand

IMPROVED PROCESS FOR THE PREPARATION OF (±)-1-(1-BENZO[B]THIEN-2-YLETHYL)-1-HYDROXYUREA

The present invention relates to an improved process for the preparation of (±)-1-(I -Benzo[b]thien-2-ylethyl)-1-hydroxyurea compound of formula 1.

PROCESS FOR THE PREPARATION OF ZILEUTON

Process for preparing a compound of formula (I), or a salt thereof, comprising reacting of a compound of formula (II) wherein X and R are as herein defined; with a compound of formula (III) [in-line-formulae]NH2OZ??(III)[/in-line-formulae] wherein Z is a hydroxy protecting group, in presence of a catalyst, to obtain a compound of formula (IV), or a salt thereof, removing the hydroxyl protecting group to obtain a compound of formula (V), or a salt thereof; converting a compound of formula (V), or a salt thereof, into a compound of formula (I), or a salt thereof; and, if desired, converting a compound of formula (I) into a salt thereof, or vice versa.

Reactions of in situ generated N-Boc nitrones with aromatic and heteroaromatic Grignard reagents: Application to the synthesis of zileuton

(Chemical Equation Presented) A new class of α-aromatic-N- hydroxylamines has been prepared by reaction of tert-butyl (phenylsulfonyl) alkyl-N-hydroxycarbamates with aromatic and heteroaromatic Grignard reagents. Reactions proceed via a base-assisted elimination of the phenylsulfonyl group leading to N-Boc nitrones. This methodology has been applied to the synthesis of zileuton.

Structure-activity relationships of N-hydroxyurea 5-lipoxygenase inhibitors

The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure- activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N- [3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (17c) was identified and selected for clinical development.

(R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]- N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor

Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5- lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N- hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]- N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4- fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene- mediated disorders.

ADDITION OF ORGANOLITHIUM COMPOUNDS TO N-THP PROTECTED NITRONE

A novel synthesis of a-branched primary hydroxylamines by addition of organolithium reagents to N-THP protected nitrone is described.