61045-91-8

Basic information

• Product Name: methyl (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylate
• Synonyms: methyl (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylate
• CAS NO: 61045-91-8
• Molecular Formula: C₁₃H₁₄N₂O₂
• Molecular Weight: 230.26246
• Mol File: 61045-91-8.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• Storage Temp.: Refrigerator, Under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Sparingly)
• CAS DataBase Reference: methyl (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: methyl (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylate(61045-91-8)
• EPA Substance Registry System: methyl (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylate(61045-91-8)

Safety Data

• Hazardous Substances Data: 61045-91-8(Hazardous Substances Data)

Usage

Uses

Methyl (R)-1-(1-Phenylethyl)-1H-imidazole-4-carboxylate is used in the synthesis of Etomidate analogues which are selective inhibitors of steroid 11β-?hydroxylation in the adrenal cortex.

Upstream product

• 1445-91-6 (S)-1-phenylethanol 
• 17325-26-7 1H-imidazole-5-carboxylic acid methyl ester 
• 67-56-1 methanol 
• 33125-97-2 etomidate 
• 5377-20-8 Metomidate 

Downstream Products

• 56649-48-0 (R)-(+)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 
• 960403-07-0 (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid2-fluoroethyl ester 

Relevant articles and documents

Development of [18F]FAMTO: A novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands

Introduction: Primary aldosteronism accounts for 6–15% of hypertension cases, the single biggest contributor to global morbidity and mortality. Whilst ~50% of these patients have unilateral aldosterone-producing adenomas, only a minority of these have curative surgery as the current diagnosis of unilateral disease is poor. Carbon-11 radiolabelled metomidate ([11C]MTO) is a positron emission tomography (PET) radiotracer able to selectively identify CYP11B1/2 expressing adrenocortical lesions of the adrenal gland. However, the use of [11C]MTO is limited to PET centres equipped with on-site cyclotrons due to its short half-life of 20.4 min. Radiolabelling a fluorometomidate derivative with fluorine-18 (radioactive half life 109.8 min) in the para-aromatic position ([18F]FAMTO) has the potential to overcome this disadvantage and allow it to be transported to non-cyclotron-based imaging centres. Methods: Two strategies for the one-step radio-synthesis of [18F]FAMTO were developed. [18F]FAMTO was obtained via radiofluorination via use of sulfonium salt (1) and boronic ester (2) precursors. [18F]FAMTO was evaluated in vitro by autoradiography of pig adrenal tissues and in vivo by determining its biodistribution in rodents. Rat plasma and urine were analysed to determine [18F]FAMTO metabolites. Results: [18F]FAMTO is obtained from sulfonium salt (1) and boronic ester (2) precursors in 7% and 32% non-isolated radiochemical yield (RCY), respectively. Formulated [18F]FAMTO was obtained with >99% radiochemical and enantiomeric purity with a synthesis time of 140 min from the trapping of [18F]fluoride ion on an anion-exchange resin (QMA cartridge). In vitro autoradiography of [18F]FAMTO demonstrated exquisite specific binding in CYP11B-rich pig adrenal glands. In vivo [18F]FAMTO rapidly accumulates in adrenal glands. Liver uptake was about 34% of that in the adrenals and all other organs were 18F]FAMTO in blood at 10 min post-administration and rapid urinary excretion. In vitro assays in human blood showed a free fraction of 37.5%. Conclusions: [18F]FAMTO, a new 18F-labelled analogue of metomidate, was successfully synthesised. In vitro and in vivo characterization demonstrated high selectivity towards aldosterone-producing enzymes (CYP11B1 and CYP11B2), supporting the potential of this radiotracer for human investigation.

New selective inhibitors of steroid 11β-hydroxylation in the adrenal cortex. Synthesis and structure-activity relationship of potent etomidate analogues

Derivatives of etomidate were evaluated as inhibitors of adrenal steroid 11β-hydroxylations. Stereoselective coupling by Mitsunobu produced chirally pure analogues to study the effect of configuration, modification of the ester, and substitution in the phenyl ring, with the aim to probe specific sites for introducing a radionuclide. Iodophenyl metomidate (IMTO) labeled with iodine-131 served as radioligand for structure-affinity relationship studies. We have characterized the kinetic parameters of specific 131I-IMTO binding on rat adrenal membranes and used the displacement of 131I-IMTO binding to evaluate functionalized MTO analogues. Our results indicated that (1) (R)-configuration is essential for high affinity, (2) highest potency resides in the ethyl, 2-propyl, and 2-fluoroethyl esters, and (3) substitution of the phenyl ring is well tolerated. The clinically used inhibitors metyrapone and ketoconazole inhibited 131I-IMTO binding with low affinity. Incubation of selected analogues with human adrenocortical NCI-h295 cells demonstrated a high correlation with the inhibitory effect on cortisol secretion.

HPLC enantioseparation with cellulose tris(3,5-dichlorophenylcarbamate) in aqueous methanol as a mobile phase

The appropriate design of mobile and stationary phase combinations allowed the use of cellulose tris(3,5-dichlorophenylcarbamate) (CDCPC) as the chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). Together with previous data obtained in n-hexane/2-propanol as a mobile phase the present study indicates very high chiral resolving ability of CDCPC.