- 2-(3-Methyl-3H-diaziren-3-yl) ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: A derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channels
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To locate general anesthetic binding sites on ligand-gated ion channels, a diazirine derivative of the potent intravenous anesthetic, R-(+)-etomidate (2-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate), has been synthesized and characterized. R-(+)-Azi
- Shaukat Husain,Ziebell, Michael R.,Ruesch, Dirk,Hong, Filbert,Arevalo, Enrique,Kosterlitz, Jonathan A.,Olsen, Richard W.,Forman, Stuart A.,Cohen, Jonathan B.,Miller, Keith W.
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- Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists
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TGR5 is emerging as an important and promising target for the treatment of diabetes, obesity and other metabolic syndromes. A series of novel 1-benzyl-1H-imidazole-5-carboxamide derivatives was designed, synthesized and evaluated in vitro and in vivo. The
- Zhao, Shizhen,Li, Xinping,Wang, Le,Peng, Wenjing,Ye, Wenling,Li, Weiguo,Wang, Yan-Dong,Chen, Wei-Dong
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- Ketone-substituted heterocyclic compound and anesthetic effect thereof
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The invention discloses a ketone-substituted heterocyclic compound and an anesthetic effect thereof. Specifically provided are a compound represented by formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a deuterated derivative thereof. The ketone-substituted heterocyclic compound provided by the invention has a good central nervous system inhibition effect, can generate sedative, hypnotic and/or general anesthesia effects, and can control the epilepsy persistent state; the ketone-substituted heterocyclic compound also has the characteristics of quick response and quick recovery while maintaining excellent anesthetic activity; meanwhile, the ketone-substituted heterocyclic compound has almost no inhibition effect on the adrenal cortex function, has small sideeffects, solves the technical problems in the field, and provides a new choice for clinically screening and/or preparing sedative, hypnotic and/or general anesthesia medicines and medicines for controlling the epilepsy persistent state.
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Paragraph 0277-0282
(2021/01/29)
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- SUBSTITUTED IMIDAZOLECARBOXYLATE DERIVATIVES AND THE USE THEREOF
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A compound is shown in formula (I). The derivatives of the compound include a stereoisomer, a pharmaceutically acceptable salt, a solvate, a prodrug, a metabolite, a deuterated derivative. The compound is a structurally novel substituted imidazole formate derivative. Substituted imidazole formate derivatives are used in preparing a drug with sedative, hypnotic and/or anesthetic effects, as well as a drug that can control the state of epilepsy. The compound has a good inhibitory effect on the central nervous system, and provides a new option for clinical screening of and/or preparation of a drug with sedative, hypnotic and/or anesthetic effects and controlling the state of epilepsy.
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Paragraph 0322; 0325-0326
(2020/12/08)
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- Phenylethyl imidazole derivative and application thereof
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The invention belongs to the technical field of medicines, and provides a novel phenylimidazole amide derivative shown as a general formula (I) (See the specification) and a geometrical isomer or pharmaceutically acceptable salt, hydrate, solvate and prodrug thereof, and preparation methods thereof. The compound can activate the activity of TGR5 and can be used for treating or preventing diseasesrelated to TGR5 activity regulation.
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Paragraph 0056; 0058-0059
(2020/10/21)
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- Etomidate derivative and preparation method thereof
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The invention discloses an etomidate analogue shown in a formula (I). The analogue which needs to be developed in the field keeps beneficial performances (such as quick action, almost no influences onblood pressure and high therapeutic index) of etomidate
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Paragraph 0036-0041
(2019/05/28)
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- Metabolite-inactive etomidate analogues alleviating suppression on adrenal function in Beagle dogs
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Owing to rapid generation in body, the metabolites of etomidate softdrug are able to accumulate in either the brain or periphery and subsequently affect the recovery from anaesthesia or cause corticosteroid suppression. This study was designed to investigate the ability of two etomidate analogues (ET-26, ET-42) with inactive metabolites to provide anaesthesia with lesser corticosteroid suppression. The 50% effective dose (ED50) of ET-26, ET-42, Etomidate, MOC-ET (an etomidate softdrug) and CPMM (an improved etomidate softdrug) required to induce anaesthesia intravenously in Beagle dogs were 1.44 mg/kg, 0.72 mg/kg, 0.43 mg/kg 23.12 mg/kg and 0.59 mg/kg, respectively. After adrenocorticotropic hormone (ACTH) stimulation, the serum concentrations of cortisol and corticosterone in the ET-26, ET-42 and CPMM groups were similar to those of controls, and significantly higher than those of the etomidate and MOC-etomidate groups (P 50 = 1.44 mg/kg) and ET-42 (ED50 = 0.72 mg/kg) were determined. Both analogues can significantly reduce the corticosteroid suppression in vivo. Metabolite-inactive etomidate derivatives with slow metabolism might provide a novel strategy to improve Etomidate associated corticosteroid suppression.
- Yang, Jun,Kang, Yi,Wang, Bin,Yang, Linghui,Liu, Jin,Zhang, Wensheng
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p. 343 - 349
(2017/01/13)
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- Anesthetic compounds and related methods of use
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Provided herein are compounds according to formula (I): Provided herein is also a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and a method for providing anesthesia in a subject by administering such a pharmaceutical composition.
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Page/Page column 51
(2015/11/09)
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- ANESTHETIC COMPOUNDS AND RELATED METHODS OF USE
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Provided herein are compounds according to formula (I): Provided herein is also a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and a method for providing anesthesia in a subject by administering such a pharmaceutical composition.
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Paragraph 00171
(2013/07/25)
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- ETOMIDATE ANALOGUES WITH IMPROVED PHARMACOKINETIC AND PHARMACODYNAMIC PROPERTIES
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The invention is directed to compounds according to formula (I): where R1 is L1C(O)OT or L1C(O)OL2C(O)OT; R2 is a substituted or unsubstituted C1-C10 alkyl, C2-C1
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Page/Page column 13
(2009/12/27)
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- New selective inhibitors of steroid 11β-hydroxylation in the adrenal cortex. Synthesis and structure-activity relationship of potent etomidate analogues
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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.
- Zolle, Ilse M.,Berger, Michael L.,Hammerschmidt, Friedrich,Hahner, Stefanie,Schirbel, Andreas,Peric-Simov, Biljana
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p. 2244 - 2253
(2008/12/22)
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- SYNTHESIS AND EVALUATION OF 18F-LABELLED ALKYL-1-[(R)-1-PHENYLETHYL]-1H-IMIDAZOLE-5-CARBOXYLATE AS A TRACER FOR THE QUANTIFICATION OF β-11-HYDROXYLASE ENZYME IN THE ADRENAL GLANDS
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Radioactively labeled derivatives of (R)-3-(1-phenylethyl)-3H-imidazole-4-carboxylic acid esters and one-step methods for preparing these compounds are provided. The radioactively labelled compounds, and pharmaceutical acceptable salts and solvates are us
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Page/Page column 15-16
(2008/06/13)
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- Racemization of lower alkyl imidazole carboxylates
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Novel methods of preparing lower alkyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylates in racemic as well as in optically pure isomeric form.
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