- Genetic incorporation of 4-fluorohistidine into peptides enables selective affinity purification
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Due to the lowered pKa of 4-fluorohistidine relative to histidine, peptides and proteins containing this amino acid are potentially endowed with novel properties. We report here the optimized synthesis of 4-fluorohistidine and show that it can efficiently replace histidine in in vitro translation reactions. Moreover, peptides containing 6×-fluorohistidine tags are able to be selectively captured and eluted from nickel resin in the presence of his-tagged protein mixtures.
- Ring, Christine M.,Iqbal, Emil S.,Hacker, David E.,Hartman, Matthew C. T.,Cropp, T. Ashton
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Read Online
- Reactions of 5-diazoimidazoles with steroid hydrazones
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The reaction of 5-diazoimidazoles with steroid hydrazones was studied. The structure of the steroid derivative was found to have a significant effect on the direction of the nitrogen transfer in the unstable intermediate tetrazene. The presence of a labile proton in the reaction mixture permits stabilization of one of the tetrazene forms such that only direction was found for the nitrogen transfer in all the reactions studied, leading to imidazole azides and iminosteroid derivatives.
- Sadchikova,Kureneva,Shtokareva,Selezneva
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Read Online
- 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 0401-0405
(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 1007-1009
(2020/12/08)
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- Substituted imidazole formate type derivative and application thereof
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The invention discloses a compound shown as a formula I or a stereoisomer thereof or pharmaceutically acceptable salts thereof or a solvate thereof or a prodrug thereof or a metabolic product thereofor a deuterated derivative thereof. The compound is a substituted imidazole formate type derivative with a novel structure and belongs to the field of pharmaceutical chemistry. The invention further discloses application of the substituted imidazole formate type derivative to preparation of drugs with calming, hypnosis and/or anesthetic effects and application of the substituted imidazole formatetype derivative to preparation of drugs capable of controlling status epilepticus. The compound disclosed by the invention has a relatively good inhibition effect on a central nervous system and provides a new choice for clinically screening and/or preparing the drugs with the calming, hypnosis and/or anesthetic effects and capable of controlling the status epilepticus. The formula I is shown in the description.
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Paragraph 0463; 0464; 0465; 0466; 0467
(2019/06/05)
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted bicyclic aza-heterocycle sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Paragraph 0547; 0548
(2017/04/04)
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- IMIDAZO [1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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The invention provides substituted imidazo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-imidazo[1,5-a]pyrirnidine-8-carboxamide compounds and variants thereof.
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Paragraph 00247
(2017/11/04)
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted bicyclic aza-heterocycle sirtuin- modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin- modulating compound in combination with another therapeutic agent.
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Page/Page column 152
(2013/05/09)
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- An enantioselective synthesis of (S)-4-fluorohistidine
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We report a new synthesis of enantiomerically pure (S)-4-fluorohisitidine based on diastereoselective alkylation of MOM-protected 4-fluoro-5-bromomethyl imidazole using the Sch?llkopf bis-lactim amino acid synthesis. Improvements in procedures for preparation of key intermediates are also described. (S)-4-Fluorohisitidine prepared by this new method was identical in all respects to material prepared by previous procedures.
- Hajduch, Jan,Cramer, John C.,Kirk, Kenneth L.
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experimental part
p. 807 - 810
(2009/04/11)
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- Novel compounds as metabotropic glutamate receptor antagonists
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The present invention relates to compounds of formula (I) wherein A, E G, J, L, M, R1, R2, and R3 are as defined in the specification and claims. The invention also relates to pharmaceutical compositions containing such compounds and methods for preparing the compounds and compositions. The compounds are metabotropic glutamate receptor antagonists and are useful for the treatment of a variety of CNS disorders.
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Page/Page column 18
(2008/06/13)
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- Synthesis of New 2-Azaadenines and 2-Azahypoxanthines from 4-Diazo-4H-imidazoles
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5-Amino-1H-imidazole-4-carboxamide hydrochloride has been converted into a series of new, potentially biologically active N6-substituted 2-azaadenines 5 via 4-diazo-4H-imidazole-5-carbonitrile (1) which was coupled with primary amines to give 5
- Andersen, Knud Erik,Pedersen, Erik B.
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p. 1012 - 1020
(2007/10/02)
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- Purines, Pyrimidines, and Imidazoles. Part 53. Synthesis of Some 5-Halogeno-analogues of Metiamide and Cimetidine
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Ethyl 5-chloroimidazole-4-carboxylate has been prepared by diazotisation of ethyl 5-amino-1-(di-O-isopropylidene-α- or α,β-D-mannofuranosyl)imidazole-4-carboxylate, reaction of the diazonium salt with copper(I) chloride and removal of the 1-substituent with hydrochloric acid, or by similar conversion of ethyl 5-amino-1-t-butylimidazole-4-carboxylate to ethyl 1-t-butyl-5-chloroimidazole-4-carboxylate, and removal of the t-butyl group with hydrogen bromide.Ethyl 5-fluoroimidazole-4-carboxylate has been prepared from ethyl 5-amino-1-t-butylimidazole-4-carboxylate by diazotisation and photolysis in the presence of tetrafluoroboric acid.Ethyl 5-chloroimidazole-4-carboxylate and ethyl 5-fluoroimidazole-4-carboxylate have been converted into the corresponding alcohols by reaction with lithium aluminium hydride. 5-Chloro-4-(hydroxymethyl)imidazole has also been prepared by electrolysis of 5-chloroimidazole-4-carboxylic acid at mercury cathode. 5-Chloroimidazole has been converted into the 5-chloroimidazolyl analogues of metiamide and cimetidine by a sequence of reactions, and 5-fluoroimidazole has been similarly converted into the 5-fluoro-analogue of metiamide.The metiamide and cimetidine analogues were found to be histamine H2-receptor antagonists.
- Brown, Tom,Shaw, Gordon,Durant, Graham J.
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p. 2310 - 2315
(2007/10/02)
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