- Preparation method of 4-iodo-1H-imidazole
-
The invention provides a preparation method of 4-iodo-1H-imidazole. The preparation method comprises the following steps: (1) enabling imidazole, iodine and a cosolvent for promoting the solubility ofiodine in water to react under an alkaline condition in the presence of water as a solvent, after the reaction is finished, adjusting the pH value to 7-9, filtering out precipitated white solids, performing extraction, reduced pressure distillation to remove the solvent, and recrystallization on the filtrate to recover imidazole, concentrating the recrystallized mother liquor, and mixing the obtained white solids and the precipitated white solids to obtain a 4-iodo-1H-imidazole crude product, and (2) recrystallizing the 4-iodo-1H-imidazole crude product twice to obtain a white crystal 4-iodo-1H-imidazole pure product. The method has the advantages of simple process, high reaction yield, low production cost and recyclable raw materials.
- -
-
Paragraph 0021-0026
(2020/04/17)
-
- Discovery of imidazoleisoindole derivatives as potent IDO1 inhibitors: Design, synthesis, biological evaluation and computational studies
-
Indoleamine-2,3-dioxygenase-1 (IDO1) is an attractive target for cancer immunotherapy. Herein, a series of novel imidazoleisoindole derivatives were prepared and evaluated for their ability to inhibit IDO1. Among these, derivative 11r was the most active compound with nanomolar potency in the Hela cell-based assay, while showed negligible cellular toxicity. UV-visible spectra study demonstrated that compounds 11p and 11r bound to IDO1 and coordinated with the heme iron. Furthermore, they could significantly promote T cell proliferation, increase IFN-γ production, and reduce the numbers of Foxp3+ regulatory T cells. Finally, induced fit docking (IFD) and quantum mechanics/molecular mechanics (QM/MM) calculation were performed to understand the interactions of these compounds to IDO1 protein, which provided a comprehensive guide for further structural modification and optimization.
- Zou, Yi,Wang, Fang,Wang, Yan,Sun, Qirui,Hu, Yue,Li, Yuezhen,Liu, Wen,Guo, Wenjie,Huang, Zhangjian,Zhang, Yihua,Xu, Qiang,Lai, Yisheng
-
p. 293 - 304
(2017/10/05)
-
- Imidazo isoindole IDO1 inhibitor as well as preparation method and application thereof
-
The invention belongs to the field of medicine, and particularly relates to an imidazo isoindole IDO1 compound with structural characteristics of the formula (I) shown in the description as well as a three-dimensional isomer or a pharmaceutically acceptable salt thereof, a preparation method thereof and application thereof as an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor. An experiment result shows that the compound of the invention has a significant inhibition effect for the activity of IDO1, can effectively promote the proliferation of cells T, prevents initial cells T from being differentiated into adjustable cells T, can invert IDO1 mediating immunosuppression, can be used for treating relevant diseases with pathological features of an IDO1 mediating kynurenine metabolic way including cancers, virus infection, neurodegenerative diseases, cataracts, organ transplant rejection, depression, autoimmune diseases and the like.
- -
-
Paragraph 0085; 0086; 0089; 0090
(2018/01/11)
-
- Preparation method of 4-halogen-1H-imidazole
-
The invention discloses a preparation method of 4-halogen-1H-imidazol. The method comprises the following steps: (1), enabling imidazole and halogen elementary substance which are taken as raw materials to be in reaction at a temperature of 60 to 100 DEG C in an alkaline condition, and filtering after the reaction, so as to obtain a filter cake 4-halogen-1H-imidazol crude product; (2), enabling the 4-halogen-1H-imidazol crude product and a reducing agent to be in reaction, filling and filtering after the reaction, and performing extraction and vacuum concentration on the filter cake, so as to obtain a 4-halogen-1H-imidazol pure product. The method is simple in technology, high in reaction yield, low in cost, and free from pollution and waste liquid discharge.
- -
-
Paragraph 0031; 0034
(2017/08/28)
-
- Scope and Mechanistic Limitations of a Sonogashira Coupling Reaction on an Imidazole Backbone
-
A Sonogashira coupling reaction method to join terminal alkynes to the imidazole backbone was developed and investigated. The method exhibits good functional group tolerance and provides target 4-alkynylated imidazoles in 70-93% yield. The alkyne reagents were characterized by means of DFT calculations, from which electrostatic potential surfaces (EPS) were produced. A clear correlation between the EPS of the triple bond and the success of the coupling reaction was revealed. If the EPS is in range -94 to -105 kJmol-1 the coupling is successful. An unsuccessful class of reagents (alkynols) was made compatible by means of an auxiliary group (tert-butyldimethylsilyl). EPSs of these modified reagents then resembled those of the model and these auxiliary-assisted reagents then coupled successfully in excellent yields.
- Sandtorv, Alexander H.,Bj?rsvik, Hans-René
-
p. 4658 - 4666
(2015/08/03)
-
- Fast halogenation of some N-heterocycles by means of N,N'-dihalo-5,5- dimethylhydantoin
-
An instantaneous, selective and high-yielding halogenation process is reported. The method operates with imidazoles, pyrazoles, and indoles under benign reaction conditions. The developed process involves the use of N,N'-dihalo-5,5-dimethylhydantoins (halo=chlorine, bromine, iodine) as halogenation reagents that are activated by catalytic quantities of a strong Bronsted acid. Moreover, the halogenation process is switchable to produce either the mono- or di-halogenated products. Issues related to the reaction mechanism are investigated and a proposal for a reaction mechanism is disclosed.
- Sandtorv, Alexander H.,Bjorsvik, Hans-Rene
-
p. 499 - 507
(2013/05/08)
-
- BENZOXAZEPIN COMPOUNDS SELECTIVE FOR PI3K P110 DELTA AND METHODS OF USE
-
Benzoxazepin Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
- -
-
Page/Page column 118
(2012/10/08)
-
- Synthesis and biological evaluation of a novel anti-malarial lead
-
Malaria is re-emerging in many tropical areas of the world and is often fatal due to drug resistance, leading to about a million deaths each year. Multiple drug resistance has required new efforts in drug discovery and development. Thus, the search for new drugs operating by novel mechanisms of action is receiving increased attention. Herein we report the synthesis and biological evaluation of a novel anti-malarial with micromolar activity against resistant strains of the parasite.
- Hammond, Nicholas L.,Choi, Seoung-Ryoung,Carvalho, Paulo,Liu, Hua,Khan, Shabana,Avery, Mitchell A.
-
experimental part
p. 401 - 407
(2012/05/04)
-
- Regioselective iodination of arenes using iodine/NaBO3· 4H2O system in ionic liquid
-
A mild, efficient, and simple protocol was developed for iodination of arenes and heterocyclic compounds with molecular iodine catalyzed by sodium perborate in ionic liquid. The methodology offered iodoarenes in good to excellent yields at room temperature. The protocol proved to be highly selective, as a single isomer was formed exclusively in most of the substrates. Copyright Taylor & Francis Group, LLC.
- Bhilare, Sachin V.,Deorukhkar, Amol R.,Darvatkar, Nitin B.,Salunkhe, Manikrao M.
-
p. 2881 - 2888
(2008/12/22)
-
- 4-Benzyl-1H-imidazoles with oxazoline termini as histamine H3 receptor agonists
-
Research on the therapeutic applications of the histamine H3 receptor (H3R) has traditionally focused on antagonists/inverse agonists. In contrast, H3R agonists have received less attention despite their potential use in s
- Wijtmans, Maikel,Celanire, Sylvain,Snip, Erwin,Gillard, Michel R.,Gelens, Edith,Collart, Philippe P.,Venhuis, Bastiaan J.,Christophe, Bernard,Hulscher, Saskia,Van Der Goot, Henk,Lebon, Florence,Timmerman, Henk,Bakker, Remko A.,Lallemand, Bénédicte I. L. F.,Leurs, Rob,Talaga, Patrice E.,De Esch, Iwan J. P.
-
supporting information; experimental part
p. 2944 - 2953
(2009/04/11)
-
- Preparation and diels-alder chemistry of 4-vinylimidazoles
-
(Chemical Equation Presented) Various 4-vinylimidazole derivatives have been prepared from the corresponding 4-iodoimidazoles or from urocanic acid. Several methods for the elaboration of these vinylimidazoles and their Diels-Alder reactions are reported. All of the vinylimidazoles prepared in the course of this study react with N-phenylmaleimide quite readily with mild thermal activation providing a single cycloadduct, in most cases the initial, nonaromatic adduct. With more electron rich substrates, there is a tendency for these initial cycloadducts to undergo aromatization, ene reaction, and oxidation although this can be circumvented to a large extent by the choice of reaction conditions. Limited reactions were observed with other dienophiles, providing the expected cycloadducts in most cases, although an abnormal adduct was obtained in one case with dimethyl acetylene dicarboxylate. These substrates also participate in regioselective Diels-Alder reactions with monoactivated dienophiles, but require fairly forcing conditions, thus only providing the aromatized cycloadducts in modest yields. An investigation of substituent effects at the 2-position of the imidazole moiety was undertaken, in which electron-donating and weakly electron-withdrawing substituents are tolerated. In addition, several substrates with terminally substituted vinyl moieties have been investigated.
- Lovely, Carl J.,Du, Hongwang,Sivappa, Rasapalli,Bhandari, Manojkumar R.,He, Yong,Dias, H. V. Rasika
-
p. 3741 - 3749
(2008/02/04)
-
- OXAZOLIDINONE DERIVATIVES AS ANTIMICROBIALS
-
The present invention relates to certain substituted phenyl oxazolidinones and to processes for the synthesis of the same. This invention also relates to pharmaceutical compositions containing the compounds of the present invention as antimicrobials. The compounds are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria, for example, multiple-resistant staphylococci, streptococci and enterococci as well as anaerobic organisms, for example, Bacterioides spp. and Clostridia spp. species, and acid fast organisms, for example, Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.
- -
-
Page/Page column 78
(2010/10/20)
-
- Synthetic studies on (1S)-1-(6,7-dimethoxy-2-naphthyl)-1-(1H-imidazol-4-yl) -2-methylpropan-1-ol as a selective C17,20-lyase inhibitor
-
An asymmetric synthesis of the selective C17,20-lyase inhibitor 2 has been established in eight steps from 2,3-dihydroxynaphthalene 9. The key steps are the enantioselective oxidation of ketone 17 to the chiral α-hydroxy ketone 18 and the diastereoselective Grignard reaction of 18 to the (2R,3S)-diol 21. In addition, a simple procedure for the preparation of imidazolyl 1,4-dimagnesium bromide has been established; the Grignard reaction of 11 using this reagent in the presence of cinchonine provided 2 with 44% ee.
- Matsunaga, Nobuyuki,Kaku, Tomohiro,Ojida, Akio,Tasaka, Akihiro
-
p. 2021 - 2028
(2007/10/03)
-
- An efficient route to 5-iodo-1-methylimidazole: Synthesis of xestomanzamine A
-
An efficient and practical route to C-5 functionalized N-methylated imidazoles is reported. 5-Iodo-1-methylimidazole was synthesized in four steps from imidazole, with complete regiospecificity, in 73% overall yield. The synthesis of xestomanzamine A, a marine natural product isolated in 1995 from an Okinawan sponge of Xestospongia sp., has been achieved using 5-iodo-1-methylimidazole in a modified Grignard reaction with a β-carboline ester moiety, in an overall yield of 59% based upon imidazole and 53% based upon tryptamine.
- Panosyan,Still
-
p. 1110 - 1114
(2007/10/03)
-
- 3-Azabicyclo[3.1.0]hexane derivatives useful in therapy
-
Compounds of formula (I), their salts and prodrugs thereof, where the substituents are as defined herein are disclosed as opiate binding agents useful in the treatment of opiate-mediated conditions. Also described are processes for making such substances.
- -
-
-
- PYRAZINONE, PYRIDINONE, PIPERIDINE AND PYRROLIDINE THROMBIN INHIBITORS
-
A compound which inhibits human thrombin and where has the structure and pharmaceutically acceptable salts thereof, wherein such as STR1 which are useful for inhibiting formation of blood platelet aggregates in blood in a mammal.
- -
-
-
- Medetomidine analogs as α2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine
-
A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their α-adrenergic activities. The methylnaphthyl analog 5a showed significant selectivity for α2-adrenoceptors and behaved as a partial α1-agonist in rat aorta preparations. In contrast, the Z-ethylene analog 8c was α1-selective and behaved as a potent α1-antagonist. Two rigid analogs (6 and 7) exhibited large differences in binding affinities at α1- vs α2-receptors, indicating that the conformational flexibility of 5a is important for the fulfillment of the α-adrenergic activities. Molecular modeling studies began with conformational analysis of classical phenethylamines and medetomidine analogs. Superimposition of medetomidine conformations with those of phenethylamines provided a tentative explanation for the α2-adrenergic activity of the new imidazoles. A common binding mode for phenethylamines and imidazoles with α2-adrenoceptors is proposed. Knowledge of the biological properties of the 4-substituted imidazoles, integrated with the information derived from computer-assisted molecular modeling, has provided new insights for the structural and conformational requirements of this class as new adrenergic drugs.
- Zhang, Xiaoyan,Yao, Xiao-Tao,Dalton, James T.,Shams, Gamal,Lei, Longping,Patil, Popat N.,Feller, Dennis R.,Hsu, Fu-Lian,George, Cliff,Miller, Duane D.
-
p. 3001 - 3013
(2007/10/03)
-
- Synthesis of 4,4'-biimidazoles
-
The palladium(0) catalysed coupling reaction of 4-iodo-1-triphenylmethylimidazole (7) or its 2-methyl analogue 8 afforded the 4,4'-biimidazoles 9 and 10, respectively. Treatment of these compounds with 60% aqueous trifluoroacetic acid gave 4,4'-biimidazole and 2,2'-dimethyl-4,4'-biimidazole as their bistrifluoroacetate salts 11 and 12, respectively.
- Cliff,Pyne
-
p. 681 - 682
(2007/10/02)
-
