- Selective functionalization of imidazoles via an iodine-copper exchange reaction
-
The reaction of protected 4,5-diiodoimidazoles with (PhMe 2CCH2)2CuLi regioselectively provides 5-cuprated imidazoles, which readily react with various electrophiles furnishing functionalized imidazoles in good yields; remarkably, these resulting mono-iodoimidazoles undergo again an iodine-copper exchange reaction in the presence of sensitive functional groups, like an aldehyde or a ketone. The Royal Society of Chemistry 2006.
- Yang, Xiaoyin,Knochel, Paul
-
-
Read Online
- 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
-
-
Read Online
- Efficient iodination of aromatic compounds using potassium ferrate supported on montmorillonite
-
Potassium ferrate impregnated on montmorillonite is a mild, cheap, and non-toxic reagent for the iodination of phenols, including naphthol, aromatic amines, and heterocyclic substrates in fair to excellent yields by a simple isolation procedure.
- Keipour, Hoda,Khalilzadeh, Mohammad A.,Mohtat, Bita,Hosseini, Abolfazl,Zareyee, Daryoush
-
-
Read Online
- Synthesis of imidazolo[5,4-b]carbazole-4,10-quinones
-
The preparation of imidazolo[5,4-b]carbazole-4,10-quinones 9 is described. The key steps of the synthesis are selective halogen-metal exchanges on the imidazole 3 and subsequent addition to carbonyl groups of ethyl-3-formylindole- 2-carboxylate 4.
- Desforges, Gwéna?lle,Bossert, Cécile,Montagne, Cyril,Joseph, Beno?t
-
-
Read Online
- A comparative study of tricarbonylmanganese photoactivatable CO releasing molecules (PhotoCORMs) by using the myoglobin assay and time-resolved IR spectroscopy
-
Tricarbonylmanganese(I) complexes of the ligands tris(imidazol-4-yl) phosphane (4-tipH), tris(1,4-diisopropylimidazol-2-yl)phosphane (2-tipiPr2), tris(pyridin-2-yl)phosphane (tpp) and tris(N-methylimidazol-2-yl)carbinol (2-ticNMe) were prepared. These act as N,N,N tripodal chelators. The solid-state structure of [Mn(CO) 3(tpp)]OTf was determined by X-ray diffraction. The potential of these complexes to act as photoactivatable CO-releasing molecules (PhotoCORMs) was studied with the UV/Vis spectroscopy-based myoglobin assay as well as by time-resolved IR spectroscopy. Within the series of compounds prepared, the steric bulk of the imidazolyl groups seems to significantly influence the CO-release kinetics and stoichiometry when using the myoglobin assay. In contrast, the time-resolved IR data suggest release of all carbonyl ligands upon irradiation. This effect points to a much closer association of myoglobin and PhotoCORMs than previously thought and will require further investigation.
- Huber, Wilhelm,Linder, Rolf,Niesel, Johanna,Schatzschneider, Ulrich,Spingler, Bernhard,Kunz, Peter C.
-
-
Read Online
- Modular synthesis of helicene-like compounds based on the imidazolium motif
-
Straightforward synthesis of novel mono- and tricationic helical compounds based on the imidazolium core has been developed. The synthetic route based on double [2+2+2] cycloaddition reactions of precursors with the imidazolium core motif is notably modular and reaches beyond established protocols used for the synthesis of imidazolium systems as well as beyond the reported protocols used to assemble compounds with helical frameworks. This approach opens rapid four-step access to a cationic species featuring nine orthoannulated rings that represents the highest order helical nitrogen-based cationic system reported to date.
- ?í?ková, Martina,?aman, David,Koval, Du?an,Ka?i?ka, Václav,Klepetá?ová, Blanka,Císa?ová, Ivana,Teply, Filip
-
-
Read Online
- Synthesis of Complexes with Abnormal "protic" N-Heterocyclic Carbenes
-
Neutral 4-iodo-N-ethylimidazole 3 oxidatively adds to [Pt(PPh3)4] to give, in the presence of different tetraalkylammonium salts, complexes trans-[4], trans-[5], and trans-[6] containing an anionic C4-bound heterocycle with an unsubstituted ring-nitrogen atom. Complex trans-[4] reacts with the proton source NH4I under protonation of the ring-nitrogen atom to produce complex trans-[7]I which bears an NH,NR-substituted aNHC ligand. The reaction of trans-[4] with CH3I yields the complex trans-[8]I which has a classical aNHC ligand with two alkylated ring-nitrogen atoms.
- Jin, Hanpeng,Tan, Tristan Tsai Yuan,Hahn, F. Ekkehardt
-
-
Read Online
- Metal-mediated base pairing in DNA involving the artificial nucleobase imidazole-4-carboxylate
-
The use of imidazole-4-carboxylate (X) as an artificial nucleobase in metal-mediated base pairing is reported. Towards this end, the corresponding deoxyribonucleoside was synthesized and structurally characterized as its sodium salt (sodium 1,2-dideoxy-1-(4-carboxyimidazol-1-yl)-D-ribofuranose). The deoxyribonucleoside was incorporated into different DNA duplexes (parallel-stranded and antiparallel-stranded), and their Cu(II)- and Ag(I)-binding behavior was investigated. It was shown that both X–Cu(II)–X and X–Ag(I)–X base pairs can be formed, with the former being more stabilizing than the latter. The formation of an X–Cu(II)–X base pair is accompanied by an increase in the duplex melting temperature of approximately 20 °C for antiparallel-stranded duplexes and of 12 °C for the parallel-stranded duplex under investigation. Imidazole-4-carboxylate represents the first imidazole-based nucleoside for Cu(II)-mediated base pairing. Moreover, it is the smallest nucleoside known to form stable Cu(II)-mediated base pairs. Structures of the X–Cu(II)–X and X–Ag(I)–X base pairs are proposed, too, based on molecular structures obtained using the model nucleobase 1-benzyl-1H-imidazole-4-carboxylate.
- Sandmann, Nikolas,Defayay, Denise,Hepp, Alexander,Müller, Jens
-
-
Read Online
- Synthesis method of 4, 5-diiodo-1H-imidazole
-
The invention relates to a synthetic method of 4, 5-diiodo-1H-imidazole. The technical problem that the solubility of raw materials is poor during synthesis of 4, 5-diiodo-1H-imidazole is mainly solved. The synthesis method comprises the following steps: under ice bath cooling, reacting imidazole with sodium hydroxide to generate imidazole sodium, and continuously reacting an intermediate with elemental iodine dissolved in tetrahydrofuran to generate a target compound. As a fine chemical product and a medical intermediate, the 4, 5-diiodo-1H-imidazole is widely applied to the fields of material chemistry, catalytic chemistry and pharmacy.
- -
-
Paragraph 0008-0009
(2021/02/06)
-
- Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
-
Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
-
p. 5852 - 5869
(2018/11/10)
-
- 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; 0087; 0088
(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 0030; 0033
(2017/08/28)
-
- 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)
-
- A three-way switchable process for suzuki cross-coupling, hydrodehalogenation, or an assisted tandem hydrodehalogenation and suzuki cross-coupling sequence
-
A three-way switchable Pd-catalyzed and microwave assisted process appropriate for selective arylation or hydrodehalogenation of the imidazole backbone was discovered and entirely optimized. The "arylation switch position" was adapted and optimized for the synthesis of 4,5-diaryl-1H-imidazoles, while the "hydrodehalogenation switch position" was used for the preparation of 4(5)-iodo-1H-imidazole. The hydrodehalogenation and the cross-coupling reactions were also successfully combined in "the third switch position" that performs an assisted tandem reaction sequence that produced 4(5)-aryl-1H-imidazole. All of the three pathways produced their corresponding products in excellent yield. Copyright
- Sandtorv, Alexander H.,Bjorsvik, Hans-Rene
-
supporting information
p. 3231 - 3243
(2013/12/04)
-
- LRRK2 INHIBITORS
-
Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.
- -
-
Page/Page column 140
(2013/02/28)
-
- Ruthenium piano-stool complexes bearing imidazole-based PN ligands
-
A variety of piano-stool complexes of cyclopentadienyl ruthenium(II) with imidazole-based PN ligands have been synthesized starting from the precursor complexes [CpRu(C10H8)]PF6, [CpRu(NCMe) 3]PF6 and [CpRu(PPh3)2Cl]. PN ligands used are imidazol-2-yl, -4-yl and -5-yl phosphines. Depending on the ligand and precursor different types of coordination modes were observed; in the case of polyimidazolyl PN ligands these were κ1P-monodentate, κ2P,N-, κ2N,N- and κ3N,N,N- chelating and μ-κP:κ2N,N-brigding. The solid-state structures of [CpRu(1a)2Cl ]·H2O (5 .H2O) and [{CpRu(μ-κ2-N,N- κ'1-P-2b)}2](C6H5PO 3H)2(C6H5PO3H 2)2, a hydrolysis product of the as well determined [{CpRu(2b)}2](PF6)2.2CH 3CN (7b.2CH3CN) were determined (1a = imidazol-2-yldiphenyl phosphine, 2b = bis(1-methylimidazol-2-yl)phenyl phosphine, 3a = tris(imidazol-2-yl)phosphine). Furthermore, the complexes [CpRu(L)2]PF6 (L = imidazol-2-yl or imidazol-4-yl phosphine) have been screened for their catalytic activity in the hydration of 1-octyne.
- Kunz, Peter C.,Thiel, Indre,Noffke, Anna Louisa,Rei?, Guido J.,Mohr, Fabian,Spingler, Bernhard
-
supporting information; experimental part
p. 33 - 40
(2012/01/06)
-
- 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)
-
- Convenient access to bis-indole alkaloids. Application to the synthesis of?topsentins
-
Topsentins and related bis-indole alkaloids may be efficiently synthesized through an addition/oxidation sequence leading to 2-(3-indolylcarbonyl)-imidazole derivatives followed by a Pd-catalyzed heteroarylation with the appropriate 3-stannylindoles.
- Mal, Sajal K.,Bohé, Luis,Achab, Sa?d
-
p. 5904 - 5914
(2008/12/20)
-
- "Molecular chameleons". Design and synthesis of a second series of flexible nucleosides
-
(Chemical Equation Presented) The second series of flexible shape-modified nucleosides is introduced. The "fleximers" feature the purine ring systems split into their individual imidazole and pyrimidine components. This structural modification serves to introduce flexibility to the nucleoside while still retaining the elements essential for recognition. As a consequence, these structurally innovative nucleosides can more readily adapt to their environment and should find use as bioprobes for investigating enzyme-coenzyme binding sites as well as nucleic acid and protein interactions. Their design and synthesis is described.
- Seley, Katherine L.,Salim, Samer,Zhang, Liang,O'Daniel, Peter I.
-
p. 1612 - 1619
(2007/10/03)
-
- 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)
-
- Aromatic iodination in aqueous solution. A new lease of life for aqueous potassium dichloroiodate
-
A re-investigation of the use of aqueous potassium dichloroiodate (KICl2) as an iodinating agent for aromatic compounds has found the reagent to be more generally applicable than previously known. The reagent has been found to give excellent yields of iodinated heterocyclic compounds, such as isatin, imidazole and pyrazole.
- Garden, Simon J.,Torres, José C.,De Souza Melo, Simone C.,Lima, Alexandre S.,Pinto, Angelo C.,Lima, Edson L.S.
-
p. 2089 - 2092
(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.
- -
-
-
- Polyfunctionalisation of imidazole via sequential imidazolyl anion formation
-
A method for achieving the sequential functionalisation of the imidazole ring in the order C-5→C-4→C-2 is described. The chemistry proceeds via the regioselective formation of positionally stable imidazolyl anions which are reacted with electrophiles (aldehydes, alkyl halides, azides, formamides, isocyanates) to afford substituted imidazoles in 31-90% yield.
- Carver, David S.,Lindell, Stephen D.,Saville-Stones, Elizabeth A.
-
p. 14481 - 14496
(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)
-
- Azoles. Part 4. Nucleophilic Substitution Reactions of Halogenoimidazoles
-
A number of N-protected derivatives of 2,4,5-tribromoimidazole, 4(5)-bromo-5(4)-nitroimidazole, and 2,4(5)-dibromo-5(4)-nitroimidazole have been prepared by standard procedures and treated with various nucleophiles.Whereas 2,4,5-tribromo (and tri-iodo)imidazole reacted with sodium benzenethiolate to give the corresponding 4,5-dihalogenoimidazole and diphenyl disulphide, 1-protected derivatives of 2,4,5-tribromoimidazole reacted with various sodium alkane (or arene)thiolates and with sodium isopropoxide, in isoprpopyl alcohol, by displacement of the 2-bromine atom. 1-Benzyl-5-bromo-4-nitroimidazole (14), 2-(5-bromo-4-nitroimidazol-1-yl)acetate (25), and 5-bromo-4-nitro-1-phenacylimidazole (26) reacted by displacement of the 5-bromine atom.The product arising from reaction of the last compound with ethyl 2-mercaptoacetate in ethanol in the presence of base, cyclised to give ethyl 3-hydroxy-7-nitro-3-phenylimidazolothiazine-2-carboxylate (35).
- Iddon, Brian,Khan, Nazir,Lim, Bee Lan
-
p. 1437 - 1444
(2007/10/02)
-
