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Chemical Structure| 288-32-4 Chemical Structure| 288-32-4
Chemical Structure| 288-32-4

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Imidazole is a widely used organic compound with various biological activities, including serving as an enzyme inhibitor and drug precursor. Imidazole is mainly used in biocatalysis, drug synthesis, and as an inhibitor of various enzymes (e.g., heparinase and some bacterial enzymes). It is also utilized in research to study enzyme mechanisms and drug actions.

Synonyms: 1,3-Diaza-2,4-cyclopentadiene; Glyoxaline

4.5 *For Research Use Only !

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Chandra, Shambhu Deo ; Gunasekera, Shanal ; Noichl, Benjamin Philipp ; Patrick, Brian O ; Perrin, David M ;

Abstract: We report a streamlined synthesis of (2S,3R,4R)-4,5-dihydroxy isoleucine (DHIle), an amino acid found in α-amanitin, which appears to be critical for toxicity. This synthetic route is transition metal-free and enables the production of significant quantities of DHIle with suitable protection for use in peptide synthesis. Its incorporation into a cytotoxic amatoxin analog is reported.

Purchased from AmBeed: ; ; ;

Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto ; Prathamesh M. Datar ; Daniel J. DiRocco ; Katherine Huntera and E. Neil G. Marsh

Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.

Nguyen, Long T. ; Rananaware, Santosh R. ; Yang, Lilia G. ; Macaluso, Nicolas C. ; Ocana-Ortiz, Julio E. ; Meister, Katelyn S. , et al.

Abstract: CRISPR-Cas-based diagnostics have the potential to elevate nucleic acid detection. CRISPR-Cas systems can be combined with a pre-amplification step in a one-pot reaction to simplify the workflow and reduce carryover contamination. Here, we report an engineered Cas12b with improved thermostability that falls within the optimal temperature range (60°C-65°C) of reverse transcription-loop-mediated isothermal amplification (RT-LAMP). Using de novo structural analyses, we introduce mutations to wild-type BrCas12b to tighten its hydrophobic cores, thereby enhancing thermostability. The one-pot detection assay utilizing the engineered BrCas12b, called SPLENDID (single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases), exhibits robust trans-cleavage activity up to 67°C in a one-pot setting. We validate SPLENDID clin. in 80 serum samples for hepatitis C virus (HCV) and 66 saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and accuracy. We obtain results in as little as 20 min, and with the extraction process, the entire assay can be performed within an hour.

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Emily Penn ; Antonio Baclig ; Devi Ganapathi ; William C. Chueh ;

Abstract: Eutectic electrolytes can attain high concentrations of redox-active species, offering a path toward high energy density redox flow batteries. Here we introduce a new entropically-driven eutectic mixing approach using organic small molecules. By mixing chemically similar redox-active species, we engineer highly concentrated, low viscosity liquids composed almost entirely of redox-active molecules. Using quinones as a model system, we discover a ternary benzoquinone eutectic mixture and a binary naphthoquinone eutectic mixture which have theoretical redox-active electron concentrations of 16.8 and 8.8 M e–, respectively. We investigate compatibility with protic supporting electrolytes and quantify ionic conductivity and viscosity of quinone eutectic electrolytes across multiple states of charge. A binary naphthoquinone eutectic electrolyte with a protic ionic liquid supporting electrolyte (7.1 M e–, theoretical volumetric capacity 188 Ah L–1) achieves a volumetric capacity of 49 Ah L–1 in symmetric static cell cycling. These preliminary results suggest that entropy-driven eutectic mixing is a promising strategy for developing high-energy density flow battery electrolytes.

Purchased from AmBeed: ; ; ; ; ; ; ;

Berg, Kaja ; Hegde, Pooja ; Pujari, Venugopal ; Brinkmann, Marzena ; Wilkins, David Z. ; Parish, Tanya , et al.

Abstract: The electron transport chain (ETC) in the cell membrane consists of a series of redox complexes that transfer electrons from electron donors to acceptors and couples this electron transfer with the transfer of protons (H+) across a membrane. This process generates proton motive force which is used to produce ATP and a myriad of other functions and is essential for the long-term survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), under the hypoxic conditions present within infected granulomas. Menaquinone (MK), an important carrier molecule within the mycobacterial ETC, is synthesized de novo by a cluster of enzymes known as the classic/canonical MK biosynthetic pathway. MenA (1,4-dihydroxy-2-naphthoate prenyltransferase), the antepenultimate enzyme in this pathway, is a verified target for TB therapy. In this study, we explored structure-activity relationships of a previously discovered MenA inhibitor scaffold, seeking to improve potency and drug disposition properties. Focusing our campaign upon three molecular regions, we identified two novel inhibitors with potent activity against MenA and Mtb (IC50 = 13-22 μM, GIC50 = 8-10 μM). These analogs also displayed substantially improved pharmacokinetic parameters and potent synergy with other ETC-targeting agents, achieving nearly complete sterilization of Mtb in combination therapy within two weeks in vivo. These new inhibitors of MK biosynthesis present a promising new strategy to curb the continued spread of TB.

Keywords: 1,4-dihydroxy-2-naphthoate prenyltransferase ; MenA ; MenA inhibitors ; Menaquinone ; Mtb ; Mycobacterium tuberculosis ; Piperidine derivatives ; SAR

Alternative Products

Product Details of Imidazole

CAS No. :288-32-4
Formula : C3H4N2
M.W : 68.08
SMILES Code : C1=NC=CN1
Synonyms :
1,3-Diaza-2,4-cyclopentadiene; Glyoxaline
MDL No. :MFCD00005183
InChI Key :RAXXELZNTBOGNW-UHFFFAOYSA-N
Pubchem ID :795

Safety of Imidazole

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314-H360
Precautionary Statements:P280-P301+P330+P331-P305+P351+P338-P310-P303+P361+P353
Class:8
UN#:3263
Packing Group:

Application In Synthesis of Imidazole

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 288-32-4 ]
  • Downstream synthetic route of [ 288-32-4 ]

[ 288-32-4 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 288-32-4 ]
  • [ 50-00-0 ]
  • [ 3724-26-3 ]
References: [1] Medicinal Chemistry Research, 2012, vol. 21, # 10, p. 3035 - 3042,8.
  • 2
  • [ 288-32-4 ]
  • [ 589-15-1 ]
  • [ 72459-46-2 ]
References: [1] New Journal of Chemistry, 2004, vol. 28, # 8, p. 1010 - 1018.
[2] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 4, p. 1992 - 2010.
[3] Journal of the American Chemical Society, 2017, vol. 139, # 24, p. 8267 - 8276.
[4] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 2, p. 178 - 182.
[5] Journal of Medicinal Chemistry, 2004, vol. 47, # 24, p. 5995 - 6008.
[6] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 16, p. 6184 - 6196.
[7] Journal of Medicinal Chemistry, 2010, vol. 53, # 4, p. 1712 - 1725.
[8] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 15, p. 4011 - 4015.
[9] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 18, p. 4752 - 4756.
[10] European Journal of Medicinal Chemistry, 2016, vol. 122, p. 684 - 701.
[11] ChemistryOpen, 2016, vol. 5, # 6, p. 566 - 573.
  • 3
  • [ 288-32-4 ]
  • [ 59363-13-2 ]
  • [ 67085-11-4 ]
YieldReaction ConditionsOperation in experiment
99.31% With sodium hydride In N,N-dimethyl-formamide at 58 - 62℃; for 3 h; Cooling with ice (2)Take a concentration of 20percent sodium hydride in DMF, under icecooling,to 2ml / s Was added dropwise with stirring speedof 20percent of the concentration of imidazole in DMF, the reaction was stirred at 60 ° C 60min, after cooling in an ice salt bathmethod, was slowly added to the intermediate product 1, the sodium hydride Of DMF, imidazole in DMF and the weight ratioof the intermediate product as a 7: 7: 5 stirred at 60 ° C in 120min reaction mix, after cooling in an ice salt bath method, areaction solution adding to said reaction mixture 25percent by weight of nhexanewas accounted for the reaction, at a speed of 3rev / sec After stirring for 15min, plus The reaction solution into account the 350percent by weight of the ice, with 3 rev / sec stirreduntil evolution ceased Shen After the precipitate was filtered, the filter cake with accounting for 1/3 times the weight of thefilter cake was washed with water once, in order to speed 2830r / min Conditions centrifugal drying 60min, with the centrifugalaccounted for 2.5 times the weight of the resulting product was dried and 0.05 Times with ethyl acetate and activated carbon,was allowed to stand at 5° C was recrystallized from 13 hours, 50 ° C and By recrystallization of the obtained product wasdried to obtain intermediate 2 detected by HPLC. Intermediate 2 71.5percent yield, wherein the desired product 1(2hydroxy4(4chlorophenyl)butanoic Yl) 1Hydrogen imidazolecontent was 99.31 percent
99.31%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 30℃; for 1 h; Cooling with ice
Stage #2: at 60℃; for 2 h; Cooling with ice
(1) take 7kg concentration of 20percent sodium hydride DMF solution,Under an ice bath condition, 7kg of imidazole DMF solution with a concentration of 20percent was added dropwise with stirring at a speed of 2ml / s and the reaction was stirred at 60 ° C for 60min; after cooling with an ice-salt bath method, 5kg of 1-chloro-4 - (4-chlorophenyl) -2-butanol stirred at 60 ° C for 120min, cooled with ice salt bath to obtain the reaction solution;(2) Take the reaction solution obtained in the step (1), add n-hexane accounting for 25percent of the weight of the reaction solution, stir for 15 min at a speed of 3 rev / sec, add ice water of 350percent Stirring at a speed of 3 revolutions / second to stop the precipitation precipitation, filtering, washing the filter cake with 1/3 times of the weight of the filter cake for 1 time, centrifuging at the speed of 2825r / min for 60 minutes, The obtained product was 2.5 times in weight and 0.05 times in ethyl acetate and activated carbon, and was allowed to stand at -5 ° C for 13 hours for recrystallization. The product obtained after recrystallization was dried at 50 ° C. After testing, the yield of the product of this example was 71.4percent.Using HPLC and standards on the target product and impuritiesThe amount of testing. After testing,The target product1- (2-hydroxy-4- (4-chlorophenyl) butyl) -1-hydro-imidazoleContent of 99.31percent1- (1-Chloro-4- (4-chlorophenyl) butan-2-yl) -1H-imidazoleContent of 0.57percent4- (4- (1-Hydroxyimidazol-1-yl) phenyl) -1-chloro-2-butanolThe content is 0.08percent.
99.31%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 60℃; for 1 h;
Stage #2: at 60℃; for 2 h;
Take 7kg of 20percent sodium hydride in DMF and add dropwise at 2ml/s in ice bath.7kg concentration of 20percent imidazole in DMF, stirred at 60 ° C reaction 60min;After cooling with an ice salt bath, 5 kg of 1-chloro-4-(4-chlorophenyl)-2-butanol was slowly added, and the reaction was stirred at 60° C. for 120 min. After cooling with an ice salt bath, the reaction liquid was obtained; The reaction solution was added with 25percent by weight of n-hexane, stirred at a rate of 3 revolutions per second for 15 minutes, and then added with ice water of 350percent by weight of the reaction solution and stirred at a rate of 3 revolutions per second to stop. Precipitation precipitation, filtration, filter cake weight 1/3 of the water filter cake washed once, at a speed of 2825r/min centrifugal drying 60min, with the weight of the product obtained by the centrifugal drying 2.5 times and 0.05 times the weight of acetic acid The ethyl ester and the activated carbon were recrystallized at -5°C for 13 hours, and the recrystallized product was dried at 50°C to give 1-(2-hydroxy-4-(4-chlorophenyl)butyl). -1 hydrogen-imidazole, purity 99.31percent.
88.2% With sodium hydride In N,N-dimethyl-formamide at 20 - 60℃; for 4.5 h; (2) Synthesis of 1- (4- (4-chlorophenyl) -2-hydroxybutyl) imidazole. The reaction flask was charged with imidazole and dry DMF. The mass ratio of imidazole to DMF was 24: Adding 3-4 portions of sodium hydride in the next portion, stirring at room temperature till no gas was generated, raising the temperature to 60 ° C, mixing 1-chloro-4- (4-chlorophenyl) -2-butanol with DMF to obtain a mixed solution 3, The mass ratio of 1-chloro-4- (4-chlorophenyl) -2-butanol and DMF in the mixed solution 3 of imidazole and sodium hydride was 24: 7.9: 80: 94.8. The mixed solution was added dropwise to the reaction flask , The dropwise addition was completed for 3.5 hours, the reaction temperature was maintained at 60 ° C, the reaction was continued for 1 hour after the dropwise addition was completed, and then cold water was slowly added until all the solids were precipitated and filtered to obtain 1- (4- (4-chlorobenzene Yl) -2-hydroxy-butyl) imidazole;
85% With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In water; toluene at 0 - 95℃; for 3 h; Example 1. Preparation of (1-f4- (4-chlorophenvl)-2-hydroxy-n-butvll-imidazole) (IV); To a solution of 56.7 g (0.26 mol) of 1-chloro-4-chlorophenyl-2-butanol (J. of Medicinal Chemistry, 1978. Vol. 21. No. 8. p. 842) in 200 ml of toluene 36.2 g (0.9 mol) of sodium hydroxide dissolved in 100 ml of water, 6.4 g (0.028 mol) of benzyltriethyammonium chloride and 35.2 g (0.51 mol) of imidazole (III) are added. The reaction mixture is heated at 93-95 °C for one hour then the temperature is returned to about 60 °C, the phases are separated and to the organic layer water (100 ml) is added. The mixture is first stirred at 22-25 °C for 1 hour then at 0-5 °C for two hours. The crystals are separated by filtration, washed with water (2 x 35 ml) of 0-5 °C to yield 74 g of wet (1- [4- (4-chlorophenyl)-2-hydroxy-n-butyl]-imidazole) which is dried at maximum 50 °C in vacuo to give 61.6 g (95 percent) of the product. Recrystallization from ethyl acetate gives 52.4 g (85 percent) of dry product melting at 104-106 °C.
71.4%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 60℃; for 1 h; Cooling with ice
Stage #2: at 60℃; for 2 h; Cooling with ice
(1) Take 7kg of 20percent sodium hydride in DMF. Under ice bath conditions, At a rate of 2 ml/s, 7 kg of a 20percent imidazole DMF solution was added dropwise while stirring. Stir the reaction at 60 ° C 60min; After cooling with ice salt bath, 5 kg of 1-chloro-4-(4-chlorophenyl)-2-butanol is added slowly, Stirring reaction at 60 ° C 120min, after cooling with ice salt bath, the reaction solution; (2) Take the reaction solution obtained in step (1), Add 25percent by weight of the reaction solution of n-hexane, After 15 min stirring at 3 rpm, Then add ice water, which accounts for 350percent of the weight of the reaction solution, Stir at a speed of 3 revs/second to stop precipitation after filtration. Wash the cake once with 1/3 of the weight of the cake, Drying at a speed of 2825r/min for 60min. With ethyl acetate and activated carbon that weighed 2.5 times and 0.05 times the weight of the centrifugally dried product, respectively. After recrystallization at -5°C for 13 hours, the recrystallized product was dried at 50°C to obtain it. Upon detection, the yield of the product of this example was 71.4percent. The target product and impurity levels were determined using HPLC and standards. After testing, The target product, 1-(2-hydroxy-4-(4-chlorophenyl)butyl)-1H-imidazole, has a content of 99.31percent. The content of 1-(1-chloro-4-(4-chlorophenyl)butan-2-yl)-1-hydro-imidazole is 0.57percent. The content of 4-(4-(1H-hydrogen-imidazol-1-yl)phenyl)-1-chloro-2-butanol was 0.08percent.

References: [1] Patent: CN105218455, 2016, A, . Location in patent: Paragraph 0055.
[2] Patent: CN105175341, 2017, B, . Location in patent: Paragraph 0048-0052.
[3] Patent: CN105175338, 2018, B, . Location in patent: Paragraph 0069-0071.
[4] Patent: CN107501190, 2017, A, . Location in patent: Paragraph 0033; 0036; 0043; 0046.
[5] Patent: WO2005/70897, 2005, A1, . Location in patent: Page/Page column 7.
[6] Patent: CN105198817, 2018, B, . Location in patent: Paragraph 0048-0052; 0055; 0059; 0061-0063; 0065.
[7] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 9, p. 3225 - 3234.
[8] Patent: CN105198816, 2018, B, . Location in patent: Paragraph 0100-0103.
[9] Patent: CN105198814, 2018, B, . Location in patent: Paragraph 0071-0073.
[10] Patent: CN105198818, 2018, B, . Location in patent: Paragraph 0107; 0108; 0109.
  • 4
  • [ 288-32-4 ]
  • [ 20671-53-8 ]
  • [ 50901-46-7 ]
References: [1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 6 - 10[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 1, p. 9 - 14.
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  • [ 288-32-4 ]
  • [ 7732-18-5 ]
  • [ 877932-98-4 ]
  • [ 110-16-7 ]
  • [ 76095-16-4 ]
References: [1] Patent: US5789597, 1998, A, .
  • 6
  • [ 288-32-4 ]
  • [ 616-38-6 ]
  • [ 79917-88-7 ]
References: [1] Patent: CN107434785, 2017, A, . Location in patent: Paragraph 0039; 0040.
 

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