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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 500-22-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
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Batch number can be found on the product's label following the word 'Batch'.
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Nicholas O. Schneider ; Kendra Gilreath ; Daniel J. Burkett ; Martin St. Maurice ; William A. Donaldson ;
Abstract: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory activities including for GSK-3β. A family of fourteen 2-heterocycle substituted methylene hydantoins (14, 17–29) were prepared and evaluated for the inhibition of GSK-3β at 25 μM. The IC50 values of five of these compounds was determined; the two best inhibitors are 5-[(4′-chloro-2-pyridinyl)methylene]hydantoin (IC50 = 2.14 ± 0.18 μM) and 5-[(6′-bromo-2-pyridinyl)methylene]hydantoin (IC50 = 3.39 ± 0.16 μM). The computational docking of the compounds with GSK-3β (pdb 1q41) revealed poses with hydrogen bonding to the backbone at Val135. The 5-[(heteroaryl)methylene]hydantoins did not strongly inhibit other metalloenzymes, demonstrating poor inhibitory activity against matrix metalloproteinase-12 at 25 μM and against human carbonic anhydrase at 200 μM, and were not inhibitors for Staphylococcus aureus pyruvate carboxylase at concentrations >1000 μM.
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Keywords: nitrogen heterocycles ; glycogen synthase kinase 3β ; computational docking
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Purchased from AmBeed: 63071-13-6 ; 53547-60-7 ; 31181-90-5 ; 34160-40-2 ; 4985-92-6 ; 1121-60-4 ; 54221-96-4 ; 55589-47-4 ; 500-22-1 ; 1805434-14-3
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Leveraging Metal Complexes for Microsecond Lifetime-Based Chloride Sensing
Morse, Jared ; Ofodum, Nnamdi ; Tang, Fung-Kit ; Schmidt, Matthias ; Lu, Xiaocun ; Leung, Kaho
Abstract: Chloride is the most abundant anion in cell physiology and plays many critical roles in maintaining cellular homeostasis. However, current chloride sensors are rare, with inherent sensitivity in their emission properties, such as vulnerability to pH changes or short emission lifetimes. These limitations restrict theirapplication in aqueous media and imaging. In this work, we employed a transition metal complex bearing pyridinium as a recognition unit for chloride and studied the phosphorescence emission properties. Iridium(III) complex 1 was synthesized as an alternative chloride-sensitive luminophore. The conjugable design also allows customization for desired applications. Complex 1 exhibited high sensitivity and selectivity in chloride sensing across different physiological environments, regardless of pH fluctuation and ionic strength. Additionally, complex 1 featured a long microsecond emission lifetime. The chloride sensing ability of complex 1 can be measured through both luminescence intensity and long-lived phosphorescent lifetime simultaneously, providing an alternative potential route for chloride imaging.
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Keywords: Chloride ; chloride detection ; chloride-sensitive luminophore ; iridium complex
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CAS No. : | 500-22-1 |
Formula : | C6H5NO |
M.W : | 107.11 |
SMILES Code : | O=CC1=CN=CC=C1 |
MDL No. : | MFCD00006382 |
InChI Key : | QJZUKDFHGGYHMC-UHFFFAOYSA-N |
Pubchem ID : | 10371 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H226-H302-H315-H317-H318-H335-H412 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P261-P264-P270-P271-P272-P273-P280-P301+P312+P330-P303+P361+P353-P304+P340+P312-P305+P351+P338+P310-P333+P313-P370+P378-P403+P233-P403+P235-P405-P501 |
Class: | 3 |
UN#: | 1989 |
Packing Group: | Ⅲ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 29.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.96 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.89 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.18 |
Solubility | 7.15 mg/ml ; 0.0667 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.48 |
Solubility | 35.4 mg/ml ; 0.33 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.91 |
Solubility | 1.33 mg/ml ; 0.0124 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.75 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylsilane; In methanol; dichloromethane; trifluoroacetic acid; | PREPARATION 8 5-Bromo-2-methyl-3-(3-pyridylmethyl)-1H-indole A solution of <strong>[1075-34-9]5-bromo-2-methyl-1H-indole</strong> (J. Chem. Soc., 1428 (1965)) (2.0 g) and 3-pyridinecarboxaldehyde (1.02 g) in dry dichloromethane (20 ml) was added dropwise over 10 minutes to a stirred solution of triethylsilane(3.30 g) in trifluoroacetic acid (20 ml) at 0° C. The solution was stirred at 0° C. for 30 minutes and then evaporated under vacuum, keeping the temperature below 35° C. The residue was dissolved in dichloromethane, and the solution was washed with 2N sodium hydroxide, water and dried (MgSO4). The solution was evaporated and the residue was chromatographed on silica gel, using dichloromethane/methanol (50:1) as eluent. The product fractions were combined and evaporated, and the residue was crystallized from ether to give the title compound (2.15 g), m.p. 188°-190° C. Found: C,59.62; H,4.43; N,9.26. C15 H13 BrN2 requires: C,59.82; H,4.35; N,9.30percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; benzoic acid; In benzene; for 12h;Heating / reflux; | Example 13 L3-(7-Methoxy-indol-1- lY )-3-pyridin-3- T(at)l-propyll-methyl-aznine The synthetic procedure of Example 12 is outlined in Scheme L below. SCHEME L Step; 2-Pyridin-3-ylmethylene-malonic acid tert-butyl ester methyl ester A mixture of pyridine-3-carboxaldehyde (2.72 g), propanedioic acid, 1,1-dimethylethyl methyl ester (4.42 g), piperidine (0.173 g) and benzoic acid (0.155 g) in benzene (100 ml) was heated at reflux with removal of water to a Dean-Stark trap for 12 hours. The cooled mixture was washed with bicarbonate solution, concentrated under vacuum and the residue was purified by column chromatography, eluting with ethyl acetate - hexane (3 : 7) to afford racemic 2-pyridin-3-ylmethylene-malonic acid tert-butyl ester methyl ester as an oil (3.21 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
N- (4-Chloro-phenyl)-2, 2-dimethyl-propionamide (3.0, 14.2 MMOL) was dissolved in 15 mL THF in a dry 100 mL flask fitted with a rubber septa and nitrogen inlet and cooled to 0C in ice water bath for 25 minutes. A solution of 2.5M BuLi in hexane (17.0 mL, 42.6 MMOL) was added and the mixture stirred for 45 minutes. To the thick yellow precipitate that formed was added a solution of pyridine-3-carboxaldehyde (3.03 g, 28.4 MMOL) in 15 mL THF. The ice bath was removed and the mixture was allowed to stir at room temperature for 45 minutes and the reaction was quenched with 25 mL H20. The mixture was transferred to a separating funnel, and the aqueous phase was discarded. The organics were DRIED IN VACUO to yield product as an orange oil. 1 H NMR (CD3) 6 8.85 (m, 1H) 8.54 (m, 1H) 8.42 (m, 1H) 8.10 (dd, J = 8. 8 HZ, 2.8Hz, 1H) 7.50 (d, J=8. 0HZ, 1H) 7.31 (m, 1H) 7.23 (m, 1H) 7.10 (m, 1H) 5.85 (m, 1H) 1.70 (d, 1H) 1.08 (s, 9H); MS (ES) m/z = 319. 1 (MH) + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | at 20℃; for 1.5h;Neat (no solvent); Ball-milling; | General procedure: A mixture of aldehyde (0.5 mmol, 1 equiv) and hydrazine (0.5 mmol, 1.0 equiv) was ball-milled at 30 Hz for the specified time (see refPreviewPlaceHolderTable 1). When the reaction was complete, the product was recovered as a solid directly in the jar and then dried overnight under vacuo |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In methanol; at 30℃; for 16h;Inert atmosphere; | General procedure: All reactions were carried out in vials under nitrogen atmosphere. Step 1: A solution of compound 15 (125 mumol, 1.0 equiv) and compound 16 (125 mumol, 1.0 equiv) in MeOH (0.3 M) was treated with NaHCO3 (250 mumol, 2.0 equiv) and stirred for 16 h at 30 °C. The reaction was then treated with NaBH4 (125 mumol, 1.0 equiv) and stirred for 3 h (LCMS check). The reaction mixture was filtered and concentrated. The crude amine was suspended in 1 N NaOH (1 mL) and extracted with dichloromethane (3 × 1 mL). The organics were pooled, dried (Na2SO4) and evacuated to afford 18. Step 2: A solution of 17 (75 mumol, 0.60 equiv) in DMF (0.1 M) was treated with HATU (75 mumol, 0.60 equiv) followed by the crude amine 18 (125 mumol, 1.0 equiv) and iPr2NEt (225 mumol, 1.8 equiv). The reactions were concentrated and purified directly by reversed phase preparative HPLC using a C18 column and eluting with acetonitrile?water (0.225percent formic acid or pH = 10 NH4OH) gradient. All compounds were deemed greater than 95percent purity by LCMS and HPLC. #10; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | In methanol; at 75℃; for 12h;Autoclave; | A 25 ml Teflon-lined autoclave containing 6-amino-2-naphthnoic acid (370 mg, 2 mmol), 3-pyridinecarboxaldehyde (210 mg, 2 mmol), and methanol (20 ml) was sealed and heated at 75 °C for 12 h, and then air-cooled slowly for 24 h. The resulting yellow crystals were filtered, and washed with methanol (10 ml × 3) to give ligand (67percent yield). Anal. Calc. for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C 74.00; H 4.30; N 10.15percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | General procedure: Trans-2-phenylcyclopropylamine hydrochloride (1.0 eq.), acetic acid (1.0eq.) and the appropriate aldehyde (0.9 eq.) were dissolved in around bottom flask in 10 mL dry DCE. The reaction mixture was stirred gently at room temperature for 2 h before sodium triacetoxyborohydride (3.0 eq.) was added in small portions to the reaction vessel. The reaction was monitored by TLC and quenched using 10 mL of an aqueous (5%) NaHCO3 solution. The organic layer was separated and the aqueous layer extracted three times with10 mL of DCE. All organic layers were combined, dried over anhydrous Na2SO4, concentrated in vacuo and purified using flash chromatography (silica gel; cyclohexane/ethyl acetate) to give the desired compound. |