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Chemical Structure| 500-22-1 Chemical Structure| 500-22-1

Structure of 500-22-1

Chemical Structure| 500-22-1

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Product Citations

Product Citations      Show More

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.

Keywords: nitrogen heterocycles ; glycogen synthase kinase 3β ; computational docking

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.

Keywords: Chloride ; chloride detection ; chloride-sensitive luminophore ; iridium complex

Purchased from AmBeed: ; ;

Alternative Products

Product Details of [ 500-22-1 ]

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

Safety of [ 500-22-1 ]

GHS Pictogram:
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:

Computational Chemistry of [ 500-22-1 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

29.96 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.96
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.29
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.89
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.23
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.55
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.69

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.18
Solubility 7.15 mg/ml ; 0.0667 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.48
Solubility 35.4 mg/ml ; 0.33 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.91
Solubility 1.33 mg/ml ; 0.0124 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.75 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.0

Application In Synthesis of [ 500-22-1 ]

* 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.

  • Downstream synthetic route of [ 500-22-1 ]

[ 500-22-1 ] Synthesis Path-Downstream   1~35

  • 2
  • [ 500-22-1 ]
  • [ 5799-75-7 ]
  • [ 124858-90-8 ]
  • 3
  • [ 500-22-1 ]
  • [ 1075-34-9 ]
  • 5-Bromo-2-methyl-3-(pyridin-3-ylmethyl)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 4
  • [ 500-22-1 ]
  • [ 65854-91-3 ]
  • [ 114995-53-8 ]
  • 5
  • [ 500-22-1 ]
  • [ 6414-69-3 ]
  • [ 541-41-3 ]
  • 4-(2-Ethoxycarbonyl-ethyl)-3-formyl-4H-pyridine-1-carboxylic acid ethyl ester [ No CAS ]
  • 6
  • [ 500-22-1 ]
  • [ 83465-22-9 ]
  • [ 83470-45-5 ]
  • 7
  • [ 500-22-1 ]
  • [ 51792-34-8 ]
  • (3,4-dimethoxy-2-thienyl)-3-pyridylmethanol [ No CAS ]
  • 8
  • [ 500-22-1 ]
  • [ 75-04-7 ]
  • [ 3000-75-7 ]
  • 9
  • [ 500-22-1 ]
  • [ 85920-63-4 ]
  • [ 122889-11-6 ]
  • (S)-5-Benzyloxymethyl-3-[1-hydroxy-eth-(Z)-ylidene]-1-pyridin-3-ylmethyl-pyrrolidine-2,4-dione [ No CAS ]
  • 10
  • [ 7647-01-0 ]
  • [ 4314-66-3 ]
  • [ 60-29-7 ]
  • [ 10026-13-8 ]
  • SnCl2 [ No CAS ]
  • [ 500-22-1 ]
  • [ 3000-75-7 ]
  • 11
  • [ 500-22-1 ]
  • [ 1979-98-2 ]
  • 5,5'-(3-pyridylmethylene)bis(4,6-dihydroxy-2-methylthiopyrimidine) [ No CAS ]
  • 12
  • [ 500-22-1 ]
  • [ 57497-39-9 ]
  • [ 1001387-10-5 ]
  • 13
  • [ 500-22-1 ]
  • [ 5654-97-7 ]
  • 14
  • [ 500-22-1 ]
  • [ 42726-73-8 ]
  • [ 871351-39-2 ]
YieldReaction ConditionsOperation 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).
  • 15
  • [ 500-22-1 ]
  • [ 65854-91-3 ]
  • [ 698395-58-3 ]
YieldReaction ConditionsOperation 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) +
  • 16
  • [ 500-22-1 ]
  • [ 35661-51-9 ]
  • [ 1158960-29-2 ]
  • 17
  • [ 500-22-1 ]
  • [ 3000-75-7 ]
  • 18
  • [ 500-22-1 ]
  • [ 35661-51-9 ]
  • [ 1158960-29-2 ]
YieldReaction ConditionsOperation 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
  • 19
  • [ 500-22-1 ]
  • [ 1122-54-9 ]
  • [ 13309-08-5 ]
  • 20
  • [ 500-22-1 ]
  • [ 17919-34-5 ]
  • [ 1379539-90-8 ]
  • 21
  • [ 88675-24-5 ]
  • [ 500-22-1 ]
  • C10H12N2O [ No CAS ]
YieldReaction ConditionsOperation 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;
  • 22
  • [ 500-22-1 ]
  • [ 119072-55-8 ]
  • [ 769-92-6 ]
  • [ 1072-84-0 ]
  • [ 1417699-82-1 ]
  • 23
  • [ 500-22-1 ]
  • [ 37718-11-9 ]
  • [ 119072-55-8 ]
  • [ 769-92-6 ]
  • [ 1417699-92-3 ]
  • 24
  • [ 500-22-1 ]
  • [ 119072-55-8 ]
  • [ 769-92-6 ]
  • [ 41716-18-1 ]
  • [ 1417700-02-7 ]
  • 25
  • [ 500-22-1 ]
  • [ 116668-47-4 ]
  • (3-py)-CH=N-C10H6-COOH [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 26
  • [ 500-22-1 ]
  • [ 1585-90-6 ]
  • [ 107-97-1 ]
  • 2-(2-hydroxyethyl)-5-methyl-4-(pyridin-3-yl)tetrahydropyrrolo-[3,4-c]pyrrole-1,3(2H,3aH)-dione [ No CAS ]
  • 27
  • [ 500-22-1 ]
  • [ 1668-54-8 ]
  • [ 1465740-10-6 ]
  • 29
  • [ 500-22-1 ]
  • [ 13214-64-7 ]
  • (E)-2-(4-methoxyphenyl)-4-(pyridin-3-ylmethylene)-oxazol-5(4H)-one [ No CAS ]
  • 30
  • [ 500-22-1 ]
  • [ 13214-64-7 ]
  • (E)-4-[2-(4-methoxyphenyl)-5-oxo-4-(pyridin-3-ylmethylene)-4,5-dihydro-1H-imidazol-1-yl]-benzenesulfonamide [ No CAS ]
  • 31
  • [ 500-22-1 ]
  • [ 1986-47-6 ]
  • (1S*,2R*)-2-phenyl-N-(pyridin-3-ylmethyl)cyclopropan-1-amine [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 32
  • [ 500-22-1 ]
  • [ 20876-36-2 ]
  • 5-(pyridin-3-ylmethylamino)indolin-2-one [ No CAS ]
  • 33
  • [ 500-22-1 ]
  • [ 16313-65-8 ]
  • [ 1027034-81-6 ]
  • 34
  • [ 500-22-1 ]
  • [ 37170-50-6 ]
  • [ 6938-06-3 ]
  • 35
  • [ 500-22-1 ]
  • [ 78364-55-3 ]
  • C13H9FN4S [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 500-22-1 ]

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[ 500-22-1 ]

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