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Chemical Structure| 16867-03-1 Chemical Structure| 16867-03-1
Chemical Structure| 16867-03-1

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2-Amino-3-hydroxypyridine

CAS No.: 16867-03-1

4.5 *For Research Use Only !

Cat. No.: A118555 Purity: 98%

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Product Citations

Product Citations      Show More

Salman, Muhammad ; Jabbar, Abdul ; Farooq, Salma , et al.

Abstract: In the present work, fve monoazo heterocyclic disperse dyes PY1–PY5 were synthesized in good yield. A 2-amino-3-hydroxypyridine was used as a coupling component with fve distinct heterocyclic diazonium salts. All the dyes are new except the dye PY4. The obtained colorants were characterized by melting point, 1 H-NMR, FT-IR, UV–Vis, FAB-LRMS, and FABHRMS. The main skeletons of the dyes PY1, PY3, and PY4 were further confrmed by 13C-NMR (BB), 1 H–1 H COSY, 1 H–13C HSQC, and 1 H–13C HMBC. The efect of pH variation on the λmax of these colorants was assessed in methanol and DMSO. Their solvatochromism analyses were performed in various organic solvents, e.g., acetic acid, methanol, acetone, acetonitrile, dimethyl sulfoxide, and dimethyl formamide. The geometries of the dyes were optimized at the B3LYP/6-311G (d,p) level, and their electronic excitation properties were determined using time-dependent density functional theory. The computed data were in good agreement with the experimental data. These colorants were applied to polyester fabric as disperse dyes and evaluated for build-up study along with complete observation of their fastness to water, washing, sublimation, rubbing, perspiration, and light. The antimicrobial exploration of these dyes was performed in detail against human pathogenic fungi including Aspergillus fumigatus, Candida glabrata, Candida albicans and Trichophyton rubrum. The dye PY5 was found to have promising inhibition against all the human pathogenic fungi used.

Keywords: Azo disperse dyes ; pH sensitivity ; Antifungal activity ; Solvent efect ; DFT ; Global reactivity parameters

Purchased from AmBeed:

Ingraham, Charles H. IV ; Stalinska, Joanna ; Carson, Sean C. , et al.

Abstract: Glioblastomas are highly aggressive brain tumors for which therapeutic options are very limited. In a quest for new anti-glioblastoma drugs, we focused on specific structural modifications to the benzoyl-phenoxy-acetamide (BPA) structure present in a common lipid-lowering drug, fenofibrate, and in our first prototype glioblastoma drug, PP1. Here, we propose extensive computational analyses to improve the selection of the most effective glioblastoma drug candidates. Initially, over 100 structural BPA variations were analyzed and their physicochemical properties, such as water solubility (- logS), calculated partition coefficient (ClogP), probability for BBB crossing (BBB_SCORE), probability for CNS penetration (CNS-MPO) and calculated cardiotoxicity (hERG), were evaluated. This integrated approach allowed us to select pyridine variants of BPA that show improved BBB penetration, water solubility, and low cardiotoxicity. Herein the top 24 compounds were synthesized and analyzed in cell culture. Six of them demonstrated glioblastoma toxicity with IC50 ranging from 0.59 to 3.24 µM. Importantly, one of the compounds, HR68, accumulated in the brain tumor tissue at 3.7 ± 0.5 µM, which exceeds its glioblastoma IC50 (1.17 µM) by over threefold.

Alternative Products

Product Details of [ 16867-03-1 ]

CAS No. :16867-03-1
Formula : C5H6N2O
Linear Structure Formula :C5H3N(NH2)(OH)
M.W : 110.11
SMILES Code : C1=CC=NC(=C1O)N
MDL No. :MFCD00006317
InChI Key :BMTSZVZQNMNPCT-UHFFFAOYSA-N
Pubchem ID :28114

Safety of [ 16867-03-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Calculated chemistry of [ 16867-03-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 30.66
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

59.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.7
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

0.15
Log Po/w (WLOGP)?

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

0.38
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.

-0.45
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

0.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.21

Water Solubility

Log S (ESOL):?

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

-1.17
Solubility 7.41 mg/ml ; 0.0673 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.

-0.95
Solubility 12.4 mg/ml ; 0.113 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

-1.03
Solubility 10.3 mg/ml ; 0.0938 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

No
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.

-6.87 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

0.0 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)

1.31

Application In Synthesis [ 16867-03-1 ]

* 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.

  • Upstream synthesis route of [ 16867-03-1 ]
  • Downstream synthetic route of [ 16867-03-1 ]

[ 16867-03-1 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 16867-03-1 ]
  • [ 78-39-7 ]
  • [ 86467-39-2 ]
YieldReaction ConditionsOperation in experiment
65.8%
Stage #1: at 120℃; for 4 h;
Stage #2: Cooling
80 mL of ethyl orthoacetate was added to 15 g (136 mmol) of 2-amino-3-hydroxypyridine, followed by addition of p-toluenesulfonic acid in a catalytic amount, and the mixture was reacted at 120° C. for 4 hours. After the reaction solution was cooled, triethylamine was added to the solution, to neutralize p-toluenesulfonic acid. Then, the solution was subjected to distillation under reduced pressure by using an evaporator, and then purified by silica gel column chromatography.Amount of the product: 12.0 g, Yield: 65.8percent.
References: [1] Monatshefte fur Chemie, 2011, vol. 142, # 1, p. 87 - 91.
[2] Heterocycles, 1995, vol. 41, # 3, p. 477 - 486.
[3] Monatshefte fur Chemie, 2007, vol. 138, # 7, p. 663 - 667.
[4] Patent: US2009/247736, 2009, A1, . Location in patent: Page/Page column 13.
[5] Tetrahedron Letters, 1990, vol. 31, # 8, p. 1155 - 1156.
[6] Synthetic Communications, 1992, vol. 22, # 20, p. 2891 - 2901.
  • 2
  • [ 16867-03-1 ]
  • [ 123-54-6 ]
  • [ 86467-39-2 ]
References: [1] Journal of Organic Chemistry, 2014, vol. 79, # 13, p. 6310 - 6314.
  • 3
  • [ 16867-03-1 ]
  • [ 64-19-7 ]
  • [ 86467-39-2 ]
References: [1] Tetrahedron Letters, 2007, vol. 48, # 13, p. 2295 - 2298.
  • 4
  • [ 16867-03-1 ]
  • [ 32894-07-8 ]
  • [ 86467-39-2 ]
References: [1] Tetrahedron Letters, 1990, vol. 31, # 8, p. 1155 - 1156.
  • 5
  • [ 16867-03-1 ]
  • [ 75-36-5 ]
  • [ 31354-48-0 ]
References: [1] Tetrahedron, 2006, vol. 62, # 10, p. 2405 - 2412.
[2] Tetrahedron Letters, 2004, vol. 45, # 7, p. 1465 - 1468.
  • 6
  • [ 16867-03-1 ]
  • [ 108-24-7 ]
  • [ 31354-48-0 ]
References: [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3730 - 3742.
  • 7
  • [ 16867-03-1 ]
  • [ 877399-47-8 ]
References: [1] Patent: CN108341802, 2018, A, .
  • 8
  • [ 16867-03-1 ]
  • [ 24424-99-5 ]
  • [ 902835-93-2 ]
YieldReaction ConditionsOperation in experiment
95% With guanidine hydrochloride In ethanol at 35 - 40℃; for 2.5 h; General procedure: Amine (1 mmol) was added to a magnetically stirred solution of guanidine hydrochloride (15 molpercent) and di-tert-butyl dicarbonate (1.2 mmol) in EtOH (1 mL), at 35-40°C and stirred for appropriate time (Table 1). After completion of the reaction (followed by TLC or GC), EtOH was evaporated under vacuum and the residue either was washed with water to remove the catalyst or was dissolved in CH2Cl2 (or EtOAc) and filtered off to separate out the catalyst. Evaporation of the organic solvent (if used in work up) gives almost a pure product. In the cases of using an excess (Boc)2O the product was washed with petroleum ether or hexane to recover the residual (Boc)2O. If necessary, the product was further purified either by crystallization (hexane and dichloromethane, or diethyl ether and petroleum ether) or silica gel column chromatography using EtOAc-hexane (1: 6) as eluent.
References: [1] Tetrahedron Letters, 2011, vol. 52, # 12, p. 1260 - 1264.
 

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