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Salman, Muhammad ; Jabbar, Abdul ; Farooq, Salma ; Rafiq, Muhammad Sohail Khan ; Munsif, Sajida ; Ul-Haq, Zaheer

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

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Ingraham, Charles H. IV ; Stalinska, Joanna ; Carson, Sean C. ; Colley, Susan B. ; Rak, Monika ; Lassak, Adam , 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 2-Amino-3-hydroxypyridine

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

Safety of 2-Amino-3-hydroxypyridine

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

Application In Synthesis of 2-Amino-3-hydroxypyridine

* 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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