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Chemical Structure| 13040-21-6

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Sarah Ann Goda ;

Abstract: We expanded the understandings of photonic crystal hydrogel fabrication and swelling behavior pertaining to their use as sensing materials. Our hydrogels are comprised of a polymer network containing a recognition group and a photonic crystal array embedded within the hydrogel network. The molecular recognition groups within the hydrogel allow us to make these sensors highly selective to target analytes. Hydrogel changes from analyte binding result in a volume phase transition (VPT). Hydrogel VPTs alter the distance between particles that make up the photonic crystal array, leading to changes in diffracted light according to the Bragg condition. Studies reported herein demonstrate the use of photonic crystal hydrogel sensors as sensing platforms that are easily adaptable. We investigated the use of oxyamine functionalized hydrogels to monitor lactate dehydrogenase’s enzymatic conversion of lactate to pyruvate. Pyruvate’s covalent attachment to the hydrogel enables a swelling response which corresponds to lactate concentrations in solution. We detected < 0.5 mM lactate in buffer solutions within an hour with detection limits < 4 mM lactate in serum solutions. This work is the first to demonstrate indirect detection of analytes by coupling enzymatic reactions with photonic crystal hydrogel sensors. DNA aptamers are small biomolecules that are highly selective in their binding and are stable under a variety of conditions. We incorporated hybridized DNA aptamers into 2DPC hydrogels forming crosslinks. These DNA crosslinks break due to analyte-DNA binding which enables hydrogel swelling. We demonstrated this aptamer sensing motif is easily modified from detecting the small molecule adenosine to the large protein thrombin. Poly (N-isopropylacrylamide) (pNIPAM) hydrogels are thermoresponsive, undergoing large VPTs at temperatures above their lower critical solution temperature (LCST). pNIPAM’s LCST is shifted due to changes in the hydrophobicity of pNIPAM’s environment from disruptions to pNIPAM’s solvation shell. This enables detection of hydrophobic analytes that can typically require complex detection methods. We are the first to investigate using shifts in pNIPAM’s LCST for detection of hydrophobic analytes such as Xe. We spectroscopically investigated Xe-protein binding to monitor favorable Xe binding environments and increase pNIPAM’s sensitivity to the presence of Xe.

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Product Details of [ 13040-21-6 ]

CAS No. :13040-21-6
Formula : C9H9NO2
M.W : 163.17
SMILES Code : C=CC(NC1=CC=CC(O)=C1)=O
MDL No. :MFCD00599810
Boiling Point : No data available
InChI Key :PMHOLXNNEPPFNZ-UHFFFAOYSA-N
Pubchem ID :275403

Safety of [ 13040-21-6 ]

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

Computational Chemistry of [ 13040-21-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 47.11
TPSA ?

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

49.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.43
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

1.32
Log Po/w (WLOGP)?

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

1.33
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.

1.15
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

1.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.29

Water Solubility

Log S (ESOL):?

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

-1.86
Solubility 2.28 mg/ml ; 0.014 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.

-1.96
Solubility 1.8 mg/ml ; 0.011 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

-2.26
Solubility 0.899 mg/ml ; 0.00551 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.

-6.36 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)

1.43

Application In Synthesis of [ 13040-21-6 ]

* 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 [ 13040-21-6 ]

[ 13040-21-6 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 814-68-6 ]
  • [ 591-27-5 ]
  • [ 13040-21-6 ]
YieldReaction ConditionsOperation in experiment
40% With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 3.5 h; Tetrahydrofuran (100 mL) and water (30 mL) was added to 3-aminophenyl (5.0 g, 0.045 mol), sodium hydrogen carbonate (5.6 g, 0.067 mol) was added thereto, and acroyl chloride (3.6 mL, 0.045 mol) was added dropwise. The reaction solution was stirred for 3.5 hours at room temperature, added with dichloromethane, and washed with an aqueous solution of ammonium chloride. The organic layer was separated, dried over sodium sulfate, filtered and distilled under reduced pressure. The resulting residue was distilled with dichloromethane and ether to obtain the title compound (2.9 g, yield: 40percent). 'H-NMR(300 MHZ, DMSO-d6) δ 5.73 (dd, 1 H), 6.24 (dd, 1 H), 6.42 (m, 2H), 7.04 (m, 2H), 7.24(s, 1 H), 9.39 (s, 1H), 9.97 (s, 1 H)
References: [1] Patent: WO2013/100631, 2013, A1, . Location in patent: Page/Page column 13; 15-16.
[2] Patent: EP2058318, 2009, A1, .
[3] European Journal of Medicinal Chemistry, 2017, vol. 133, p. 329 - 339.
[4] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 10, p. 2724 - 2729.
[5] European Journal of Medicinal Chemistry, 2017, vol. 135, p. 60 - 69.
[6] Patent: CN106749042, 2017, A, . Location in patent: Paragraph 0079; 0080; 0090; 0091; 0092.
[7] Chemical Biology and Drug Design, 2018, .
[8] Patent: CN108658874, 2018, A, . Location in patent: Paragraph 0038; 0044; 0045.
  • 2
  • [ 814-68-6 ]
  • [ 591-27-5 ]
  • [ 13040-21-6 ]
  • [ 35289-74-8 ]
References: [1] Synthetic Communications, 2009, vol. 39, # 15, p. 2723 - 2736.
 

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