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Structure of 2446-83-5

Chemical Structure| 2446-83-5

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Product Citations

Dawson, Miranda ;

Abstract: The brain is in continuous communication with the rest of the body. Nerves connect the peripheral and central nervous system, and complex vasculature networks selectively permit passage of small molecules with an exogenous origin into the brain parenchyma. Although brain-body interactions underpin a host of cognitive and physiological phenomena, they are often overlooked in studies of brain biology and mental function. We studied aspects of the interaction between brain and body using functional and molecular magnetic resonance imaging (MRI), in combination with other tools. In a first project, we examined properties of the blood-brain barrier (BBB). The BBB is a highly selective collection of endothelial cells and tight junction proteins that restrict passage of extracerebral substances from the blood vessels into the brain tissue. We disrupted and bypassed the BBB to deliver an MRI contrast agent and quantitatively assessed the resulting contrast dynamics. We discovered that individual brain regions display method-independent susceptibility to BBB disruption and washout, suggesting principles for calibrating drug delivery and understanding the propensity for chemical exchange across the BBB. We then used one of the wide-field brain delivery techniques to apply a novel contrast agent for the study of the cholinergic system, a neurochemical pathway important for motor control mechanisms in both the central and peripheral nervous systems. Kinetic modeling of probe distributions revealed intrinsic localization of cholinergic enzymes. Finally, we applied related neuroimaging tools to an animal model of substance abuse, a pathology for which brain-body interactions are particularly engaged but underappreciated. We designed a study to investigate the role of the insula, a cortical mediator of peripheral physiological signals, in responses to opioid exposure. With molecular imaging approaches, we show the insula shapes drug-dependent brain phenotypes and physiological responses during substance exposure and withdrawal. In all, this work serves as a demonstration of the power of quantitative neuroimaging methods for multifaceted investigation of brain and body relationships.

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Alternative Products

Product Details of [ 2446-83-5 ]

CAS No. :2446-83-5
Formula : C8H14N2O4
M.W : 202.21
SMILES Code : O=C(/N=N/C(OC(C)C)=O)OC(C)C
MDL No. :MFCD00008875

Safety of [ 2446-83-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H335-H350-H373-H401-H410
Precautionary Statements:P201-P202-P260-P264-P271-P273-P280-P302+P352-P304+P340+P312-P305+P351+P338-P308+P313-P332+P313-P337+P313-P362-P391-P403+P233-P405-P501
Class:9
UN#:3082
Packing Group:

Computational Chemistry of [ 2446-83-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 6
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 48.77
TPSA ?

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

77.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.9
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

2.55
Log Po/w (WLOGP)?

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

2.53
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.

1.63
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

1.19
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.16

Water Solubility

Log S (ESOL):?

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

-2.3
Solubility 1.0 mg/ml ; 0.00496 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-3.82
Solubility 0.0305 mg/ml ; 0.000151 mol/l
Class?

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

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

-1.01
Solubility 19.9 mg/ml ; 0.0984 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.

-5.72 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

0.0
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.

1.0 alert
Brenk?

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

2.0 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)

2.85

Application In Synthesis of [ 2446-83-5 ]

* 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 [ 2446-83-5 ]

[ 2446-83-5 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 2446-83-5 ]
  • [ 29949-85-7 ]
  • [ 84985-43-3 ]
  • C34H29Cl3N2O7P(1+)*C8H15N2O4(1-) [ No CAS ]
  • 2
  • [ 178043-48-6 ]
  • [ 827-99-6 ]
  • [ 2446-83-5 ]
  • 3,5-Dichloro-4-(3-(4-trifluoromethoxyphenoxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With triphenylphosphine; In tetrahydrofuran; PRODUCTION EXAMPLE 29 Production of Compound (185) by Production Process G To a solution of 1.10 g of 3,5-dichloro-4-(3-hydroxypropoxy)-1-(3,3-dichloro-2-propenyloxy)benzene, 0.56 g of <strong>[827-99-6]3-trifluoromethoxyphenol</strong> and 0.83 g of triphenylphosphine dissolved in 20 ml of tetrahydrofuran was added dropwise a solution of 0.64 g of diisopropylazodicarboxylate dissolved in 10 ml of tetrahydrofuran, while stirring at room temperature. After stirring at room temperature for 24 hours, the reaction mixture was concentrated to obtain a residue. The residue was subjected to silica gel chromatography, which afforded 1.03 g of 3,5-dichloro-4-(3-(4-trifluoromethoxyphenoxy) propoxy)-1-(3,3-dichloro-2-propenyloxy)benzene (64% yield), nD23.4 1.5343.
  • 3
  • [ 1570-64-5 ]
  • [ 2446-83-5 ]
  • [ 19740-72-8 ]
  • [ 54852-68-5 ]
  • 4
  • [ 107-75-5 ]
  • [ 2446-83-5 ]
  • dipropan-2-yl 1-(7-hydroxy-3,7-dimethyloctanoyl)hydrazine-1,2-dicarboxylate [ No CAS ]
  • 5
  • [ 2446-83-5 ]
  • [ 1195-33-1 ]
  • diisopropyl 1-(4-bromobenzenesulfonyl)hydrazine-1,2-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In methanol; at 20℃; for 12h;Green chemistry; General procedure: To a mixture of sulfinic acids 1 (0.6 mmol) and azodicarboxylates 2 (0.5 mmol) in a 25 mL round-bottomed flack at room temperature, was added the CH3OH (2 mL). The reaction vessel was allowed to stir at room temperature for 12h. After the reaction, the solvent was then removed under vacuum. The residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent to give the desired product 3.
  • 6
  • [ 1088-00-2 ]
  • [ 2446-83-5 ]
  • [ 603-35-0 ]
  • C26H27N2O4P [ No CAS ]
  • [ 86825-70-9 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 0℃;Inert atmosphere; Ph3P (94.4mg, 0.36mmol) and <strong>[1088-00-2]9-phenyl-9-phosphafluorene</strong> (93.6mg, 0.36mmol) were dissolved in dry THF (3mL) under nitrogen in a 10mm NMR tube. The solution was cooled to 0C and DIAD (18μL, 0.09mmol) then added dropwise over 1min to the swirled, cooled solution. A cap was placed on the tube and sealed with Parafilm before recording the 31P NMR spectrum at 10C on a 300MHz instrument within 5min. The experiment was repeated using methyl iodide in place of DIAD. All spectra were acquired at an operating frequency of 121.47MHz using a 45 flip angle, 3s recycle delay, and a 0.33s acquisition time with gated decoupling. Negative 31P chemical shifts are upfield of external phosphoric acid (85%).
  • 7
  • [ 50461-74-0 ]
  • [ 2446-83-5 ]
  • C15H28N2O7 [ No CAS ]
  • 8
  • [ 2446-83-5 ]
  • [ 51419-59-1 ]
  • diisopropyl 1-[1-chloro-1-(4-methylphenyl)methanesulfonyl]-hydrazine-1,2-dicarboxylate [ No CAS ]
  • 9
  • [ 2446-83-5 ]
  • [ 5451-55-8 ]
  • C18H34N2O4 [ No CAS ]
  • 10
  • [ 2446-83-5 ]
  • [ 2012-74-0 ]
  • C18H27ClN2O4 [ No CAS ]
 

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Technical Information

Categories

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