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Structure of 147071-00-9

Chemical Structure| 147071-00-9

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Product Details of [ 147071-00-9 ]

CAS No. :147071-00-9
Formula : C9H8N2O2
M.W : 176.17
SMILES Code : O=C(C1=CC2=C(NC=C2)C=N1)OC
MDL No. :MFCD07778440
InChI Key :JKZKPRSBRUHIER-UHFFFAOYSA-N
Pubchem ID :44549263

Safety of [ 147071-00-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 147071-00-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 9
Fraction Csp3 0.11
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 47.37
TPSA ?

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

54.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.37
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

1.17
Log Po/w (WLOGP)?

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

1.35
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

1.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.19

Water Solubility

Log S (ESOL):?

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

-2.05
Solubility 1.57 mg/ml ; 0.00892 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.

-1.92
Solubility 2.12 mg/ml ; 0.012 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

-2.98
Solubility 0.183 mg/ml ; 0.00104 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

Yes
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.

-6.54 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)

1.76

Application In Synthesis of [ 147071-00-9 ]

* 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 [ 147071-00-9 ]

[ 147071-00-9 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 868551-31-9 ]
  • [ 147071-00-9 ]
YieldReaction ConditionsOperation in experiment
86% With hydrogen In methanol at 25 - 50℃; for 40.666 h; To a 500 mL Parr bottle was added methyl 4- [(E(at)-2-(dimethylamino)vinyl]-5-nitropyridine-2-carboxylate g, 75.2 mmol) and anhydrous methanol (200 mL). The mixture was purged with nitrogen gas for 10 min. To this suspension was added Pd(10percent)/C (1.90 g, 10 w/w percent), and the suspension was degassed for 5 more minutes. The hydrogenation began with 43 psi H2 without heating. The reaction became exothermic as indicated by the rising temperature (about 2-3 °C per min) inside the Parr bottle (monitored by a thermal coupling thermometer). As the temperature inside of the reaction reached 45 °C, the hydrogen gas flow into the Parr bottle was stopped, and the mixture was allowed to cool down to 25 °C for 30 min. The color of the liquid of the suspension changed from purple red to light green and then colorless in the first hour of the reduction, and about 30 psi H2 was consumed. The hydrogen pressure was brought to 50 psi, and the hydrogenation was continued at 50 °C for 20 h. There was no more hydrogen gas consumed in the last 20 h. After cooling the reaction mixture to 20 °C, the solid mixture, which contained Pd (10percent)/C product, was filtered. The solid mixture was suspended in DMSO (200 mL), and the suspension was heated on a hot plate to 80 °C internal temperature with stirring for 10 min. The hot suspension was filtered and the Pd(10percent)/C solid was washed with a small portion of DMSO (50 mL). The DMSO filtrate and washing were combined and poured into water (600 mL). Off white solid product precipitated out, and the suspension was stirred for 1 h before filtering, and lyophilizing. The title compound was obtained as an off-white solid product was obtained (11.3 g, >95 percent pure, 86 percent yield). 1H NMR (300 MHz, DMSO-d6) 8 ppm 3.84 (s, 3H) 6.68 (d, J=2.8 Hz, 1 H) 7.73 (d, J=3.0 Hz, 1 H) 8.36 (s, 1 H) 8.80 (s, 1 H) 11.99 (s, 1 H). LCMS: (APCI, M-H-) = 175
References: [1] Patent: WO2005/103003, 2005, A2, . Location in patent: Page/Page column 71-72.
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 22, p. 7211 - 7219.
[3] Patent: WO2006/27694, 2006, A1, . Location in patent: Page/Page column 83-84.
 

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