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Chemical Structure| 73721-78-5 Chemical Structure| 73721-78-5

Structure of 73721-78-5

Chemical Structure| 73721-78-5

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Product Details of [ 73721-78-5 ]

CAS No. :73721-78-5
Formula : C9H8N2O5
M.W : 224.17
SMILES Code : O=C(O)C1=C([N+]([O-])=O)C=CC=C1NC(C)=O
MDL No. :MFCD08276267
InChI Key :HHNTZMHFBQIQAK-UHFFFAOYSA-N
Pubchem ID :153453

Safety of [ 73721-78-5 ]

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

Computational Chemistry of [ 73721-78-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.11
Num. rotatable bonds 4
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 56.54
TPSA ?

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

112.22 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.92
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

0.66
Log Po/w (WLOGP)?

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

1.06
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.

0.14
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

-1.29
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.3

Water Solubility

Log S (ESOL):?

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

-1.66
Solubility 4.91 mg/ml ; 0.0219 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.

-2.59
Solubility 0.573 mg/ml ; 0.00255 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

-1.55
Solubility 6.36 mg/ml ; 0.0284 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.

-7.2 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.

0.56

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

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)

2.19

Application In Synthesis of [ 73721-78-5 ]

* 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 [ 73721-78-5 ]

[ 73721-78-5 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 73721-78-5 ]
  • [ 5623-11-0 ]
  • 2
  • [ 412341-84-5 ]
  • [ 7732-18-5 ]
  • [ 73721-78-5 ]
  • 4
  • 6-nitro-acetylanthranil [ No CAS ]
  • [ 73721-78-5 ]
  • 5
  • [ 73721-78-5 ]
  • [ 24666-56-6 ]
  • [ 1620018-94-1 ]
YieldReaction ConditionsOperation in experiment
35% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In water; N,N-dimethyl-formamide; at 20.0℃; for 24.0h;Inert atmosphere; Step 3. Synthesis of rac-2-Acetamido-N-(2,6-dioxopiperidin-3-yi)-6-nitrobenzamide [00302] The starting acid (3.10 g, 13.8 mmol) was mixed with hydroxybenzotriazole (HOBt, 2.12 g of the hydrate, 13.8 mmol) and l-ethyl-3-(3-dimethylaminopropyl)- carbodiimide hydrochloride (EDC, 2.54 g, 13.3 mmol), under a nitrogen atmosphere. N,N- dimethylformamide (DMF, 21.4 mL) was added and the mixture was stirred for 30 minutes at room temperature. rac-3-Aminopiperidine-2,6-dione hydrochloride (5.01 g, 30.4 mmol) was added, followed by Nu,Nu-diisopropylethylamine (DIEA, 9.63 mL, 55.3 mmol). The reaction mixture was stirred at 20C, while monitoring by HPLC. After 24 hours, the reaction mixture showed approximately 40% conversion to the desired product containing some remaining starting acid, but no amine. Then, the reaction mixture was slowly poured into 200 mL water with vigorous stirring. After 20 minutes, a white precipitate began to form. The mixture was placed in the refrigerator for 18 hours. Then, the precipitate was isolated by filtration. The filter cake was washed with 50 mL ether, and air dried to provide the title compound (1.60 g, 4.79 mmol, 35%) as a white powder. XH NMR (300 MHz, DMSO-d6) delta 1 1.16 (s, 1H), 9.40 (s, 1H), 9.34 (d, J = 8.0 Hz, 1H), 8.53 (d, J = 7.5 Hz, 1H), 7.89 (dd, J = 8.2, 0.98 Hz, 1H), 7.66 (t, J = 8.3 Hz, 1H), 4.79 (m, 1H), 2.85(m, 1H), 2.59 (m, 1H), 2.21 (m, 1H), 2.20 (s, 3H), 2.03 (m, 1H). MS (ESI-) calc. for [Ci4H14N406-H]" 333.3, found 333.2.
  • 6
  • [ 412341-84-5 ]
  • [ 73721-78-5 ]
  • 7
  • [ 50573-74-5 ]
  • [ 73721-78-5 ]
  • 8
  • [ 73721-78-5 ]
  • [ 1620018-95-2 ]
  • 9
  • [ 73721-78-5 ]
  • [ 1620018-93-0 ]
  • C14H12(2)H2N4O3 [ No CAS ]
  • 10
  • [ 50573-74-5 ]
  • [ 75-36-5 ]
  • [ 73721-78-5 ]
YieldReaction ConditionsOperation in experiment
Alkaline conditions; Reaction of compound 1 with acetyl chloride andbase, such as Et3N, Hunig?s Base, or imidazole in eitheracetonitrile or tetrahydrofuran at either room temperature orC. provided compound la.
  • 11
  • [ 412341-84-5 ]
  • [ 64-19-7 ]
  • [ 73721-78-5 ]
YieldReaction ConditionsOperation in experiment
for 2191.5h; Acetic anhydride was selected as an acylation and dehydration reagent. Initially, compound 1 was refluxed in neat acetic anhydride (4.8 equivalents), followed by cooling and filtration to provide compound 2, which contained 5 wt % of acetic acid and was converted to an acetylated compound 1 ,2-acetamido-6-nitrobenzoic acid 1 a, over a three month period under ambient storage in a glass bottle. In order to improve the stability of compound 2, the amount of acetic anhydride was reduced to 2.2 equivalents and isopropyl acetate was used as an alternative solvent.
 

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