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Structure of 116008-52-7

Chemical Structure| 116008-52-7

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Product Details of [ 116008-52-7 ]

CAS No. :116008-52-7
Formula : C4H5N3O2
M.W : 127.10
SMILES Code : O=C(C1=C(N)C=NN1)O
MDL No. :MFCD09991897
InChI Key :SHRRRNSPESGSCM-UHFFFAOYSA-N
Pubchem ID :22566198

Safety of [ 116008-52-7 ]

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

Computational Chemistry of [ 116008-52-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 3.0
Molar Refractivity 29.95
TPSA ?

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

92.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

-0.06
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

-0.05
Log Po/w (WLOGP)?

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

-0.3
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.

-1.37
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

-0.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.41

Water Solubility

Log S (ESOL):?

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

-0.94
Solubility 14.5 mg/ml ; 0.114 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.

-1.43
Solubility 4.71 mg/ml ; 0.037 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

-0.21
Solubility 78.6 mg/ml ; 0.618 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.

-7.11 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

2.0
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

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)

1.52

Application In Synthesis of [ 116008-52-7 ]

* 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 [ 116008-52-7 ]

[ 116008-52-7 ] Synthesis Path-Downstream   1~9

  • 2
  • [ 116008-52-7 ]
  • [ 28466-26-4 ]
  • 3
  • [ 5334-40-7 ]
  • [ 116008-52-7 ]
  • 4
  • 4-amino-pyrazole-dicarboxylic acid-(3.5)-diethyl ester [ No CAS ]
  • [ 116008-52-7 ]
  • 5
  • [ 116008-52-7 ]
  • trans-3-(naphth-2-yl)-but-2-enoic acid chloride [ No CAS ]
  • Trans-3-(naphth-2-yl)-but-2-enoic acid-N-(3-carboxy-1H-pyrazol-4-yl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; In N-methyl-acetamide; EXAMPLE 125 Trans-3-(naphth-2-yl)-but-2-enoic acid-N-(3-carboxy-1H-pyrazol-4-yl)-amide Prepared analogously to Example 31 from trans-3-(naphth-2-yl)-but-2-enoic acid chloride and <strong>[116008-52-7]4-amino-1H-pyrazol-3-carboxylic acid</strong> in dimethylformamide with the addition of pyridine.
  • 6
  • [ 1621-91-6 ]
  • [ 116008-52-7 ]
YieldReaction ConditionsOperation in experiment
Scheme 33--Route to Preferred Groups 49 [4,3-d] ring fusion Nitration of pyrazole-3-carboxylic acid followed by reduction gives 4-aminopyrazole-3-carboxylic acid.
  • 7
  • [ 5334-40-7 ]
  • [ 116008-52-7 ]
YieldReaction ConditionsOperation in experiment
75% With iron(III) chloride hexahydrate; pyrographite; hydrazine hydrate; In water; for 30.0h;Reflux; General procedure: Reduction of the nitrogroup was carried out according to a published method.21The corresponding nitro acid 1, 3 (0.032 mol) wassuspended in H2O (30 ml). Activated carbon (0.8 g),N2H4·H2O (95%, rho 1.023 g/cm3) (6.55 ml, 6.71 g, 0.134 mol),and FeCl3·6H2O (64 mg) were added to the suspension withstirring. The reaction mixture was heated under reflux for30 h. The hot solution was filtered, the filtrate wasevaporated to dryness under reduced pressure. Theresulting dry residue was dissolved in H2O (20 ml) andcarefully acidified with 2 M aqueous HCl to pH 4-5. Theformed precipitate was filtered off and washed with a smallamount of H2O. The product was dried in a vacuumdesiccator over P2O5 to constant weight.
  • 8
  • [ 116008-52-7 ]
  • 4-azido-1H-pyrazole-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% General procedure: The corresponding amino acid2, 4 (0.0173 mol) was dissolved in 2 aqueous l (50 ml),and the formed solution was cooled to 0 in an ice bath.Aqueous NaNO2 (0.019 mol) was dropwise added to thereaction mixture. The mixture was stirred for 30 min, thenaqueous NaN3 (0.026 mol) was carefully added. Thereaction mixture was stirred for 3-4 h. The formed precipitatewas filtered off on a fritted glass filter and washed witha small amount of H2O, then dried in a vacuum desiccatorover P2O5 to constant weight. The filtrate was extractedwith EtOAc, the organic phase was separated and driedover anhydrous Na2SO4. The dried organic phase wasevaporated under reduced pressure on the rotary evaporatorto afford a solid. Both solids were combined.
  • 9
  • [ 64-17-5 ]
  • [ 116008-52-7 ]
  • ethyl 4-amino-1H-pyrazole-3-carboxylate hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With thionyl chloride; for 12.0h;Reflux; Amino acid 4 (2 g, 0.0157 mol) wassuspended in absolute EtOH (20 ml). SOCl2 (1.17 ml,1.92 g, 0.0161 mol) was added dropwise to the suspension.The mixture was heated under reflux for 12 h untilhomogenization. A cherry-colored solution formed. Thesolvent was evaporated to dryness under reduced pressureon the rotary evaporator. The solid residue was dried in avacuum desiccator to constant weight. Yield 3.0 g (99%),pink solid, mp 114-115C. 1H NMR spectrum (400 MHz, DMSO-d6), delta, ppm (J, Hz): 10.22 (4, br. s, NH, +NH3);8.03 (1H, s, -3 pyrazole); 4.28 (2, q, J = 7.0,OCH2H3); 1.30 (3, t, J = 7.1, OCH2H3). 13C NMRspectrum (101 MHz, DMSO-d6), delta, ppm: 160.5; 133.7;127.3; 116.6; 60.8; 14.1. Found, m/z: 178.05868 [M+Na]+.C6H9N3NaO2. Calculated, m/z: 178.05870.
 

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Technical Information

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