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Structure of 101258-16-6

Chemical Structure| 101258-16-6

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Product Details of [ 101258-16-6 ]

CAS No. :101258-16-6
Formula : C5H6N2OS
M.W : 142.18
SMILES Code : C1=C(N=C(S1)N)C(=O)C
MDL No. :MFCD06090850
InChI Key :XLYLXMPLFPQUDL-UHFFFAOYSA-N
Pubchem ID :3111964

Safety of [ 101258-16-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 101258-16-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 36.71
TPSA ?

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

84.22 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.33
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

0.62
Log Po/w (WLOGP)?

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

0.94
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.

-0.77
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

1.66
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.76

Water Solubility

Log S (ESOL):?

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

-1.46
Solubility 4.96 mg/ml ; 0.0349 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 1.55 mg/ml ; 0.0109 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

-1.25
Solubility 8.07 mg/ml ; 0.0568 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.

-6.73 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)

2.25

Application In Synthesis of [ 101258-16-6 ]

* 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 [ 101258-16-6 ]

[ 101258-16-6 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 762271-84-1 ]
  • [ 101258-16-6 ]
YieldReaction ConditionsOperation in experiment
59%
Stage #1: With trifluoroacetic acid In chloroform at 20℃; for 1.5 h;
Stage #2: With sodium hydrogencarbonate In chloroform; water
Trifluoroacetic acid (5 ml) was added to a solution (10 ml) of the above-produced acetyl compound in chloroform followed by stirring at room temperature for one and a half hour. The reaction solution was concentrated, neutralized with a saturated aqueous solution of sodium hydrogen carbonate and filtered to give 149 mg (yield: 59percent) of the title compound as a white solid.1H-NMR (CDCl3) δ: 2.48 (3H, s), 7.35 (1H, s) ESI-MS (m/e): 143 [M+H]+
References: [1] Patent: EP1598349, 2005, A1, . Location in patent: Page/Page column 127.
  • 2
  • [ 116008-78-7 ]
  • [ 101258-16-6 ]
YieldReaction ConditionsOperation in experiment
57% With ammonium hydroxide In water at 0℃; for 0.25 h; (1c)
1-(2-Amino-thiazol-4-yl)-ethanone hydrochloride (5.6 g 29.1 mmol) was dissolved in water (15 mL) and cooled in an ice bath.
To this was added dropwise 17 N ammonium hydroxide (15 mL, 105 mmol).
The resulting mixture was stirred for 15 minutes than filtered and washed with cold water (3*), cold methanol (3*50 mL), ethyl ether (3*10 mL).
The precipitate was dried first by passing air through the material and then in vacuo to give 1-(2-amino-thiazol-4-yl)-ethanone as a pale yellow solid (2.6 g, 57percent).
References: [1] Patent: US2006/41146, 2006, A1, . Location in patent: Page/Page column 10.
  • 3
  • [ 5559-62-6 ]
  • [ 17356-08-0 ]
  • [ 101258-16-6 ]
YieldReaction ConditionsOperation in experiment
78% at 20℃; for 72 h; To a solution of thiourea (6.79 g, 89.2 mmol) in absolute ethanol (100 mL) was added 1-chloro-butane-2,3-dione (prepared as described by Bonnema, J. et al., Rec. Trav. Chim. Pays-Bas 1960, 79, 1137) (10.75 g, 89.2 mmol) and the mixture stirred at room temperature for 72 hours. The dark brown suspension was concentrated in vacuo, the residue taken up in water (350 mL), acidified with 1M aqueous hydrochloric acid (20 mL) and extracted with ethyl acetate (2.x.100 mL). The aqueous layer was then neutralized with solid sodium bicarbonate to form a light brown solid which was isolated by filtration. The precipitate was washed with 1:1 hexanes/ether (100 mL), 1:1 hexanes/ethyl acetae (100 mL) and then dried in vacuo over potassium hydroxide to give 1-(2-amino-thiazol-4-yl)-ethanone as a light brown solid (9.91 g, 78percent).
References: [1] Patent: US2006/63814, 2006, A1, . Location in patent: Page/Page column 61.
[2] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1947, vol. 224, p. 841.
  • 4
  • [ 5308-51-0 ]
  • [ 17356-08-0 ]
  • [ 101258-16-6 ]
YieldReaction ConditionsOperation in experiment
67% at 20℃; Step 2 1-(2-Aminothiazol-4-yl)ethanone: A mixture of 1-bromobutane-2,3-dione (10.4 g, 63.41 mmol) and thiourea (1.6 g, 21.05 mmol) in EtOH (100 mL) was stirred at room temperature overnight. A solid was collected by filtration. The filter cake was washed with CH2Cl2 (2.x.100 mL) and dried to yield the desired compound, 2.0 g (67percent), as a light yellow solid
References: [1] Patent: US2007/27184, 2007, A1, . Location in patent: Page/Page column 17; 24.
 

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