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Chemical Structure| 112018-26-5 Chemical Structure| 112018-26-5

Structure of H-D-Asp(OEt)-OEt·HCl
CAS No.: 112018-26-5

Chemical Structure| 112018-26-5

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Product Details of [ 112018-26-5 ]

CAS No. :112018-26-5
Formula : C8H16ClNO4
M.W : 225.67
SMILES Code : O=C(OCC)[C@H](N)CC(OCC)=O.[H]Cl
MDL No. :MFCD11225843
InChI Key :AJOXZAAREAYBQR-FYZOBXCZSA-N
Pubchem ID :12416467

Safety of [ 112018-26-5 ]

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

Computational Chemistry of [ 112018-26-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 7
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 52.81
TPSA ?

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

78.62 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

0.6
Log Po/w (WLOGP)?

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

0.63
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.

0.42
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

0.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.38

Water Solubility

Log S (ESOL):?

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

-1.16
Solubility 15.8 mg/ml ; 0.07 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.

-1.82
Solubility 3.38 mg/ml ; 0.015 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

-0.94
Solubility 26.0 mg/ml ; 0.115 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.

-7.25 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.

0.0 alert
Brenk?

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

1.0 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)

2.63

Application In Synthesis of [ 112018-26-5 ]

* 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 [ 112018-26-5 ]

[ 112018-26-5 ] Synthesis Path-Downstream   1~15

  • 2
  • [ 64-17-5 ]
  • [ 111934-05-5 ]
  • [ 112018-26-5 ]
  • 3
  • [ 37842-62-9 ]
  • [ 112018-26-5 ]
  • (R)-diethyl 2-(5-amino-4-carbamoylimidazo-1-yl)succinate [ No CAS ]
  • 4
  • [ 39637-99-5 ]
  • [ 112018-26-5 ]
  • [ 111934-09-9 ]
  • 5
  • [ 112018-26-5 ]
  • [ 66717-69-9 ]
  • 6
  • [ 2448-45-5 ]
  • [ 112018-26-5 ]
  • C25H30N2O7 [ No CAS ]
  • 7
  • [ 112018-26-5 ]
  • (R)-diethyl 2-(hypoxanthin-9-yl)succinate [ No CAS ]
  • 8
  • [ 911222-16-7 ]
  • [ 112018-26-5 ]
  • 9
  • [ 123098-58-8 ]
  • [ 112018-26-5 ]
  • 10
  • [ 24424-99-5 ]
  • [ 112018-26-5 ]
  • [ 428440-11-3 ]
YieldReaction ConditionsOperation in experiment
97% With triethylamine; In 1,4-dioxane; water; at 0 - 20℃; for 2.33333h; [00223] (Boc)2O (44.7 g, 0.21mol) was added portion-wise over 10 min to a 0 0C solution of compound 19.2 (42 g, 0.19 mol), trimethyl amine (51.9 mL, 0.37 mol), dioxane (140 mL) and water (56 mL). After another 10 min, the ice bath was removed and the reaction mixture was stirred while warming to room temperature for another 2 hours. The reaction mixture was diluted in ethyl acetate (150 mL) and washed with 0.5 N HCl (200 mL x 3). The organic layer was dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo giving compound 19.3 (52 g, yield 97%) which was used directly in the next step.
  • 11
  • [ 112018-26-5 ]
  • [ 56059-30-4 ]
  • [ 1191937-49-1 ]
  • 12
  • [ 64-17-5 ]
  • [ 1783-96-6 ]
  • [ 112018-26-5 ]
YieldReaction ConditionsOperation in experiment
99% [00222] Acetyl chloride (54.6 mL, 0.75 mol) was added drop- wise into ethanol (316 mL) at 0-5 0C. When the addition was completed, the ice bath was removed and the solution allowed to stir while warming to room temperature for another 30 min. D-aspartic acid 19.1 (25 g, 0.188 <n="77"/>mol) was then added. The reaction mixture was refluxed for 2 hours. The reaction solution was then concentrated in vacuo and placed under high vacuum (0.4 mm Hg) overnight. Compound 19.2 was obtained as a white solid (42 g, 99%) and used directly in the next step.
  • 13
  • [ 64-17-5 ]
  • [ 565461-05-4 ]
  • [ 112018-26-5 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; at 20℃; for 25h;Cooling with ice; General procedure: AAEs were synthesized using a slight modification of an establishedmethod (Furukawa et al., 2016). Briefly, a suspension of 2.0 g of anamino acid in 20 mL of the required alcohol (e.g., methanol for methylester, ethanol for ethyl ester) was stirred vigorously in an ice bath.Then, thionyl chloride (mole ratio of thionyl chloride: aminoacid=1.5:1) was added dropwise to the slurry, and the mixture waskept on ice for 1 h. The resultant solution was stirred thoroughly for24 h at room temperature (Scheme 1a) and then concentrated underreduced pressure after completion of the reaction. The oily residue wasdissolved in alcohol (10 mL) and the solvent was evaporated underreduced pressure to yield the AAE hydrochloride salt. Then, 10 mL ofdistilled water was added to the solution, followed by neutralizationwith ammonia solution (mole ratio of ammonia: AAE salt=2:1). Diethylether (50 mL) was added, and the solution was stirred for 2 h atroom temperature (Scheme 1b). The organic layer was extracted andconcentrated under reduced pressure to yield the AAE. The yields of allthe synthesized compounds were ?72.0% (Table S1). All the synthesizedcompounds were characterized by 1H and 13C nuclear magneticresonance spectroscopy (NMR) and elemental analysis to check theirstructures and purities.
  • 14
  • [ 112018-26-5 ]
  • salicylate aspartic diethyl ester [ No CAS ]
  • 15
  • [ 112018-26-5 ]
  • [ 20268-79-5 ]
YieldReaction ConditionsOperation in experiment
With ammonia; In diethyl ether; water; at 20℃; for 2h; General procedure: AAEs were synthesized using a slight modification of an establishedmethod (Furukawa et al., 2016). Briefly, a suspension of 2.0 g of anamino acid in 20 mL of the required alcohol (e.g., methanol for methylester, ethanol for ethyl ester) was stirred vigorously in an ice bath.Then, thionyl chloride (mole ratio of thionyl chloride: aminoacid=1.5:1) was added dropwise to the slurry, and the mixture waskept on ice for 1 h. The resultant solution was stirred thoroughly for24 h at room temperature (Scheme 1a) and then concentrated underreduced pressure after completion of the reaction. The oily residue wasdissolved in alcohol (10 mL) and the solvent was evaporated underreduced pressure to yield the AAE hydrochloride salt. Then, 10 mL ofdistilled water was added to the solution, followed by neutralizationwith ammonia solution (mole ratio of ammonia: AAE salt=2:1). Diethylether (50 mL) was added, and the solution was stirred for 2 h atroom temperature (Scheme 1b). The organic layer was extracted andconcentrated under reduced pressure to yield the AAE. The yields of allthe synthesized compounds were ?72.0% (Table S1). All the synthesizedcompounds were characterized by 1H and 13C nuclear magneticresonance spectroscopy (NMR) and elemental analysis to check theirstructures and purities.
 

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