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Chemical Structure| 17916-88-0 Chemical Structure| 17916-88-0

Structure of N-Ac-D-Val-OH
CAS No.: 17916-88-0

Chemical Structure| 17916-88-0

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Synonyms: N-Acetyl-D-valine

4.5 *For Research Use Only !

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Product Details of [ 17916-88-0 ]

CAS No. :17916-88-0
Formula : C7H13NO3
M.W : 159.18
SMILES Code : [H][C@@](NC(C)=O)(C(C)C)C(O)=O
Synonyms :
N-Acetyl-D-valine
MDL No. :MFCD00026457
InChI Key :IHYJTAOFMMMOPX-ZCFIWIBFSA-N
Pubchem ID :76475

Safety of [ 17916-88-0 ]

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

Computational Chemistry of [ 17916-88-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.71
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 40.54
TPSA ?

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

66.4 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.21
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

0.04
Log Po/w (WLOGP)?

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

0.23
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.

0.19
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

-0.04
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.33

Water Solubility

Log S (ESOL):?

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

-0.59
Solubility 41.1 mg/ml ; 0.258 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.

-0.99
Solubility 16.4 mg/ml ; 0.103 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

-0.5
Solubility 50.2 mg/ml ; 0.316 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.

-7.24 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.

0.56

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)

1.58

Application In Synthesis of [ 17916-88-0 ]

* 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 [ 17916-88-0 ]

[ 17916-88-0 ] Synthesis Path-Downstream   1~21

  • 1
  • [ 640-68-6 ]
  • [ 108-24-7 ]
  • [ 17916-88-0 ]
  • 3
  • N-acetyl-DL-valine methyl ester [ No CAS ]
  • [ 17916-88-0 ]
  • 4
  • [ 96574-46-8 ]
  • [ 17916-88-0 ]
  • 5
  • [ 56430-36-5 ]
  • [ 17916-88-0 ]
  • [ 96-81-1 ]
  • 6
  • [ 52152-47-3 ]
  • [ 17916-88-0 ]
  • [ 96-81-1 ]
  • 7
  • [ 194661-11-5 ]
  • [ 17916-88-0 ]
  • [ 96-81-1 ]
  • 8
  • N-acetyl-DL-valine hexyl ester [ No CAS ]
  • [ 17916-88-0 ]
  • [ 96-81-1 ]
  • 9
  • [ 194661-10-4 ]
  • [ 17916-88-0 ]
  • [ 96-81-1 ]
YieldReaction ConditionsOperation in experiment
Also catalytic actions on the following substrates were confirmed: N-acetyl-D-valine; N-acetyl-D-alanine; and N-acetyl-D-leucine.
  • 13
  • [ 17916-88-0 ]
  • [ 804556-46-5 ]
  • Ac-D-Val-PyPro-Gly-D-Leu-NMe2 [ No CAS ]
  • 14
  • 2-methyl-4-iso-propyl-4H-oxazolin-5-one [ No CAS ]
  • [ 17916-88-0 ]
  • 15
  • N-acetyl-D,L-valine [ No CAS ]
  • [ 17916-88-0 ]
  • 16
  • [ 243968-43-6 ]
  • [ 17916-88-0 ]
  • [ 330192-92-2 ]
YieldReaction ConditionsOperation in experiment
90% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); dichloromethane; at 20℃; EXAMPLE 45; 7-((2-(R)-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid;. To a solution of <strong>[17916-88-0]Ac-D-Val-OH</strong> (0.17 g, 1.09 mmol) dissolved in dichloromethane (15 ml) was added N,N-dimethylformamide (1 ml), 1-hydroxybenzotriazole (0.15 g, 1.09 mmol) and 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (0.21 g, 1.09 mmol). The reaction mixture was stirred for 15 min. at room temperature at which time a solution of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.31 g, 1.09 mmol) in dichloromethane (10 ml) was added followed by N,N-diisopropylethylamine (0.186 ml, 1.09 mmol). The resulting mixture was stirred over night at room temperature diluted with dichloromethane (10 ml) washed with 10 % aqueous citric acid (20 ml), sodium hydrogencarbonate, dried (MgSO4), filtered and the solvent was evaporated invacuo affording 415 mg (90 %) of 7-((2-(R)-acetylamino-3-methyl-butyrylamino)methyl)-2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.1H-NMR (CDCl3) δ 0.88 (t, 3H), 0.98 (t, 2H), 1.55 (s, 9H), 2.02 (d, 1H), 2.77 m, (2H), 3.40 (m, 1H), 4.14 (m, 1H). LC-MS: Rt = 5.17 min., m/z: 426.4 [M+H]+
90% Example 45 7-((2-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; To a solution of <strong>[17916-88-0]Ac-D-Val-OH</strong> (0.17 g, 1.09 mmol) dissolved in dichloromethane (15 ml) was added N,N-dimethylformamide (1 Ml), 1-hydroxybenzotriazole (0.15 g, 1.09 mmol) and 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (0.21 g, 1.09 mmol). The reaction mixture was stirred for 15 min. at room temperature at which time a solution of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.31 g, 1.09 mmol) in dichloromethane (10 ml) was added followed by N-N-diisopropylethylamine (0.186 ml, 1.09 mmol). The resulting mixture was stirred over night at room temperature diluted with dichloromethane (10 ml) washed with 10% aqueous citric acid (20 ml), sodium hydrogencarbonate, dried (MgSO4), filtered and the solvent was evaporated in vacuo affording 415 mg (90%) of 7-((2-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.1H NMR (CDCl3) δ 0.88 (t, 3H), 0.98 (t, 2H), 1.55 (s, 9) 2.02 (d, 1H), 2.77 m, (2H), 3.40 (m, 1H), 4.14 (m, 1H).To a mixture of 7-((2-acetylamino-3-methyl-butyrylamino)methyl)-2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.4 g, 0.94 mmol) dissolved in dichloromethane (10 ml) and triethylamine (0.26 g, 1.87 mmol) cooled to 0 C. was added a solution of imidazol-1-yl-oxo-acetic acid tert-butyl ester (0.37 g, 1.87 mmol) in dichloromethane (10 ml). The resulting mixture was stirred for 18 h at room temperature diluted with dichloromethane (20 ml) washed with 1N hydrochloric acid (15 ml), saturated sodium hydrogencarbonate, dried (MgSO4), filtered and the solvent evaporated in vacuo which afforded 515 mg (97%) of 7-((2-acetylamino-3-methyl-butyrylamino)methyl)-2-(tert-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.LC-MS: Rt=7.11, Mw=554.4.HPLC: Rt=34.16, Area (%)=100, %.To a solution of the above 7-((2-acetylamino-3-methyl-butyrylamino)-methyl)-2-(tert-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.5 g, 0.90 mmol) dissolved in dichloromethane (3 ml) was added trifluoroacetic acid (1 ml) and the reaction mixture was stirred for 18 h at room temperature. Trifluoroacetic acid (4 ml) was added and the mixture was stirred for an additional 3 hours at room temperature. The volatiles were evaporated in vacuo (and stripped 3 times with dichloromethane) affording 282 mg (71%) of the title compound.Calculated for C18H23N3O8S, 2×H2O; C, 45.28%; H, 5.70%; N, 8.80%. Found: C, 45.20%; H, 5.50%; N, 8.80%.LC-MS: Rt=3.60, Mw=442.2
  • 17
  • [ 60218-18-0 ]
  • [ 17916-88-0 ]
  • [ 543-27-1 ]
  • [ 76718-84-8 ]
YieldReaction ConditionsOperation in experiment
With 4-methyl-morpholine; triethylamine; In dichloromethane; N,N-dimethyl acetamide; water; S. 2-[4-(N-Acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide A suspension of 11.41 g (71.7 mmol) of <strong>[17916-88-0]N-acetyl-D-valine</strong> and 150 ml of dichloromethane is stirred at room temperature and 7.9 ml (71.7 mmol) of N-methylmorpholine is added. The resulting solution is cooled to -10 C. and 9.3 ml (71.7 mmol) of isobutyl chloroformate is added. The reaction mixture is stirred at -15+-5 C. for 45 min and an ice cold solution of 11.09 g (48 mmol) of 2-(4-aminophenyl)-4-hydroxy-5-pyrimidine carboxylic acid, 7.4 ml (52.8 mmol) of triethylamine, and 200 ml of N,N-dimethylacetamide is added while keeping the temperature below -10 C. The mixture is stirred at 0-5 C. for 2 hrs and overnight at room temperature. A small amount of solid is filtered and the filtrate is evaporated to dryness. Water is added to the residue and the resulting solid filtered, washed with water, ethyl acetate, and ether and dried to give 8.9 g of 2-[4-(N-acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid. A second crop, obtained from the aqueous filtrate, weighs 2.35 g. [α]D23 +4.50 (cl, pH 7).
  • 18
  • [ 6642-21-3 ]
  • [ 17916-88-0 ]
  • [ 96-81-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,S)-cis-2-(2-diphenylphosphinoethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In methanol; at 20℃; for 3h;Product distribution / selectivity; In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC.
With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,R)-trans-2-(2-diphenylphosphinoethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In tetrahydrofuran; at 20℃; for 3h;Product distribution / selectivity; In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC.
With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,R,R)-trans-2-(2-diphenylphosphino-2-methylethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In tetrahydrofuran; at 20℃; for 3h;Product distribution / selectivity; In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC.
With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,R,S)-trans-2-(2-diphenylphosphino-2-methylethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In tetrahydrofuran; at 20℃; for 3h;Product distribution / selectivity; In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC.

  • 19
  • [ 17916-88-0 ]
  • [ 108-94-1 ]
  • [ 112790-04-2 ]
  • [ 1072014-00-6 ]
  • [ 1072014-01-7 ]
  • 20
  • [ 17916-88-0 ]
  • [ 108-94-1 ]
  • [ 43041-59-4 ]
  • [ 1072014-00-6 ]
  • [ 1072014-01-7 ]
  • 21
  • [ 1007882-27-0 ]
  • [ 17916-88-0 ]
  • [ 76-05-1 ]
  • N-[(2R)-1-[(2S)-2-{5-[4-(4-{2-[(2S)-1-[(2R)-2-acetamido-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]acetamide trifluoroacetic acid [ No CAS ]
 

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