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Chemical Structure| 220497-98-3 Chemical Structure| 220497-98-3

Structure of Fmoc-D-Pra-OH
CAS No.: 220497-98-3

Chemical Structure| 220497-98-3

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Product Details of [ 220497-98-3 ]

CAS No. :220497-98-3
Formula : C20H17NO4
M.W : 335.35
SMILES Code : C#CC[C@@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)C(O)=O
MDL No. :MFCD01311781
InChI Key :DJGMNCKHNMRKFM-GOSISDBHSA-N
Pubchem ID :7006567

Safety of [ 220497-98-3 ]

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

Computational Chemistry of [ 220497-98-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 25
Num. arom. heavy atoms 12
Fraction Csp3 0.2
Num. rotatable bonds 7
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 92.95
TPSA ?

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

75.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.44
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

3.26
Log Po/w (WLOGP)?

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

3.08
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.

2.7
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

3.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.93

Water Solubility

Log S (ESOL):?

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

-3.87
Solubility 0.0456 mg/ml ; 0.000136 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.52
Solubility 0.0101 mg/ml ; 0.00003 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-4.98
Solubility 0.0035 mg/ml ; 0.0000104 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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

Yes
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

Yes
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.

-6.03 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

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<0.0
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)

3.88

Application In Synthesis of [ 220497-98-3 ]

* 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 [ 220497-98-3 ]

[ 220497-98-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 220497-98-3 ]
  • [ 1192597-09-3 ]
  • 6,7-dihydroxy-4-(azidomethyl)coumarin [ No CAS ]
  • [ 108-24-7 ]
  • [ 198561-07-8 ]
  • C55H59N19O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% General procedure: Peptide synthesis was conducted manually in disposable Torviq polypropylene syringes fitted with a Teflon sinter. All reactant equivalents are based on the resin loading level for a given amount of resin. Loading of Amino Acid onto Rink Amide AM Resin and Capping. Rink Amide AM resin at a loading level of 0.41 mmol g-1 was placed in a sinter-fitted syringe and allowed to swell in anhydrous CH2Cl2 for 1 h. After removal of CH2Cl2, the resin was treated with a solution of 20percent v/v piperidine in DMF (35 mL 10 min) and the resin was then drained and rinsed with DMF (3 x 5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Afterwards, a solution of Fmoc-protected amino acid (1.5 equiv.), N,N-diisopropylethylamine (DIPEA) (3.0 equiv.), and HATU (2.5 equiv.) in DMF (0.06 M) was added to the reaction syringe. After agitation at room temperature for 2 h, the resin was filtered off and washed with DMF (3 x 5 mL) and CH2Cl2 (3 x 5 mL). Capping was accomplished by treatment of the resin with 20percent v/v acetic anhydride in pyridine (35 min) and subsequent washing with DMF (3 x 6 mL), CH2Cl2 (3 x 6 mL),and DMF (3 x 6 mL). Click Reaction on Resin. The resin-bound peptide was transferred to a 10 mL flask containing CuSO4*5H2O and sodium ascorbate, a solution of azide (2 equiv. or 4 equiv. relative to resin capacity) in DMF (0.05 M) was then added. The suspension was allowed to stirat 25 °C for 16 or 40 h and filtered through a 10 mL syringe tube fitted with a frit. The resin was then rinsed successively with DMF (3 x 5 mL), DDTC/DMF solution (1 g DDTC in 100 mL DMF, 15 x 6 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Fmoc Deprotection. Fmoc deprotection was carried out by suspending the resin in 20percent v/v piperidine/DMF (3 x 5 mL x 10 min) and agitating the syringe at room temperature for 3 x 10 min. The suspension wasthen filtered and the resin was washed with DMF (3 x 5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). SPPS Peptide Coupling. A solution of Fmoc-protected amino acid (1.5 equiv.), DIPEA (3.0 equiv.), and HATU (2.5 equiv.) in DMF (0.06 M) was added to the reaction syringe containing the resin. The resulting suspension was agitated at room temperature for 2 h and the resin was then rinsed with DMF (3 x 5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Acetylation. After Fmoc deprotection, the resin was treated with 20percent v/v acetic anhydride/pyridine (3 x 5 mL x 5 min), followed by washing with DMF (3 x5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Cleavage of Peptides from the Resin. After acetylation, the resin was washed with DMF (3 x 5 mL) and CH2Cl2 (3 x 5 mL). The resin was then treated with a solution of TFA/H2O/TIS (95 : 2.5 : 2.5 v/v, 21 h) and washed with CH2Cl2 (2 x 2 mL). All solutions were combined and evaporated to give the desired crude product. Tripeptide 6. Tripeptide 6 was prepared following the procedure described above for 5 in 42percent yield; [a]D20 +54.2 (c 0.20 MeOH). nmax/cm-1 3345 (br), 1756, 1679, 1613, 1601, 1472, 1375, 1225. dH (500 MHz, CD3OD) 8.38 (d, J 4.5, 4H), 7.85 (s, 1H), 7.68 (m, 6H), 7.24 (m, 8H), 7.07 (s, 1H), 6.71 (s, 1H), 5.74 (s, 2H), 5.63 (s, 1H), 4.66 (m, 1H), 4.52 (m, 6H), 3.80 (m, 8H), 3.16 (m, 3H), 3.06 (m, 2H), 2.98 (m, 5H), 1.89 (s, 3H). dC (125 MHz, CD3OD) 175.6, 173.5, 173.4, 172.9, 163.3, 159.9, 152.5, 151.6, 150.2, 149.4, 144.9, 144.8, 144.7, 144.2, 138.7, 125.6, 125.0, 124.8, 123.9, 110.9, 110.6, 109.3, 104.1, 60.6, 54.9, 54.8, 54.4, 51.1, 28.6, 28.5, 28.0, 22.6. HRMS (ESI) 1136.4668; calcd. for C55H59N19O8Na [M+Na]+ 1136.4686.
  • 2
  • [ 220497-98-3 ]
  • [ 1192597-09-3 ]
  • [ 108-24-7 ]
  • [ 198561-07-8 ]
  • C40H47N15O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% General procedure: Peptide synthesis was conducted manually in disposable Torviq polypropylene syringes fitted with a Teflon sinter. All reactant equivalents are based on the resin loading level for a given amount of resin. Loading of Amino Acid onto Rink Amide AM Resin and Capping. Rink Amide AM resin at a loading level of 0.41 mmol g-1 was placed in a sinter-fitted syringe and allowed to swell in anhydrous CH2Cl2 for 1 h. After removal of CH2Cl2, the resin was treated with a solution of 20percent v/v piperidine in DMF (35 mL 10 min) and the resin was then drained and rinsed with DMF (3 x 5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Afterwards, a solution of Fmoc-protected amino acid (1.5 equiv.), N,N-diisopropylethylamine (DIPEA) (3.0 equiv.), and HATU (2.5 equiv.) in DMF (0.06 M) was added to the reaction syringe. After agitation at room temperature for 2 h, the resin was filtered off and washed with DMF (3 x 5 mL) and CH2Cl2 (3 x 5 mL). Capping was accomplished by treatment of the resin with 20percent v/v acetic anhydride in pyridine (35 min) and subsequent washing with DMF (3 x 6 mL), CH2Cl2 (3 x 6 mL),and DMF (3 x 6 mL). Click Reaction on Resin. The resin-bound peptide was transferred to a 10 mL flask containing CuSO4*5H2O and sodium ascorbate, a solution of azide (2 equiv. or 4 equiv. relative to resin capacity) in DMF (0.05 M) was then added. The suspension was allowed to stirat 25 °C for 16 or 40 h and filtered through a 10 mL syringe tube fitted with a frit. The resin was then rinsed successively with DMF (3 x 5 mL), DDTC/DMF solution (1 g DDTC in 100 mL DMF, 15 x 6 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Fmoc Deprotection. Fmoc deprotection was carried out by suspending the resin in 20percent v/v piperidine/DMF (3 x 5 mL x 10 min) and agitating the syringe at room temperature for 3 x 10 min. The suspension wasthen filtered and the resin was washed with DMF (3 x 5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). SPPS Peptide Coupling. A solution of Fmoc-protected amino acid (1.5 equiv.), DIPEA (3.0 equiv.), and HATU (2.5 equiv.) in DMF (0.06 M) was added to the reaction syringe containing the resin. The resulting suspension was agitated at room temperature for 2 h and the resin was then rinsed with DMF (3 x 5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Acetylation. After Fmoc deprotection, the resin was treated with 20percent v/v acetic anhydride/pyridine (3 x 5 mL x 5 min), followed by washing with DMF (3 x5 mL), CH2Cl2 (3 x 5 mL), and DMF (3 x 5 mL). Cleavage of Peptides from the Resin. After acetylation, the resin was washed with DMF (3 x 5 mL) and CH2Cl2 (3 x 5 mL). The resin was then treated with a solution of TFA/H2O/TIS (95 : 2.5 : 2.5 v/v, 21 h) and washed with CH2Cl2 (2 x 2 mL). All solutions were combined and evaporated to give the desired crude product. Dipeptide 3. Dipeptide 3 was obtained as a colourless solid (34 mg, 41 percent) following the procedure described above for the synthesis of 2. [a]D20 +68.4 (c 0.20 MeOH). nmax /cm-1 3122, 3031, 1786, 1663, 1602, 1588, 1562, 1435, 1347, 1173, 1156. dH (500 MHz, CD3OD) 8.40 (m, 4H), 7.71 (m, 6H), 7.25 (m, 8H), 4.63 (m, 1H), 4.50 (m, 5H), 3.80 (s, 8H), 3.14 (m, 4H), 3.03 (m, 4H), 1.94 (s, 3H). dC (125 MHz, CD3OD) 175.4, 173.7, 173.3, 160.0, 159.9, 149.5, 149.4, 144.5, 144.0, 138.7, 124.8, 123.9, 60.7, 55.1, 54.9, 54.7, 54.2, 28.5, 28.4, 22.5. HRMS (ESI) 808.3865; calcd. for C40H47N15O3Na [M+Na]+ 808.3879.
 

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