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Chemical Structure| 138775-05-0 Chemical Structure| 138775-05-0

Structure of Fmoc-N-Me-D-Phe-OH
CAS No.: 138775-05-0

Chemical Structure| 138775-05-0

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Synonyms: N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-N-methyl-D-phenylalanine

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Product Details of [ 138775-05-0 ]

CAS No. :138775-05-0
Formula : C25H23NO4
M.W : 401.45
SMILES Code : O=C(O)[C@@H](CC1=CC=CC=C1)N(C(OCC2C3=C(C4=C2C=CC=C4)C=CC=C3)=O)C
Synonyms :
N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-N-methyl-D-phenylalanine
MDL No. :MFCD00153392
InChI Key :GBROUWPNYVBLFO-HSZRJFAPSA-N
Pubchem ID :978357

Safety of [ 138775-05-0 ]

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

Computational Chemistry of [ 138775-05-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 30
Num. arom. heavy atoms 18
Fraction Csp3 0.2
Num. rotatable bonds 8
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 114.56
TPSA ?

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

66.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.57
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

4.83
Log Po/w (WLOGP)?

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

4.56
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.

3.63
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

3.99
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.92

Water Solubility

Log S (ESOL):?

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

-5.29
Solubility 0.00207 mg/ml ; 0.00000515 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-5.97
Solubility 0.000433 mg/ml ; 0.00000108 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

-7.04
Solubility 0.0000368 mg/ml ; 0.0000000916 mol/l
Class?

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

Poorly 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

Yes
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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.32 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

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<3.0
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)

4.06

Application In Synthesis of [ 138775-05-0 ]

* 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 [ 138775-05-0 ]

[ 138775-05-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 77128-73-5 ]
  • [ 77128-70-2 ]
  • [ 138775-05-0 ]
  • C49H67N7O8 [ No CAS ]
  • 2
  • C28H25NO3 [ No CAS ]
  • [ 77128-73-5 ]
  • [ 138775-05-0 ]
  • 3
  • [ 29022-11-5 ]
  • [ 35661-39-3 ]
  • [ 77128-73-5 ]
  • [ 76-05-1 ]
  • [ 138775-05-0 ]
  • C25H32N4O5*C2HF3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 2.1 Loading of the 2-chlorotritylchloride resin. General procedure.The synthesis was done in a plastic syringe equipped with Teflon filters. The 2-chlorotritylchloride resin (100-300 mesh, 1.20 mmol/g) was swelled in CH2Cl2 (3 × 30 sec). A solution of the first protected amino acid (Fmoc-AA-OH, 1.0 eq for a resin load of 0.6-0.8 mmol/g) in CH2Cl2 and DIPEA (3.0 eq) were incorporated as a coupling system and were gently shaken for 10 min Then an extra 7.0 eq. of DIPEA was added and shaking was continued for 50 min. MeOH (0.8 mL/ g of resin) was added to the previous mixture in order to cap unreacted functional groups on the resin, and shaken for 10 min. After filtering, the resin was washed with CH2Cl2 (x3), DMF (x3) and CH2Cl2 (x3). The loading capacity was estimated by Fmoc determination after the first residue attachment.2.2 Fmoc removal and quantificationFmoc protecting group was removed by treating the resin with piperidine-DMF solution (1:4) for 1, 5 and 5 minutes successively.For quantification, all the solvents were collected into a 25 mL volumetric flask. DMF was added to a volume of 25 mL. For a resin loading and amount of 0.6 mmol/g and 400 mg of resin, the volumetric flask was shaken and 200 muL were transferred into a 10 mL volumetric flask. DMF was added to a volume of 10 mL. The flask was shaken and UV absorption measured at 290 nm. Fmoc loading was calculated taking into account that extinction coefficient for the dibenzofulvene-piperidine adduct at 290 nm is 5800 l/mol/cm.2.3 SPPS general procedure for elongation of the peptide chain.The Fmoc-AA-2-chlorotritylchloride resin was shaken with 20% piperidine in DMF (1 x 1 min and 2 x 5 min), in order to deprotect N-terminus. Then, the resin was washed with DMF (x3), CH2Cl2 (x3) and DMF (x3). A solution of Fmoc-AA-OH (3 eq.) and DIPEA (6 eq.) in DMF was added to the resin, followed by a solution of HBTU or HATU (2.9 eq) in DMF. The mixture was stirred for 60 min. After the coupling was completed, the resin was washed with DMF (×3) and CH2Cl2 (x3). Deprotection and coupling cycles were repeated with the appropriate amino acids to provide the desired compound. Completion of the coupling was monitored by colorimetric assays; Kaiser test in case of primary amines and Chloranil test for secondary amines. Analytical HPLC was also realized after each coupling step for further process control. Unless otherwise stated, the peptide was cleaved from the resin by treatment with 1-10% TFA in CH2Cl2 for 2-3 minutes at room temperature followed by filtration and collection of the filtrate in MeOH. The treatment was repeated three times and then the resin washed with CH2Cl2 (x5) and MeOH (x3). Solvents were removed in vacuo to obtain the crude peptide.
 

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