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Chemical Structure| 117014-32-1 Chemical Structure| 117014-32-1

Structure of 117014-32-1

Chemical Structure| 117014-32-1

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Product Details of [ 117014-32-1 ]

CAS No. :117014-32-1
Formula : C23H25NO6
M.W : 411.45
SMILES Code : O=C(O)[C@@H](NC(OC(C)(C)C)=O)CC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O
MDL No. :MFCD00076916
InChI Key :NHLRMCFWGFPSLT-IBGZPJMESA-N
Pubchem ID :164019

Safety of [ 117014-32-1 ]

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

Computational Chemistry of [ 117014-32-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 30
Num. arom. heavy atoms 12
Fraction Csp3 0.35
Num. rotatable bonds 10
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 110.53
TPSA ?

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

101.93 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.82
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

3.5
Log Po/w (WLOGP)?

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

3.71
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.

2.56
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

3.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.18

Water Solubility

Log S (ESOL):?

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

-4.23
Solubility 0.0241 mg/ml ; 0.0000586 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.

-5.32
Solubility 0.00195 mg/ml ; 0.00000475 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

-5.74
Solubility 0.000749 mg/ml ; 0.00000182 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

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

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

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

Yes
Log Kp (skin permeation)?

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

-6.32 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

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<2.0
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)

4.27

Application In Synthesis of [ 117014-32-1 ]

* 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 [ 117014-32-1 ]

[ 117014-32-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 57294-38-9 ]
  • [ 13836-37-8 ]
  • [ 37736-82-6 ]
  • [ 117014-32-1 ]
  • [ 84624-27-1 ]
  • [ 18942-49-9 ]
  • [ 108-24-7 ]
  • [ 47355-10-2 ]
  • [ 25024-53-7 ]
  • Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH<SUB>2 </SUB> [ No CAS ]
YieldReaction ConditionsOperation in experiment
The title peptide was synthesized on an Applied Biosystems (Foster City, Calif.) model 430A peptide synthesizer which was modified to do accelerated Boc-chemistry solid phase peptide synthesis. See Schnolzer, et al., Int. J. Peptide Protein Res., 40:180 (1992). 4-methylbenzhydrylamine (MBHA) resin (Peninsula, Belmont, Calif.) with the substitution of 0.91 mmol/g was used. The Boc amino acids (Novabiochem, San Diego, Calif. and Chem-Impex, Wood Dale, Ill.) used were: Boc-Cha-OH, Boc-Asp(OFm)-OH, Boc-His(DNP)-OH, Boc-D-Phe-OH, Boc-Arg(Tos)-OH, <strong>[47355-10-2]<strong>[47355-10-2]Boc-Trp(For)</strong>-OH</strong>, Boc-Gaba-OH, and Boc-Lys(Fmoc)-OH. The synthesis was carried out on a 0.20 mmol scale. The Boc groups were removed by treatment with 100% TFA for 2×1 minute. Boc amino acids (2.5 mmol) were pre-activated with HBTU (2.0 mmol) and DIEA (1.0 mL) in 4 mL of DMF and were coupled without prior neutralization of the peptide-resin TFA salt. Coupling times were 5 minutes. (0223) At the end of the assembly of Boc-Asp(OFm)-His(DNP)-D-Phe-Arg(Tos)-Trp(For)-Gaba-Lys(Fmoc)-MBHA, the peptide-resin was transferred into a reaction vessel on a shaker. The resin was treated twice with 25% piperidine in DMF for 15 minutes per session, washed with DMF, and shaken with bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) (6 eq, 0.3 mmol), DIEA (1 mL), and 4-(dimethylamino)pyridine (DMAP) (24 mg) in DMF (2 mL) for 12 hours. After washing with DMF, the resin was treated twice with 100% TFA for 2 minutes per treatment, washed with DMF and DCM, and then dried under reduced pressure. One fourth of the peptide-resin (0.05 mmol) was used for the next coupling with Boc-Cha-OH (10 eq, 0.5 mmol) in the presence of HBTU (9 eq, 0.45 mmol) and DIEA (0.25 mL) in DMF for 10 minutes. After the deprotection with 100% TFA in two sessions lasting approximately 2 minutes each, the peptide-resin was then washed with DMF. The final capping step was done by shaking the resin with acetic anhydride (40 eq, 2.0 mmol) and DIEA (20 eq, 1.0 mmol) in DMF for 1 hour. After washing with DMF, the resin was treated twice with a solution of 20% mercaptoethanol/10% DIEA in DMF, each treatment lasting approximately 30 minutes, to remove the DNP group on the Histidine side chain. The formyl group on the side chain of Tryptophan was removed by shaking with a solution of 15% ethanolamine/15% water/70% DMF twice for 30 minutes per shaking. The peptide-resin was washed with DMF and DCM and dried under reduced pressure. The final cleavage was done by stirring the peptide-resin in 10 mL of HF containing 1 mL of anisole and dithiothreitol (30 mg) at 0 C. for 75 minutes. HF was removed by a flow of nitrogen. The residue was washed with ether (6×10 mL) and extracted with 4N HOAc (6×10 mL). (0224) The peptide mixture in the aqueous extract was purified on reverse-phase preparative high pressure liquid chromatography (HPLC) using a reverse phase VYDAC C18 column (Nest Group, Southborough, Mass.). The column was eluted with a linear gradient (10% to 50% of solution B over 40 minutes) at a flow rate of 10 mL/minute (Solution A=water containing 0.1% TFA; Solution B=acetonitrile containing 0.1% of TFA). Fractions were collected and checked on analytical HPLC. Those containing pure product were combined and lyophilized to dryness. 5.1 mg of a white solid was obtained. Yield was 8.9%. Purity was 94.5% based on analytical HPLC analysis. Electro-spray mass spectrometer (MS(ES))S analysis gave the molecular weight at 1148.5 (in agreement with the calculated molecular weight of 1148.3). (0225) Other peptides of the invention can be prepared by a person of ordinary skill in the art using synthetic procedures analogous to those disclosed generally hereinabove and/or to those disclosed specifically in the foregoing examples, as were the compounds depicted in Tables 1A and 1B. (0226) Other peptides of the invention can be prepared by a person of ordinary skill in the art using synthetic procedures analogous to those disclosed generally hereinabove and/or to those disclosed specifically in the foregoing examples, as were the compounds depicted in Tables 1A and 1B.
 

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