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Chemical Structure| 86060-81-3 Chemical Structure| 86060-81-3

Structure of Fmoc-Cys(Acm)-OH
CAS No.: 86060-81-3

Chemical Structure| 86060-81-3

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Product Details of [ 86060-81-3 ]

CAS No. :86060-81-3
Formula : C21H22N2O5S
M.W : 414.47
SMILES Code : O=C(O)[C@H](CSCNC(C)=O)NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O
MDL No. :MFCD00038769
InChI Key :CSMYOORPUGPKAP-IBGZPJMESA-N
Pubchem ID :128799

Safety of [ 86060-81-3 ]

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

Computational Chemistry of [ 86060-81-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 29
Num. arom. heavy atoms 12
Fraction Csp3 0.29
Num. rotatable bonds 11
Num. H-bond acceptors 5.0
Num. H-bond donors 3.0
Molar Refractivity 110.19
TPSA ?

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

130.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.92
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

2.75
Log Po/w (WLOGP)?

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

2.81
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.

1.72
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

2.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.36

Water Solubility

Log S (ESOL):?

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

-3.72
Solubility 0.0785 mg/ml ; 0.000189 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.

-5.14
Solubility 0.00303 mg/ml ; 0.00000732 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 0.000752 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

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.

-6.88 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

1.0
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)

4.45

Application In Synthesis of [ 86060-81-3 ]

* 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 [ 86060-81-3 ]

[ 86060-81-3 ] Synthesis Path-Downstream   1~6

  • 1
  • 2-chlorotrityl chloride polystyrene resin [ No CAS ]
  • [ 162502-65-0 ]
  • [ 27144-18-9 ]
  • [ 29022-11-5 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 86060-81-3 ]
  • [ 109425-55-0 ]
  • C93H116N11O16PolS2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Synthesis of the peptide is carried out by a regular stepwise Fmoc SPPS procedure starting from 2-Cl-Trt-chloride resin. The first amino acid (Fmoc-Gly) is loaded on the resin as described in previous examples to obtain a loading of about 0.7 mmol/g of amino acid/resin. After washing of the resin and removal of the Fmoc group by treatment with piperidine/DMF, the second amino acid (Fmoc-Orn(Boc)) is introduced to continue sequence elongation. Fmoc protected amino acids are activated in situ using TBTU/HOBt and subsequently coupled to the resin over about 50 minutes. Diisopropylethylamine or collidine is used during coupling as an organic base. Completion of the coupling is indicated by ninhydrin test. After washing of the resin, the Fmoc protecting group on the alpha-amine is removed with 20% piperidine in DMF for 20 min. These steps are repeated each time with another amino acid according to the peptide sequence. All amino acids used are Fmoc-Nalpha protected. Trifunctional amino acids are side chain protected as follows: Cys(Acm), Thr(tBu), Asn(Trt), and Orn(Boc). Three equivalents of the activated amino acids are used in the coupling reactions. At the end of the synthesis, the peptide-resin is washed with DMF, followed by DCM, and dried under vacuum to obtain dry peptide-resin.
  • 2
  • C34H28N2O7 [ No CAS ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-18-9 ]
  • [ 103213-32-7 ]
  • [ 86060-81-3 ]
  • [ 116611-64-4 ]
  • [ 223416-45-3 ]
YieldReaction ConditionsOperation in experiment
Chelmical synthesis: Peptides were synthesized on a Rink amide resin, 0.45 mmol/g [Fmoc-Cys(Trityl)-Wang; Novabiochem, San Diego, Calif.] usinig N-(9-fluorenyl)methoxycarboxyl chemistry and standard side chain protection except on cysteine residues. Cysteine residues were protected in pairs with either S-trityl on the first and third cysteines or S-acetamidomethyl on the second and fourth cysteines. Amino acid derivatives were from Advanced Chemtech (Louisville, Ky.). The peptides were removed from the resin and precipitated, and a two-step oxidation protocol was used to selectively fold the peptides as described previously (Luo et al., 1999). Briefly, the first disulfide bridge was closed by dripping the peptide into an equal volume of 20 mM potassium feliicyanide and 0.1 M Tris, pH 7.5. The solution was allowed to react for 30 min, and the monocyclic peptide was purified by reverse-phase HPLC. Simultaneous removal of the S-acetamidomethyl groups and closure of the second disulfide bridge was carried out by iodine oxidation. The monocyclic peptide and HPLC eluent was dripped into an equal volume of iodine (10 mM) in H20/trifluoroacetic acid/acetonitrile (78:2:20 by volume) and allowed to react for 10 min. The reaction was terminated by the addition of ascorbic acid diluted 20-fold with 0.1percent trifluoroacetic acid and the bicyclic product purified by HPLC. Mass Spectrometry: Measurements were performed at the Salk Institute for Biological Studies (San Diego, Calif.) under the direction of Jean Rivier. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry and liquid secondary ionization mass spectrometry were used.
  • 3
  • C23H27N2O4Pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 920519-33-1 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 67436-13-9 ]
  • [ 86060-81-3 ]
  • [ 102410-65-1 ]
  • mouse linear [A10,A22]-hepcidin-1 (C7: SH, C23: SH; C11: S-Acm, C19: S-Acm; C13: S-tBu, C14: S-tBu) [ No CAS ]
  • 4
  • C23H27N2O4Pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 920519-33-1 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 67436-13-9 ]
  • [ 86060-81-3 ]
  • [ 102410-65-1 ]
  • mouse linear [A11,A19]-hepcidin-2 (C7: SH, C23: SH; C10: S-Acm, C13: S-Acm; C14: S-tBu C22: S-tBu) [ No CAS ]
  • 5
  • [ 135248-89-4 ]
  • [ 625-51-4 ]
  • [ 86060-81-3 ]
  • 6
  • N-alpha-Fmoc-N-beta-O-t-butyl-L-aspartyl-N-α-(2,4-dimethoxybenzyl)glycine [ No CAS ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 13734-34-4 ]
  • [ 957780-56-2 ]
  • [ 35661-39-3 ]
  • [ 920519-33-1 ]
  • (2S)-N-((9H-fluoren-9-ylmethyloxy)carbonyl)aspartic acid-4-((3-ethyl)pent-3-yl) ester [ No CAS ]
  • Fmoc-Gly-Ser(ψMe,MePro)-OH [ No CAS ]
  • Fmoc-Gln(Trt)-Thr(ψMe,MePro)-OH [ No CAS ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 86060-81-3 ]
  • [ 109425-51-6 ]
  • [ 77284-32-3 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [Cys105,Nle125,170,Cys(Acm)165,182,189,Asn107,Asp109](105-191)hGH-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
101.1 mg General procedure: The syntheses of the fragments were performed on an automatic peptide synthesizer under microwave conditions using an 8-fold excess of 0.5 M amino acids, 0.5 M HATU/NMP, 2 M DIEA /NMP or 1.0 M DIC/NMP and 0.5 M Oxyma /NMP. The final concentration of Fmoc-amino acids was 0.2 M. The coupling cycles were conducted according to Table 1. Fmoc deprotection was carried out using 35% piperidine/NMP containing 0.1 M HOBt at room temperature for 2 and 6 min, followed by 4 min at 48 C.
 

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