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Chemical Structure| 204777-78-6 Chemical Structure| 204777-78-6

Structure of Fmoc-Lys(ivDde)-OH
CAS No.: 204777-78-6

Chemical Structure| 204777-78-6

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Synonyms: Fmoc-L-Lys(ivDde)-OH

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Product Details of [ 204777-78-6 ]

CAS No. :204777-78-6
Formula : C34H42N2O6
M.W : 574.71
SMILES Code : O=C(O)[C@H](CCCCN/C(CC(C)C)=C1C(CC(C)(C)CC\1=O)=O)NC(OCC2C3=C(C4=C2C=CC=C4)C=CC=C3)=O
Synonyms :
Fmoc-L-Lys(ivDde)-OH
MDL No. :MFCD01631658
InChI Key :LHJJUCZESVFWSO-MHZLTWQESA-N
Pubchem ID :135443653

Safety of [ 204777-78-6 ]

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

Computational Chemistry of [ 204777-78-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 42
Num. arom. heavy atoms 12
Fraction Csp3 0.47
Num. rotatable bonds 14
Num. H-bond acceptors 6.0
Num. H-bond donors 3.0
Molar Refractivity 162.44
TPSA ?

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

121.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.99
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

6.76
Log Po/w (WLOGP)?

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

6.0
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.

2.97
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

6.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.24

Water Solubility

Log S (ESOL):?

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

-6.95
Solubility 0.0000646 mg/ml ; 0.000000112 mol/l
Class?

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

Poorly soluble
Log S (Ali)?

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

-9.12
Solubility 0.000000432 mg/ml ; 0.0000000008 mol/l
Class?

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

Poorly 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

-9.39
Solubility 0.000000234 mg/ml ; 0.0000000004 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

Low
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.

-5.01 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

1.0
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

1.0
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.

0.55

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

2.0 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)

5.53

Application In Synthesis of [ 204777-78-6 ]

* 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 [ 204777-78-6 ]

[ 204777-78-6 ] Synthesis Path-Downstream   1~7

  • 1
  • coenzyme A trilithium salt [ No CAS ]
  • [ 611-95-0 ]
  • QTARKSTGGK(1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl)APRKQLATK [ No CAS ]
  • [ 79-08-3 ]
  • [ 88574-06-5 ]
  • [ 204777-78-6 ]
  • [ 198561-07-8 ]
  • histone QTARKSTGGK(1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl)PRKQLATK-lysine 14-coenzyme A-benzophenone-L-propargylglycine [ No CAS ]
  • 2
  • coenzyme A trilithium salt [ No CAS ]
  • [ 611-95-0 ]
  • SGRGKGGKGLGKGGAK(1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl)RHR [ No CAS ]
  • [ 79-08-3 ]
  • [ 88574-06-5 ]
  • [ 204777-78-6 ]
  • [ 198561-07-8 ]
  • histone SGRGKGGKGLGKGGAK(1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl)RHR-lysine 16-coenzyme A-benzophenone-L-propargylglycine [ No CAS ]
  • 3
  • coenzyme A trilithium salt [ No CAS ]
  • [ 611-95-0 ]
  • [ 79-08-3 ]
  • [ 88574-06-5 ]
  • [ 204777-78-6 ]
  • [ 198561-07-8 ]
  • [ 1612162-71-6 ]
  • 4
  • [ 41654-04-0 ]
  • [ 13574-13-5 ]
  • C23H20N3O3Pol [ No CAS ]
  • [ 123639-61-2 ]
  • [ 204777-78-6 ]
  • C50H66N7O12Pol [ No CAS ]
  • 5
  • polyethylene glycol polyamide resin [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • Palm-γGlu-γGlu-OSu [ No CAS ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 71989-35-0 ]
  • [ 132327-80-1 ]
  • [ 71989-33-8 ]
  • [ 94744-50-0 ]
  • [ 32926-43-5 ]
  • [ 143824-78-6 ]
  • [ 204777-78-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • H-dSer-Q-G-T-F-T-S-D-L-S-K-Q-K((S)-4-carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)butyryl)-D-E-E-A-A-R-L-F-I-E-W-L-Aib-A-G-G-P-S-S-G-A-P-P-P-S-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
The solid phase synthesis as described in Methods was carried out on Novabiochem Rink-Amide resin (4-(2',4'-Dimethoxyphenyl-Fmoc-aminomethyl)-phenoxyacetamido- norleucylaminomethyl resin), 100-200 mesh, loading of 0.23 mmol/g. The Fmoc- synthesis strategy was applied with HBTU/DIPEA-activation. In position 14 Fmoc- Lys(ivDde)-OH and in position 1 Boc-His(Trt)-OH were used in the solid phase synthesis protocol. The ivDde-group was cleaved from the peptide on resin according to literature (S.R. Chhabra et al., Tetrahedron Lett. 39, (1998), 1603). Hereafter Palm- yGlu-yGlu-OSu was coupled to the liberated amino-group employing DIPEA as base. The peptide was cleaved from the resin with King's cocktail (D. S. King, C. G. Fields, G. B. Fields, Int. J. Peptide Protein Res. 36, 1990, 255-266). The crude product was purified via preparative HPLC on a Waters column (XBridge, BEH130, Prep C18 5muMu) using an acetonitrile/water gradient (both buffers with 0,1 percent TFA). The purified peptide was analysed by LCMS (Method A). Deconvolution of the mass signals found under the peak with retention time 12.61 min revealed the peptide mass 4581 ,5 which is in line with the expected value of 4581 ,1 . Peptide Synthesizer (Protein Technologies Inc) or similar automated synthesizer using standard Fmoc chemistry and HBTU/DIPEA activation. DMF was used as the solvent. Deprotection : 20percent piperidine/DMF for 2 x 2.5 min. Washes: 7 x DMF. Coupling 2:5:10 200 mM AA / 500 mM HBTU / 2M DIPEA in DMF 2 x for 20 min. Washes: 5 x DMF. In cases where a Lys-side-chain was modified, Fmoc-L-Lys(ivDde)-OH or Fmoc-L- Lys(Mmt)-OH was used in the corresponding position. After completion of the synthesis, the ivDde group was removed according to a modified literature procedure (S.R. Chhabra et al., Tetrahedron Lett. 39, (1998), 1603), using 4percent hydrazine hydrate in DMF. The Mmt group was removed by repeated treatment with 1 percent TFA in dichloromethane. The following acylations were carried out by treating the resin with the N-hydroxy succinimide esters of the desired acid or using coupling reagents like HBTU/DIPEA or HOBt/DIC. All the peptides that have been synthesized were cleaved from the resin with King's cleavage cocktail consisting of 82.5percent TFA, 5percent phenol, 5percent water, 5percent thioanisole, 2.5percent EDT The crude peptides were then precipitated in diethyl or diisopropyl ether, centrifuged, and lyophilized. Peptides were analyzed by analytical HPLC and checked by ESI mass spectrometry. Crude peptides were purified by a conventional preparative RP-HPLC purification procedure.
  • 6
  • C22H39N6O9Pol [ No CAS ]
  • Fmoc‐D‐Cys(Trt)‐OPfp [ No CAS ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-38-3 ]
  • [ 115520-21-3 ]
  • [ 132388-59-1 ]
  • [ 71989-23-6 ]
  • [ 109425-51-6 ]
  • [ 88574-06-5 ]
  • [ 143824-78-6 ]
  • [ 204777-78-6 ]
  • C96H142N26O27S2 [ No CAS ]
  • 7
  • [ 29022-11-5 ]
  • C22H39N6O9Pol [ No CAS ]
  • Fmoc‐D‐Cys(Trt)‐OPfp [ No CAS ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-38-3 ]
  • [ 115520-21-3 ]
  • [ 132388-59-1 ]
  • [ 71989-23-6 ]
  • [ 88574-06-5 ]
  • [ 143824-78-6 ]
  • [ 204777-78-6 ]
  • C90H135N23O26S2 [ No CAS ]
 

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