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Chemical Structure| 167690-53-1 Chemical Structure| 167690-53-1

Structure of Fmoc-trans-4-Amc-OH
CAS No.: 167690-53-1

Chemical Structure| 167690-53-1

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Product Details of [ 167690-53-1 ]

CAS No. :167690-53-1
Formula : C23H25NO4
M.W : 379.45
SMILES Code : O=C(O)[C@H]1CC[C@@H](CC1)CNC(OCC2C3=CC=CC=C3C4=CC=CC=C24)=O
MDL No. :MFCD00273480

Safety of [ 167690-53-1 ]

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

Computational Chemistry of [ 167690-53-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 28
Num. arom. heavy atoms 12
Fraction Csp3 0.39
Num. rotatable bonds 7
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 107.09
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.

3.05
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

4.05
Log Po/w (WLOGP)?

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

4.42
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.

3.44
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

3.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.72

Water Solubility

Log S (ESOL):?

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

-4.6
Solubility 0.00955 mg/ml ; 0.0000252 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.

-5.34
Solubility 0.00173 mg/ml ; 0.00000455 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

-6.03
Solubility 0.000358 mg/ml ; 0.000000944 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

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

Yes
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.

-5.74 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<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)

4.15

Application In Synthesis of [ 167690-53-1 ]

* 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 [ 167690-53-1 ]

[ 167690-53-1 ] Synthesis Path-Downstream   1~2

  • 1
  • C39H49ClN3O7Pol [ No CAS ]
  • [ 96402-49-2 ]
  • [ 167690-53-1 ]
  • C60H73ClN5O9Pol [ No CAS ]
  • 2
  • Fmoc-Lys(ivDde)-Wang resin [ No CAS ]
  • [ 27913-58-2 ]
  • C14H23NO5 [ No CAS ]
  • [ 167690-53-1 ]
  • [ 137076-54-1 ]
  • C67H95IN12O19 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Fmoc-Lys(ivDde)-Wang resin (0.3 mmol, 0.61 mmol/g loading) was suspended in DMF for 30 mm. Fmoc was then removed by treating the resin with 20% piperidine in DMF (3 x 8 mm). The isocyanate derivative of di-t-butyl ester of glutamate (3 eq.) was prepared according to literatureprocedures,17 and added to the lysine-immobilized resin and reacted for 16 h. After washing the resinwith DMF, the ivDde-protecting group was removed with 2% hydrazine in DMF (5 x 5 mi. Fmoc-2- Nal-OH was then coupled to the side chain of Lys followed by Fmoc-tranexamic acid, FmocLys(ivDde)-OH, and Fmoc-Gly-OH via solid-phase peptide synthesis using Fmoc-based chemistry. Allcouplings were carried out in DMF using Fmoc-protected amino acid (3 eq.), HBTU (3 eq.), HOBT (3eq.), and DIEA (8 eq.). Afterwards, elongation was continued with the addition of <strong>[27913-58-2]4-<strong>[27913-58-2](p-iodophenyl)butyric acid</strong></strong> (for HTK03024), 4-(p-chlorophenyl)butyric acid (for HTK03055), 4-phenylbutyric acid (for HTK03056), 4-(p-bromophenyl)butyric acid (for HTK03058), 3-phenyipropanoic acid (for HTK03082), 4-(p-fluorophenyl)butyric acid (for HTK03085), 4-(p-methoxyphenyl)butyric acid(for HTK03086), 4-(p-(t-butyloxycarbonyl)aminophenyl)butyric acid (for HTK03087), 4-(p-nitrophenyl)butyric acid (for HTK03089), or 4-(p-tolyl)butyric acid (for HTKO3O9O) were coupled to thesame peptide-bound resin using Fmoc-based chemistry. After selective removal of the ivDdeprotecting group with 2% hydrazine in DMF (5 x 5 mm), the chelator DOTA was then coupled to theside chain of Lys to give the precursors. The peptide was then deprotected and simultaneously cleaved from the resin by treatingwith 95/5 trifluoroacetic acid (TFA)/triisopropylsilane (TIS) for 2 h at room temperature. After filtration,the peptide was precipitated by the addition of cold diethyl ether to the TFA solution. The crude peptide was purified by HPLC using the semi-preparative column. The eluates containing the desired peptidewere collected, pooled, and lyophilized. For HTK03024, the HPLC conditions were 37% acetonitrile inwater with 0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 8.8 mi ESI-MS: calculated[M+H] for HTK03024 C67H96N120191 1499.6; found [M+H] 1499.6. For HTK03055, the HPLCconditions were 35% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min. The retentiontime was 9.7 mi ESI-MS: calculated [M+H] for HTK03055 C67H96N12019C1 1407.7; found [M+H]1407.7. For HTK03056, the HPLC conditions were 0-80% acetonitrile in waterwith 0.1% TFA ata flowrate of 4.5 mL/min in 20 mm. The retention time was 13.4 mi ESI-MS: calculated [M+H] forHTK03056 C67H97N12019 1373.7; found [M+H] 1373.8. For HTK03058, the HPLC conditions were 0-80% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min in 20 mm. The retention time was13.4 mi ESI-MS: calculated [M+H] for HTK03058 C67H96N12O19Br 1451.6; found [M+H] 1451.6. ForHTK03082, the HPLC conditions were 31% acetonitrile in water with 0.1% TFA at a flow rate of 4.5mL/min. The retention time was 11.1 mi ESI-MS: calculated [M+H] for HTK03082 C66H95N120191359.7; found [M+H] 1359.9. For HTK03085, the HPLC conditions were 34% acetonitrile in waterwith0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 9.0 mi ESI-MS: calculated [M+H] forHTK03085 C67H96N12019F 1391.7; found [M+H] 1391.9. For HTK03086, the HPLC conditions were33% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 9.1 mm.ESI-MS: calculated [M+H] for HTK03086 C68H99N12020 1403.7; found [M+H] 1404.1. For HTK03087,the HPLC conditions were 23% acetonitrile in water with 0.1% TFA ata flow rate of 4.5 mL/min. Theretention time was 13.9 mi ESI-MS: calculated [M+H] for HTK03087 C67H98N13019 1388.7; found[M+H] 1389.0. For HTK03089, the HPLC conditions were 33% acetonitrile in water with 0.1% TFA ataflow rate of 4.5 mL/min. The retention time was 10.6 mi ESI-MS: calculated [M+H] for HTK03089C67H96N13021 1418.7; found [M+H] 1419.0. For HTKO3O9O, the HPLC conditions were 35% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 9.1 mm. ESI-MS:calculated [M+H] for HTKO3O9O C68H99N12019 1387.7; found [M+H] 1387.9.
 

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