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Chemical Structure| 908847-42-7 Chemical Structure| 908847-42-7

Structure of Fmoc-Trp(6-Cl)-OH
CAS No.: 908847-42-7

Chemical Structure| 908847-42-7

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Product Details of [ 908847-42-7 ]

CAS No. :908847-42-7
Formula : C26H21ClN2O4
M.W : 460.91
SMILES Code : O=C(O)[C@@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)CC4=CNC5=C4C=CC(Cl)=C5
MDL No. :MFCD16883068
InChI Key :FDXGPPBWOOAVEL-DEOSSOPVSA-N
Pubchem ID :46781641

Safety of [ 908847-42-7 ]

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

Computational Chemistry of [ 908847-42-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 33
Num. arom. heavy atoms 21
Fraction Csp3 0.15
Num. rotatable bonds 8
Num. H-bond acceptors 4.0
Num. H-bond donors 3.0
Molar Refractivity 126.53
TPSA ?

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

91.42 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.49
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

5.4
Log Po/w (WLOGP)?

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

5.36
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.

3.62
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

5.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.42

Water Solubility

Log S (ESOL):?

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

-6.04
Solubility 0.000418 mg/ml ; 0.000000907 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.

-7.07
Solubility 0.0000388 mg/ml ; 0.0000000842 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

-8.81
Solubility 0.000000712 mg/ml ; 0.0000000016 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

Yes
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.

-5.28 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

1.0
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)

4.05

Application In Synthesis of [ 908847-42-7 ]

* 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.

  • Upstream synthesis route of [ 908847-42-7 ]

[ 908847-42-7 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 82911-69-1 ]
  • [ 33468-35-8 ]
  • [ 908847-42-7 ]
YieldReaction ConditionsOperation in experiment
98% With sodium hydrogencarbonate In water; acetone for 3 h; This compound was synthesized according to the synthetic scheme described in FIGURE 6. To the solution 6-chloroindole (500 mg, 3.31 mmol, I eq) in acetic acid (10 mL) L-serine (695 mg, 6.62 mmol, 2 eq) and acetic anhydride (3.1 mL, 33.1 mmol, 10 eq) were added and the mixture was stirred under Ar at 73°C for 4 h. The reaction mixture was concentrated to half of the volume, diluted with water and extracted with EtOAc. The organic layers were combined, dried over sodium sulfate and evaporated to yield crude product N°-acetyl-6-chloro-D,L-tryptophan 686 mg, 74percent yield). 111 NMR (500 MHz, CD3OD) 81.91 (s, 3H), 3.15-3.3 1 (m, 2H), 4.67 (t, IH), 6.97 (dd, IH), 7.10 (s, 1H), 7.33 (d, IH), 7.53 (d, IH). The A°-acetyl-6-chloro-D,L-tryptophan (686 mg, 145 mmol) was dissolved in phosphate buffer (50 mL) containing 1 mM CoCl26H2O and pH 8.0. To the reaction mixture acylase I was added (500 mg) and the reaction was stirred at 37°C for 24 h with occasional adjustment of pH to 8.0 with LIOH. The reaction mixture was heated to 60°C for 5 mm, cooled to room temperature and filtered through celite. The filtrate was acidified to pH around 3 using HCI and extracted with EtOAc. The aqueous layer was lyophilized and used as crude product for the next reaction. Estimated yield of 43percent (based on theoretical yield for the Lenantiomer), 125.4 mg. 6-chloro-L-tryptophan (125.4 mg, 0.527 mmol, 1 eq) was dissolved in a water/acetone mixture (1:1, v/v) to which NaHCO3 (88.5 rng, 1.05 mmol, 2 eq) was added. Fmoc-OSu (195.6 rng, 0.58 mmol, 1.1 eq) was dissolved in acetone and added to the reaction mixture portion wise over the course of 3 h. Following reaction completion the acetone was evaporated and the aqueous layer acidified with acetic acid to pH about 3 followed by EtOAc extraction. The organic layers were combined, dried over sodium sulfate and evaporated. The crude product was purified with flash column chromatography and solvent system hexanes:EtOAc:AcOH (10:9:1) to yield pure Fmoc-6-chloro-L-tryptophan (237 mg, 98percent). ‘H NMR (500 MHz, CD3OD), 83.16-3.32 (m, 211), 4.65 (t, 1H), 6.98 (dd, 1H), 7.12 (s, 1H), 7.3- 7.55 (m, 8H), 7.79 (d, 211). MS (ESI) calculated for C26H21C1N204 [M+Hj: m/z 460.12, found460.4.
References: [1] Patent: WO2015/153761, 2015, A2, . Location in patent: Paragraph 00256.
[2] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 5, p. 2038 - 2046.
  • 2
  • [ 28920-43-6 ]
  • [ 33468-35-8 ]
  • [ 908847-42-7 ]
YieldReaction ConditionsOperation in experiment
87% With sodium hydrogencarbonate In 1,4-dioxane; water for 6 h; To a cooled solution of 6-chloro-Ltryptophan-OH (0.5 g, 2.1 mmol) in dioxane/water (9:1) was added 2 equiv of NaHCO3 and 1.2 equiv of Fmoc-Cl in dioxane, and the mixture was stirred for 6 hr. The solution was concentrated, followed by 3x washing with ethyl acetate. The aqueous layer was acidified and the precipitate was collected and dried in vacuum to give the desired product (0.84 g, 87percent): 1H-NMR (400 MHz, CD3OD) δ 7.70 (d, J = 7.6 Hz, 2H), 7.30-7.60 (m, 7H) ,7.17-7.26 (m, 2H), 7.09 (s, 1H), 6.92-6.96 (m, 1H), 4.45 (m, 1H), 4.23 (m, 1H), 4.13 ( m, 1H), 3.96-4.06 (m, 1H), 3.84 (d, J = 6.8 Hz, 1H), 3.30-3.36 (m, 1H), 3.13-3.16 (m, 1H) .
References: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 5, p. 1472 - 1475.
  • 3
  • [ 17422-33-2 ]
  • [ 908847-42-7 ]
References: [1] Patent: WO2015/153761, 2015, A2, .
  • 4
  • [ 50517-10-7 ]
  • [ 908847-42-7 ]
References: [1] Patent: WO2015/153761, 2015, A2, .
 

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