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Chemical Structure| 14907-27-8 Chemical Structure| 14907-27-8

Structure of H-D-Trp-OMe·HCl
CAS No.: 14907-27-8

Chemical Structure| 14907-27-8

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Product Details of [ 14907-27-8 ]

CAS No. :14907-27-8
Formula : C12H15ClN2O2
M.W : 254.71
SMILES Code : N[C@H](CC1=CNC2=CC=CC=C12)C(OC)=O.[H]Cl
MDL No. :MFCD00038992
InChI Key :XNFNGGQRDXFYMM-HNCPQSOCSA-N
Pubchem ID :11448200

Safety of [ 14907-27-8 ]

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

Computational Chemistry of [ 14907-27-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 9
Fraction Csp3 0.25
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 68.64
TPSA ?

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

68.11 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.35
Log Po/w (WLOGP)?

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

2.01
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.

1.11
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

2.04
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.5

Water Solubility

Log S (ESOL):?

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

-3.03
Solubility 0.239 mg/ml ; 0.000939 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.

-3.42
Solubility 0.0968 mg/ml ; 0.00038 mol/l
Class?

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

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

-3.46
Solubility 0.0881 mg/ml ; 0.000346 mol/l
Class?

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

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

Yes
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

No
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

No
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

No
Log Kp (skin permeation)?

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

-6.19 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.

0.55

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

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<0.0
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)

2.29

Application In Synthesis of [ 14907-27-8 ]

* 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 [ 14907-27-8 ]

[ 14907-27-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 14907-27-8 ]
  • [ 63521-92-6 ]
  • [ 172946-57-5 ]
  • 2
  • [ 28785-06-0 ]
  • [ 14907-27-8 ]
  • [ 1417796-76-9 ]
  • [ 1417796-77-0 ]
  • 3
  • [ 14907-27-8 ]
  • [ 1397-89-3 ]
  • amphotericin B N-(D)-methoxytryptophanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
93.85% With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl acetamide; at 20℃; Example 7 Synthesis of Amide 7: N-(D)-tryptophanamide of AmB In another preferred embodiment the invention provides the AmB analogue denominated amide 7: N-(D)-tryptophanamide of AmB, represented by formula VII; using D-tryptophan as the starting amine. Fort this derivative the same structural aspects of the synthesis of amide 6 were taken into account and it was observed in its synthesis the possible effect on the antibiotic activity that has the change in the stereochemistry of this derivative regarding amide 6. For L-tryptophan and D-tryptophan, before the amide synthesis, it was necessary to perform the sterification reaction of the carboxylic acid to protect it in form of hydrochloride of the methyl ester of tryptophan. This synthesis was performed by reacting 1 equivalent of the amino acid L-tryptophan or D-tryptophan (L-Trp or D-Trp) with excess MeOH and 2 equivalents of Me3SiCl to procure the white precipitate of the hydrochloride of the methyl ester of L-tryptophan or D-tryptophan. Scheme 6 shows the reaction mechanism proposed for this synthesis. The first step in the reaction consists of the nucleophilic addition of the tryptophan carboxyl function (E) on the Si of Me3SiCl (F) inducing the displacement of the Cl- ion. The silicon esters (intermediates G and H) are in an equilibrium in which it is proposed that the deprotonated form is more susceptible to the nucleophilic addition of MeOH. This will form the hydrochloride of the methyl ester tryptophan with trymethylsilanol as a byproduct of the reaction. The hydrochloride of the tryptophan methyl ester is used for the synthesis of the amides of AmB incorporating only an excess of Et3N as basic reagent in the method of Jarzebski. This liberates the form of the methyl ester of the tryptophan to act as amine in the reaction. It is reported that by incorporating the tryptophan structure in AmB polyene molecules they fluoresce under UV light. The tryptophan methyl ester was used for the synthesis of AmB amides as a means to procure amides that fluoresce under UV light. This is a desirable characteristic for experiments of electrophysiology in unit channel as because of this, the channels would present this type of fluorescence. Characterization of Amide N-(D)-tryptophanamide of AmB. The IR spectrum of the product is almost identical to that of amide 6, showing only slight differences in the intensity of the signals. The derivative had a value of Rf=0.62 for which it is qualitatively considered that this product is non-polar regarding AmB. These two results help confirm that amide 7 has the same structure of amide 6, and its epimer. During the process of purification of amide 7 two products were isolated: amide 7a and amide 7b. The IR spectra of both amides have a similar difference to that of amide 2a and amide 2b in the absorption band of the polyhydroxylated chain. Here the difference in the intensity of the bands is not too large. Because of this it is believed that this is the same structure, and it is supposed that the solvation with ether (of the purification) occurred in the polyhydroxylated chain for the amide 7b. Moreover, it is likely that the antibiotic behavior is diminished because the actual concentration of the derivative could be less than that contemplated in the preparation of the amide solution. It is noteworthy that the rest of the spectra of both products are the same. Here, being the epimer (D) of the N-(L)-tryptophanamide, the same values of the derivative 6 are contemplated. Therefore, this synthesis is to determine whether the difference the epimers (L)-(D) stereochemistry will affect the antibiotic activity.
 

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