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Chemical Structure| 20866-46-0 Chemical Structure| 20866-46-0

Structure of Boc-His(Boc)-OH
CAS No.: 20866-46-0

Chemical Structure| 20866-46-0

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Product Details of [ 20866-46-0 ]

CAS No. :20866-46-0
Formula : C16H25N3O6
M.W : 355.39
SMILES Code : O=C(O)[C@@H](NC(OC(C)(C)C)=O)CC1=CN(C(OC(C)(C)C)=O)C=N1
MDL No. :MFCD00065577
InChI Key :IXHPIPUIOSSAIS-NSHDSACASA-N
Pubchem ID :7023100

Safety of [ 20866-46-0 ]

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

Computational Chemistry of [ 20866-46-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 25
Num. arom. heavy atoms 5
Fraction Csp3 0.62
Num. rotatable bonds 10
Num. H-bond acceptors 7.0
Num. H-bond donors 2.0
Molar Refractivity 89.33
TPSA ?

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

119.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.69
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

1.91
Log Po/w (WLOGP)?

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

2.19
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.

0.34
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

0.52
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.53

Water Solubility

Log S (ESOL):?

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

-2.73
Solubility 0.655 mg/ml ; 0.00184 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.

-4.05
Solubility 0.0318 mg/ml ; 0.0000895 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

-2.04
Solubility 3.2 mg/ml ; 0.00902 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

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

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.

-7.11 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

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)

3.79

Application In Synthesis of [ 20866-46-0 ]

* 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 [ 20866-46-0 ]

[ 20866-46-0 ] Synthesis Path-Downstream   1~3

  • 2
  • boc-O-benzyl-threonine resin [ No CAS ]
  • [ 13734-41-3 ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 2488-15-5 ]
  • [ 13734-34-4 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 23680-31-1 ]
  • [ 73821-95-1 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 47689-67-8 ]
  • [ 47355-10-2 ]
  • [ 65420-40-8 ]
  • [ 98115-14-1 ]
  • [ 20866-46-0 ]
  • His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Cys-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 1 Synthesis of Glucagon Cys17(1-29) and Similar MonoCys Analogs (0283) 0.2mmole Boc Thr(OBzl) Pam resin (SynChem Inc) in a 60ml reaction vessel and the following sequence was entered and run on a modified Applied Biosystems 430A Peptide Synthesizer using FastBoc HBTU-activated single couplings. (0284) HSQGTFTSDYSKYLDSCRAQDFVQWLMNT (SEQ ID NO: 35) The following side chain protecting groups were used: Arg(Tos), Asp(OcHex), Asn(Xan), Cys(pMeBzl), Glu(OcHex), His(Boc), Lys(2Cl-Z), Ser(Bzl), Thr(Bzl), Trp(CHO), and Tyr(Br-Z). The completed peptidyl resin was treated with 20% piperidine/dimethylformamide to remove the Trp formyl protection then transferred to an HF reaction vessel and dried in vacuo. 1.0ml p-cresol and 0.5 ml dimehyl sulfide were added along with a magnetic stir bar. The vessel was attached to the HF apparatus (Pennisula Labs), cooled in a dry ice/methanol bath, evacuated, and aprox. 10ml liquid hydrogen fluoride was condensed in. The reaction was stirred in an ice bath for 1hr then the HF was removed in vacuo. The residue was suspended in ethyl ether; the solids were filtered, washed with ether, and the peptide extracted into 50 ml aqueous acetic acid. An analytical HPLC was run [0.46 x 5 cm Zorbax C8, 1 ml/min, 45C, 214nm, A buffer of 0.1%TFA, B buffer of 0.1%TFA/90%ACN, gradient=10%B to 80%B over 10min.] with a small sample of the cleavage extract. The remaining extract was loaded onto a 2.2 x 25cm Kromasil C18 preparative reverse phase column and an acetonitrile gradient was run using a Pharmacia FPLC system. 5min fractions were collected while monitoring the UV at 214nm (2.0A). A=0.1%TFA, B=0.1%TFA/50%acetonitrile. Gradient = 30%B to 100%B over 450min. (0285) The fractions containing the purest product (48-52) were combined frozen, and lyophilized to give 30.1mg. An HPLC analysis of the product demonstrated a purity of>90% and MALDI mass spectral analysis demonstrated the desired mass of 3429.7. Glucagon Cys21, Glucagon Cys24, and Glucagon Cys29 were similarly prepared.
  • 3
  • [ 15761-39-4 ]
  • [ 13734-41-3 ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 2488-15-5 ]
  • [ 13734-34-4 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 23680-31-1 ]
  • [ 73821-95-1 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 47689-67-8 ]
  • [ 47355-10-2 ]
  • [ 65420-40-8 ]
  • [ 98115-14-1 ]
  • [ 20866-46-0 ]
  • HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGPSSGAPPPS [ No CAS ]
YieldReaction ConditionsOperation in experiment
198.1 mg EXAMPLE 2 Synthesis of Glucagon-Cex and Other C-Terminal Extended Analogs. (0286) 285mg (0.2mmole) methoxybenzhydrylamine resin (Midwest Biotech) was placed in a 60ml reaction vessel and the following sequence was entered and run on a modified Applied Biosystems 430A peptide synthesizer using FastBoc HBTU-activated single couplings. (0287) HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGPSSGAPPPS (SEQ ID NO: 36) The following side chain protecting groups were used: Arg(Tos), Asp(OcHex), Asn(Xan), Cys(pMeBzl), Glu(OcHex), His(Boc), Lys(2Cl-Z), Ser(Bzl), Thr(Bzl), Trp(CHO), and Tyr(Br-Z). The completed peptidyl resin was treated with 20% piperidine/dimethylformamide to remove the Trp formyl protection then transferred to HF reaction vessel and dried in vacuo. 1.0ml p-cresol and 0.5 ml dimehyl sulfide were added along with a magnetic stir bar. The vessel was attached to the HF apparatus (Pennisula Labs), cooled in a dry ice/methanol bath, evacuated, and aprox. 10ml liquid hydrogen fluoride was condensed in. The reaction was stirred in an ice bath for 1hr then the HF was removed in vacuo. The residue was suspended in ethyl ether; the solids were filtered, washed with ether, and the peptide extracted into 50 ml aqueous acetic acid. An analytical HPLC was run [0.46 x 5 cm Zorbax C8, 1 ml/min, 45C, 214nm, A buffer of 0.1%TFA, B buffer of 0.1%TFA/90%ACN, gradient=10%B to 80%B over 10min.] on an aliquot of the cleavage extract. The extract was loaded onto a 2.2 x 25cm Kromasil C18 preparative reverse phase column and an acetonitrile gradient was run for elution using a Pharmacia FPLC system. 5min fractions were collected while monitoring the UV at 214nm (2.0A). A=0.1%TFA, B=0.1%TFA/50%acetonitrile. Gradient = 30%B to 100%B over 450min. Fractions 58-65 were combined, frozen and lyophilized to give 198.1mg. (0288) HPLC analysis of the product showed a purity of greater than 95%. MALDI mass spectral analysis showed the presence of the desired theoretical mass of 4316.7 with the product as a C-terminal amide. Oxyntomodulin and oxyntomodulin-KRNR were similarly prepared as the C-terminal carboxylic acids starting with the appropriately loaded PAM-resin.
 

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