Structure of Fmoc-Phe(3-I)-OH
CAS No.: 210282-31-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 210282-31-8 |
| Formula : | C24H20INO4 |
| M.W : | 513.32 |
| SMILES Code : | O=C(O)[C@@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)CC4=CC=CC(I)=C4 |
| MDL No. : | MFCD01632252 |
| InChI Key : | SSKOJXLIQFVOGC-QFIPXVFZSA-N |
| Pubchem ID : | 46737402 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 30 |
| Num. arom. heavy atoms | 18 |
| Fraction Csp3 | 0.17 |
| Num. rotatable bonds | 8 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 122.38 |
| TPSA ? Topological Polar Surface Area: Calculated from |
75.63 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.49 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.29 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.83 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.1 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.01 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.34 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-6.27 |
| Solubility | 0.000275 mg/ml ; 0.000000535 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-6.63 |
| Solubility | 0.000121 mg/ml ; 0.000000235 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-8.2 |
| Solubility | 0.00000323 mg/ml ; 0.0000000063 mol/l |
| Class? Solubility class: Log S scale |
Poorly soluble |
| 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) |
Yes |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.68 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<3.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.12 |
* 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.

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| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| General procedure: Peptide amides were synthesized on Rink Amide resin following Fmoc-based solid-phase peptide synthesis (SPPS) standard protocols in a polypropylene syringe with polyethylene frit using SPPS grade CH2Cl2 or DMF. Fmoc-protected amino acids (3 eq) were mixed with HBTU (3 eq) and DIPEA (3 eq) in DMF and added to the swollen resin beads. The mixture was shaken for 120 mins and washed with DMF (3x), iPrOH (3x) and DCM (3x). Complete coupling was checked by Kaiser ninhydrine test. If complete, the Fmoc protecting group was removed by treatment with 20% 4-methylpiperidine in DMF for 5 min, followed by 15 min and washed. The final amino acid, Boc-Dmt-OH (2 eq) was coupled with DIC (2 eq) and HOBt (2 eq). After assembling of the peptide on solid phase, the peptide was submitted to solid-phase Suzuki-Miyaura derivatization for the (hetero)aryl substituted tetrapeptides. For vinylated peptides, it was found that acidic cleavage of vinylated peptides on resin afforded several unwanted side products. This could be avoided by first performing the peptide cleavage and next a solution-phase Suzuki-Miyaura coupling. This strategy was chosen for the assembly of vinylated tetrapeptides. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| General procedure: Peptide amides were synthesized on Rink Amide resin following Fmoc-based solid-phase peptide synthesis (SPPS) standard protocols in a polypropylene syringe with polyethylene frit using SPPS grade CH2Cl2 or DMF. Fmoc-protected amino acids (3 eq) were mixed with HBTU (3 eq) and DIPEA (3 eq) in DMF and added to the swollen resin beads. The mixture was shaken for 120 mins and washed with DMF (3x), iPrOH (3x) and DCM (3x). Complete coupling was checked by Kaiser ninhydrine test. If complete, the Fmoc protecting group was removed by treatment with 20% 4-methylpiperidine in DMF for 5 min, followed by 15 min and washed. The final amino acid, Boc-Dmt-OH (2 eq) was coupled with DIC (2 eq) and HOBt (2 eq). After assembling of the peptide on solid phase, the peptide was submitted to solid-phase Suzuki-Miyaura derivatization for the (hetero)aryl substituted tetrapeptides. For vinylated peptides, it was found that acidic cleavage of vinylated peptides on resin afforded several unwanted side products. This could be avoided by first performing the peptide cleavage and next a solution-phase Suzuki-Miyaura coupling. This strategy was chosen for the assembly of vinylated tetrapeptides. |

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| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 55.2% | General procedure: Peptides were synthesized using a solid phase peptide synthesis protocol using an Aapptec FocusXC automated peptide synthesizer coupled with a heating system using the Fmoc chemistry andWang resin as solid support [34]. To prepare the resin for synthesis, a reaction vessel equipped with asintered glass bottom was charged with Fmoc-Leu-Wang resin (0.2 mM), and swelled in a mixture ofdichloromethane and DMF (1:1) for 15 min. The resin was then transferred to a peptide synthesizerreaction vessel. The resin was deprotected twice using 20% piperidine in DMF for 5 min at 70 C.Subsequently, an Fmoc-protected amino acid was double coupled with the Leucine-wang resin bytreating with N,N'-diisopropylcarbodiimide (3.0 equiv., 0.2 M in DMF) and Oxyma (3.0 equiv., 0.2 M inDMF) at 70 C for 8 min. Completion of coupling reactions was monitored by a Kaiser?s test for theinitial peptide [40]. Each coupling was followed by removal of the Fmoc group using 20% piperidinein DMF at 70 C for 5 min and repeated once. The cycle of the Fmoc removal and coupling wasrepeated with subsequent Fmoc-protected amino acids to generate the desired resin-bound peptide.Cleavage of the peptide from resin and concomitant deprotection of the side chain protecting groupswas carried out by shaking in TFA/triisopropylsilane/H20 (95/2.5/2.5; 5 mL), at ambient temperature for3 h. Subsequent filtration aorded the peptide in the filtrate and the volume was reduced to 0.2 mL.Then, the crude peptides were precipitated by adding cold diethyl ether, and the crude peptides werethen purified by RP-HPLC. Synthesized peptides were characterized by NMR, and the high-resolutionmass spectroscopy. |

A118835 [220400-04-4]
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