Structure of N-Ac-Nle-OH
CAS No.: 15891-49-3
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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. : | 15891-49-3 |
Formula : | C8H15NO3 |
M.W : | 173.21 |
SMILES Code : | CCCC[C@H](NC(C)=O)C(O)=O |
MDL No. : | MFCD00151961 |
InChI Key : | JDMCEGLQFSOMQH-ZETCQYMHSA-N |
Pubchem ID : | 6995109 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 45.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.52 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.77 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.76 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.81 |
Solubility | 27.0 mg/ml ; 0.156 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.42 |
Solubility | 6.54 mg/ml ; 0.0378 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.29 |
Solubility | 8.94 mg/ml ; 0.0516 mol/l |
Class? Solubility class: Log S scale |
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) |
No |
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) |
No |
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 |
-7.03 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.85 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
This peptide is synthesized by solid-support synthesis with a Rink amide-type resin, the functionalization of which is between 0.3 and 0.6 mmol/g of resin.Firstly, the Rink amide resin is prepared by washing with DMF (2 washes) and then the deprotection is performed as described below. For each amino acid to be coupled, the steps consisting in coupling of the amino acid, washing of the resin, deprotection of the amine function of the main chain of the amino acid, and again washing of the resin are repeated.Coupling: 2 equivalents of BOP (or HBTU), 2 equivalents of DIEA (or NMM) and 2 equivalents of Fmoc-AA-OH for 2 hours in DMF.Washing: 2 washes with DMF, 1 wash with methanol, 2 washes with dichloromethane and 1 wash with DMF.Deprotection: 80/20 DMF/piperidine mixture with 2% of ethanediol (free-radical scavenger), once for 3 minutes, and then 7 minutes.Washing: (idem above).After the various amino acid couplings, the peptide is cleaved from the resin using a 50/50 TFA/dichloromethane mixture with 2% of ethanediol, for 1 h 30 min.The dichloromethane and the TFA are evaporated off under a stream of nitrogen, and then precipitation with diethyl ether and purification of preparative liquid chromatography, with a C18 reverse-phase column, are performed.The synthesis of Ac-Nle-Ala-His-DPhe-Arg-Trp-NH2 is carried out with the following protected amino acids (Fmoc-AA-OH): Fmoc-Trp(Boc)-OH Fmoc-Arg(Pmc)-OH Fmoc-DPhe-OH Fmoc-His(Trt)-OH Fmoc-Ala-OH Ac-Nle-OH Abbreviations: Fmoc: 9-fluorenylmethoxycarbonyl TFA: trifluoroacetic acid DMF: dimethylformamide BOP: 1-benzotriazolyloxytris(dimethylamino)-phosphonium hexafluorophosphate HBTU: 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetra-methyluronium hexafluorophosphate DIEA: diisopropylethylamine NMM: N-methylmorpholine |