Structure of Boc-Glu-OH
CAS No.: 2419-94-5
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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.
Synonyms: N-Boc-L-glutamic acid
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CAS No. : | 2419-94-5 |
Formula : | C10H17NO6 |
M.W : | 247.25 |
SMILES Code : | O=C(O)CC[C@@H](C(O)=O)NC(OC(C)(C)C)=O |
Synonyms : |
N-Boc-L-glutamic acid
|
MDL No. : | MFCD00037297 |
InChI Key : | AQTUACKQXJNHFQ-LURJTMIESA-N |
Pubchem ID : | 2724758 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.7 |
Num. rotatable bonds | 8 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 58.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
112.93 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.41 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.1 |
Solubility | 19.5 mg/ml ; 0.0788 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.35 |
Solubility | 1.11 mg/ml ; 0.00449 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.44 |
Solubility | 89.2 mg/ml ; 0.361 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 |
-7.52 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 |
0.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.87 |
* 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 |
---|---|---|
77% | N-protected amino acid 29 (0.247 g, 1.0 mmol), HOBT (0.270 g, 2.0 mmol), and DCC (0.412 g, 2.0 mmol) were dissolved in DMF (10 ml) and stirred at 25° C. for 1 h. Compound 4 (2.268 g, 2.0 mmol) was added and the stirring was continued for 48 h at 25° C. The precipitate was filtered and the DMF was removed by evaporation under reduced pressure. The residue was triturated with hot acetone (100 ml). The precipitate was filtered and dried under vacuum. Derivative 28 was obtained as a white solid (77percent yield). TLC analysis of 28 performed on silica plates (1-butanol:ethanol:NH4OH:water-4:5:6:2) showed one major spot (Rf=0.16). 1H NMR (DMSO-d6) delta: 1.38 (s, 9H), 1.71-2.15 (m, 4H), 3.16-3.49 (m, 84H), 4.30-4.44 (m, 12H), 4.68 (m, 14H), 5.62-5.78 (m, 28H). HPLC (Luna 5u NH2 100 A, size 250-4.6 mm, mobile phase 65percent acetonitrile-35percent H2O, flow 1.2 ml/min), Rt=44.6 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
450 mg | With 4-methyl-morpholine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In N,N-dimethyl-formamide; at 0 - 4℃; for 29.75h;Inert atmosphere; | Boc-L-Glu (134.9 mg) and BOP (724 mg) were dissolved in anhydrous DMF (4 mL) andwere stirred at 0 C under a nitrogen atmosphere. This solution was then added to a solutionof H2N-PEG(12u)-Me (685 mg) and NIVI1VI (179.8 1iL) in DMF (3 mL), which had previously been stirred for 75 mm. The combined solution was then stirred under nitrogen at 0 C for 4.5 h. Additional BOP (241 mg) and NIVI1VI (60 1iL) were added and the reaction mixture left for 24 h at 4 C. The volatiles were removed in vacuo and the resulting residue was purified by reverse phase C 18-column chromatography eluting with eluting with buffer A (v/v):water:5% acetonitrile:0.1% formic acid and buffer B (v/v): acetonitrile:0.1% formic acid (100:0 v/v to 65:3 5 v/v). The organic solvent was removed in vacuo and the aqueous solvent was removed by lyophilisation. The material was repurified by normal phase flash chromatography eluting with ethyl acetate:methanol (100:0 v/v to 0:100 v/v). The organic solvent was removed in vacuo and the aqueous solvent was removed by lyophilisation to givecompound 15 as a colourless oil (450 mg). m/z [M+H] (1331, 100%), [M+2H]2 (666,100%). |