Structure of Fmoc-Cys(tBu)-OH
CAS No.: 67436-13-9
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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-(((9H-Fluoren-9-yl)methoxy)carbonyl)-S-(tert-butyl)-L-cysteine
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Batch number can be found on the product's label following the word 'Batch'.
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 67436-13-9 |
Formula : | C22H25NO4S |
M.W : | 399.50 |
SMILES Code : | O=C(O)[C@H](CSC(C)(C)C)NC(OCC1C2=CC=CC=C2C3=CC=CC=C13)=O |
Synonyms : |
N-(((9H-Fluoren-9-yl)methoxy)carbonyl)-S-(tert-butyl)-L-cysteine
|
MDL No. : | MFCD00037130 |
InChI Key : | IXAYZHCPEYTWHW-IBGZPJMESA-N |
Pubchem ID : | 7009544 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 28 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 9 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 112.03 |
TPSA ? Topological Polar Surface Area: Calculated from |
100.93 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.55 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.32 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.76 |
Solubility | 0.00692 mg/ml ; 0.0000173 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.15 |
Solubility | 0.00028 mg/ml ; 0.000000702 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.17 |
Solubility | 0.000269 mg/ml ; 0.000000673 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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.67 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<3.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.33 |
* 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 |
---|---|---|
All peptides were synthesized on a 0.2 mmol scale using manual Fmoc-SPPS chemistry under flow using a 3 minute cycle for each amino acid. Specifically, all reagents and solvents are delivered to a stainless steel reactor containing resins at a constant flow rate using HPLC pump; temperature of the reactor was maintained at 60 °C during the synthesis using water bath. Procedure for each amino acid coupling cycle included a 30 second coupling with 1 mmol Fmoc-protected amino acid, 1 mmol HBTU, and 500 of diisopropyl ethyl amine (DIEA) in 2.5 mL of DMF at a flow rate of 6 mL/min (note that for coupling of cysteine and tryptophan, 190 of DIEA was used to prevent racemization); 1 minute wash with DMF at a flow rate of 20 mL/min; 20 second deprotection with 50percent (v/v) piperidine in DMF at a flow rate of 20 mL/min; and 1 minute wash with DMF at a flow rate was 20 mL/min. After completion of the stepwise SPPS, the resin was washed thoroughly with DCM and dried under vacuum. The peptide is simultaneously cleaved from the resin and side-chain deprotected by treatment with 2.5percent (v/v) water, 2.5percent (v/v) 1 ,2- ethanedithiol (EDT), and 1percent (v/v) triisoproprylsilane in neat trifluoroacetic acid (TFA) for 2 hours at room temperature. The resulting solution containing peptide was evaporated by blowing a stream of nitrogen gas over its surface for 15 minutes, then triturated and washed with cold diethyl ether three times. The obtained gummy-like solid was dissolved in 50percent H20: 50percent acetonitrile containing 0.1percent TFA and lyophilized. These same solvent compositions were used in majority of experiments and will be referred to as A: 0.1percent TFA in H20 and B: 0.1percent TFA in acetonitrile. c. Peptide Purification The crude peptide was dissolved in 95percent A: 5percent B with 6 M guanidinium hydrochloride and purified by semi-preparative RP-HPLC (Agilent Zorbax SB C18 column: 21.2 x 250 mm, 7 mutaueta, linear gradient: 5-50percent B over 90 min, flow rate: 5 mL/min). 1 of each HPLC fraction was mixed with 1 mu^ of alpha-cyano-4-hydroxycinnamic acid (CHCA) matrix in 75percent A: 25percent B, spotted with MALDI, and checked for fractions with desired molecular mass. The purity of fractions was confirmed by analytical RP-HPLC (Agilent Zorbax SB C3 column: 2.1 x 150 mm, 5 muiotaeta, gradient: 0-2 minutes 5percent B, 2-11 minutes 5- 65percent B, 11-12 minutes 65percent B, flow rate: 0.8 mL/min). HPLC fractions containing only product materials were confirmed by LC-MS analysis, combined, and then lyophilized. Peptides synthesized using fast flow-based SPPS and purified by RP-HPLC are listed in Table SI . |