Structure of Fmoc-trans-4-Amc-OH
CAS No.: 167690-53-1
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CAS No. : | 167690-53-1 |
Formula : | C23H25NO4 |
M.W : | 379.45 |
SMILES Code : | O=C(O)[C@H]1CC[C@@H](CC1)CNC(OCC2C3=CC=CC=C3C4=CC=CC=C24)=O |
MDL No. : | MFCD00273480 |
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 | 0.39 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 107.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
75.63 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.05 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.6 |
Solubility | 0.00955 mg/ml ; 0.0000252 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.34 |
Solubility | 0.00173 mg/ml ; 0.00000455 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.03 |
Solubility | 0.000358 mg/ml ; 0.000000944 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) |
Yes |
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 |
-5.74 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) |
4.15 |
* 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 |
---|---|---|
Fmoc-Lys(ivDde)-Wang resin (0.3 mmol, 0.61 mmol/g loading) was suspended in DMF for 30 mm. Fmoc was then removed by treating the resin with 20% piperidine in DMF (3 x 8 mm). The isocyanate derivative of di-t-butyl ester of glutamate (3 eq.) was prepared according to literatureprocedures,17 and added to the lysine-immobilized resin and reacted for 16 h. After washing the resinwith DMF, the ivDde-protecting group was removed with 2% hydrazine in DMF (5 x 5 mi. Fmoc-2- Nal-OH was then coupled to the side chain of Lys followed by Fmoc-tranexamic acid, FmocLys(ivDde)-OH, and Fmoc-Gly-OH via solid-phase peptide synthesis using Fmoc-based chemistry. Allcouplings were carried out in DMF using Fmoc-protected amino acid (3 eq.), HBTU (3 eq.), HOBT (3eq.), and DIEA (8 eq.). Afterwards, elongation was continued with the addition of <strong>[27913-58-2]4-<strong>[27913-58-2](p-iodophenyl)butyric acid</strong></strong> (for HTK03024), 4-(p-chlorophenyl)butyric acid (for HTK03055), 4-phenylbutyric acid (for HTK03056), 4-(p-bromophenyl)butyric acid (for HTK03058), 3-phenyipropanoic acid (for HTK03082), 4-(p-fluorophenyl)butyric acid (for HTK03085), 4-(p-methoxyphenyl)butyric acid(for HTK03086), 4-(p-(t-butyloxycarbonyl)aminophenyl)butyric acid (for HTK03087), 4-(p-nitrophenyl)butyric acid (for HTK03089), or 4-(p-tolyl)butyric acid (for HTKO3O9O) were coupled to thesame peptide-bound resin using Fmoc-based chemistry. After selective removal of the ivDdeprotecting group with 2% hydrazine in DMF (5 x 5 mm), the chelator DOTA was then coupled to theside chain of Lys to give the precursors. The peptide was then deprotected and simultaneously cleaved from the resin by treatingwith 95/5 trifluoroacetic acid (TFA)/triisopropylsilane (TIS) for 2 h at room temperature. After filtration,the peptide was precipitated by the addition of cold diethyl ether to the TFA solution. The crude peptide was purified by HPLC using the semi-preparative column. The eluates containing the desired peptidewere collected, pooled, and lyophilized. For HTK03024, the HPLC conditions were 37% acetonitrile inwater with 0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 8.8 mi ESI-MS: calculated[M+H] for HTK03024 C67H96N120191 1499.6; found [M+H] 1499.6. For HTK03055, the HPLCconditions were 35% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min. The retentiontime was 9.7 mi ESI-MS: calculated [M+H] for HTK03055 C67H96N12019C1 1407.7; found [M+H]1407.7. For HTK03056, the HPLC conditions were 0-80% acetonitrile in waterwith 0.1% TFA ata flowrate of 4.5 mL/min in 20 mm. The retention time was 13.4 mi ESI-MS: calculated [M+H] forHTK03056 C67H97N12019 1373.7; found [M+H] 1373.8. For HTK03058, the HPLC conditions were 0-80% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min in 20 mm. The retention time was13.4 mi ESI-MS: calculated [M+H] for HTK03058 C67H96N12O19Br 1451.6; found [M+H] 1451.6. ForHTK03082, the HPLC conditions were 31% acetonitrile in water with 0.1% TFA at a flow rate of 4.5mL/min. The retention time was 11.1 mi ESI-MS: calculated [M+H] for HTK03082 C66H95N120191359.7; found [M+H] 1359.9. For HTK03085, the HPLC conditions were 34% acetonitrile in waterwith0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 9.0 mi ESI-MS: calculated [M+H] forHTK03085 C67H96N12019F 1391.7; found [M+H] 1391.9. For HTK03086, the HPLC conditions were33% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 9.1 mm.ESI-MS: calculated [M+H] for HTK03086 C68H99N12020 1403.7; found [M+H] 1404.1. For HTK03087,the HPLC conditions were 23% acetonitrile in water with 0.1% TFA ata flow rate of 4.5 mL/min. Theretention time was 13.9 mi ESI-MS: calculated [M+H] for HTK03087 C67H98N13019 1388.7; found[M+H] 1389.0. For HTK03089, the HPLC conditions were 33% acetonitrile in water with 0.1% TFA ataflow rate of 4.5 mL/min. The retention time was 10.6 mi ESI-MS: calculated [M+H] for HTK03089C67H96N13021 1418.7; found [M+H] 1419.0. For HTKO3O9O, the HPLC conditions were 35% acetonitrile in water with 0.1% TFA at a flow rate of 4.5 mL/min. The retention time was 9.1 mm. ESI-MS:calculated [M+H] for HTKO3O9O C68H99N12019 1387.7; found [M+H] 1387.9. |
Tags: 167690-53-1 synthesis path| 167690-53-1 SDS| 167690-53-1 COA| 167690-53-1 purity| 167690-53-1 application| 167690-53-1 NMR| 167690-53-1 COA| 167690-53-1 structure
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