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Chemical Structure| 378247-75-7 Chemical Structure| 378247-75-7

Structure of Fmoc-ACC-OH
CAS No.: 378247-75-7

Chemical Structure| 378247-75-7

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Product Details of [ 378247-75-7 ]

CAS No. :378247-75-7
Formula : C26H19NO6
M.W : 441.43
SMILES Code : O=C(O)CC(C1=C(O2)C=C(NC(OCC3C4=C(C5=C3C=CC=C5)C=CC=C4)=O)C=C1)=CC2=O
MDL No. :MFCD13195295
InChI Key :RCUKLQDGAASIAX-UHFFFAOYSA-N
Pubchem ID :10993900

Safety of [ 378247-75-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 378247-75-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 33
Num. arom. heavy atoms 22
Fraction Csp3 0.12
Num. rotatable bonds 7
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 122.59
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

105.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.41
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.62
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

4.59
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.33
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

4.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.67

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-4.89
Solubility 0.0057 mg/ml ; 0.0000129 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.53
Solubility 0.0013 mg/ml ; 0.00000295 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-8.49
Solubility 0.00000142 mg/ml ; 0.0000000032 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

Yes
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.42 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<2.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

4.26

Application In Synthesis of [ 378247-75-7 ]

* 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.

  • Downstream synthetic route of [ 378247-75-7 ]

[ 378247-75-7 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 122889-11-6 ]
  • [ 378247-75-7 ]
  • C21H21N3O5 [ No CAS ]
  • 2
  • [ 123639-61-2 ]
  • [ 378247-75-7 ]
  • [ 1558029-85-8 ]
  • 3
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 71989-14-5 ]
  • [ 64-19-7 ]
  • [ 378247-75-7 ]
  • Fmoc-Glu(pg)-OH [ No CAS ]
  • C38H46N6O13 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Synthesis of NH2-ACC-Rink Amide resin. Preparation of ACC wascarried out as described previously according to Maly et al.18 To glass reactionvessel, 1 eq (6.24 mmol, 13 g) of Rink AM resin was added and stirred gentlyonce per 10 min in DCM for 1 h, and then filtered and washed 3 times with DMF.Fmoc-protecting group was removed using 20percent piperidine in DMF (5, 5, and25 min), filtered each time and washed with DMF (six times). Next, 2.50 eq of Fmoc-ACC-OH (15.6 mmol, 6.9 g) was preactivated with 2.50 eq HOBt monohydrate (15.6 mmol, 2.34 g) and 2.50 eq DICI (15.6 mmol, 2.0 ml) in DMFand mixture was added to the resin. Reaction was stirred gently for 24 h at room temperature. Resin was washed four times with DMF and reaction was repeatedusing 1.5 eq of above reagents to improve yield of ACC coupling to the resin. Afterreaction, resin was washed with DMF and Fmoc group was removed using 20percentpiperidine in DMF (5, 5, and 25 min), filtered and washed with DMF (six times). Synthesis of NH2-Asp(t-Bu)-ACC-Rink Amide resin. Next, 2.5 eqFmoc-Asp(t-Bu)-OH (15.6 mmol, 6.42 g) with 2.5 eq HATU (15.6 mmol, 5.93 g),2.5 eq collidine (15.6 mmol, 2.03 ml) in DMF were activated for 2 min and added tofilter cannula with 1 eq (6.24 mmol) NH2-ACC-resin and reaction was carried outfor 24 h. Next, resin was washed four times with DMF and reaction was repeatedusing 1.5 eq of above reagents. After washing with DMF, Fmoc-protecting groupwas removed using 20percent piperidine in DMF (5, 5, and 25 min). Resin wasadditional washed with DCM (3 times) and MeOH (3 times) and dried over P2O5. Synthesis of individual optimized substrates. The 2.5 eqFmoc-P2-OH was preactivated with 2.5 eq HOBt and 2.5 eq DICI in DMF andadded to cartridge with 1 eq NH2-Asp(t-Bu)-ACC-resin (all substrates containedAsp at P1 position) and followed by gentle agitation for 3 h. Then, it was filteredand washed with DMF (six times). Fmoc-protecting group was removed using 20percent piperidine in DMF (5, 5, and 25 min). Ninhydrin test was carried out each time aftercoupling and deprotection. A solution of 2.5 eq Fmoc-P3-OH, 2.5 eq HOBt, and2.5 eq DICI in DMF was added to the resin and the slurry was agitated for 3 h.After removal of the solution, the resin was washed with DMF (six times), andcoupling and deprotection of Fmoc-P4-OH was carried in identical conditions likeP2 position. N-terminus was protected with acetyl group using 5 eq AcOH, 5 eqHBTU, and 5 eq DIPEA in DMF as previous described. After solvent removal, theresin was washed with DMF (six times), DCM (three times), and MeOH (threetimes) dried over P2O5 and cleaved from the resin with a mixture of TFA/TIPS/H2O(percent, v/v/v 95 : 2.5 : 2.5). The crude product was purified by HPLC and lyophilized.Its purity was confirmed by analytical HPLC. Each optimized substrate wasanalyzed using HRMS. Optimized substrates were dissolved in peptide gradeDMSO to 20mM concentration and stored at -80 °Cuntil use.
  • 4
  • [ 625845-42-3 ]
  • [ 71989-14-5 ]
  • [ 64-19-7 ]
  • [ 161420-87-7 ]
  • [ 378247-75-7 ]
  • C40H53N7O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Synthesis of NH2-ACC-Rink Amide resin. Preparation of ACC wascarried out as described previously according to Maly et al.18 To glass reactionvessel, 1 eq (6.24 mmol, 13 g) of Rink AM resin was added and stirred gentlyonce per 10 min in DCM for 1 h, and then filtered and washed 3 times with DMF.Fmoc-protecting group was removed using 20% piperidine in DMF (5, 5, and25 min), filtered each time and washed with DMF (six times). Next, 2.50 eq of Fmoc-ACC-OH (15.6 mmol, 6.9 g) was preactivated with 2.50 eq HOBt monohydrate (15.6 mmol, 2.34 g) and 2.50 eq DICI (15.6 mmol, 2.0 ml) in DMFand mixture was added to the resin. Reaction was stirred gently for 24 h at room temperature. Resin was washed four times with DMF and reaction was repeatedusing 1.5 eq of above reagents to improve yield of ACC coupling to the resin. Afterreaction, resin was washed with DMF and Fmoc group was removed using 20%piperidine in DMF (5, 5, and 25 min), filtered and washed with DMF (six times). Synthesis of NH2-Asp(t-Bu)-ACC-Rink Amide resin. Next, 2.5 eqFmoc-Asp(t-Bu)-OH (15.6 mmol, 6.42 g) with 2.5 eq HATU (15.6 mmol, 5.93 g),2.5 eq collidine (15.6 mmol, 2.03 ml) in DMF were activated for 2 min and added tofilter cannula with 1 eq (6.24 mmol) NH2-ACC-resin and reaction was carried outfor 24 h. Next, resin was washed four times with DMF and reaction was repeatedusing 1.5 eq of above reagents. After washing with DMF, Fmoc-protecting groupwas removed using 20% piperidine in DMF (5, 5, and 25 min). Resin wasadditional washed with DCM (3 times) and MeOH (3 times) and dried over P2O5. Synthesis of individual optimized substrates. The 2.5 eqFmoc-P2-OH was preactivated with 2.5 eq HOBt and 2.5 eq DICI in DMF andadded to cartridge with 1 eq NH2-Asp(t-Bu)-ACC-resin (all substrates containedAsp at P1 position) and followed by gentle agitation for 3 h. Then, it was filteredand washed with DMF (six times). Fmoc-protecting group was removed using 20% piperidine in DMF (5, 5, and 25 min). Ninhydrin test was carried out each time aftercoupling and deprotection. A solution of 2.5 eq Fmoc-P3-OH, 2.5 eq HOBt, and2.5 eq DICI in DMF was added to the resin and the slurry was agitated for 3 h.After removal of the solution, the resin was washed with DMF (six times), andcoupling and deprotection of Fmoc-P4-OH was carried in identical conditions likeP2 position. N-terminus was protected with acetyl group using 5 eq AcOH, 5 eqHBTU, and 5 eq DIPEA in DMF as previous described. After solvent removal, theresin was washed with DMF (six times), DCM (three times), and MeOH (threetimes) dried over P2O5 and cleaved from the resin with a mixture of TFA/TIPS/H2O(%, v/v/v 95 : 2.5 : 2.5). The crude product was purified by HPLC and lyophilized.Its purity was confirmed by analytical HPLC. Each optimized substrate wasanalyzed using HRMS. Optimized substrates were dissolved in peptide gradeDMSO to 20mM concentration and stored at -80 Cuntil use.
  • 5
  • [ 108-30-5 ]
  • [ 29022-11-5 ]
  • [ 95753-55-2 ]
  • [ 378247-75-7 ]
  • C26H25N5O10 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: To a 10 mL glass peptide synthesis vessel was added Rink Amide AM resin (0.60 g, 0.31 mmol)and DMF (4 mL). The mixture was gently agitated with a wrist-action Burrel shaker for 1h andthen filtered. A 20% solution of piperidine in DMF (4 mL) was added and the mixture wasagitated for 30 min. The resin was filtered and then washed with DMF (3 × 4 mL). 7-N-(Fluorenylmethoxycarbonyl)aminocoumarin-4-acetic acid1 (0.40 g, 0.91 mmol), HOBt.H2O (140mg, 0.95 mmol) and DMF (4 mL) was added to the resin followed by DIC (144 muL, 0.93 mmol).The mixture was agitated for 24h, filtered and then washed with DMF (3 × 4mL), THF (3 × 4mL)and MeOH (3 × 4mL) respectively.General Procedure for Coupling the First Fmoc-Amino Acid to the ACC-ResinTo a 10 mL glass peptide synthesis vessel was added ACC-resin (0.31 mmol) and DMF (4 mL).The mixture was gently agitated with a wrist-action Burrel shaker for 1h and then filtered. A 20%solution of piperidine in DMF (4 mL) was added and the mixture was agitated for 30 min. Theresin was filtered and then washed with DMF (3 × 4 mL). In a separate scintillation vial wereadded Fmoc-amino acid (1.32 mmol), HOBt (200 mg, 1.32 mmol), DMF (4 mL) and DIC (200 muL,1.29 mmol). After a preactivation time of 5 min, the mixture was added to the resin and agitatedovernight. The resin was filtered and washed with DMF (3 × 4 mL).Representative Synthesis of a Di-peptide -ACCAs a representative example, the synthesis of N-suc-L-Phe-Gly-ACC is described. To a 10 mLglass peptide synthesis vessel was added Fmoc-Gly-ACC-resin (0.1 mmol) and DMF (3 mL). The mixture was gently agitated for 1h and then filtered. A 20% solution of piperidine in DMF (3mL) was added and the mixture was agitated for 30 min. The resin was filtered and then washedwith DMF (3 × 3 mL). In a separate scintillation vial were added Fmoc-L-Phe-OH (190 mg, 0.5mmol), HOBt (76 mg, 0.5 mmol), DMF (3 mL) and DIC (76 muL, 0.5 mmol). After a preactivationtime of 5 min, the mixture was added to the resin and agitated for 5h. The resin was filtered andwashed with DMF (3 × 4 mL). A 20% solution of piperidine in DMF (3 mL) was added and themixture was agitated for 30 min. The resin was filtered and then washed with DMF (3 × 3 mL).Succinic anhydride (100 mg, 1.0 mmol), DMF (3mL) and DIPEA (150 muL, 0.9 mmol) were addedand the mixture was agitated overnight, filtered and then washed with DMF (3 × 4 mL). Asolution of TFA:iPr3SiH:H2O (95:2.5:2.5, 3 mL) was added and the mixture was agitatedovernight. The resin was filtered and washed with TFA (2 × 3 mL). The combined filtrate wasconcentrated and the residue was washed with ether (3 × 3 mL) to give suc-L-Phe-Gly-ACC aspale yellow solid (32 mg, 62%). Amino terminus of some peptides was capped as the acetylderivative. This was accomplished by premixing AcOH (5 equiv), HOBt (5 equiv) and DIC (5equiv) in DMF and adding the mixture to the resin. The resulting mixture was agitated for 5h,filtered, and then washed with DMF. For ACC-peptides 11-18, the amino terminus was coupledwith the corresponding dicarboxylic acid as follows: In a separate scintillation vial were addeddicarboxylic acid (5 equiv), HOBt (5 equiv), DMF and DIC (5 equiv). After a pre-activation time of5 min, the mixture was added to the resin and agitated overnight. The resin was filtered andwashed with DMF (3 × 4 mL). The purification of all ACC-peptides was performed either bysimply washing the solid thoroughly with ether or by reverse-phase HPLC (ACN/H2O-0.1% TFA,15 - 60% for 20 min, 20 mL/min, 254 nm detection for 22.5 min). Purity check for all ACCpeptideswas completed by analytical reverse-phase HPLC (ACN/H2O-0.1% TFA, 10 - 60% for20 min, 1 mL/min, 254 nm detection for 23 min). Retention times are indicated as tR.
  • 6
  • [ 123639-61-2 ]
  • [ 64-19-7 ]
  • [ 135112-28-6 ]
  • Fmoc-L-Hyp(Bzl)-OH [ No CAS ]
  • [ 159766-56-0 ]
  • [ 378247-75-7 ]
  • C50H61N7O12 [ No CAS ]
  • 7
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 123639-61-2 ]
  • [ 64-19-7 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 378247-75-7 ]
  • Ac-Ala-Arg-Leu-P1-(7-amino-4-carbamoylmethylcoumarin), P1 = L-Glu(Bzl) [ No CAS ]
  • 8
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 122889-11-6 ]
  • [ 64-19-7 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 378247-75-7 ]
  • Ac-Ala-Arg-Leu-P1-(7-amino-4-carbamoylmethylcoumarin), P1 = L-Ser(Bzl) [ No CAS ]
  • 9
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 96402-49-2 ]
  • [ 64-19-7 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 378247-75-7 ]
  • Ac-Ala-Arg-Leu-P1-(7-amino-4-carbamoylmethylcoumarin), P1 = L-1Nal [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 378247-75-7 ]

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