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Chemical Structure| 621-37-4 Chemical Structure| 621-37-4
Chemical Structure| 621-37-4

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3-Hydroxyphenylacetic acid

CAS No.: 621-37-4

3-Hydroxyphenylacetic acid is an endogenous metabolite.

Synonyms: 3-HPAA;NSC 14360;meta-Hydroxyphenylacetic Acid

4.5 *For Research Use Only !

Cat. No.: A127796 Purity: 97%

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Product Details of [ 621-37-4 ]

CAS No. :621-37-4
Formula : C8H8O3
M.W : 152.15
SMILES Code : C1=C(C=CC=C1O)CC(O)=O
Synonyms :
3-HPAA;NSC 14360;meta-Hydroxyphenylacetic Acid
MDL No. :MFCD00004337
InChI Key :FVMDYYGIDFPZAX-UHFFFAOYSA-N
Pubchem ID :12122

Safety of [ 621-37-4 ]

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

Calculated chemistry of [ 621-37-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 40.01
TPSA ?

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

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.02
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

0.85
Log Po/w (WLOGP)?

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

1.02
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.

1.05
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

1.06
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.0

Water Solubility

Log S (ESOL):?

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

-1.59
Solubility 3.91 mg/ml ; 0.0257 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.64
Solubility 3.47 mg/ml ; 0.0228 mol/l
Class?

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

Very 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

-1.58
Solubility 3.97 mg/ml ; 0.0261 mol/l
Class?

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

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

Yes
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

No
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

No
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

No
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

No
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.

-6.62 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

1.0
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

0.0 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<1.0
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)

1.15

Application In Synthesis [ 621-37-4 ]

* 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 [ 621-37-4 ]

[ 621-37-4 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 60211-57-6 ]
  • [ 621-37-4 ]
  • [ 29022-11-5 ]
  • resin-bound phenol [ No CAS ]
  • {2-[3-(3,5-dichloro-benzyloxy)-phenyl]-acetylamino}-acetic acid [ No CAS ]
  • 2
  • [ 30235-28-0 ]
  • [ 621-37-4 ]
  • methanesulfonic acid 3-[(4-pyridin-4-yl-thiazol-2-ylcarbamoyl)-methyl]-phenyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With N-(1-methanesulfonyl) benzotriazole; triethylamine; In tetrahydrofuran; at 160℃; for 0.166667h;Microwave; Methanesulfonic acid 3- [ (4-PYRIDIN-4-YL-THIAZOL-2-YLCARBAMOYL)-METHYL]- phenyl ester: 4- (4-PYRIDYL)-2-AMINOTHIAZOLE (317 mg, 1.79 MMOL), 3-HYDROXYPHENYLACETIC acid (343 mg, 2.25 mmol) and N- (1-METHANESULFONYL) benzotriazole (927 mg, 4.70 mmol) were placed in a microwave reaction vessel (Personal Chemistry, Uppsala, Sweden). THF (2 mL) was added followed by triethylamine (1.24 mL, 8.93 mmol) and the mixture heated in the sealed tube at 160C for 10 minutes. Upon cooling to room temperature the solvent was concentrated and ethanol added. The mixture was stored at -20C and then the precipitated product was filtered, washed with ethanol and dried. (910 mg, 65%). LH NMR (500 MHz, DMSO-d6) 12.62 (1H, s), 8.63 (2H, d), 7.98 (1H, s), 7.84 (2H, d), 7.47 (1H, m), 7.36 (2H, m), 7.27 (1H, m), 3.89 (2H, s), 3.40 (3H, s). LC-MS Rt = 2.1 min, [M+H] + = 390, [M-H]-= 388.
  • 3
  • [ 621-37-4 ]
  • [ 146137-78-2 ]
  • [ 1182350-33-9 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In tetrahydrofuran; acetonitrile; at 70℃; for 72h; Step 1: [3-(2-Formyl-4-trifluoromethyl-phenoxy)-phenyll -acetic acid[00412] 3-Hydroxyphenylacetic acid (1.Og, 5.2mmol), 2-fluoro-5-(trifluoromethyl)benzaldehyde (l.Og, 6.6mmol), and potassium carbonate (2.2g, 15.6mmol) were combined in THF (2OmL) and MeCN (2OmL) and heated to 700C for 3 days. After acidic work-up, the crude material was purified by silica gel chromatography (20-100% EtO Ac in hexanes) to give the desired product (0.25g).
Example 12: Synthesis of (3-{2-|((lS^R)-2-Hydroxy-l-methyl-2-phenyl-ethylamino)-mcthyll- 4-trifluoromethyl-phenoxy}-phcnyl)-acetic acid (Compound 1-12); Step 1: [3-(2-Formyl-4-trifluoromethyl-phenoxy)-phenyl]-acetic acid; [00425] 3-Hydroxyphenylacetic acid (Ig, 5.2mmol), 2-fluoro-5-(trifluoromethyl)benzaldehyde (Ig, 6.6mmol), and potassium carbonate (2.2g, 15.6mmol) were combined in THF (2OmL) and MeCN (2OmL), and the reaction was stirred at 70C for 3 days. After acidic workup, the crude material was purified by silica gel chromatography (20-100% EtOAc in hexanes) to give the title compound.
  • 4
  • [ 30235-28-0 ]
  • [ 621-37-4 ]
  • [ 692870-92-1 ]
 

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