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Chemical Structure| 150560-58-0

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Product Citations

Product Citations

Prinsloo, Izak F. ; Petzer, Jacobus P. ; Cloete, Theunis T. ; Petzer, Anel ;

Abstract: The small mol., isatin, is a well-known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC50 values of 12.3 and 4.86μM for MAO-A and MAO-B, resp. While the interaction of isatin with MAO-B has been characterized, only a few studies have explored structure-activity relationships (SARs) of MAO inhibition by isatin analogs. The current study therefore evaluated a series of 14 isatin analogs as in vitro inhibitors of human MAO-A and MAO-B. The results indicated good potency MAO inhibition for some isatin analogs with five compounds exhibiting IC50 < 1μM. 4-Chloroisatin (1b) and 5-bromoisatin (1f) were the most potent inhibitors with IC50 values of 0.812 and 0.125μM for MAO-A and MAO-B, resp. These compounds were also found to be competitive inhibitors of MAO-A and MAO-B with Ki values of 0.311 and 0.033μM, resp. Among the SARs, it was interesting to note that C5-substitution was particularly beneficial for MAO-B inhibition. MAO inhibitors are established drugs for the treatment of neuropsychiatric and neurodegenerative disorders, while potential new roles in prostate cancer and cardiovascular disease are being investigated.

Keywords: competitive ; inhibition ; isatin ; monoamine oxidase ; structure-activity relationship

Alternative Products

Product Details of [ 150560-58-0 ]

CAS No. :150560-58-0
Formula : C11H11NO2
M.W : 189.21
SMILES Code : O=C1NC2=C(C=C(C(C)C)C=C2)C1=O
MDL No. :MFCD02947184
InChI Key :LFNQRSQKXQFHDB-UHFFFAOYSA-N
Pubchem ID :589802

Safety of [ 150560-58-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 150560-58-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.27
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 56.74
TPSA ?

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

46.17 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.48
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

1.96
Log Po/w (WLOGP)?

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

1.37
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.

1.08
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

2.48
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-2.5
Solubility 0.6 mg/ml ; 0.00317 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.55
Solubility 0.528 mg/ml ; 0.00279 mol/l
Class?

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

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

-3.6
Solubility 0.0472 mg/ml ; 0.000249 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

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

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.

-6.06 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.

0.55

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<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)

1.75

Application In Synthesis of [ 150560-58-0 ]

* 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.

  • Upstream synthesis route of [ 150560-58-0 ]

[ 150560-58-0 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 68701-52-0 ]
  • [ 150560-58-0 ]
YieldReaction ConditionsOperation in experiment
98.7% at 20 - 30℃; for 2.16667 h; To 294 g of 95percent sulfuric acid was added 41.2 g of isonitrosoaceto-p-isopropylanilide at room temperature. Then, the temperature was raised to 30 ° C. over 10 minutes, and the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, the reaction solution was added dropwise to a separate vessel charged with 419 g of water, and the precipitate was filtered. Washed with 1,300 g of water and dried in a dryer at 60 ° C. to obtain 37.3 g of 5-isopropyl isatin. The yield was 98.7percent, the purity was 98.1 wtpercent, and the melting point was 137 to 140 ° C. In this example, the molar ratio of isonitrosoaceto-p-isopropylanilide to sulfuric acid is 1: 14.3.
References: [1] Patent: JP2018/150285, 2018, A, . Location in patent: Paragraph 0024-0031; 0036.
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1585 - 1587.
  • 2
  • [ 1421739-77-6 ]
  • [ 150560-58-0 ]
YieldReaction ConditionsOperation in experiment
64% at 80℃; for 0.416667 h; Cooling with ice General procedure: A round-bottom flask is charged with concentrated sulfuric acid (33 ml) and is magnetically stirred at 50 °C open to the atmosphere. To the acid was added 2-[(benzyloxy)imino]-N-(4-n-hexylphenyl) (11 g, 32.5 mmole) in portions over 30 minutes. On completion of the addition the mixture was heated at 80 °C for an additional 10 minutes then allowed to cool to room temperature. The dark viscous solution was subsequently added in portions with rapid stirring to ice (750 ml). The crude product was isolated by vacuum filtration, and the filter cake washed with water. The crude product was dried under vacuum to give 6.3 g (85 percent) of an orange solid.#10;#10;
References: [1] Tetrahedron Letters, 2013, vol. 54, # 8, p. 1008 - 1011.
  • 3
  • [ 302-17-0 ]
  • [ 99-88-7 ]
  • [ 150560-58-0 ]
References: [1] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 809 - 819.
  • 4
  • [ 201230-82-2 ]
  • [ 150560-58-0 ]
References: [1] Synthesis, 2003, # 13, p. 2047 - 2052.
[2] Synlett, 1999, # SPEC. ISS., p. 945 - 947.
  • 5
  • [ 79-37-8 ]
  • [ 99-88-7 ]
  • [ 150560-58-0 ]
References: [1] Acta Chimica Slovenica, 2010, vol. 57, # 2, p. 466 - 469.
  • 6
  • [ 99-88-7 ]
  • [ 150560-58-0 ]
References: [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 1, p. 21 - 39.
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 7, p. 1585 - 1587.
  • 7
  • [ 51605-97-1 ]
  • [ 150560-58-0 ]
References: [1] Synthesis, 2003, # 13, p. 2047 - 2052.
 

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