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Structure of 284462-37-9

Chemical Structure| 284462-37-9

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Product Citations

Product Citations

Kumpati, Greeshma P ;

Abstract: Benzoxaborole structure contains a phenyl ring fused with a heterocyclic oxaborole ring moiety. Benzoxaboroles are considerably more stable and exhibit high hydrolytic resistance compared with corresponding phenylboronic acids. The enhanced acidity of benzoxaboroles allows them to be predominantly in anionic forms in aqueous solution at physiological pH, which causes them to exhibit higher water solubility and better pharmacokinetic properties than phenylboronic acids. Increasing interest in benzoxaborole compounds is mainly due to their broad-spectrum biological activity including antimicrobial, anti-inflammatory and other medicinal properties. Quinoline is a highly privileged nitrogen containing a bicyclic ring system where a benzene ring is fused to a pyridine ring. The quinoline moiety is found in many natural products and has been traditionally used as a medicine for treating a wide variety of diseases. Quinoline-based molecules have been found to exhibit a diverse range of pharmacological properties with uses as antimalarial, antibacterial, anticonvulsant, cardiotonic, anticancer, anthelmintic, antifungal, anti-inflammatory and analgesic agents. In this regard, we envisioned that introduction of aminobenzoxaborole unit on quinolines would result in novel molecular entities with favorable pharmacological and pharmaceutical properties for developing therapeutic agents for a wide variety of diseases. The aims of the current work include: 1) Develop a new synthetic methodology for the rapid creation of aminobenzoxaborole containing quinolines; and 2) Explore the efficacy of synthesized candidate compounds as antibacterial, antifungal, antiviral, antiinflammatory, and antimalarial agents. As a part of this thesis, we developed a novel synthetic methodology for preparing quinolino aminobenzoxaboroles. The synthesized compounds were initially evaluated for their cytotoxic properties against various human and murine proliferating cancer cells. All the compounds were found to be well tolerated did not display toxicity even at high concentrations. Encouraged by their lack of toxicity, the test compounds were evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis and for their antifungal activity against C. neoformans and C. albicans. Some of the synthesized derivatives exhibited good and selective activity against M. smegmatis. Future studies will involve evaluation of synthesized candidate compounds as antitubercular, antiviral, antimalarial, and anti-inflammatory agents.

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Product Details of [ 284462-37-9 ]

CAS No. :284462-37-9
Formula : C13H13N3O2
M.W : 243.26
SMILES Code : NC2=CC=C(OC1=CC=NC(=C1)C(=O)NC)C=C2
MDL No. :MFCD08692047
InChI Key :RXZZBPYPZLAEFC-UHFFFAOYSA-N
Pubchem ID :16655129

Safety of [ 284462-37-9 ]

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

Computational Chemistry of [ 284462-37-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 12
Fraction Csp3 0.08
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 68.15
TPSA ?

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

77.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.17
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

1.31
Log Po/w (WLOGP)?

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

1.82
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.

0.6
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

1.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.45

Water Solubility

Log S (ESOL):?

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

-2.4
Solubility 0.962 mg/ml ; 0.00396 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.

-2.53
Solubility 0.714 mg/ml ; 0.00293 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

-4.32
Solubility 0.0117 mg/ml ; 0.0000481 mol/l
Class?

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

Moderately 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

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.

-6.85 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.

0.55

Medicinal Chemistry

PAINS?

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

1.0 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)

1.99

Application In Synthesis of [ 284462-37-9 ]

* 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 [ 284462-37-9 ]

[ 284462-37-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 114780-06-2 ]
  • [ 123-30-8 ]
  • [ 220000-87-3 ]
  • [ 284462-37-9 ]
  • [ 284462-86-8 ]
YieldReaction ConditionsOperation in experiment
70%; 69% [0137] A solution of 4-aminophenol (256 mg, 2.35 mmol) in dry N,Ndimethylformamide (40 mL) was treated with potassium tert-butoxide (274 mg, 2.44 mmol), and the reddish-brown mixture was stirred at room temperature for 1 hour. The contents were treated with 3a and 3b (400 mg, 2.35 mmol) and potassium carbonate (974 mg, 7.05 mmol) and then heated to 80 C under argon for 4 h. The mixture was cooled to room temperature and poured into ethyl acetate (100 mL) and brine (400 mL). The combined organics were washed with brine, dried over sodium sulfate, and concentrated. The crude reaction mixture was purified by column chromatography (dichloromethane/methanol) to afford the desired 4-(4-aminophenoxy)-N- methylpyridine-2-carboxamide 4a (400 mg, 1 .65 mmol, 70%) and 4-(4- aminophenoxy)-N,N-dimethylpyridine-2-carboxamide (69%) 4b after column as a light-brown solid.
  • 2
  • [ 284462-37-9 ]
  • [ 35691-20-4 ]
  • N-methyl-4-(4-((4-(pyrrolidin-1-yl)pyrimidin-2-yl)amino)phenoxy)picolinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
56.1% With toluene-4-sulfonic acid; In 1,4-dioxane; at 80℃; for 12h; General procedure: To a solution of key intermediates 14a-b, 14c-d and 14e in 1,4-dioxane was added 4-substituted-2-chloro-pyrimidine and p-toluene sulfonic acid, and heated to 80 C for 12 h. The reaction was monitored by TLC until completed. The solution was evaporated to afford a crude product, which was purified by column chromatography (CH2Cl2/CH3OH, 100:1) on silica gel to afford the target compounds 17-19, 20-27, 28-36 and 37-40.
 

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