Home Cart Sign in  
Chemical Structure| 218301-22-5 Chemical Structure| 218301-22-5

Structure of 218301-22-5

Chemical Structure| 218301-22-5

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Product Citations

Christian N. Lotz ; Alina Krollenbrock ; Lea Imhof ; Michael Riscoe ; Jennifer Keiser ;

Abstract: Schistosomiasis caused by Schistosoma spp. is a disease that causes a considerable health burden to millions of people worldwide. The limited availability of effective drugs on the market and the increased risk of resistance development due to extensive usage, highlight the urgent need for new antischistosomal drugs. Recent studies have shown that robenidine derivatives, containing an aminoguanidine core, exhibit promising activities against Plasmodium falciparum, motivating further investigation into their efficacy against Schistosoma mansoni, due to their similar habitat and the resulting related cellular mechanisms like the heme detoxification pathway. The conducted phenotypic screening of robenidine and 80 derivatives against newly transformed schistosomula and adult Schistosoma mansoni yielded 11 candidates with low EC50 values for newly transformed schistosomula (1.12–4.63 μM) and adults (2.78–9.47 μM). The structure-activity relationship revealed that electron-withdrawing groups at the phenyl moiety, as well as the presence of methyl groups adjacent to the guanidine moiety, enhanced the activity of derivatives against both stages of Schistosoma mansoni. The two compounds 2,2′-Bis[(3-cyano-4-fluorophenyl)methylene] carbonimidic Dihydrazide Hydrochloride (1) and 2,2′-Bis[(4-difluoromethoxyphenyl) ethylidene] carbonimidic Dihydrazide Hydrochloride (19), were selected for an in vivo study in Schistosoma mansoni-infected mice based on their potency, cytotoxicity, pharmacokinetic-, and physicochemical properties, but failed to reduce the worm burden significantly (worm burden reduction <20%). Thus, robenidine derivatives require further refinements to obtain higher antischistosomal specificity and in vivo activity.

Keywords: Robenidine derivative ; Aminoguanidine ; Schistosoma mansoni ; Drug discovery ; Structure-activity relationship

Purchased from AmBeed: ; ; ; ; ; ; ;

Alternative Products

Product Details of [ 218301-22-5 ]

CAS No. :218301-22-5
Formula : C8H4FNO
M.W : 149.12
SMILES Code : N#CC1=CC(C=O)=CC=C1F
MDL No. :MFCD01863558
InChI Key :MOFRJTLODZILCR-UHFFFAOYSA-N
Pubchem ID :2769582

Safety of [ 218301-22-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 218301-22-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 36.5
TPSA ?

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

40.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.24
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

1.2
Log Po/w (WLOGP)?

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

1.93
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.

1.2
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

2.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.59

Water Solubility

Log S (ESOL):?

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

-1.86
Solubility 2.07 mg/ml ; 0.0139 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.

-1.65
Solubility 3.3 mg/ml ; 0.0222 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

-2.69
Solubility 0.303 mg/ml ; 0.00203 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.

-6.36 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)

1.53

Application In Synthesis of [ 218301-22-5 ]

* 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 [ 218301-22-5 ]

[ 218301-22-5 ] Synthesis Path-Downstream   1~3

  • 1
  • 6-chloro-N-(piperidin-4-yl)thieno[2,3-d]pyrimidin-4-amine dihydrochloride [ No CAS ]
  • [ 218301-22-5 ]
  • [ 866206-54-4 ]
  • [ 866206-62-4 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 47 5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluoro benzonitrile The title compound was prepared (392 mg, 41%) from 6-chloro-N-(piperidin-4-yl)thieno[2,3-d]pyrimidin-4-amine dihydrochloride (655 mg, 2.4 mmol) and 2-fluoro-5-formylbenzonitrile (399 mg, 2.7 mmol) by following the general procedure described for Preparation 11. 1H NMR (400 MHz, CDCl3) d 8.43 (s, 1H), 7.63 (m, 1H), 7.55 (m, 1H), 7.16 (m, 1H), 7.00 (s, 1H), 4.93 (d, 1H), 4.19 (m, 1H), 3.50 (s, 2H), 2.83 (d, 2H), 2.23 (dt, 2H), 2.10 (d, 2H), 1.59 (m, 2H); MS (ESI) m/z: Calculated for C19H18ClFN5S, 402.1. Observed: 402.2 (M++1).
EXAMPLE 47 5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluoro benzonitrile The title compound was prepared (392 mg, 41%) from 6-chloro-N-(piperidin-4-yl)thieno[2,3-d]pyrimidin-4-amine dihydrochloride (655 mg, 2.4 mmol) and 2-fluoro-5-formylbenzonitrile (399 mg, 2.7 mmol) by following the general procedure described for Preparation 11. 1H NMR (400 MHz, CDCl3) delta 8.43 (s, 1H), 7.63 (m, 1H), 7.55 (m, 1H), 7.16 (m, 1H), 7.00 (s, 1H), 4.93 (d, 1H), 4.19 (m, 1H), 3.50 (s, 2H), 2.83 (d, 2H), 2.23 (dt, 2H), 2.10 (d, 2H), 1.59 (m, 2H); MS (ESI) m/z: Calculated for C19H18ClFN5S, 402.1; Observed: 402.2 (M++1).
  • 2
  • [ 218301-22-5 ]
  • [ 347174-05-4 ]
  • ethyl 3-(3-cyano-4-fluorobenzylamino)-4-(cyclohexylamino)-benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: SI, Figure 4. General procedure of the reductive amination reactions: synthesis of AA9-AA24 compounds (Tables 1 and 2). The <strong>[347174-05-4]ethyl 3-amino-4-(cyclohexylamino)benzoate</strong> (AA1) and derivatives (1 equiv.)and benzaldehyde (1 equiv) were heated in DCE for 1h at 80 oC in the presence of molecular sieves (4 A), then the mixture was cooled down to room temperature before addition of the NaBH(OAc)3 (1.6 equiv.) in small portions over 3h. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 17h. The reaction mixture was quenched with aqueous saturated NaHCO3, and the product was extracted with EtOAc. The EtOAc extract was dried (MgSO4), and the solvent was evaporated. The residue was purified by flash-column chromatography on silica gel, using a mixture of solvent of DCM: MeOH (50:1), to provide the desired AA9-AA24 compounds (Tables 1-2).
  • 3
  • [ 22237-13-4 ]
  • [ 218301-22-5 ]
  • 2-fluoro-5-(4-ethoxybenzyl)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% 2-Fluoro-5-formylbenzonitrile (10g, 1eq) was dissolved in 100mL 1,4-dioxane, p-toluenesulfonyl hydrazide (13.7g, 1eq) was added, stirred at room temperature for 3 hours, and then added Potassium carbonate (13.9 g, 1.5 eq), 4-ethoxyphenylboronic acid (12.2 g, 1 eq), warmed to 100 C. and stirred for 12 hours. After TLC monitoring the reaction of the raw materials, filter, spin dry the filtrate, add petroleum ether and stir for half an hour, filter, and spin dry the filtrate to obtain 15 g of 2-fluoro-5-(4-ethoxybenzyl)benzonitrile (the yield is 88%).
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 218301-22-5 ]

Fluorinated Building Blocks

Chemical Structure| 1003708-42-6

A250649 [1003708-42-6]

3-Fluoro-5-formylbenzonitrile

Similarity: 0.93

Chemical Structure| 894779-76-1

A156473 [894779-76-1]

4-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 77532-90-2

A465290 [77532-90-2]

5-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 433939-88-9

A455727 [433939-88-9]

2,6-Difluoro-4-formylbenzonitrile

Similarity: 0.88

Chemical Structure| 146137-79-3

A182608 [146137-79-3]

4-Fluoro-3-formylbenzonitrile

Similarity: 0.87

Aryls

Chemical Structure| 1003708-42-6

A250649 [1003708-42-6]

3-Fluoro-5-formylbenzonitrile

Similarity: 0.93

Chemical Structure| 894779-76-1

A156473 [894779-76-1]

4-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 77532-90-2

A465290 [77532-90-2]

5-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 433939-88-9

A455727 [433939-88-9]

2,6-Difluoro-4-formylbenzonitrile

Similarity: 0.88

Chemical Structure| 146137-79-3

A182608 [146137-79-3]

4-Fluoro-3-formylbenzonitrile

Similarity: 0.87

Aldehydes

Chemical Structure| 1003708-42-6

A250649 [1003708-42-6]

3-Fluoro-5-formylbenzonitrile

Similarity: 0.93

Chemical Structure| 894779-76-1

A156473 [894779-76-1]

4-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 77532-90-2

A465290 [77532-90-2]

5-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 433939-88-9

A455727 [433939-88-9]

2,6-Difluoro-4-formylbenzonitrile

Similarity: 0.88

Chemical Structure| 146137-79-3

A182608 [146137-79-3]

4-Fluoro-3-formylbenzonitrile

Similarity: 0.87

Nitriles

Chemical Structure| 1003708-42-6

A250649 [1003708-42-6]

3-Fluoro-5-formylbenzonitrile

Similarity: 0.93

Chemical Structure| 894779-76-1

A156473 [894779-76-1]

4-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 77532-90-2

A465290 [77532-90-2]

5-Fluoro-2-formylbenzonitrile

Similarity: 0.89

Chemical Structure| 433939-88-9

A455727 [433939-88-9]

2,6-Difluoro-4-formylbenzonitrile

Similarity: 0.88

Chemical Structure| 146137-79-3

A182608 [146137-79-3]

4-Fluoro-3-formylbenzonitrile

Similarity: 0.87