Home Cart Sign in  
Chemical Structure| 74936-72-4 Chemical Structure| 74936-72-4

Structure of 74936-72-4

Chemical Structure| 74936-72-4

*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

Alternative Products

Product Details of [ 74936-72-4 ]

CAS No. :74936-72-4
Formula : C16H16N2O6
M.W : 332.31
SMILES Code : O=C(C1=C(C)NC(C)=C(C(OC)=O)C1C2=CC=CC([N+]([O-])=O)=C2)O
MDL No. :MFCD00475478
InChI Key :JPXPPUOCSLMCHK-UHFFFAOYSA-N
Pubchem ID :173322

Safety of [ 74936-72-4 ]

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

Computational Chemistry of [ 74936-72-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 24
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 5
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 90.2
TPSA ?

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

121.45 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.74
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

2.19
Log Po/w (WLOGP)?

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

1.71
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.

0.59
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

-0.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.24

Water Solubility

Log S (ESOL):?

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

-3.14
Solubility 0.244 mg/ml ; 0.000733 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.

-4.37
Solubility 0.014 mg/ml ; 0.0000422 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

-3.12
Solubility 0.25 mg/ml ; 0.000752 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

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

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

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.

-6.77 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

2.0 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<0.0
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)

3.73

Application In Synthesis of [ 74936-72-4 ]

* 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 [ 74936-72-4 ]

[ 74936-72-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 74936-72-4 ]
  • [ 91599-74-5 ]
  • 2
  • [ 558-42-9 ]
  • [ 74936-72-4 ]
  • [ 890045-70-2 ]
YieldReaction ConditionsOperation in experiment
58% Example 1; l-Chloro-2-methyl-2-propyl methyl 1 ,4-dihydro-2,6-dimethyl-4-(3- nitrophenyl)- 1 -pyridine-3 , 5 -dicarboxylate; 31 g (0.26 moles) of thionyl chloride were added dropwise under stirring to a mixture of 78 g (0.235 moles) of 2,6-dimethyl-5-methoxycarbonyl-4- (3-nitrophenyl)-l,4-dihydropyridine-3-carboxylic acid, 420 ml methylene dichloride and 110 ml dimethyl formamide kept at temperature of -20C - +2° under nitrogen. After terminating the addition of the thionyl chloride the stirring was continued under nitrogen for a further hour. To the above mixture a solution of 26 g (0.24 moles) of l-chloro-2-methyl-2-propanol in 60 ml methylene dichloride was added dropwise while stirring under nitrogen at a temperature of -50C - O0C. The stirring was continued for 3 EPO <DP n="4"/>hours at O0C, afterwards the mixture was allowed to stand for 24 hours at room temperature. The solvent was evaporated under vacuum and the residue was dissolved in 1200 ml of ethylacetate. The organic solution was washed with saturated solution of sodium chloride and afterwards with a solution of 5percent Na2CO3. The organic layer was separated and dried with Na2SO4. The organic solution was evaporated to 500 ml and allowed to stand at O0C for 24 hours. The l-Chloro-2-methyl-2-prorhoyl methyl 1,4- dihydro-2,6-dimethyl-4-(3-nitrophenyl)-l-pyridine-3,5-dicarboxylate thus obtained was filtered and dried at 5O0C under vacuum. The weight was 58 g ( 58 percent yield) of about 98percent purity as determined by HPLC analysis, shown in Figure 1.The method for performing the HPLC was as follows:HPLC: Merck-Hitachi with autosamplerColumn: Symmetry C 18, 4,6 x 250mm (Waters)Detector: UV 237nmMobile Phase: 60percent Acetonitrile + 40percent buffer pH 4.0Flow rate: lml/minInjection Volume: 20mulTemparature: 3O0CThe buffer pH 4.0 was prepared by dissolving 5.14g potassium di- hydrogen phosphate and 2.4 ml triethylamine in 980 ml water with mixing. The pH of the solution was adjusted to 4.0 with phosphoric acid and distilled water was added to make 1 liter, and the solution was mixed.The product has the following 1H NMR Spectrum (300 MHz, CDCI3): 8.11 (lH,m), 8.04 (lH,m), 7.64 (lH,d, J=7.5Hz), 7.37 (lH,t, J=8.1Hz), 3.64 (3H,s), 2.97 (lH,s) 2.90 (lH,s) 2.35 (3H,s) 2.34 (3H,s), 1.47 (3H,s), 1.44 (3H,s).
  • 3
  • [ 14813-01-5 ]
  • [ 74936-72-4 ]
  • [ 91599-74-5 ]
YieldReaction ConditionsOperation in experiment
36.2% Under ultrasound, 10 g of dihydropyridine main ring , i.e.,[2,6-dimethyl -4-(3-nitrophenyl)-l ,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester] was placed into 200 mL reaction flask, and 14 mL Nu,Nu-dimethylformamide (DMF) and 56 mL dichloromethane was added. To the resultant homogeneous suspension was added 2.4 mL of thionyl chloride under ice-bath, then the mixture was stirred for 1 hour to obtain a clear solution.Then, 6.3 g of pyridine (alcohol) side chain, i.e., [l-benzyl-3 -hydroxypiperidine] was added and stirred for 2.5 hours under ice-bath.The reaction solution was washed with 40 mL water (x 4) and 40 mL saturated saline solution (x 1). The dichloromethane solution was dried for two hours by adding 4 g of anhydrous sodium sulfate. Then, sodium sulfate solid was removed by filtering, and dichloromethane was recycled under reduced pressure to obtain a yellow to red crude crystal (herein after referred to as crude crystal of benidipine hydrochloride). The crude crystal mentioned above was dissolved in 100 mL acetone, and ultrasounded at 150 W and 40 MHz for 7 minutes, filtered under reduced pressure and dried to obtain 5.9 g of crystal as yellow powder (yield 36.2%)
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 74936-72-4 ]

Aryls

Chemical Structure| 21829-09-4

A119433 [21829-09-4]

Dimethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Similarity: 1.00

Chemical Structure| 76093-33-9

A200176 [76093-33-9]

(R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

Similarity: 1.00

Chemical Structure| 21606-04-2

A133332 [21606-04-2]

2-(Methoxycarbonyl)-6-nitrobenzoic acid

Similarity: 0.84

Chemical Structure| 132866-11-6

A152276 [132866-11-6]

3-(1-((3,3-Diphenylpropyl)(methyl)amino)-2-methylpropan-2-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride

Similarity: 0.83

Chemical Structure| 59382-59-1

A235851 [59382-59-1]

Methyl 2-methyl-3-nitrobenzoate

Similarity: 0.83

Esters

Chemical Structure| 21829-09-4

A119433 [21829-09-4]

Dimethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Similarity: 1.00

Chemical Structure| 76093-33-9

A200176 [76093-33-9]

(R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

Similarity: 1.00

Chemical Structure| 686747-51-3

A256507 [686747-51-3]

Methyl 5-nitro-1H-indole-3-carboxylate

Similarity: 0.89

Chemical Structure| 21606-04-2

A133332 [21606-04-2]

2-(Methoxycarbonyl)-6-nitrobenzoic acid

Similarity: 0.84

Chemical Structure| 132866-11-6

A152276 [132866-11-6]

3-(1-((3,3-Diphenylpropyl)(methyl)amino)-2-methylpropan-2-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride

Similarity: 0.83

Carboxylic Acids

Chemical Structure| 76093-33-9

A200176 [76093-33-9]

(R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

Similarity: 1.00

Chemical Structure| 6958-37-8

A485898 [6958-37-8]

5-Nitro-1H-indole-3-carboxylic acid

Similarity: 0.84

Chemical Structure| 21606-04-2

A133332 [21606-04-2]

2-(Methoxycarbonyl)-6-nitrobenzoic acid

Similarity: 0.84

Chemical Structure| 16533-45-2

A213031 [16533-45-2]

2-(Ethoxycarbonyl)-6-nitrobenzoic acid

Similarity: 0.82

Chemical Structure| 1955-46-0

A206002 [1955-46-0]

Methyl 5-nitroisophthalate

Similarity: 0.77

Nitroes

Chemical Structure| 21829-09-4

A119433 [21829-09-4]

Dimethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Similarity: 1.00

Chemical Structure| 76093-33-9

A200176 [76093-33-9]

(R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

Similarity: 1.00

Chemical Structure| 686747-51-3

A256507 [686747-51-3]

Methyl 5-nitro-1H-indole-3-carboxylate

Similarity: 0.89

Chemical Structure| 6958-37-8

A485898 [6958-37-8]

5-Nitro-1H-indole-3-carboxylic acid

Similarity: 0.84

Chemical Structure| 21606-04-2

A133332 [21606-04-2]

2-(Methoxycarbonyl)-6-nitrobenzoic acid

Similarity: 0.84