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Chemical Structure| 112811-72-0 Chemical Structure| 112811-72-0
Chemical Structure| 112811-72-0

*Storage: Sealed in dry,Room Temperature.

1-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid

CAS No.: 112811-72-0

4.5 *For Research Use Only !

Cat. No.: A491721 Purity: 98%

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Product Details of [ 112811-72-0 ]

CAS No. :112811-72-0
Formula : C14H11F2NO4
M.W : 295.24
SMILES Code : C1(CC1)N3C2=C(C(=C(C=C2C(C(=C3)C(=O)O)=O)F)F)OC
MDL No. :MFCD05864420
InChI Key :WQJZXSSAMGZVTM-UHFFFAOYSA-N
Pubchem ID :7019465

Safety of [ 112811-72-0 ]

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

Calculated chemistry of [ 112811-72-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 10
Fraction Csp3 0.29
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 70.34
TPSA ?

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

68.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.81
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

2.71
Log Po/w (WLOGP)?

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

3.1
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.

1.48
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

2.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.37

Water Solubility

Log S (ESOL):?

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

-3.53
Solubility 0.0867 mg/ml ; 0.000294 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.

-3.8
Solubility 0.0465 mg/ml ; 0.000158 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

-3.43
Solubility 0.109 mg/ml ; 0.000368 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.

-6.18 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

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<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)

2.36

Application In Synthesis [ 112811-72-0 ]

* 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 [ 112811-72-0 ]
  • Downstream synthetic route of [ 112811-72-0 ]

[ 112811-72-0 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 112811-72-0 ]
  • [ 151213-40-0 ]
  • [ 186826-86-8 ]
YieldReaction ConditionsOperation in experiment
3.3 g
Stage #1: With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20 - 85℃; for 36 h; Inert atmosphere
Stage #2: With hydrogenchloride In water at 15℃; for 1 h; Inert atmosphere
Under nitrogen protection, 1-cyclopropyl-6, 7-difluoro-1, 4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid 10.0 g (0·0339 mοl) and (S,S) -2,8-diazabicyclo[4,3,0] nonane 5 .13g(0.0406mol)were added to 70 mL acetonitrile, it was stirred at 20 ° C~30 ° C and 1,8-diazabicyclo[5·4·0]undec-7-ene 7.74 g (0.0508 mol) was added, it was stirred at 75 ° C~85 ° C for 36 h. Concentrated in vacuo (temperature 45 ° C ~ 65 ° C, pressure -0 · 08MPa ~ -0.1MPa) to remove most of the solvent, it was then dissolved in chloroform, the mass concentration is 2percent aqueous acetic acid solution (the mass concentration refers to the mass of acetic acid as a percentage of the total mass of the aqueous acetic acid solution), the mass concentration was 10percent saline (the mass concentration refers to the mass of sodium chloride as a percentage of the total mass of brine were sequentially added, respectively, then the mixture was stirred, allowed to stand, and the aqueous layer was separated. The organic layer was concentrated in vacuo (temperature 35 ° C ~ 55 ° C, pressure -0.08MPa ~ -0.1MPa) to remove most of the solvent, ethyl acetate was added, and the mixture was cooled to 10 ° C to 20 ° C and stirred for 2 hours to 3 hours. Centrifugation, rinsed three times with ethyl acetate, dried in vacuo (vacuum degree -0.01MPa~-0.1MPa, temperature 45~55°C) dried for 14 to 18 hours, to obtain 4.01g of moxifloxacin , yield 29.5percent.HPLC purity 93.54percent. Under nitrogen protection, add 4.0 g of moxifloxacin to 2.5 mL of water and 10 mL of methanol.Stir at 170 ° C for 1 hour, filter, and cool to 35 ° C.The pH was adjusted to 1.4 to 1.8 by the addition of 6N hydrochloric acid. Cool to 15 ° C and stir for 1 hour.It was filtered, washed with water, and stirred at 15 ° C for 1 hour in a solution of water 5 mL and concentrated hydrochloric acid.Filtered, washed with water, vacuum dried (vacuum degree - 0.01 MPa ~ -0.1 MPa, temperature 45 ~ 55 ° C) for 16 hours, to obtain 3.3 g of moxifloxacin hydrochloride,Yield 75.6percent (total yield 22.3percent, based on 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ). The HPLC purity was 99.23percent, and the maximum single impurity was 0.47percent.
References: [1] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 121, p. 254 - 258.
[2] Patent: CN109096276, 2018, A, . Location in patent: Paragraph 0090-0093.
  • 2
  • [ 112811-72-0 ]
  • [ 186826-86-8 ]
References: [1] Patent: EP2551268, 2013, A1, .
[2] Patent: US2013/59880, 2013, A1, .
[3] Patent: WO2014/87292, 2014, A1, .
[4] Patent: CN109096276, 2018, A, .
[5] Patent: CN109096276, 2018, A, .
 

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