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Chemical Structure| 164148-92-9 Chemical Structure| 164148-92-9

Structure of 164148-92-9

Chemical Structure| 164148-92-9

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Product Details of [ 164148-92-9 ]

CAS No. :164148-92-9
Formula : C14H20N2O2
M.W : 248.32
SMILES Code : NC2=CC=C1CN(CCC1=C2)C(=O)OC(C)(C)C
MDL No. :MFCD03426351
InChI Key :OLOIFCYZWOTWRO-UHFFFAOYSA-N
Pubchem ID :2756371

Safety of [ 164148-92-9 ]

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

Computational Chemistry of [ 164148-92-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 76.03
TPSA ?

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

55.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.66
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.

2.04
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.

1.94
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

1.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.06

Water Solubility

Log S (ESOL):?

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

-2.66
Solubility 0.539 mg/ml ; 0.00217 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.

-2.75
Solubility 0.44 mg/ml ; 0.00177 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

-3.11
Solubility 0.193 mg/ml ; 0.000776 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

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

Yes
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.

-6.42 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.

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)

2.18

Application In Synthesis of [ 164148-92-9 ]

* 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 [ 164148-92-9 ]

[ 164148-92-9 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 23687-26-5 ]
  • [ 164148-92-9 ]
  • 3-{1-ethoxy-1-phenylmethylidene}-5-nitro-2-indolinone [ No CAS ]
  • [ 72299-67-3 ]
YieldReaction ConditionsOperation in experiment
Prepared from 3-{1-ethoxy-1-phenylmethylidene}-5-nitro-2-indolinone and 1.1 equivalents of an oily mixture of 2-Boc-6-amino-1,2,3,4-tetrahydro-isoquinoline [prepared from <strong>[23687-26-5]6-amino-isoquinoline</strong>, melting point 218-220° C., by catalytic hydrogenation to obtain 6-amino-1,2,3,4-tetrahydro-isoquinoline (melting point: 69-71° C.) and subsequent reaction with 0.9 equivalents of di-tert.butyl pyrocarbonate (=(Boc)2 O)] in DMF by heating to 100° C. for 3.5 hours, pouring into water, filtering and washing the precipitate with water and EtOH.
  • 2
  • [ 37718-11-9 ]
  • [ 164148-92-9 ]
  • [ 1035225-07-0 ]
YieldReaction ConditionsOperation in experiment
24% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 216h; Intermediate 34: 1 ,1-Dimethylethyl 6-r(1 H-pyrazol-4-ylcarbonyl)aminol-3,4-dihvdro- 2(1 HVisoalphauinolinecarboxylate; To a solution of 1 H-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (800 mg, 7.1 mmol), N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.48 g, 7.74 mmol), 1- hydroxybenzotriazole hydrate (1.04 g, 7.74 mmol) and triethylamine (1.8 ml_, 12.9 mmol) in DCM was added 1 , 1 -dimethylethyl 6-amino-3,4-dihydro-2(1 /-/)- isoquinolinecarboxylate (1.6 g, 6.45 mmol) and the reaction mixture was stirred at room temperature for 9 days. The organic phase was washed with 1 N sodium hydroxide, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography eluting with DCM/MeOH: 90/10 to give the title compound as a solid (580 mg, 24percent). LC/MS: m/z 341 (M-H)+, Rt: 2.70 min.
  • 3
  • [ 164148-92-9 ]
  • [ 60211-57-6 ]
  • [ 1246966-88-0 ]
YieldReaction ConditionsOperation in experiment
27% Synthesis of 6-(3,5-Dichloro-benzyloxycarbonylamino)-3,4-dihydro-1 H- isoquinoline-2-carboxylic acid tert-butyl ester (46)Starting material 45 (250 mg, 1.4 mmol) and 1 ,1 '-carbonyl diimidazol (275 mg, 1.7 mmol) were dissolved in 2 ml DCM and stirred at room temperature for 3 h. Then starting material 44 (350 mg, 1.4 mmol) was added and the resulting mixture was stirred over night at room temperature. The reaction mixture was diluted with ethyl acetate, the organic phase was washed with water 3 times, dried over Na2SO4, filtered and concentrated in vacuo. The remaining solid was purified over the prep. HPLC (Method 1), pure fractions were combined and concentrated in vacuo yielding the desired product 46 as brown solid (170 mg, 0.377 mmol, 27%).
  • 4
  • [ 23687-26-5 ]
  • [ 164148-92-9 ]
 

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