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Structure of 423165-07-5

Chemical Structure| 423165-07-5

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Product Details of [ 423165-07-5 ]

CAS No. :423165-07-5
Formula : C13H22N4
M.W : 234.34
SMILES Code : CC(C1=NN=C(C)N1[C@@H]2C[C@H](N3)CC[C@H]3C2)C
MDL No. :MFCD12912695
InChI Key :CEIRCCADSFHOQD-FOSCPWQOSA-N
Pubchem ID :11356762

Safety of [ 423165-07-5 ]

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

Computational Chemistry of [ 423165-07-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 5
Fraction Csp3 0.85
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 72.16
TPSA ?

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

42.74 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.1
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

1.64
Log Po/w (WLOGP)?

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

1.78
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.

1.96
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

1.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.83

Water Solubility

Log S (ESOL):?

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

-2.41
Solubility 0.908 mg/ml ; 0.00387 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.

-2.15
Solubility 1.66 mg/ml ; 0.00707 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

-2.55
Solubility 0.654 mg/ml ; 0.00279 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

Yes
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

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

Yes
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.

-6.57 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

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<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)

4.21

Application In Synthesis of [ 423165-07-5 ]

* 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.

  • Upstream synthesis route of [ 423165-07-5 ]
  • Downstream synthetic route of [ 423165-07-5 ]

[ 423165-07-5 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 423165-13-3 ]
  • [ 423165-07-5 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogen In ethanol at 20℃; for 18 h; [109] Synthesis of 3-(3-isopropyl-5-methyl-4H-1.2.4-triazol-4-yl)-8- azabicvclor3.2.11octane 103 (Y2a = Y2b = Y2c = H). To a solution of the triazole 102 (0.28 g, 0.86 mmol) in EtOH (9 mL) at ambient temperature was added 20 wt percent Pd(OH)2/C (140 mg). The mixture was purged with argon then placed under an H2 atmosphere and stirred at ambient temperature for 18h. The reaction mixture was filtered through a pad of celite, the pad washed with EtOH, and the filtrate was concentrated in vacuo to yield 103 (0.20 g, -100percent).; The triazole 102 in EtOH was treated with Pd(OH)2/C (140 mg) under an H2 atmosphere to yield amine 103.
94% With hydrogen In methanol at 20℃; Step 12
3-(3-Isopropyl-5-methyl-[1,2,4]triazol-4-yl)-8-aza-bicyclo[3.2.1]octane:
A solution of 8-benzyl-3-(3-isopropyl-5-methyl-[1,2,4]triazol-4-yl)-8-aza-bicyclo[3.2.1]octane (2.0 g, 6.17 mmol) in methanol (30 mL) was treated with 10percent palladium on carbon (0.25 g) under a hydrogen atmosphere (50 psi) at ambient temperature, overnight.
The mixture was filtered through a pad of Celite and the filtrate was concentrated to give the title compound. Yield: 1.36 g (94percent).
1H-NMR (CDCl3.) δ: 1.39 (d, J=6.9 Hz, 6H), 1.72-2.20 (m, 8H), 2.50 (s, 3H), 2.99 (m, 1H), 3.70 (m, 1H), 4.30 (m, 1H).
58% With ammonium formate In ethanol for 12 h; Reflux; Inert atmosphere Step 6:
3-(3-isopropyl-5-methyl-tetrahydro-1,2,4-triazol-4-yl)-exo-8-azabicyclo[3.2.1]octane
Ammonium formate (630 mg, 10 mmol) was added in a solution of the product prepared in step 5 (321 mg, 1 mmol) and 10percent Pd/C (32 mg) in ethanol (10 mL).
The reaction mixture was stirred and refluxed for 12 hours under nitrogen atmosphere, and then vaporized off the solvent under reduced pressure, diluted with dichloromethane, and washed with water.
The aqueous phase was extracted with dichloromethane, and the combined organic phase was dried with sodium sulfate, and concentrated to obtain the product as a white solid (135 mg, yield: 58percent).
1HNMR (CDCl3, 300 MHz) δ: 4.39-4.27 (m, 1H), 3.47 (s, 2H), 3.07-2.98 (m, 1H), 2.53 (s, 3H), 2.26-2.18 (m, 2H), 1.99-1.96 (m, 2H), 1.79-1.76 (d, 4H, J=8.1 Hz), 1.40-1.38 (d, 6H, J=6.9 Hz).
References: [1] Patent: WO2008/63600, 2008, A2, . Location in patent: Page/Page column 11-12; 28.
[2] Patent: US2008/146605, 2008, A1, . Location in patent: Page/Page column 41.
[3] Patent: US2011/251192, 2011, A1, . Location in patent: Page/Page column 21.
  • 2
  • [ 76272-34-9 ]
  • [ 423165-07-5 ]
References: [1] Patent: US2011/251192, 2011, A1, .
  • 3
  • [ 542-05-2 ]
  • [ 423165-07-5 ]
References: [1] Patent: US2011/251192, 2011, A1, .
  • 4
  • [ 28957-72-4 ]
  • [ 423165-07-5 ]
References: [1] Patent: US2011/251192, 2011, A1, .
  • 5
  • [ 76272-36-1 ]
  • [ 423165-07-5 ]
References: [1] Patent: US2011/251192, 2011, A1, .
  • 6
  • [ 376348-67-3 ]
  • [ 423165-07-5 ]
References: [1] Patent: US2011/251192, 2011, A1, .
 

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