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Chemical Structure| 53617-36-0 Chemical Structure| 53617-36-0
Chemical Structure| 53617-36-0

*Storage: Keep in dark place,Inert atmosphere,Room temperature.

1-Methyl-4-(piperidin-4-yl)piperazine

CAS No.: 53617-36-0

4.5 *For Research Use Only !

Cat. No.: A514097 Purity: 98%

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Product Citations

Product Citations

Hiroto Kataoka ; Tetsuya Saita ; Asuki Oka , et al.

Abstract: Brigatinib and gilteritinib are oral tyrosine kinase inhibitors (TKIs). We aimed to develop a simple and sensitive indirect competitive enzyme-linked immunosorbent assay (ELISA) to quantify brigatinib and gilteritinib in various biological matrices. Antiserum against these TKIs was obtained from mice by using 3-methoxy-4-(-4-(4-methylpiperazin-1-yl) piperidin-1-yl) aniline as a hapten, which has a common substructure with these TKIs. The generated antibody was used to develop an indirect competitive ELISA for these TKIs in human serum. The lower limit of quantification of brigatinib and gilteritinib in human serum was 6.2 and 6.8 ng/mL, respectively. The developed ELISA was used to examine the pharmacokinetics of these TKIs after oral administration in mice and rats. This ELISA is expected to be a valuable tool in pharmacokinetic studies of these TKIs.

Keywords: brigatinib ; gilteritinib ; enzyme-linked immunosorbent assay ; tyrosine kinase inhibitor

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Product Details of [ 53617-36-0 ]

CAS No. :53617-36-0
Formula : C10H21N3
M.W : 183.29
SMILES Code : CN1CCN(C2CCNCC2)CC1
MDL No. :MFCD03274729
InChI Key :MRYYJGQKVGZGSB-UHFFFAOYSA-N
Pubchem ID :795707

Safety of [ 53617-36-0 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314-H302+H312
Precautionary Statements:P264-P270-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403-P501
Class:8
UN#:3259
Packing Group:

Calculated chemistry of [ 53617-36-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 66.29
TPSA ?

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

18.51 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.41
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

0.2
Log Po/w (WLOGP)?

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

-1.16
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.

0.64
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

0.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.57

Water Solubility

Log S (ESOL):?

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

-1.04
Solubility 16.9 mg/ml ; 0.092 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.

-0.15
Solubility 131.0 mg/ml ; 0.712 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

-1.26
Solubility 10.1 mg/ml ; 0.0552 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

Low
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

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

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.

-7.28 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

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)

1.73

Application In Synthesis [ 53617-36-0 ]

* 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.

  • Downstream synthetic route of [ 53617-36-0 ]

[ 53617-36-0 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 53617-36-0 ]
  • [ 314298-13-0 ]
  • [ 1356962-90-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 15h; Intermediate 12 1-(1-(5-Methoxy-2-methyl-4-nitrophenyl)piperidin-4-yl)-4-methylpiperazine 1-Fluoro-5-methoxy-2-methyl-4-nitrobenzene (INTERMEDIATE 7, 0.370 g, 2.00 mmol), 1-methyl-4-(piperidin-4-yl)piperazine (0.367 g, 2.00 mmol), and potassium carbonate (0.415 g, 3.00 mmol) in DMSO (2.0 mL) were stirred at 80 C. for 15 h. DCM (20 mL) and water (20 mL) were added to the reaction mixture. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to give the title product. (0.640 g, 92%).1H NMR (400 MHz, CHLOROFORM-d) delta ppm 7.85-7.77 (m, 1H), 6.54 (s, 1H), 3.94 (s, 3H), 3.35 (d, 2H), 2.78-2.63 (m, 5H), 2.60-2.48 (m, 4H), 2.32 (s, 3H), 2.24 (s, 3H), 1.99 (d, 2H), 1.72 (dd, 2H). m/z 349.
  • 2
  • [ 454-16-0 ]
  • [ 53617-36-0 ]
  • 1-[1-(2-methoxy-4-nitrophenyl)piperidin-4-yl]-4-methylpiperazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 15h; To a solution of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong>6 (4.74 g, 27.7 mmol) in DMF (47 mL) were added1-methyl-4-(piperidin-4-yl) piperazine (5.33 g, 29.1 mmol) andK2CO3 (4.59 g, 33.2 mmol). The reaction mixture was stirredat 80°C for 15 h. Water was added to this reaction mixture under cooling in an ice bath, and the resulting precipitate was filtered and washed with water to give 7 (8.79 g, 95percent) asa yellow solid. 1H-NMR (400 MHz, DMSO-d6) delta: 1.44?1.60(2H, m), 1.77?1.89 (2H, m), 2.06?2.61 (9H, m), 2.14 (3H, s),2.65?2.80 (2H, m), 3.63?3.76 (2H, m), 3.90 (3H, s), 7.00 (1H,d, J=8.8 Hz), 7.67 (1H, d, J=2.4 Hz), 7.82 (1H, dd, J=2.4,8.8 Hz). ESI-MS m/z: 335 [M+H]+.
  • 3
  • [ 808744-34-5 ]
  • [ 53617-36-0 ]
  • C17H25N5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos; for 3h;Heating; To a solution of 7-bromoimidazo[l,2-a]pyridine (200.0 mg, 1.02 mmol, 1.00 eq) and l-methyl-4-(4- piperidyl)piperazine (447.8 mg, 2.44 mmol, 2.40 eq) in dioxane (5.00 mL) was added Pd2(dba)3 (186.8 mg, 204 umol, 0.20 eq), XPhos (389.0 mg, 816 umol, 0.80 eq), and t-BuONa (392.1 mg, 4.08 mmol, 4.00 eq). The resulting mixture was de-gassed and purged with nitrogen, then heated to 110C under nitrogen atmosphere for 3 hours until there was no more starting material remaining by LC/MS analysis. The reaction mixture was cooled to room temperature and concentrated under vacuum to provide a residue, which was purified by prep-TLC (1 : 1 DCM/MeOH) to give compound 352 (150.0 mg, 441 umol, 43% yield, 88% purity) as ayellow oil.
 

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