Home Cart Sign in  
Chemical Structure| 89031-84-5 Chemical Structure| 89031-84-5

Structure of 89031-84-5

Chemical Structure| 89031-84-5

*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

Product Citations

Tian, Gui-Long ; Hsieh, Chia-Ju ; Taylor, Michelle ; Lee, Ji Youn ; Riad, Aladdin A. ; Luedtke, Robert R. , et al.

Abstract: The difference in the secondary binding site (SBS) between the dopamine 2 receptor (D2R) and dopamine 3 receptor (D3R) has been used in the design of compounds displaying selectivity for the D3R versus D2R. In the current study, a series of bitopic ligands based on Fallypride were prepared with various secondary binding fragments (SBFs) as a means of improving the selectivity of this benzamide analog for D3R versus D2R. We observed that compounds having a small alkyl group with a heteroatom led to an improvement in D3R versus D2R selectivity. Increasing the steric bulk in the SBF increase the distance between the pyrrolidine N and Asp110, thereby reducing D3R affinity. The best-in-series compound was (2S,4R)-trans-27 which had a modest selectivity for D3R versus D2R and a high potency in the β-arrestin competition assay which provides a measure of the ability of the compound to compete with endogenous dopamine for binding to the D3R. The results of this study identified factors one should consider when designing bitopic ligands based on Fallypride displaying an improved affinity for D3R versus D2R.

Keywords: Dopamine 2 receptor ; Dopamine 3 receptor ; Fallypride ; Bitopic ligands ; PET imaging

Alternative Products

Product Details of [ 89031-84-5 ]

CAS No. :89031-84-5
Formula : C9H21BrOSi
M.W : 253.25
SMILES Code : C[Si](C(C)(C)C)(OCCCBr)C
MDL No. :MFCD00216589
InChI Key :QGMROEZDWJTIDW-UHFFFAOYSA-N
Pubchem ID :607486

Safety of [ 89031-84-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 89031-84-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 5
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 62.2
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.36
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

3.98
Log Po/w (WLOGP)?

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

3.79
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.

2.99
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

1.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.15

Water Solubility

Log S (ESOL):?

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

-3.59
Solubility 0.0655 mg/ml ; 0.000258 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.

-3.88
Solubility 0.0338 mg/ml ; 0.000133 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

-3.78
Solubility 0.042 mg/ml ; 0.000166 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

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.

-5.02 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

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<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)

4.64

Application In Synthesis of [ 89031-84-5 ]

* 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.

  • Downstream synthetic route of [ 89031-84-5 ]

[ 89031-84-5 ] Synthesis Path-Downstream   1~5

  • 2
  • [ 89031-84-5 ]
  • [ 405939-39-1 ]
  • [ 405939-40-4 ]
  • 3
  • [ 40711-33-9 ]
  • [ 89031-84-5 ]
  • [ 1192313-21-5 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In N,N-dimethyl-formamide; at 60℃; To a suspension of ethyl 5-oxo-2,5-dihydro-1 H-pyrazole-3-carboxylate (5.47 g, prepared with an analogous procedure to that described in Preparation 1 ) and Na2CO3 (4.46 g) in dry DMF (36 ml_), [(3-bromopropyl)oxy](1 ,1-dimethylethyl)dimethylsilane (8.52 ml.) was added drop wise and the mixture was stirred at 6O0C overnight. [(3-bromopropyl)oxy](1 ,1- dimethylethyl)dimethylsilane (0.8 mL) was added and the mixture was stirred for additional 4h. After cooling, the mixture was diluted with AcOEt, washed with chilly water and brine, dried, filtered and evaporated under reduced pressure. The crude was purified by flash chromatography on silica column eluting with Cy/AcOEt with a gradient of Cy from 100% to 80% to give the title compound as yellow oil (5.63 g).1H NMR (CDCI3) delta: 10.53 (s, 1 H); 6.23 (s, 1 H); 4.38 (q, 2H); 4.27 (t, 2H); 3.79 (t, 2H); 2.0(m, 2H); 1.39 (t, 3H); 0.9 (s, 9H); 0.05 (s, 6H).MS (m/z): 328 [MH]+.
  • 4
  • [ 496807-97-7 ]
  • [ 89031-84-5 ]
  • 1-(3-[tert-butyl(dimethyl)silyl]oxy}propyl)-3,3-difluoropiperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
612 mg With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 1.5h; 1-(3-[tert-butyl(dimethyl)silyl]oxy}propyl)-3 FontWeight="Bold" FontSize="10" 3-difluoropiperidine To a solution of <strong>[496807-97-7]3,3-difluoropiperidine hydrochloride</strong> (518 mg) in DMF (15 mL) was added cesium carbonate (3.21 g) and (3-bromopropoxy)-tert-butyldimethylsilane (0.838 mL). The resulting reaction mixture was heated to 50C for 1.5 hours before cooling back to room temperature. Water and ethyl acetate were added to the reaction mixture. The mixture was extracted with ethyl acetate (2x). The combined organics were washed with water (2x), brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (ISCO, 0 to 40% ethyl acetate in hexanes with 1% triethylamine) gave the desired product (612 mg). NMR (400 MHz, CDC13): delta (ppm) 4.20 (t, 1H), 3.71-3.64 (m, 2H), 3.46 (t, 1H), 2.62 (t, 1H), 2.50-2.47 (m, 1H), 2.44-2.42 (m, 1H), 2.05-1.98 (m, 1H), 1.91-1.82 (m, 2H), 1.77-1.67 (m, 4H), 0.89 (d, 9H), 0.05 (s, 3H), 0.04 (s, 3H).
612 mg With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 1.5h; To a solution of <strong>[496807-97-7]3,3-difluoropiperidine hydrochloride</strong> (518 mg) in DMF (15 mL) was added cesium carbonate (3.21 g) and (3-bromopropoxy)-tert-butyldimethylsilane (0.838 mL). The resulting reaction mixture was heated to 50 C. for 1.5 hours before cooling back to room temperature. Water and ethyl acetate were added to the reaction mixture. The mixture was extracted with ethyl acetate (2×). The combined organics were washed with water (2×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (ISCO, 0 to 40% ethyl acetate in hexanes with 1% triethylamine) gave the desired product (612 mg). 1H NMR (400 MHz, CDCl3): delta (ppm) 4.20 (t, 1H), 3.71-3.64 (m, 2H), 3.46 (t, 1H), 2.62 (t, 1H), 2.50-2.47 (m, 1H), 2.44-2.42 (m, 1H), 2.05-1.98 (m, 1H), 1.91-1.82 (m, 2H), 1.77-1.67 (m, 4H), 0.89 (d, 9H), 0.05 (s, 3H), 0.04 (s, 3H).
  • 5
  • [ 101-06-4 ]
  • [ 89031-84-5 ]
  • N,N-dibenzyl-2-[3-[tert-butyl(dimethyl)silyl]oxypropoxy]ethanamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
1 g To a solution of crude 2-(dibenzylamino) ethanol (2.0 g) in DMF (30 mL) was added NaH (purity: 95%, 0.42 g, 16.6 mmol) portionwise at 0 C. The mixture was stirred for 30 minutes, then to the mixture was added 3-bromopropoxy-tert-butyl-dimethyl-silane (3.2 g, 12.5 mmol). The mixture was warmed to 60 C. and stirred at this temperature for 12 hours. After the reaction mixture was cooled to room temperature, the reaction was quenched with saturated aqueous ammonium chloride solution. The resulting mixture was extracted with DCM. The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography to give N, N-dibenzyl-2-[3-[tert-butyl (dimethyl) silyl]oxypropoxy]ethanamine (1.0 g).
1 g Step 2: Preparation of N, Lambda-dibenzy 1-2- 13- 1 fc'/Y-buty I (dimethyl)silylj oxypropoxy] ethanamine To a solution of crude 2-(dibenzylamino ) ethanol ( 2.0 g) in DMF (30 niL) was added Nai l (purity: 95%, 0.42 g. 16.6 mmol) portionwise at 0 C. The mixture was st irred for 30 minutes, then to the mixture was added 3-bromopropoxy-feri-butyi-dimethyl-silane (3.2 g, 12.5 mmol). The mixture was warmed to 60 C and st irred at this temperature for 12 hours. After the reaction mixture was cooled to room temperature, the reaction was quenched with saturated aqueous ammonium chloride solution. The resulting mixture was extracted with DCM. The organic layer was dried over anhydrous Na2S04 and concentrated. The residue was purified by column chromatography to give N, Lambda - d i be n zy 1 - 2 - [ 3 - [ r rt-b u t y 1 (dimethyl ) silyl j oxypropoxy] ethanaminc (1.0 g).
 

Historical Records

Technical Information

Categories