Home Cart Sign in  
Chemical Structure| 62595-74-8 Chemical Structure| 62595-74-8

Structure of 3-Bromopiperidine-2,6-dione
CAS No.: 62595-74-8

Chemical Structure| 62595-74-8

3-Bromopiperidine-2,6-dione

CAS No.: 62595-74-8

4.5 *For Research Use Only !

Cat. No.: A875928 Purity: 97%

Change View

Size Price

US Stock

Global Stock

In Stock
250mg łÇʶÊÊ Inquiry Inquiry
1g łÇ˶ÊÊ Inquiry Inquiry
5g ł§Ê¶ÊÊ Inquiry Inquiry
25g łÇ§Ë¶ÊÊ Inquiry Inquiry
100g łÿËͶÊÊ Inquiry Inquiry
500g łÇÿď˶ÊÊ Inquiry Inquiry

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 250mg

    łÇʶÊÊ

  • 1g

    łÇ˶ÊÊ

  • 5g

    ł§Ê¶ÊÊ

  • 25g

    łÇ§Ë¶ÊÊ

  • 100g

    łÿËͶÊÊ

  • 500g

    łÇÿď˶ÊÊ

In Stock

- +

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

Rathje, Oliver H. ; Perryman, Lara ; Payne, Richard J. ; Hamprecht, Dieter W. ;

Abstract: Mixed Lineage Kinase domain-Like pseudokinase (MLKL) is implicated in a broad range of diseases due to its role as the ultimate effector of necroptosis and has therefore emerged as an attractive drug target. Here, we describe the development of PROteolysis TArgeting Chimeras (PROTACs) as a novel approach to knock down MLKL through chem. means. A series of candidate degraders were synthesized from a high-affinity pyrazole carboxamide-based MLKL ligand leading to the identification of a PROTAC mol. that effectively degraded MLKL and completely abrogated cell death in a TSZ model of necroptosis. By leveraging the innate ability of these PROTACs to degrade MLKL in a dose-dependent manner, the quant. relationship between MLKL levels and necroptosis was interrogated. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further our understanding of the role of MLKL within the necroptotic pathway.

Alternative Products

Product Details of [ 62595-74-8 ]

CAS No. :62595-74-8
Formula : C5H6BrNO2
M.W : 192.01
SMILES Code : O=C(C(Br)CC1)NC1=O
MDL No. :MFCD11053059
InChI Key :RYSICGXZRVMXDP-UHFFFAOYSA-N
Pubchem ID :12570775

Safety of [ 62595-74-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 62595-74-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.6
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 39.02
TPSA ?

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

46.17 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.94
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

0.21
Log Po/w (WLOGP)?

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

-0.19
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.

0.48
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

1.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.53

Water Solubility

Log S (ESOL):?

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

-1.16
Solubility 13.2 mg/ml ; 0.0687 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.

-0.74
Solubility 35.0 mg/ml ; 0.183 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

-1.72
Solubility 3.64 mg/ml ; 0.019 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

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

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.

-7.32 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)

2.34

Application In Synthesis of [ 62595-74-8 ]

* 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 [ 62595-74-8 ]

[ 62595-74-8 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 62595-74-8 ]
  • [ 82771-60-6 ]
  • 3-(7-chloro-3,4-dihydroisoquinolin-2(1H)-yl)piperidine-2,6-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 16h; 7- Chloro-1,2,3,4-tetrahydroisoquinoline (75.0 mg) was dissolved in DMF (0.7 mL). MA6-019 (86.0 mg) and DIPEA (a56.8 muL) were added into the mixture and stirred for 16 h. Purification by washing with aq. NaHCO3 (5 mL) and trituration from ethyl acetate/hexanes gave MA7-074 as a biege solid (77 mg, 62%). HPLC: >99% [tR = 11.6 min, 15% MeOH, 85 water (with 0.1% TFA), 20 min]. 1H NMR (400 MHz, DMSO) delta 10.71 (s, 1H), 7.17-7.11 (m , 3H), 3.94 (d, J = 16 Hz, 1H), 3.79 (d, J = 16 Hz, 1H), 3.65 (dd J = 8.0, J = 4.0, 1H), 2.90-2.95 (m, 1H), 2.90-2.81 (m, 1H), 2.70-2.80 (m, 2H), 2.65-2.50 (m, 2H), 2.20-2.08 (m, 1H), 1.95-1.85 (m, 1H). HRMS (ESI+): m/z calcd for C14H16ClN2O2 (M+H)+ 279.0894, found 279.0894, m/z calcd for C14H15ClN2O2Na (M+Na)+ 301.0714, found 301.0711. HPLC-MS: HPLC-MS (ESI+): m/z 279.2 [40%, (M+H)+], 277.1 [100%, (M-H)-].
  • 2
  • [ 69189-26-0 ]
  • [ 62595-74-8 ]
  • C14H15N3O3 [ No CAS ]
  • 3
  • [ 1198-97-6 ]
  • [ 62595-74-8 ]
  • 3-(2-oxo-4-phenylpyrrolidin-1-yl)piperidine-2,6-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
9% 3-(2-Oxo-4-phenylpyrrolidin-l-yl)piperidine-2,6-dione. To a stirred solution of 4- phenylpyrrolidin-2-one (21 1 mg, 1.31 mmol) in DMF (2 mL) was added NaH (57.6 mg, 1.44 mmol, 60% w/w dispersed into mineral oil) at 0 C under nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0 C. To the above mixture was added dropwise a solution of 3- bromopiperidine-2,6-dione (125.7 mg, 0.65 mmol) in DMF (0.5 mL) at 0 C. The resulting mixture was stirred for additional 3 hours at room temperature. The resulting mixture was quenched with AcOH (0.5 mL) and concentrated under reduced pressure. The crude product was purified by prep-HPLC with the following conditions: Column: XBridge Shield RP18 EVO Column, 5 urn, 19 x 150 mm; Mobile Phase A: water (plus 0.05% FA), Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 15% B to 45% B in 7 min; Detector: UV 220 nm; Rt: 5.72 min). Desired fractions were collected and concentrated under reduced pressure. The residue was lyophilized to afford 3-(2-oxo-4-phenylpyrrolidin-l-yl)piperidine-2,6-dione, 29, as a white solid (29.4 mg, 9%):1H NMR (400 MHz, DMSO-d6) delta 10.94 (br s, 1H), 7.40 - 7.31 (m, 4H), 7.27 (dt, J = 5.9, 2.8 Hz, 1H), 4.93 - 4.86 (m, 1H), 3.79 - 3.56 (m, 2H), 3.33 - 3.15 (m, 1H), 2.90 - 2.69 (m, 2H), 2.60 - 2.50 (m, 1H), 2.48 - 2.36 (m, 1H), 2.35 - 2.16 (m, 1H), 1.92 - 1.80 (m, 1H); LC/MS (ESI, m/z): [(M + 1)]+= 273.2.
9% To a stirred solution of 4- phenylpyrrolidin-2-one (21 1 mg, 1.31 mmol) in DMF (2 mL) was added NaH (57.6 mg, 1.44 mmol, 60% w/w dispersed into mineral oil) at 0 C under nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0 C. To the above mixture was added dropwise a solution of 3- bromopiperidine-2,6-dione (125.7 mg, 0.65 mmol) in DMF (0.5 mL) at 0 C. The resulting mixture was stirred for additional 3 hours at room temperature. The resulting mixture was quenched with AcOH (0.5 mL) and concentrated under reduced pressure. The crude product was purified by prep-HPLC with the following conditions: Column: XBridge Shield RP18 EVO Column, 5 urn, 19 x 150 mm; Mobile Phase A: water (plus 0.05% FA), Mobile Phase B: ACN; Flow rate: 20 mL/min; Gradient: 15% B to 45% B in 7 min; Detector: UV 220 nm; Rt: 5.72 min). Desired fractions were collected and concentrated under reduced pressure. The residue was lyophilized to afford 3-(2-oxo-4-phenylpyrrolidin-l-yl)piperidine-2,6-dione, 1-29, as a white solid (29.4 mg, 9%): 1H NMR (400 MHz, OMSO-d6) delta 10.94 (br s, 1H), 7.40 - 7.31 (m, 4H), 7.27 (dt, J = 5.9, 2.8 Hz, 1H), 4.93 - 4.86 (m, 1H), 3.79 - 3.56 (m, 2H), 3.33 - 3.15 (m, 1H), 2.90 - 2.69 (m, 2H), 2.60 - 2.50 (m, 1H), 2.48 - 2.36 (m, 1H), 2.35 - 2.16 (m, 1H), 1.92 - 1.80 (m, 1H); LC/MS (ESI, m/z): [(M + 1)]+ = 273.2.
  • 4
  • [ 19932-85-5 ]
  • [ 62595-74-8 ]
  • 3-(6-bromo-2-oxobenzo[d]oxazol-3(2H)-yl)piperidine-2,6-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% To a stirred solution of <strong>[19932-85-5]6-bromo-3H-1,3-benzoxazol-2-one</strong> (1, 6 g, 28.04 mmol) in THF (200 mL) was added sodium hydride (60% dispersion in mineral oil) (1.29 g, 56.07 mmol) portionwise and the mixture was heated at 60 C for 1 h. This mixture was added dropwise via cannula to a stirred solution of 3-bromopiperidine-2,6-dione (2, 8.07 g, 42.05 mmol) in THF (50 mL) at 60 C and stirred for 2 h. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organics were washed with water and brine, dried over anhydrous sodium sulphate and concentrated. The residue was purified by silica gel chromatography (50% Ethyl acetate:Hexanes) to obtain 3-(6-bromo-2-oxobenzo[d]oxazol-3(2H)-yl)piperidine-2,6-dione (3, 2.9 g, 8.71 mmol, 31% yield). LCMS (ES-): m/z 323.0 [M-H]- 1H NMR (400 MHz, DMSO- D6) ^ ^11.23 (s, 1H), 7.73 (s, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.26 (d, J=8.36 Hz, 1H), 5.41-5.37 (m, 1H), 2.87-2.84 (m, 1H), 2.71-2.64 (m, 2H), 2.18-2.15 (m, 1H)
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

Related Functional Groups of
[ 62595-74-8 ]

Bromides

Chemical Structure| 34433-86-8

A974804 [34433-86-8]

3-Bromopiperidin-2-one

Similarity: 1.00

Chemical Structure| 99584-96-0

A488228 [99584-96-0]

2,5-Dibromohexanediamide

Similarity: 0.77

Chemical Structure| 72479-05-1

A102880 [72479-05-1]

(S)-5-Bromomethyl-2-pyrrolidinone

Similarity: 0.74

Chemical Structure| 98612-60-3

A149809 [98612-60-3]

(R)-5-(Bromomethyl)pyrrolidin-2-one

Similarity: 0.74

Chemical Structure| 1138445-61-0

A256156 [1138445-61-0]

2-Bromo-N-hexadecylacetamide

Similarity: 0.74

Amides

Chemical Structure| 34433-86-8

A974804 [34433-86-8]

3-Bromopiperidin-2-one

Similarity: 1.00

Chemical Structure| 99584-96-0

A488228 [99584-96-0]

2,5-Dibromohexanediamide

Similarity: 0.77

Chemical Structure| 72479-05-1

A102880 [72479-05-1]

(S)-5-Bromomethyl-2-pyrrolidinone

Similarity: 0.74

Chemical Structure| 98612-60-3

A149809 [98612-60-3]

(R)-5-(Bromomethyl)pyrrolidin-2-one

Similarity: 0.74

Chemical Structure| 1138445-61-0

A256156 [1138445-61-0]

2-Bromo-N-hexadecylacetamide

Similarity: 0.74

Related Parent Nucleus of
[ 62595-74-8 ]

Piperidines

Chemical Structure| 34433-86-8

A974804 [34433-86-8]

3-Bromopiperidin-2-one

Similarity: 1.00

Chemical Structure| 1121-89-7

A100684 [1121-89-7]

Piperidine-2,6-dione

Similarity: 0.69

Chemical Structure| 675-20-7

A187204 [675-20-7]

Piperidin-2-one

Similarity: 0.67

Chemical Structure| 1123-40-6

A112146 [1123-40-6]

4,4-Dimethylpiperidine-2,6-dione

Similarity: 0.64

Chemical Structure| 25077-25-2

A118832 [25077-25-2]

1-Methylpiperidine-2,6-dione

Similarity: 0.64