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Chemical Structure| 87-48-9

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5-Bromoindoline-2,3-dione

CAS No.: 87-48-9

4.5 *For Research Use Only !

Cat. No.: A194051 Purity: 98%

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Product Citations

Product Citations

Prinsloo, Izak F. ; Petzer, Jacobus P. ; Cloete, Theunis T. , et al.

Abstract: The small mol., isatin, is a well-known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC50 values of 12.3 and 4.86μM for MAO-A and MAO-B, resp. While the interaction of isatin with MAO-B has been characterized, only a few studies have explored structure-activity relationships (SARs) of MAO inhibition by isatin analogs. The current study therefore evaluated a series of 14 isatin analogs as in vitro inhibitors of human MAO-A and MAO-B. The results indicated good potency MAO inhibition for some isatin analogs with five compounds exhibiting IC50 < 1μM. 4-Chloroisatin (1b) and 5-bromoisatin (1f) were the most potent inhibitors with IC50 values of 0.812 and 0.125μM for MAO-A and MAO-B, resp. These compounds were also found to be competitive inhibitors of MAO-A and MAO-B with Ki values of 0.311 and 0.033μM, resp. Among the SARs, it was interesting to note that C5-substitution was particularly beneficial for MAO-B inhibition. MAO inhibitors are established drugs for the treatment of neuropsychiatric and neurodegenerative disorders, while potential new roles in prostate cancer and cardiovascular disease are being investigated.

Keywords: competitive ; inhibition ; isatin ; monoamine oxidase ; structure-activity relationship

Product Details of [ 87-48-9 ]

CAS No. :87-48-9
Formula : C8H4BrNO2
M.W : 226.03
SMILES Code : O=C1NC2=C(C=C(Br)C=C2)C1=O
MDL No. :MFCD00149345
InChI Key :MBVCESWADCIXJN-UHFFFAOYSA-N
Pubchem ID :6889

Safety of [ 87-48-9 ]

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

Calculated chemistry of [ 87-48-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 49.86
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.

1.08
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

1.33
Log Po/w (WLOGP)?

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

1.01
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.

0.91
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

2.19
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.3

Water Solubility

Log S (ESOL):?

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

-2.45
Solubility 0.803 mg/ml ; 0.00355 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.

-1.9
Solubility 2.84 mg/ml ; 0.0126 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

-3.64
Solubility 0.0521 mg/ml ; 0.000231 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

Yes
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.

-6.73 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)

1.66

Application In Synthesis [ 87-48-9 ]

* 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 [ 87-48-9 ]

[ 87-48-9 ] Synthesis Path-Downstream   1~17

  • 1
  • [ 13211-01-3 ]
  • [ 87-48-9 ]
  • 3-ethyl-2-biphenyl-4-yl-6-bromo-quinoline-4-carboxylic acid [ No CAS ]
  • 2
  • [ 347-84-2 ]
  • [ 87-48-9 ]
  • [ 361-28-4 ]
  • 3
  • [ 87-48-9 ]
  • [ 16313-65-8 ]
  • 4
  • [ 30065-27-1 ]
  • [ 87-48-9 ]
  • 2-(1H-benzimidazol-2-ylthio)-N-(5-bromo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetohydrazide [ No CAS ]
  • 6
  • [ 87-48-9 ]
  • [ 93247-78-0 ]
  • [ 1027787-84-3 ]
YieldReaction ConditionsOperation in experiment
With piperidine; In ethanol; at 20℃; for 48 - 96h; Example 39 Preparation of QR-0303 and QR-0289[00386] Compounds QR-0303 and QR-0289 were prepared by reactions depicted in Scheme 45 below. <n="120"/>Scheme 45[00387] The procedure was as follows.[00388] A solution of 5-substituted isatin (5 mmol), indole-7-carboxylic acidmethyl ester (5 mmol), and piperidine (0.5 mmol) were stirred in ethanol at roomtemperature for 2-4 d. When TLC indicated the reaction was complete, the reactionmixture was concentrated and the product washed with EtOAc and hexane. Theproduct was used in the next step without further purification. To a solution of theproduct (4 mmol) in dry THF at O0C was added BH3-THF (10 mL, 10 mmol)dropwise over 10 min. The solution was stirred at room temperature overnight, andthen quenched by the dropwise addition of MeOH (30 mL). The solvent wasremoved under vacuum, giving crude product which was stirred with LiOH (10 mmol) in MeOHZH2O ( 1 : 1 , 40 mL) at 70 0C for 2h. The mixture was concentrated and the pH adjusted to 2 with IN HCl. The aqueous layer was extracted with EtOAc (2 x 20 mL) and the organic layer dried with MgSO4. Final product was purified by flash column chromatography to yield the following compounds.[00389] QR-0303 (32percent yield). 1H NMR (DMSO): 7.19 (t, I H. J=7.7), 7.28(d, I H, J=8.6), 7.45 (d, I H, J=8.6), 7.62 (d, I H, J=2.3). 7.76 (d, I H. J=2.3), 7.79 (d. <n="121"/>111..1=1.7).7.83 (d. IH, J=8.6), 8.02 (d, IH. J=7.8).11.15 (s, IH), 11.49 (s, IH), 13.12 (s, IH); 13C NMR (DMSO): 109.09, 109.79, 112.07, 114.15, 114.22, 119.05.121.74, 123.96, 124.30, 124.57, 124.78, 125.40.128.13, 128.33, 135.53, 135.55, 168.47.[00390] QR-0289 (27percent yield). 1H NMR (DMSO): 3.76 (s, 3H), 6.82 (d. IH,J=8.7), 7.14 (d, IH. J=2.0), 7.19 (t, IH, J=7.6).7.36 (d, IH, J=8.7), 7.60 (d, IH,J=2.2).7.63 (d, IH, J=2.2), 7.82 (d, IH, J=7.3), 8.03 (d, 1H,J=7.8), 11.11 (s, 2H), 13.10 (s, IH); 13C NMR (DMSO): 55.82, 101.60.109.10, 110.72, 111.83, 112.81, 114.13, 118.85.123.58, 123.62, 124.64.125.54.126.87.128.31.132.06.135.56,153.97,168.52.
  • 7
  • [ 54030-56-7 ]
  • [ 87-48-9 ]
  • [ 1043252-29-4 ]
  • 8
  • [ 87-48-9 ]
  • [ 504-02-9 ]
  • [ 1194-22-5 ]
  • [ 1246222-51-4 ]
  • 9
  • [ 20197-92-6 ]
  • [ 87-48-9 ]
  • [ 774222-99-0 ]
  • 10
  • [ 87-48-9 ]
  • [ 133997-05-4 ]
  • [ 1314306-38-1 ]
  • 11
  • [ 87-48-9 ]
  • [ 78364-55-3 ]
  • 2-(2-(5-bromo-2-oxoindolin-3-ylidene)hydrazino)-6-fluorobenzothiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With acetic acid; In ethanol;Reflux; General procedure: 6-Fluoro-2-(2-(5-(un)substituted-2-oxoindolin-3-ylidene)hydrazino)benzothiazoles 5a-c. General Procedure C. A mixture of compound 2 (0.183 g, 0.001 mol), the appropriate isatin (0.001 mol) and glacial acetic acid (0.1 mL) in ethanol (20 mL) was heated at reflux temperature for 4-6 h. The precipitated yellow to orange solid was collected by filtration, washed with ethanol, dried and crystallized from methanol to yield compounds 5a-c.
  • 12
  • [ 1131-18-6 ]
  • [ 87-48-9 ]
  • [ 50607-30-2 ]
  • 5-bromo-3'-methyl-1'-phenyl-6',7',8',9'-tetrahydrospiro[indoline-3,4'-pyrazolo[3,4-b][1,6]naphthyridine]-2,5'(1'H)-dione [ No CAS ]
  • 13
  • [ 4149-06-8 ]
  • [ 347-84-2 ]
  • [ 87-48-9 ]
  • 5-bromo-6'-(4-fluorophenyl)-2',5'-diphenyl-1',2'-dihydrospiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,3'(7'H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With acetic acid; In water; at 90℃; for 6h;Green chemistry; General procedure: The mixture of isatin (1 mmol), 3-amino-1-phenyl-1H-pyrazol-5(4H)-one (1 mmol), 1,2-diarylethan-1-one, 2,3-dihydroinden-1-one (1 mmol) or 3,4-dihydronaphthalen-1(2H)-one (1 mmol), H2O (6 mL), HOAc (2 mL) was put in a reaction flask under 90 C about 5-7 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be isolated out at same time. Then, compound 4 was recrystallized from DMF, however, the pure products of 6 and 8 were filtered from water, dried, without further recrystallization.
  • 14
  • [ 5432-53-1 ]
  • [ 87-48-9 ]
  • C20H17BrN2O2 [ No CAS ]
  • 15
  • [ 32412-39-8 ]
  • [ 87-48-9 ]
  • 6-bromo-2-(5-bromo-2-thienyl)-3-methylquinoline-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% 5.00 g (22.12 mmol) of 5-bromo-1H-indole-2,3-dione were initially charged in 61.2 ml of acetic acid, and 4.85 g (22.12 mmol) of 1-(5-bromo-2-thienyl)propan-1-one were added. The reaction mixture was stirred at 75 C. for 5 min. Subsequently, 20.4 ml (244 mmol) of conc. hydrochloric acid were added, and stirring of the mixture was continued at 105 C. overnight. After cooling to RT, the reaction mixture was concentrated under reduced pressure, 200 ml of toluene were added and the mixture was concentrated again. Addition of toluene and concentration were repeated twice. The resulting residue was dissolved with heating in a mixture of 100 ml of methanol and 50 ml of THF/DMSO/DMF and purified by preparative HPLC [column: Chromatorex Spring Column C18, 10 μm, 290 mm×100 mm; flow rate: 250 ml/min; detection: 210 nm; temperature: 22 C.; injection: 30 ml, gradient methanol/(water+0.1% formic acid) 50:50→90:10; run time 39 min)]. 6.77 g (72% of theory, 100% purity) of the title compound was obtained. 1H-NMR (400 Mhz, DMSO-d6): δ [ppm]=14.50 (br. s, 1H), 7.97-7.88 (m, 2H), 7.86 (d, 1H), 7.63 (d, 1H), 7.36 (d, 1H), 2.66 (s, 3H). LC/MS (Method 9, ESIpos): Rt=2.26 min, m/z=425/427/429 [M+H]+.
  • 16
  • [ 87-48-9 ]
  • [ 145091-87-8 ]
  • [ 109-77-3 ]
  • C16H12BrN5O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With 2-amino-2-hydroxymethyl-1,3-propanediol; In ethanol; at 20℃; for 3h; General procedure: To a well-stirred solution of isatin and malononitrile(1 mmol each) in ethanol (95%, 4 mL) was added dimedone,4-hydroxycoumarin, 4-hydroxy-N-methylquinolin-2-one,or 2-methyl-pyrazol-2-one [generated in situ from ethylacetoacetate and hydrazine hydrate, 1 mmol each]. To thissolution was added THAM (30 mol %) and stirring wascontinued at ambient temperature. Upon completion of thereaction (TLC), water (5 mL) was added and stirring wascontinued for 10 min more. Resultant solid product wasfiltered, washed repeatedly with water, and dried. The dried solid was washed thrice with hexaneechloroformmixture (1:1, v/v) and dried again. Resultant product didnot require any further purification.
  • 17
  • [ 87-48-9 ]
  • [ 1597-32-6 ]
  • C13H7BrFN3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With acetic acid; In ethanol; at 40 - 50℃; General procedure: For the synthesis of Schiffbase, 1-3 substituted isatin was treated with commercially available different aromatic amines (1:1) in ethanol (30 mL) containing a few drops of glacial acetic acid. The resulting reaction mixture was heated at 40 -50 C for 3-4 h. The progress of the reaction was checked by TLC. After the completion of the reaction, the reaction mixture was cooled at room temperature, concentrated, poured into ice cold water and basified with 2 M NaOH (pH 10) resulting in the formation of a precipitate. The precipitate was filtered, washed with water and dried over CaCl 2 in the vacuum chamber to obtain the crude prod- uct. The product was then purified by column chromatography and finally crystallized using ethanol.
 

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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

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