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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
PTP Inhibitor II is a cell-permeable protein tyrosine phosphatase (PTP) inhibitor, it covalently binds the catalytic domain of the Src homology region 2 domain-containing phosphatase (SHP-1(ΔSH2)) with Ki value of 128 μM.
Synonyms: α-Bromo-4’-methoxyacetophenone; NSC 129010; Protein Tyrosine Phosphatase Inhibitor II
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Fabian Fischer ; Julian Schliehe-Diecks ; Jia-Wey Tu ; Tanja Gangnus ; Yu Lin Ho ; Mara Hebeis , et al.
Abstract: Histone deacetylase inhibitors (HDACi) are established anticancer drugs, especially in hematological cancers. This study aimed to design, synthesize, and evaluate a set of HDACi featuring a pentyloxyamide connecting unit linker region and substituted phenylthiazole cap groups. A structural optimization program yielded HDACi with nanomolar inhibitory activity against histone deacetylase class I/IIb enzymes. The novel inhibitors (4d and 4m) showed superior antileukemic activity compared to several approved HDACi. Furthermore, 4d and 4m displayed synergistic activity when combined with chemotherapeutics, decitabine, and clofarabine. In vitro pharmacokinetic studies showed the most promising profile for 4d with intermediate microsomal stability, excellent plasma stability, and concentration-independent plasma protein binding. Additionally, 4d demonstrated comparable in vivo pharmacokinetics to vorinostat. When administered in vivo, 4d effectively inhibited the proliferation of leukemia cells without causing toxicity. Furthermore, the binding modes of 4d and 4m to the catalytic domain 2 of HDAC6 from Danio rerio were determined by X-ray crystallography.
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CAS No. : | 2632-13-5 |
Formula : | C9H9BrO2 |
M.W : | 229.07 |
SMILES Code : | COC1=CC=C(C(CBr)=O)C=C1 |
Synonyms : |
α-Bromo-4’-methoxyacetophenone; NSC 129010; Protein Tyrosine Phosphatase Inhibitor II
|
MDL No. : | MFCD00000201 |
InChI Key : | XQJAHBHCLXUGEP-UHFFFAOYSA-N |
Pubchem ID : | 4965 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302+H312+H332-H314-H290 |
Precautionary Statements: | P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diethyl ether; at 20℃;Inert atmosphere; | General procedure: The 6,7-dimethoxy-3,4-dihydroisoquinoline (1.91 g, 10.0 mmol) was dissolved in dry diethyl ether (30 ml) and ethyl bromoacetate, benzyl bromide or the corresponding α-bromoacetophenone (15 mmol) was added. The reaction mixture was stirred overnight at room temperature under an argon atmosphere. The yellow precipitate was filtered off, washed with diethyl ether and dried in vacuo to give the products as a yellow powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium ethanolate; In ethanol; at 0 - 20℃; | To the solution of EtONa (4.08 g, 60 mmol) in EtOH (60 mL) was added compound 104 (10 g, 60 mmol) at 0 0C under nitrogen. The mixture was stirred for 20 minutes and 2-bromo-4'-methyloxy-acetophenone was added. After stirring at room temperature overnight, the mixture was concentrated and the residue was taken up in ethyl acetate, washed with water, brine, dried and concentrated to give a residue which was purified by column chromatography to afford the product 402 as a solid (5.2 g, 67 %yield). 1H NMR (DMSOd6) delta 10.62 (s, IH), 7.41 (d, J = 6.6 Hz, 2H), 6.88 (d, J = 6.6 Hz, 2H), 6.30 (d, J = 3.0 Hz, IH), 5.59 (s, 2H), 4.13 (q, J = 6.9 Hz, 2H), 3.74 (s, 3H), 1.24 (t, J = 7.2 Hz, 3 H). LC-MS: 260 (M+l). |
67% | To the solution of EtONa (4.08 g, 60 mmol) in EtOH (60 mL) was added compound 104 (10 g, 60 mmol) at 0 0C under nitrogen. The mixture was stirred for20 minutes and 2-bromo-4'-methyloxy-acetophenone was added. After stirring at room temperature overnight, the mixture was concentrated and the residue was taken up in ethyl acetate, washed with water, brine, dried and concentrated to give a residue which was purified by column chromatography to afford the product 402 as a solid (5.2 g, 67 %yield). 1H NMR (DMSO-d6) delta 10.62 (s, 1eta), 7.41 (d, J = 6.6 Hz,2H), 6.88 (d, J = 6.6 Hz, 2H), 6.30 (d, J = 3.0 Hz, IH), 5.59 (s, 2H), 4.13 (q, J = 6.9 Hz, 2H), 3.74 (s, 3H), 1.24 (t, J = 7.2 Hz, 3 H). LC-MS: 260 (M+l). | |
General procedure: The following is representative: <strong>[57508-48-2]ethyl 3-amino-3-iminopropanoate hydrochloride</strong> (3) (8.3 g, 50.0 mmol) and NaOEt (5.1 g, 75.0 mmol) were dissolved in abs. EtOH at 0 C and stirred for 20 min under argon. The mixture was heated to 60 C, and 2-bromo-1-phenylethanone (4b) (5.0 g, 25.0 mmol) was added portion wise over 5 min. After 1.5 h the mixture was cooled to 20 C and the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and extracted with EtOAc (3 × 80 mL). The organic layer was washed with water (3 × 20 mL) and brine (3 × 20 mL). The combined water fractions were back extracted with EtOAc (2 × 20 mL). The organic phases were dried over MgSO4, and the solvent was evaporated under reduced pressure. Purification was by silica-gel column chromatography (EtOAc/n-pentane, 7/3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; | Step 12.1: 2-Amino-3-ethoxycarbonyl-5-(4-methoxy-phenyl)-1H-pyrrole Analogously to Step 8.1, 1.67 g (10 mmol) of 2-amidino-acetic acid ethyl ester hydro-chloride in 20 ml of abs. ethanol are reacted with 716 mg (10 mmol) of sodium ethanolate and 1.145 g (5.0 mmol) of 4-methoxy-phenacyl bromide (Fluka; Buchs/Switzerland) to form the title compound; m.p. 141-142 C.; TLC-Rf =0.4 (hexane/ethyl acetate [1:1]); FAB-MS: (M+H)+ =261. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In hexane; ethyl acetate; acetone; | Step A A mixture of 2-hydroxy-5-benzyloxyacetophenone (93 g, 380 mmoles), p-methoxyphenacyl bromide (88 g, 384 mmoles) and potassium carbonate (106 g, 768 mmoles) in acetone (1.5 L) was refluxed for 46 hours. The reaction mixture was cooled and filtered. The filtrate was evaporated in vacuo. The residue was chromatographed on silica gel using 10% ethylacetate in hexane as eluent to yield (127 g, 89%) of 2-(p-methoxybenzyl)-3-methyl-5-benzyloxybenzofuran, E48. 1 H NMR delta: 2.55 (s, 3H, CH3), 3.85 (s, 3H, CH3 O), 5.1 (s, 2H, benzylic proton), 7.00 (d, J=9 Hz, 2H, proton ortho to methoxy), 7.15 (m, 2H, aromatic proton), 7.45 (m, 6H, benzylic proton +1 proton), 8.15 (d, J=9 Hz, 2H, proton ortho to benzoyl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | In ethanol; for 5h;Heating / reflux; | 2-Bromo-4'-methoxyacetophenone (1.64 g, 7.14 mmol) was added to a solution of 2- amino-3-benzyloxypyrazine (Compound m in scheme 1,1. 5 g, 6.80 mmol) in ethanol (10 mL). The reaction mixture was refluxed for 5 h. The reaction mixture was allowed to cool to r. t. and an off- white coloured solid precipitated out. The solid was collected and washed with ice-cold ethanol to give a white solid (1. 08 g, 66%). lH-NMR (CDC13) 6 11.4 (d, J4. 2 Hz, 1H), 8.23 (s, 1H), 7. 86 (t, J 2.9 Hz, 1H), 7. 83 (t, J2. 1 Hz, 1H), 7.52 (dd, J0. 7 & 5.5 Hz, 1H), 7.04 (t, J2. 9 Hz, 1H), 7.02 (t, J2. 0 Hz, 1H), 6.94 (t, J3.0 Hz, 1H), 3.79 (s, 3H) ; MS (ESI) 242.0 ([M+H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity; | Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With N,N-dimethyl-aniline; at 150℃; for 12h; | To a solution of <strong>[6299-67-8]2,3-dimethoxyaniline</strong> (0.92 mL, 6.85 mmol) dissolved in N,N-dimethylaniline (10 mL) was added 4-methoxybromoacetophenone 4 (0.79 g, 3.43 mmol). The solution was heated to reflux and stirred at 150 C for 12 h. Upon completion of the reaction, the reaction mixture was cooled to room temperature and extracted with EtOAc (3 * 50 mL). The combined organic extract was dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography using a prepacked 100 g silica column [solvent (A) EtOAc; solvent (B) hexanes; gradient: 5%A/95%B (4 CV), 5%A/95%B → 40%A/60%B (10 CV), 40%A/60%B (4 CV); flow rate: 40 mL/min; monitored at 254 and 280 nm] resulted in the desired 6,7-dimethoxy-2-phenylindole 8 (0.50 g, 1.76 mmol, 51%, Rf = 0.35 (80:20 hexanes:EtOAc)) as a tan solid. 1H NMR (CDCl3, 500 MHz): δ 8.61 (br s, 1H, NH), 7.61 (d, J = 8.7 Hz, 2H, ArH), 7.28 (d, J = 8.5 Hz, 1H, ArH), 6.97 (d, J = 8.7 Hz, 2H, ArH), 6.87 (d, J = 8.6 Hz, 1H, ArH), 6.66 (d, J = 2.1 Hz, 1H, ArH), 4.09 (s, 3H, OCH3), 3.97 (s, 3H, OCH3), 3.85 (s, 3H, OCH3). 13C NMR (CDCl3, 125 MHz): δ 159.2, 147.1, 138.0, 134.2, 131.3, 126.4, 126.0, 125.3, 115.3, 114.5, 108.5, 98.8, 61.1, 57.4, 55.4. HPLC: 15.30 min, purity at 254 nm 90.6%. HRMS (ESI+): m/z calculated for C17H18NO3 [M+H]+ 284.1281, found 284.1282. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In ethanol; at 70℃; | General procedure: The properly substituted bromoacetophenone 4, 6-15, 17-19 (1 equiv) and thioureas a-n (1 equiv) were solubilized in dry ethanol (5mLmmol-1 of bromoacetophenone) and reacted at 70C until consumption of the starting materials as indicated by TLC. After cooling, the solvent was evaporated and the residue obtained was washed with diethyl ether (3×10mL) to give the title compounds as a powder in good overall yields. In some cases, the crude material was purified by flash column chromatography. Yields, purification methods and purity are reported in details in the SI. Analytical data for compounds n, 6a, 8a, 15a, matched the data published previously [27,33,32,31]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | General procedure: General Procedure. 2-Hydroxyanthraquinone (4)/2-hydroxyxanthone (5)/2-hydroxycarbazole(6) (10 mmol), K2CO3 (10 mmol), and dry N,N-dimethylformamide (DMF) (50 mL) were stirred at room temperature (r.t.) for 30 min. To this soln. was added 2-(bromoacetyl) naphthalene/different substituents 2-bromoacetophenone (10 mmol) in dry DMF (10 mL) in one portion. The resulting mixture was stirred at r.t. for 24 h (TLC monitoring)and then poured into ice-water (100 mL). The yellow solid thus obtained was collected and purified by column chromatography on silica gel using CH2Cl2/MeOH 20:1. The proper fractions were combined and evaporated to furnish a residual solid which was crystallized from Et2O and CH2Cl2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In ethanol; at 80 - 85℃; for 24h; | General procedure: 4.2.3.1. 6-(4-Chlorophenyl)-2-methyl imidazo[2,1-b][1,3,4]thiadiazole(3a). A mixture of 2a (2 g, 17.39 mmol) and 4-chloro phenacyl bromide (4.032 g, 17.39 mmol) was refluxed in dry ethanol (20 mL)for 24 h. The excess of solvent was removed under reduced pressureand the solid hydrobromide salt was suspended in water, and neutralized by the aqueous sodium carbonate solution to get free base. It was then filtered, washed with water, dried, and recrystallized from ethanol to get compound 3a as light yellow solid. Yield: 3.4 g, 80% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | General procedure: A mixture of thiochroman-4-one 1 (1 mmol), benzaldehyde 2(1 mmol), thiourea 3 (1 mmol) was stirred in presence of ionic liquid,[Bmim]HSO4 (1 mL) at 80 C for 20 min followed by the additionof 3-bromo-1-phenylpropan-1-one 4 (1 mmol) and theresulting mixture was further stirred at 80 C for 40-70 min. Theprogress of reaction was monitored by TLC. After completion ofthe reaction, the mixture was diluted with 20 mL of water,2 20 mL of EtOAc was added and shaken vigorously. The organiclayer was separated from the solution. The aqueous layer wasevaporated, the ionic liquid was dried at 60-70 C under vacuumand then reused. The results have shown that the [Bmim]HSO4ionic liquid could be reused at least for four times. The productwas purified by column chromatography on neutral alumina(100-200 mesh), eluted with a solvent system of ethyl acetate-hexane to afford the title compounds 5a-n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With polyethylene glycol (PEG-400); In water; for 0.116667h;Microwave irradiation; Green chemistry; | To stirred solution of polyethylene glycol (PEG-400) (2 mL) in water (2 mL) were added 1-(2-amino-4-methylthiazol-5-yl)ethanone (2 mmol)/ethyl 2-amino-4-methylthiazole-5-carboxylate (2 mmol) and α-bromo aralkyl ketones (phenacyl bromides) (2 mmol), and the mixture was heated at 90 C or subject to microwave irradiation at 300 W, until reaction completion as indicated by TLC. After reaction completion, the reaction mixture was cooled at room temperature, and the solid product formed was collected by filtration, washed with water, and recrystallized from ethanol to give pure product. The recovered PEG with water was reused for five further cycles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With polyethylene glycol (PEG-400); In water; for 0.1h;Microwave irradiation; Green chemistry; | To stirred solution of polyethylene glycol (PEG-400) (2 mL) in water (2 mL) were added 1-(2-amino-4-methylthiazol-5-yl)ethanone (2 mmol)/ethyl 2-amino-4-methylthiazole-5-carboxylate (2 mmol) and α-bromo aralkyl ketones (phenacyl bromides) (2 mmol), and the mixture was heated at 90 C or subject to microwave irradiation at 300 W, until reaction completion as indicated by TLC. After reaction completion, the reaction mixture was cooled at room temperature, and the solid product formed was collected by filtration, washed with water, and recrystallized from ethanol to give pure product. The recovered PEG with water was reused for five further cycles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 20℃; for 0.5h; | General procedure: To a solution of the intermediate thioureas (1 eq., 0.1 M) in EtOH was added 2-bromoacetophenone (1.25 eq). The solution was stirred at room temperature until completion of the reaction followed by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.8% | In acetone; at 60℃; | General procedure: To a solution of 2-amino-4-methylthiazole-5-carboxylate (9, 1.00g, 5.37mmol) in acetone (20ml), the respective 2-bromo-1-(4-substituted-phenyl)ethanone (10-12, 5.37mmol) was added. The solution was refluxed for 24h. Reaction mixture was concentrated under reduced pressure and then purified with column chromatography using hexane:ethylacetate (60:40) to get 13, 14 and 15 |
Tags: PTP inhibitor 1 | α-Bromo-4’-methoxyacetophenone | Benzene Compounds | Protective Groups | Others | Phosphatase | Organic Building Blocks | Other Inhibitors/Agonists | Small Molecule Positive Drugs | Steroids | Biological Buffers | Fluorescence Labeling Reagents | Fluorescent Dyes | Structure | 2632-13-5
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P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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