BENDROFLUMETHIAZIDE CAS 73-48-3
Introduction：Basic information about BENDROFLUMETHIAZIDE CAS 73-48-3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
BENDROFLUMETHIAZIDE Basic information
| Product Name: | BENDROFLUMETHIAZIDE |
| Synonyms: | BENDROFLUMETHIAZIDE;BENDROFLUMETHIAZIDE-D5;1,1-dioxo-3-(phenylmethyl)-6-(trifluoromethyl)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide;3-(benzyl)-1,1-diketo-6-(trifluoromethyl)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide;rac Bendroflumethiazide;Bendroflumethiazide (200 mg);Bendroflumethiazide (200 mg)H0C4020.994mg/mg(ai);6-trifluoromethyl-3-benzyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine,1,1 |
| CAS: | 73-48-3 |
| MF: | C15H14F3N3O4S2 |
| MW: | 421.41 |
| EINECS: | 200-800-1 |
| Product Categories: | Isotope;BISOLVON;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds |
| Mol File: | 73-48-3.mol |
BENDROFLUMETHIAZIDE Chemical Properties
| Melting point | 205-207°C |
| Boiling point | 602.1±65.0 °C(Predicted) |
| density | 1.4711 (estimate) |
| storage temp. | Refrigerator |
| solubility | Practically insoluble in water, freely soluble in acetone, soluble in ethanol (96 per cent). |
| form | Solid |
| pka | pKa 8.53±0.05(H2O t=25 I=0.2) (Uncertain) |
| color | Crystals from MeOH/CHCl3 |
| Water Solubility | 40mg/L(room temperature) |
| EPA Substance Registry System | 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-3-(phenylmethyl)-6-(trifluoromethyl)-, 1,1-dioxide (73-48-3) |
Safety Information
| WGK Germany | 2 |
| RTECS | DK8225000 |
| HS Code | 2935904000 |
| Hazardous Substances Data | 73-48-3(Hazardous Substances Data) |
| Toxicity | LD50 oral in mouse: > 10gm/kg |
| Description | Bendroflumethiazide (Item No. 21311) is an analytical reference standard categorized as a diuretic. Diuretics, including bendroflumethiazide, have been abused as performance-enhancing drugs and masking agents in sports doping. This product is intended for research and forensic applications. |
| Chemical Properties | White Solid |
| Originator | Naturetin,Squibb,US,1959 |
| Uses | Bendroflumethiazide may be used for the same indications as the aforementioned drugs;however, it is primarily used as an adjuvant agent for relieving edema associated with cardiacinsufficiency, liver cirrhosis, and edema caused by taking corticosteroids. |
| Uses | Diuretic; antihypertensive. |
| Uses | expectorant |
| Definition | ChEBI: A sulfonamide consisting of 7-sulfamoyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position 6 is substituted by a trifluoromethyl group and that at position 3 is substituted by a benzyl group. |
| Manufacturing Process | The process is described in US Patent 3,392,168 as follows: (A) Preparation of 5-Trifluoromethylaniline-2,4-Disulfonylchloride - 113 ml ofchlorosulfonic acid is cooled in an ice bath, and to the acid is added dropwisewhile stirring 26.6 grams of α,α,α-trifluoro-m-toluidine. 105 grams of sodiumchloride is added during 1-2 hours, where after the temperature of thereaction mixture is raised slowly to 150° - 160°C which temperature ismaintained for three hours. After cooling the mixture, ice-cooled water isadded, whereby 5-trifluoromethylaniline-2,4-disulfonyl chloride separates outfrom the mixture. (B) Preparation of 5-Trifluoromethyl-2,4-Disulfamylaniline - The 5-trifluoromethylaniline-2,4-disulfonyl chloride obtained in step (A) is taken upin ether and the ether solution dried with magnesium sulfate. The ether isremoved from the solution by distillation, the residue is cooled to 0°, and 60ml of ice-cooled, concentrated ammonia water is added while stirring. Thesolution is then heated for one hour on a steam bath and evaporated in vacuoto crystallization. The crystallized product is 5-trifluoromethyl-2,4-disulfamylaniline, which is filtered off, washed with water and dried in avacuum-desiccator over phosphorus pentoxide. After recrystallization from amixture of 30% ethanol and 70% water, the compound has a MP of 247°-248°C. (C) Preparation of 3-Benzyl-6-Trifluoromethyl-7-Sulfarnyl-3,4-Dihydro-1,2,4-Benzothiadiazine-1,1-Dioxide - 6.4 grams of 5-trifluoromethyl-2,4-disulfamylaniline is dissolved in 12 ml of dioxane, 2.7 ml ofphenylacetaldehyde and a catalytic amount of p-toluenesulfonic acid areadded. After boiling for a short time under reflux, the reaction mixturecrystallizes, and, after filtration and recrystallization from dioxane, the desired product is obtained with a MP of 224.5°-225.5°C. (D) Alternative to (C) - 9.6 grams of 5-trifluoromethyl-2,4-disulfarnylanilineand 4.9 grams of ω-ethoxystyrene are dissolved in 35 ml of n-butanol. 0.5grams of p-toluenesulfonic acid is added, and the mixture is heated on asteam bath while stirring. When the solution is clear, 55 ml of hexane isadded, whereafter the mixture is heated further for one and a half hours.After cooling, the substance identical to that of Example (C) is filtered off andhas a MP of 222°-223°C. Sterile compositions containing Bendroflumethiazide for parenteraladministration may be prepared as described in US Patent 3,265,573. |
| Brand name | Naturetin(Apothecon). |
| Therapeutic Function | Diuretic, Antihypertensive |
| Clinical Use | Thiazide diuretic: Hypertension Oedema |
| Safety Profile | Poison by intravenous route.Human systemic effects by ingestion: convulsions andsomnolence. Mutation data reported. When heated todecomposition it emits toxic fumes of F-, SOx, and NOx. |
| Synthesis | Bendroflumethiazide, 1,1-dioxide 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazin-7-sulfonamide (21.3.6), is synthesized by the same scheme of making the aforementioned drugs using phenylacetaldehyde or its acetale as acarbonyl component, and using 2,4-disulfonamido-5-trifluoromethylaniline (21.3.5) as ano-aminosulfonamide component. |
| Drug interactions | Potentially hazardous interactions with other drugs Analgesics: increased risk of nephrotoxicity with NSAIDs; antagonism of diuretic effect. Anti-arrhythmics: hypokalaemia leads to increased cardiac toxicity; effects of lidocaine and mexiletine antagonised. Antibacterials: avoid administration with lymecycline. Antidepressants: increased risk of hypokalaemia with reboxetine; enhanced hypotensive effect with MAOIs; increased risk of postural hypotension with tricyclics. Antiepileptics: increased risk of hyponatraemia with carbamazepine. Antifungals: increased risk of hypokalaemia with amphotericin. Antihypertensives: enhanced hypotensive effect; increased risk of first dose hypotension with postsynaptic alpha-blockers like prazosin; hypokalaemia increases risk of ventricular arrhythmias with sotalol. Antipsychotics: hypokalaemia increases risk of ventricular arrhythmias with amisulpride; enhanced hypotensive effect with phenothiazines; hypokalaemia increases risk of ventricular arrhythmias with pimozide - avoid. Atomoxetine: hypokalaemia increases risk of ventricular arrhythmias. Cardiac glycosides: increased toxicity if hypokalaemia occurs. Ciclosporin: increased risk of nephrotoxicity and hypomagnesaemia. Cytotoxics: increased risk of ventricular arrhythmias due to hypokalaemia with arsenic trioxide; increased risk of nephrotoxicity and ototoxicity with platinum compounds. Lithium excretion reduced, increased toxicity. |
| Metabolism | There are indications that bendroflumethiazide is fairly extensively metabolised.About 30% is excreted unchanged in the urine with the remainder excreted as uncharacterised metabolites. |
| References | [1] D S MAJID L G N. Blockade of distal nephron sodium transport attenuates pressure natriuresis in dogs.[J]. Hypertension, 1994, 23 6 Pt 2: 1040-1045. DOI: 10.1161/01.hyp.23.6.1040 [2] VONGPATANASIN W. Hydrochlorothiazide is not the most useful nor versatile thiazide diuretic.[J]. Current Opinion in Cardiology, 2015, 30 4: 361-365. DOI: 10.1097/hco.0000000000000178 |
BENDROFLUMETHIAZIDE Preparation Products And Raw materials
| Raw materials | Iron-->Benzotrifluoride-->3-Aminobenzotrifluoride-->Benzotrichloride-->Phenylacetaldehyde-->3-Nitrobenzotrifluoride-->Ammonia-->Chlorosulfonic acid |
