2259-96-3

Basic information

• Product Name: CYCLOTHIAZIDE
• Synonyms: 2,4-benzothiadiazine-3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-4-dihydro-2h-1;2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-chloro-3-(5-norbornen-2-yl)-,1,1-dioxide;2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1,1-dioxide;2h-1,2,4-benzothiadiazine-7-sulfonamide,3-bicyclo(2.2.1)hept-5-en-2-yl-6-chlor;35483;4-benzothiadiazine-7-sulfonamide,3,4-dihydro-6-chloro-3-(5-norbornen-2-2h-2;4-benzothiadiazine-7-sulfonamide,6-chloro-3,4-dihydro-3-(5-norbornen-2-2h-2;6-chloro-3-(2-norbornen-5-yl)-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine1,1
• CAS NO: 2259-96-3
• Molecular Formula: C₁₄H₁₆ClN₃O₄S₂
• Molecular Weight: 389.88
• EINECS: 218-859-7
• Product Categories: Glutamate receptor;Glutamate;Amines;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 2259-96-3.mol
• Article Data: 0

Chemical Properties

• Melting Point: 234°
• Boiling Point: 627.3 °C at 760 mmHg
• Flash Point: 333.2 °C
• Appearance: White Solid
• Density: 1.3781 (rough estimate)
• Vapor Pressure: 1.19E-15mmHg at 25°C
• Refractive Index: 1.6100 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (up to 35 mg/ml) or in Ethanol (up to 9 mg/ml)
• PKA: pKa 9.1(30% EtOH) (Uncertain)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• Merck: 14,2754
• CAS DataBase Reference: CYCLOTHIAZIDE(CAS DataBase Reference)
• NIST Chemistry Reference: CYCLOTHIAZIDE(2259-96-3)
• EPA Substance Registry System: CYCLOTHIAZIDE(2259-96-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• RTECS: DK9610000
• Hazardous Substances Data: 2259-96-3(Hazardous Substances Data)

Usage

Description

Cyclothiazide (2259-96-3) is a positive allosteric modulator of AMPA receptors acting at a site distinct from that of 2,3-benzodiazepines.1,2 Clinically useful diuretic and antihypertensive agent.3 Induces robust epileptiform activity, inducing seizures but without neuronal death.4,5 Can be used to produce a new animal model for epilepsy.5

Originator

Anhydron,Lilly,US,1963

Uses

Different sources of media describe the Uses of 2259-96-3 differently. You can refer to the following data:
1. Diuretic; antihypertensive. A subunit-specific inhibitor of GABAC receptors.
2. Cyclothiazide has been used as a α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) desensitization blocker to study the effects of γ2 on receptor desensitization.
3. Diuretic; antihypertensive. A subunit-specific inhibitor of GABAC receptors

Definition

ChEBI: 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted at positions 3, 5 and 6 by a 2-norbornen-5-yl group, chlorine, and a sulfonamide group, respectively. A thiazide diuretic, it has been used in the management of hypertension a d oedema.

Manufacturing Process

A mixture of 8.5 g (0.03 mol) of 6-chloro-4-amino-benzene-1,3- disulfonamide, 4.0 g (0.033 mol) of 2,5-endomethylene-δ3- tetrahydrobenzaldehyde and 25 cc of diethyleneglycol-dimethyl ether was heated for 2 hours at 100°C. During this time the major portion of the initially undissolved crystals went into solution; thereafter, the reaction mixture was allowed to stand for 14 hours at room temperature, during which the remaining undissolved crystals also went into solution. The reddish, clear solution thus obtained was admixed with 50 cc of chloroform. The greyishwhite precipitate formed thereby was separated by vacuum filtration, washed with a small amount of chloroform, dried and recrystallized from aqueous methanol. 7.5 g of white crystalline needles having a melting point of 229° to 230°C were obtained.

Brand name

Anhydron (Lilly).

Therapeutic Function

Diuretic, Antihypertensive

General Description

Cyclothiazide is a benzothiadiazine, which has a similar structure to diazoxide.

Biological Activity

Positive allosteric modulator of AMPA receptors that potently inhibits AMPA receptor desensitization. Selective for the flip variant of each of the four receptor subunits. Also available as part of the AMPA Receptor Tocriset? .

Biochem/physiol Actions

Blocks the rapid desensitization of the AMPA glutamate receptors and markedly prolongs the decay time of the evoked excitatory post-synaptic current.

References

1) Donevan and Rogawski (1998), Allosteric regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors by thiocyanate and cyclothiazide at a common modulatory site distinct from that of 2,3-benzodiazepines; Neuroscience 87 615 2) Desai et al. (1995), Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor complex that does not recognize competitive or noncompetitive AMPA receptor antagonists; J. Pharmacol. Exp. Ther. 272 38 3) Jeunemaitre et al. (1988), Long-term metabolic effects of spironolactone and thiazides combined with potassium-sparing agents for treatment of essential hypertension; Am. J. Cardiol. 62 1072 4) Qi et al. (2006), Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo; J. Physiol. 571 605 5) Kong et al. (2010), Cyclothiazide induces seizure behavior in freely moving rats; Brain Res. 1355 207

InChI:InChI=1/C14H16ClN3O4S2/c15-10-5-11-13(6-12(10)23(16,19)20)24(21,22)18-14(17-11)9-4-7-1-2-8(9)3-7/h1-2,5-9,14,17-18H,3-4H2,(H2,16,19,20)/t7-,8+,9?,14?/m0/s1

Upstream product

• 121-30-2 chloraminophenamide 
• 5453-80-5 5-Norbornene-2-carboxaldehyde