22503-72-6

Basic information

• Product Name: IDRA 21
• Synonyms: IDRA 21;7-CHLORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE;7-CHLORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE 1,1-DIOXIDE;7-CHLORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE S,S-DIOXIDE;IDRA 21,98%;2H-1,2,4-Benzothiadiazine,7-chloro-3,4-dihydro-3-Methyl-, 1,1-dioxide;AMPAKINE;7-chloro-3-methyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide
• CAS NO: 22503-72-6
• Molecular Formula: C₈H₉ClN₂O₂S
• Molecular Weight: 232.69
• Mol File: 22503-72-6.mol

Chemical Properties

• Melting Point: 209 °C(Solv: acetic acid (64-19-7))
• Boiling Point: 405.1°Cat760mmHg
• Flash Point: 198.8°C
• Appearance: /
• Density: 1.394g/cm³
• Vapor Pressure: 8.98E-07mmHg at 25°C
• Refractive Index: 1.571
• Storage Temp.: Store at RT
• Solubility: DMSO (Slightly), Methanol (Slightly, Sonicated)
• PKA: 9.78±0.40(Predicted)
• CAS DataBase Reference: IDRA 21(CAS DataBase Reference)
• NIST Chemistry Reference: IDRA 21(22503-72-6)
• EPA Substance Registry System: IDRA 21(22503-72-6)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 22503-72-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
IDRA 21 is used as a cognitive enhancer for patients with cognitive impairments such as Alzheimer's disease. It works by inhibiting AMPA receptor desensitization, which in turn increases excitatory synaptic strength and may help ameliorate memory deficits.
Additionally, IDRA 21 is used as a research tool to study the role of AMPA receptors in cognitive functions and the potential therapeutic effects of modulating these receptors in various neurological disorders.
Used in Research and Development:
IDRA 21 serves as a valuable compound in the development of new drugs targeting AMPA receptors. Its ability to cross the blood-brain barrier and enhance cognition makes it an important molecule for exploring novel therapeutic strategies for cognitive impairments and other related conditions.

Biological Activity

Inhibits AMPA receptor desensitization and enhances cognition by a related mechanism. More able to cross the blood-brain barrier than cyclothiazide (6-Chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2H-1,2,4-benzothiazidiazine-7-sulfonamide-1,1-dioxide ).

InChI:InChI=1/C8H9ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-5,10-11H,1H3

Synthetic route

2-amino-5-chlorobenzenesulfonamide (5790-69-2) + ethanol (64-17-5) → IDRA 21 (22503-72-6)

Conditions	Yield
With tert.-butylhydroperoxide at 110℃; for 12h;	80%

2-amino-5-chlorobenzenesulfonamide (5790-69-2) + acetaldehyde (75-07-0) → IDRA 21 (22503-72-6)

Conditions	Yield
In acetonitrile
With camphorsulfonic acid In acetonitrile at 20℃; Sealed tube;

4-Chlor-2-acetylsulfamoyl-acetanilid (90794-87-9) → IDRA 21 (22503-72-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH 2: acetonitrile View Scheme

2-acetylamino-benzenesulfonic acid acetylamide (17800-60-1) → IDRA 21 (22503-72-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: Cl2 / acetic acid 2: aq. NaOH 3: acetonitrile View Scheme

IDRA 21 (22503-72-6) → N-acetyl-5-chloro-2-nitrobenzenesulfonamide (19900-92-6)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 12h; Cooling with ice;	99%

IDRA 21 (22503-72-6) → 5-chloro-2-(ethylamino)benzenesulfonamide (38443-06-0)

Conditions	Yield
With sodium cyanoborohydride In acetic acid at 20℃; for 3h; regioselective reaction;	93%

IDRA 21 (22503-72-6) → 2-amino-5-chloro-N-ethylbenzenesulfonamide (5790-62-5)

Conditions	Yield
With sodium cyanoborohydride In ethanol; water at 70℃; for 6h; regioselective reaction;	86%

IDRA 21 (22503-72-6) → C16H14Cl2N4O6S2

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 12h; Cooling with ice;	19%

IDRA 21 (22503-72-6) + methyl iodide (74-88-4) → (+/-)-7-chloro-2,3-dimethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (38442-77-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 70 - 80℃;

Upstream product

• 5790-69-2 2-amino-5-chlorobenzenesulfonamide 
• 75-07-0 acetaldehyde 
• 64-17-5 ethanol 
• 17800-60-1 2-acetylamino-benzenesulfonic acid acetylamide 
• 90794-87-9 4-Chlor-2-acetylsulfamoyl-acetanilid 

Downstream Products

• 19900-92-6 N-acetyl-5-chloro-2-nitrobenzenesulfonamide 
• 38443-06-0 5-chloro-2-(ethylamino)benzenesulfonamide 
• 5790-62-5 2-amino-5-chloro-N-ethylbenzenesulfonamide 

Relevant articles and documents

Metal-free oxidative cyclization of 2-amino-benzamides, 2-aminobenzenesulfonamide or 2-(aminomethyl)anilines with primary alcohols for the synthesis of quinazolinones and their analogues

A general metal-free oxidative cyclization process has been developed for the synthesis of quinazolinones, benzothiadiazines and quinazolines. By this protocol, a range of substituted 2-aminobenzamides, 2-aminobenzenesulfonamide and 2-(aminomethyl)anilines react with various alcohols, leading to the desired annulated products smoothly. This protocol features many advantages as broad substrate scope, mild reaction conditions, low environmental pollution, high atom-economy and good to excellent yields.

Synthesis and Pharmacology of Mono-, Di-, and Trialkyl-Substituted 7-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides Combined with X-ray Structure Analysis to Understand the Unexpected Structure-Activity Relationship at AMPA Receptors

Positive allosteric modulators of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)-type ionotropic glutamate receptors are promising compounds for treatment of neurological disorders, for example, Alzheimer's disease. Here, we report synthesis and pharmacological evaluation of a series of mono-, di-, or trialkyl-substituted 7-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides, comprising in total 16 new modulators. The trisubstituted compounds 7b, 7d, and 7e revealed potent activity (EC2× = 2.7-4.3 μM; concentration of compound responsible for a 2-fold increase of the AMPA mediated response) as AMPA receptor potentiators in an in vitro cellular fluorescence assay (FLIPR). The 4-cyclopropyl compound 7f was found to be considerably less potent (EC2× = 60 μM), in contrast to previously described 4-monoalkyl-substituted benzothiadiazine dioxides for which the cyclopropyl group constitutes the best choice of substituent. 7b was subjected to X-ray structural analysis in complex with the GluA2 ligand-binding domain. We propose an explanation of the unexpected structure-activity relationship of this new series of mono-, di-, and trialkyl-substituted 1,2,4-benzothiadiazine 1,1-dioxide compounds. The methyl substituent in the 3-position directs the binding mode of the 1,2,4-benzothiadiazine 1,1-dioxide (BTD) scaffold. When a methyl substituent is present in the 3-position of the BTD, additional methyl substituents in both the 2- A nd 4-positions increase potency, whereas introduction of a 4-cyclopropyl group does not enhance potency of 2,3,4-alkyl-substituted BTDs. A hydrogen bond donor in the 2-position of the BTD is not necessary for modulator potency.