22232-71-9

Basic information

• Product Name: Mazindol
• Synonyms: 1-a)isoindol-5-ol,2,5-dihydro-5-(4-chlorophenyl)-3h-imidazo(;1-a)isoindol-5-ol,5-(4-chlorophenyl)-2,5-dihydro-3h-imidazo(;1-a)isoindol-5-ol,5-(p-chlorophenyl)-2,5-dihydro-3h-imidazo(;1-a]isoindol-5-ol,5-(4-chlorophenyl)-2,5-dihydro-3h-imidazo[;3H-Imidazo[2,1-a]isoindol-5-ol, 5-(4-chlorophenyl)-2,5-dihydro-;5-(p-chlorophenyl)-2,5-dihydro-3h-imidazo(2,1-a)isoindol-5-ol;5-(p-Chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol;5H-Imidazo(2,1-a)isoindol-5-ol, 5-(4-chlorophenyl)-2,3-dihydro-
• CAS NO: 22232-71-9
• Molecular Formula: C₁₆H₁₃ClN₂O
• Molecular Weight: 284.74
• EINECS: 244-857-0
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 22232-71-9.mol

Chemical Properties

• Melting Point: 215-217°C
• Boiling Point: 454.908 °C at 760 mmHg
• Flash Point: 228.921 °C
• Appearance: white/powder
• Density: 1.39
• Vapor Pressure: 4.57E-09mmHg at 25°C
• Refractive Index: 1.6330 (estimate)
• Storage Temp.: Controlled Substance, -20?C Freezer
• Solubility: DMSO: 10 mg/mL
• PKA: pKa 8.6 (Uncertain)
• CAS DataBase Reference: Mazindol(CAS DataBase Reference)
• NIST Chemistry Reference: Mazindol(22232-71-9)
• EPA Substance Registry System: Mazindol(22232-71-9)

Safety Data

• Hazard Codes: T
• Statements: 23/24/25
• Safety Statements: 36/37/39-45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: NI2975000
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 22232-71-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Mazindol is used as an appetite depressant for weight loss management. It works by stimulating the central nervous system, which helps to reduce appetite and increase energy levels, making it easier for individuals to control their food intake and lose weight.
Mazindol is also used as an anorexic agent, which helps to promote weight loss by reducing the desire to eat. This can be particularly useful for individuals who struggle with overeating or binge eating.
In addition to its weight loss benefits, Mazindol is used as a central nervous system stimulant, which can help to increase alertness, focus, and energy levels. This can be beneficial for individuals who need a boost in mental performance or who are experiencing fatigue.
As a controlled substance, Mazindol is regulated due to its potential for abuse and addiction. It is important to use this medication under the guidance of a healthcare professional to ensure safe and effective treatment.

Originator

Sanorex ,Sandoz ,US ,1973

Manufacturing Process

Step 1: 1-(p-Chlorophenyl)-3-Ethoxy-11H-Isoindole - Crystalline triethyloxonium borontetrafluoride (21 g) (prepared from 23 g of borontrifluoride etherate and 11 g of epichlorohydrin) is dissolved in 100 ml of absolute methylenechloride. 3-(p-Chlorophenyl) phthalimidine (21 g) is added and the reaction mixture is stirred overnight at room temperature. The resulting solution is poured onto 50 ml of saturated sodium carbonate, extracted with 500 ml of ether and dried. Upon evaporation of the solvent there is obtained crude material which is recrystallized from methylene chloride/hexane (1:1) to yield 1-(p-chlorophenyl)-3-ethoxy-1H-isoindole; MP 102° to 103°C.Step 2: 5-(p-Chlorophenyl)-5-Hydroxy-2,3-Dihydro-5H-Imidazo[2,1- a]Isoindole - 1-(p-Chlorophenyl)-3-ethoxy-1H-isoindole (1 g), 2 g of ethyleneimine hydrotetrafluoroborate moistened with methylene chloride (containing approximately 0.66 g of dry salt) is refluxed in 25 ml of absolute toluene for 2 hours in an atmosphere of nitrogen. The resulting mixture is poured into 2 N sodium carbonate solution (25 ml) and extracted with ether. The ether solution is contacted with air for 6 days at room temperature to give the desired product. The crude material is recrystallized from acetone/hexane (1:1) to give 5-(p-chlorophenyl)-5-hydroxy-2,3-dihydro-5Himidazo[2,1-a]isoindole; MP 198° to 199°C.

Therapeutic Function

Antiobesity

World Health Organization (WHO)

Mazindol, an anorectic agent, was introduced into medicine in 1970 as an aid to weight reduction. It is controlled under Schedule IV of the 1971 Convention on Psychotropic Substances. It remains available in many countries with highly evolved drug regulatory authorities. (Reference: (UNCPS4) United Nations Convention on Psychotropic Substances (IV), , , 1971)

InChI:InChI=1/C16H13ClN2O/c17-12-7-5-11(6-8-12)16(20)14-4-2-1-3-13(14)15-18-9-10-19(15)16/h1-8,20H,9-10H2

Upstream product

• 936-49-2 2-phenyl-2-imidazoline 
• 1126-46-1 Methyl 4-chlorobenzoate 
• 6038-49-9 9b-(p-chlorophenyl)-1,2,3,9b-tetrahydro-1H-imidazo[2,1-a]isoindol-5-one 
• 22590-16-5 9b-(4-chloro-phenyl)-1-(toluene-4-sulfonyl)-1,2,3,9b-tetrahydro-imidazo[2,1-a]isoindol-5-one 
• 107-15-3 ethylenediamine 
• 23864-94-0 2-(4-chlorobenzoyl)-benzaldehyde 

Downstream Products

• 23864-93-9 4'-chloro-2-(imidazolin-2-yl)benzophenone hydrochloride 

Relevant articles and documents

Synthesis of halogenated analogs of 5-(4-chlorophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo[2,1-a]-isoindole or mazindol for exploration of the dopamine transporter

In order to study the presynaptic dopamine transporter in the human brain by single photon emission tomography (SPET) or positron emission tomography (PET) we have developed new halogenated mazindol derivatives using a pathway involving a reaction between a dilithio derivative of 2-phenyl-2-imidazoline and appropriate methyl or ethyl halogenobenzoates. After HPLC purification and chemical characterization, the affinity for the dopamine transporter was studied in vitro with [3H]-GBR 12935 and compared to mazindol and nomifensine. Affinity potencies were determined as follows: mazindol > brominated derivatives > iodinated derivatives > nomifensine > fluorinated derivatives. The properties were related to the structure of these compounds and showed the importance of the nature of the substituent on the primary phenyl ring of mazindol for affinity to the dopamine transporter.

USE OF ISOINDOLES FOR THE TREATMENT OF NEUROBEHAVIORAL DISORDERS

The present invention generally relates to the use of drugs for the treatment of neurobehavioral disorders or symptoms of a neurobehavioral disorder associated with dysfunction of the trimonoamine modulating system (TMMS). More specifically, the invention describes methods for the treatment of a neurobehavioral disorder and/or treatment or prevention of symptoms of a neurobehavioral disorder by administering suitable Isoindole derivatives alone or in combination with other agents so as to provide relatively equal inhibitory effect on serotonin, dopamine and norepinephrine transporters.

Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter

A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [125I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H → 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4′,7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT Ki = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers.

Directed Lithiation of 2-Phenyl- and 2-(o-Methylphenyl)imidazoline

2-Phenyl- and 2-(o-methylphenyl)imidazoline have been converted into their ortho- and α-lithiated species, respectively, by treatment with n-BuLi-hexane in THF.Treatment of these reagents with a variety of nucleophiles gave ortho- and α-substituted products.

Preparation of imidazo[2,1-a]isoindole compounds

The present invention relates to a process for the preparation of certain known imidazo[2,1-a]isoindoles of the general formula I: STR1 wherein X represents a hydrogen atom, a halogen atom or a lower alkoxy group. The said isoindoles, which may be prepared from novel lactams, have been shown to have utility as psychic energizers and anorectics.

Imidazolinyl phenyl carbonyl compounds acid addition salts and related compounds

This invention is concerned with tetrahydropyrimidinyl phenyl carbonyl acid addition salts, imidazolinyl phenyl carbonyl acid addition salts, dihydroimidazoisoindolols, tetrahydropyrimidoisoindolols, and tetrahydropyrimidoisoindolol acid addition salts which are all pharmacologically efficacious as anti-depressants. The tetrahydropyrimidinyl phenyl carbonyl acid addition salts, the tetrahydropyrimidoisoindolols and the tetrahydropyrimidoisoindolol acid addition salts are also efficacious as diuretics while the imidazolinyl phenyl carbonyl acid addition salts and the dihydroimidazoisoindolols are efficacious as anorexiants. This invention is also concerned with several processes for the preparation of these compounds.

Anti-ulcer therapy

A method of treating gastric ulcers in a warm-blooded animal with salts of an imidazolinyl phenyl carbonyl compound or a dihydroimidazoisoindolol is disclosed.

2,3-Dihydro-5-alkoxy-5-phenyl-5H-imidazo[2,1-a]isoindoles

Novel 2[2-(1,3-diazacycloalk-2-enyl)]benzophenone compounds and novel 1,3-diazacycloalkenyl[2,1-a]isoindole compounds having useful analgesic and psychostimulant properties are prepared inter alia by condensation of o-benzoylbenzaldehydes with aliphatic diamines.

Process for imidazo isoindoles

Imidazo isoindoles, e.g. 5-(p-chlorophenyl)-5-hydroxy-2,3-dihydro-5H-imidazo[2,1a]isoindol, may be prepared by treating a corresponding 2-benzoyl benzoic acid with a substituted ethylene diamine, and treating a resulting intermediate first with concentrated acid and then with base. The products are active as anorexic agents.