28797-61-7

Usage

Uses

Used in Pharmaceutical Industry:
Pirenzepine is used as a therapeutic agent for the treatment of peptic ulcers. It functions by reducing gastric acid secretion, which helps to alleviate the symptoms and promote healing of ulcers. Additionally, it reduces muscle spasm, providing relief from discomfort associated with gastrointestinal disorders.
Used in Antifungal Applications:
Pirenzepine is also utilized as an antifungal agent, demonstrating effectiveness against various fungal infections. Its ability to target specific receptors and modulate their activity contributes to its antifungal properties, making it a valuable component in the development of treatments for fungal diseases.

Originator

Microsules Bernabo, Microsules Bernabo

Manufacturing Process

48.4 g of 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepin-6-one were refluxed in 900 ml of absolute dioxane for 15 minutes. Thereafter, over a period of 45 minutes, 28 ml of chloroacetyl chloride and 52 ml of triethylamine were simultaneously added dropwise to the mixture. The mixture was refluxed for eight hours and then vacuum-filtered after having cooled. The filtrate was evaporated in vacuum. The crystalline residue was recrystallized from acetonitrile in the presence of activated charcoal. MP: 212°-213°C (with decomposition). Yield: 85% of theory.A mixture of 67.5 g of 11-chloroacetyl-5,11-dihydro-6H-pyrido[2,3b][1,4]benzodiazepin-6-one, 183 ml of N-methylpiperazine and 1.37 liters of absolute benzene was refluxed for 18 hours. Thereafter, the crystalline precipitate was vacuum filtered off, dissolved in aqueous 20% hydrochloric acid, the solution was evaporated in vacuum, the crystalline residue wasdissolved in 250 ml of water while heating, the solution was admixed with 150 ml of isopropanol and active charcoal, filtered, and 2.5 liters of isopropanol were added to the filtrate. After cooling, the precipitate was vacuum filtered off, yielding 70% of theory of the 5,11-dihydro-11-[(4'-methyl-1'-piperazinyl)acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one dihydrochloride, M.P. 257259°C (decomp.).The free base of pirenzepine, obtained from the dihydrochloride by making an aqueous solution thereof alkaline with dilute sodium hydroxide and extracting it with chloroform, had MP: 226°-228°C after recrystallization from methanol/ether.

Therapeutic Function

Antiulcer, Antiemetic

Biological Activity

M 1 muscarinic receptor selective antagonist. Inverse agonist activity reported.

Enzyme inhibitor

This hygroscopic antiulcerative (FWfree-base = 351.41 g/mol; CAS 28797-61- 7) is a gastric acid inhibitor and selective M1 muscarinic receptor antagonist, and the antisecretory properties of pirenzepine on gastric acid and pepsin secretion may be attributed to this antagonistic activity on muscarinic M1 receptors.

InChI:InChI=1/C19H21N5O2/c1-22-9-11-23(12-10-22)13-17(25)24-16-7-3-2-5-14(16)19(26)21-15-6-4-8-20-18(15)24/h2-8H,9-13H2,1H3,(H,21,26)/p+2

Upstream product

• 109-01-3 1-methyl-piperazine 
• 956-30-9 2-amino-N-(2-chloropyridin-3-yl)benzamide 
• 54245-42-0 [11C]methyl iodide 
• 63257-31-8 N-Demethyl-Pirenzepin 
• 28797-48-0 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one 
• 84772-30-5 3-(2'-aminobenzoyl)aminopiperidin-2-one 
• 84772-31-6 2,3,4,4a,5,11-hexahydro-6H-pyrido<2,3-b><1,4>benzodiazepin-6-one 
• 118-48-9 isatoic anhydride 
• 1892-22-4 3-aminopiperidin-2-one 
• 885-70-1 5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one 
• 84446-19-5 1-oxo-11-(2'-chloroacetyl)-5,11-dihydro-6H-pyrido<2,3-b><1,4>benzodiazepin-6-one 
• 84446-15-1 3-(2'-bromobenzoyl)amino-2-chloropyridine 1-oxide 
• 84446-16-2 3-(2'-chlorobenzoyl)amino-2-chloropyridine 1-oxide 
• 88369-72-6 3-(2'-aminobenzoyl)amino-2-chloropyridine 1-oxide 

Relevant academic research and scientific papers

Enhanced arecoline derivatives as muscarinic acetylcholine receptor M1 ligands for potential application as PET radiotracers

Supported by their involvement in many neurodegenerative disorders, muscarinic acetylcholine receptors (mAChRs) are an interesting target for PET imaging. Nevertheless, no radiotracer is established in clinical routine. Within this work we aim to develop novel PET tracers based on the structure of arecoline. Fifteen novel arecoline derivatives were synthesized, characterized and tested for their affinity to the mAChRs M1-M5 and the conceivable off-target acetylcholinesterase. Five arecoline derivatives and arecoline were labeled with carbon-11 in good yields. Arecaidine diphenylmethyl ester (3b), arecaidine bis(4-fluorophenyl)methyl ester (3c) and arecaidine (4-bromophenyl)(4-fluorophenyl)methyl ester (3e) showed a tremendous gain in mAChR affinity compared to arecoline and a pronounced subtype selectivity for M1. Metabolic stability and serum protein binding of [11C]3b and [11C]3c were in line with properties of established brain tracers. Nonspecific binding of [11C]3c was prevalent in kinetic and endpoint experiment on living cells as well as in autoradiography on native mouse brain sections, which motivates us to decrease the lipophilicity of this substance class prior to in vivo experiments.

Unexpected Formation of a 11H-Pyridoquinazolin-11-one Derivative from 5,11-Dihydro-6H-pyrido-1,4-benzodiazepin-6-one

The unexpected formation of 11H-pyridoquinazolin-11-one derivative 6 from 5,11-dihydro-6H-pyrido-1,4-benzodiazepin-6-one (2) has been observed.Its structure 6 was determined by X-ray crystallography.Detailed nmr study provided a complete set of proton and carbon-13 nmr parameters of compound 6 in solution.

EXPERIMENTAL ANTIULCER AGENTS: N-SUBSTITUTED 2-(4-METHYL-1-PIPERAZINYL)ACETAMIDES AS PIRENZEPINE MODELS AND SOME RELATED COMPOUNDS

Reactions of N-cyclohexyl-2-chloroacetamide, N-phenyl-2-chloroacetamide, N-(4-dimethylaminophenyl)-2-chloroacetamide, N-(2-nitrophenyl)-N-phenyl-2-chloroacetamide, its 3-nitrophenyl and 4-nitrophenyl analogues, N-(2-benzylphenyl)-2-chloroacetamide, 5-(chloroacetyl)dibenzazepine, and its 10,11-dihydro derivative with piperazine, 1-methylpiperazine, 2-(1-piperazinyl)ethanol, and 3-(1-piperazinyl)propanol resulted in compounds II, III, V -XV, XVIII, XXI, and XXIII, simple analogues of the antiulcer agent pirenzepine (I).Contributions to the syntheses and characterization of mianserin (XIX), bisnor analogue of imipramine (XXV), and pirenzepine (I) are presented.Two 2-aryl-2-(2-pyridyl)thioacetamides XXXVIII and XL were synthesized via nitriles XXXIX and XLI.Compounds XI (VUFB-17 104) and XXI (VUFB-17 113) were found to be rather effective as anti-ulcer agents and anticholinergics.

New Synthesis of 11-Acyl-5,11-dihydro-6H-pyridobenzodiazepin-6-ones and Related Studies

New synthesis of 11-acyl-5,11-dihydro-6H-pyridobenzodiazepin-6-ones (42-44) is reported.The crucial steps (Scheme VI) represented N-oxidation of 1 (1A) to 35 (35A), facilitated ring-closure of 36 into 37, its subsequent N-α-chloroacetylation to 38, aminolysis to 39-41 (involving N-O anchimeric assistance as depicted in 38A) and deoxygenation to 42-44 (Scheme VII).The central intermediate 37 is also obtained on oxygenation of 2, a new synthesis of which was reported in the previous paper of this series .Other attempts of cyclisation "from the top" or "from the bottom" (Scheme I) are described.Thus, interaction of 1 with acetamide afforded 3 and 4 instead of the expected 2A.Compound 5 cyclised into 3-pyridoquinazolone 6 while its 2-(4'-methylpiperazin-1'-yl) analogue 9 was observed to be unstable for the attempted ring-opening and reclosure to 42. "From the bottom" cyclisations of 10A-10C, via intermediary amines 11A-11C failed and pyridoquinazolinone 13 was isolated (Scheme V).The attempted oxidative cyclisation of the compounds 15 and 18 into 2 and 42, respectively, 13 afforded imidazolopyridine derivative (18-19), while 15 remained unchanged. 3-Acylamino-2-arylaminopyridines (21-24), cyclised into the imidazolopyridines 29-30.Model compounds 45-50 were prepared to study selective aminolysis of the chlorine atoms in 2-chloro-3-(2'-chlorobenzoyl)aminopyridine 1, and its N-oxide 35.