61192-50-5

Usage

Chemical compound

5-hydroxy-1-methyl-5-pyridin-3-yl-pyrrolidin-2-one

Molecular structure

Contains a pyrrolidone ring, a pyridine ring, and a hydroxyl group

Derived from

Neurotransmitter dopamine

Commonly found in

Dopamine receptor agonists

Therapeutic potential

Studied for potential effects on neurodegenerative diseases and Parkinson's disease

Application

Potential development of new medications for neurological disorders due to its interaction with dopamine receptors

InChI:InChI=1/C10H12N2O2/c1-12-9(13)4-5-10(12,14)8-3-2-6-11-7-8/h2-3,6-7,14H,4-5H2,1H3/t10-/m1/s1

Upstream product

• 230308-26-6 2-acetoxy-1-methyl-5-(3-pyridyl)pyrrole 
• 626-55-1 3-Bromopyridine 
• 1121-07-9 N-methylsuccinimide 
• 61192-47-0 methyl 4-oxo-4-(pyridin-3-yl)butyrate 
• 4192-31-8 4-oxo-4-(pyridin-3-yl)butanoic acid 
• 593-51-1 methylamine hydrochloride 
• 500-22-1 3-pyridinecarboxaldehyde 
• 74093-56-4 (S)-3,3-dibromocotinine 
• 75919-07-2 (R,S)-1-methyl-5-(3'-pyridyl)-5-methoxypyrrolin-2-one 
• 230308-22-2 1-methyl-5-methoxy-5-(3-pyridyl)-2-pyrrolidinone 
• 122745-79-3 5-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one 
• 15569-85-4 cotinine 

Downstream Products

• 713-05-3 4-(3-pyridyl)-4-oxo-N-methylbutyramide 

Relevant academic research and scientific papers

Rapid and one-pot synthesis of tri- to tetradeca-deutero nicotines

A very rapid one-pot synthesis of (±)-nicotine and tri- to tetradeca-deuterated nicotines is described where the synthetic sequence requires less than 4 h.

Evaluation of Nitrosamide Formation in the Cytochrome P450-Mediated Metabolism of Tobacco-Specific Nitrosamines

N′-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are carcinogenic tobacco-specific nitrosamines believed to play a vital role in the initiation of tobacco-related cancers. For their carcinogenicities to be exhibited, both NNN and NNK must be metabolically activated by cytochrome P450s, specifically P450 2A6 and P450 2A13, respectively. Prior research has focused on α-hydroxylation, which leads to the formation of several DNA adducts that have been identified and quantified in vivo. However, some studies indicate that P450s can retain substrates within their active sites and perform processive oxidation. For nitrosamines, this would oxidize the highly unstable α-hydroxynitrosamines to potentially more stable nitrosamides, which could also alkylate DNA. Thus, we hypothesized that both NNN and NNK are processively oxidized in vitro to nitrosamides by P450 2A6 and P450 2A13, respectively. To test this hypothesis, we synthesized the NNN- and NNK-derived nitrosamides, determined their half-lives at pH 7.4 and 37 °C, and monitored for nitrosamide formation in an in vitro P450 system with product analysis by LC/NSI+-HRMS/MS. Half-lives of the nitrosamides were determined by HPLC-UV and ranged from 7-35 min, which is more than 40 times longer than the corresponding α-hydroxynitrosamines. Incubation of NNN in the P450 2A6 system resulted in the formation of the nitrosamide N′-nitrosonorcotinine (NNC) at low levels. Similarly, the nitrosamide 4-(methylnitrosamino)-1-(3-pyridyl)-1,4-butanedione (CH2-oxo-NNK) was detected in low amounts in the incubation of NNK with the P450 2A13 system. The other possible NNK-derived nitrosamide, 4-(nitrosoformamido)-1-(3-pyridyl)-1-butanone (CH3-oxo-NNK), was not observed in the P450 2A13 reactions. CH2-oxo-NNK readily formed O6meGua in reactions with dGuo and calf thymus DNA. These results demonstrate that NNC and CH2-oxo-NNK are novel metabolites of NNN and NNK, respectively. Though low-forming, their increased stability may allow for mutagenic DNA damage in vivo. More broadly, this study provides the first account of a cytochrome P450-mediated conversion of nitrosamines to nitrosamides, which warrants further studies to determine how general this phenomenon is in nitrosamine metabolism.

Studies on the pyrrolinone metabolites derived from the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (β-nicotyrine)

Previous studies have established that the tobacco alkaloid 1-methyl-2- (3-pyridyl)pyrrole (β-nicotyrine) is biotransformed by rabbit lung and liver microsomal preparations to an equilibrium mixture of the corresponding 3- and 4-pyrrolin-2-ones. Autoxidation of these pyrrolin-2-ones generates the chemically stable 5-hydroxy-5-(3-pyridinyl)-3-pyrrolin-2-one. This paper summarizes efforts to document more completely the pathway leading to this hydroxypyrrolinone. Chemical and spectroscopic evidence implicates the 2- hydroxy-1-methyl-5-(3-pyridinyl)pyrrole (2-hydroxy-β-nicotyrine) as the key intermediate in this reaction pathway. Of potential toxicological interest is the detection of radical species derived from the autoxidation of this compound.

METABOLIC STUDIES WITH MODEL CYTOCHROME p-450 SYSTEMS

The biomimetic potential of metalloporphyrin catalysts has been studied using nicotine as the substrate.Results indicate the formation of products identical to those obtained from in vivo metabolism.