Linopirdine

Base Information

• Chemical Name: Linopirdine
• CAS No.: 105431-72-9
• Molecular Formula: C26H21 N3 O
• Molecular Weight: 391.472
• Hs Code.: 2933790090
• UNII: I5TB3NZ94T
• DSSTox Substance ID: DTXSID6045163
• Nikkaji Number: J399.573I
• Wikipedia: Linopirdine
• Wikidata: Q6554730
• NCI Thesaurus Code: C82306
• Pharos Ligand ID: D5LDVLDUNMFY
• Metabolomics Workbench ID: 67466
• ChEMBL ID: CHEMBL319111
• Mol file: 105431-72-9.mol

Synonyms:3,3-bis(4-pyridylmethyl)-1-phenylindolin-2-one;3,3-dipyridylmethyl-1-phenyl-2-indolinone;DuP 996;DuP-996;linopirdine

Chemical Property of Linopirdine

Chemical Property:

• Vapor Pressure: 4.45E-17mmHg at 25°C
• Melting Point: 186-186.5 °C
• Boiling Point: 655.9 ºC at 760 mmHg
• PKA: 6.01±0.10(Predicted)
• Flash Point: 350.5 ºC
• PSA: 46.09000
• Density: 1.255 g/cm³
• LogP: 4.94310
• Storage Temp.: Desiccate at RT
• Solubility.: DMSO: >10mg/mL
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 391.168462302
• Heavy Atom Count: 30
• Complexity: 555

Purity/Quality:

98%Min ^*data from raw suppliers

Linopirdine dihydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC=C(C=C1)N2C3=CC=CC=C3C(C2=O)(CC4=CC=NC=C4)CC5=CC=NC=C5
• Description: Linopirdine is an enhancer of the stimulus-evoked but not basal release of several neurotransmitters, including acetylcholine, dopamine, serotonin, and glutamate. It increases acetylcholine release in rat hippocampal CA1 neurons by blocking voltage-gated, calcium-activated and leak (M-type; Kv7.2/7.3; KCNQ2/3) K+ current with an IC50 value of 2.4 μM. Inhibition of M-channels is reported to result in the depolarization of CA3 pyramidal neurons and activated presynaptic voltage-gated P/Q- and N-type calcium channels, which leads to Ca2+ influx and increased neurotransmitter release. Linopirdine has been shown to produce a number of effects including EEG patterns of enhanced vigilance, induction of c-fos expression in cerebral cortex, reduction of the increase of cerebral glucose utilization induced by hypoxia, and improved performance in animal models of learning and memory. Linopirdine has also been identified as an agonist of transient receptor potential vanilloid type 1 (EC50 = 115 μM in HEK293 cells voltage clamped at -60 mV).
• Uses: Alzheimer’s disease treatment (cognition enhancer).

Technology Process of Linopirdine

There total 12 articles about Linopirdine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 90.0%

1,3-dihydro-3-(4-pyridinylmethylene)-1-phenyl-2H-indole-2-one (154479-63-7) → linopirdine (105431-72-9)

Guidance literature:

With sodium hydroxide; In methanol; water;

Reference yield: 90.0%

1-phenyl-1,3-dihydro-indol-2-one (3335-98-6) + 4-picolylchloride hydrochloride (1822-51-1) → linopirdine (105431-72-9)

Guidance literature:

With potassium fluoride on basic alumina; for 0.05h; microwave irradiation;

DOI:10.1081/SCC-120023425

Reference yield: 76.0%

4-(bromomethyl)pyridine (54751-01-8) + methyl (2-nitrophenyl)acetate (30095-98-8) + phenylboronic acid (98-80-6) → linopirdine (105431-72-9)

Guidance literature:

methyl (2-nitrophenyl)acetate; phenylboronic acid; With diphenylsilane; at 120 ℃; for 4h;

With sodium hydride; In mineral oil; at 0 ℃; for 0.333333h;

4-(bromomethyl)pyridine; In N,N-dimethyl-formamide; toluene; mineral oil; at 50 ℃; for 6.5h;

DOI:10.1002/anie.201914851

upstream raw materials:

4-picolylchloride hydrochloride

1,3-dihydro-1-phenyl-3-(4-pyridinylmethyl)-2H-indol-2-one

1-phenyl-1,3-dihydro-indol-2-one

1-phenyl-indole-2,3-dione

Refernces

• 1、 Li, Gen,Luzung, Michael R.,Nykaza, Trevor V.,Radosevich, Alexander T.,Yang, Junyu. "PIII/PV=O Catalyzed Cascade Synthesis of N-Functionalized Azaheterocycles". supporting information. p. 4505 - 4510. Retrieved 2020/02/05.
• 2、 Bryant III,Huhn,Hensen,Pierce,Stammbach. "A large scale preparation of the cognitive enhancer linopirdine". . p. 1617 - 1625. Retrieved 2007/10/02.