101246-66-6

Basic information

• Product Name: PHENSERINE
• Synonyms: (3as-cis)-amate(ester;3-b)indol-5-ol,1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-pyrrolo(phenylcarb;(-)-N-PHENYLCARBAMOYLESEROLINE;PHENSERINE;(3aS,8aR)-1,2,3,3a,8,8a-Hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-ol5-(N-phenylcarbamate);1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-pyrrolo[2,3-b]indol-5-ol phenylcarbamate (ester)
• CAS NO: 101246-66-6
• Molecular Formula: C₂₀H₂₃N₃O₂
• Molecular Weight: 337.42
• Mol File: 101246-66-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 151-152 °C
• Boiling Point: 468.7°Cat760mmHg
• Flash Point: 237.3°C
• Appearance: off-white/
• Density: 1.228g/cm³
• Vapor Pressure: 5.85E-09mmHg at 25°C
• Refractive Index: 1.633
• Storage Temp.: 2-8°C
• Solubility: H2O:
• PKA: 13.05±0.70(Predicted)
• CAS DataBase Reference: PHENSERINE(CAS DataBase Reference)
• NIST Chemistry Reference: PHENSERINE(101246-66-6)
• EPA Substance Registry System: PHENSERINE(101246-66-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• RTECS: UY8586000
• Hazardous Substances Data: 101246-66-6(Hazardous Substances Data)

Usage

Uses

Phenserine is inhibitor of amyloid precursor protein (APP). Used in Alzheimer’s treatments.

Biological Activity

Physostigmine analog that inhibits acetylcholinesterase. Inhibits production of amyloid precursor protein (APP) and A β . Improves morris water maze performance of scopolamine-treated rats.

Enzyme inhibitor

This long-acting AChE inhibitor and A?42-lowering agent (FW = 337,42 g/mol; CAS 101246-66-6), also known as (–) -N-phenylcarbamoyl eseroline, is a carbamate analogue of eserine (or physostigmine) that inhibits acetylcholinesterase and is under active investigation for its potential in cholinomimetic therapy to reduce cognitive impairments associated with aging and Alzheimer's Disease. Phenserine is a potent and highly selective AChE inhibitor (IC50 = 22 nM), displaying 70x greater inhibitory action than observed with butyrylcholinesterase, or BChE (IC50 = 1560 nM), both in vitro and in clinical trials for treatment of Alzheimer's disease (1-5). Compared to physostigmine and tacrine, phenserine appears to be less toxic and robustly enhances cognition in animal models. In rats, phenserine achieves maximum acetylcholinesterase inhibition of 73.5% at 5 min, maintaining high and relatively constant inhibition for >8 hours. Phenserine decreased the levels of secreted b-amyloid precursor protein (b- APP) in the cerebrospinal fluid (CSF) of forebrain cholinergic system- lesioned rats, whereas DFP, a relatively non-specific cholinesterase inhibitor, failed to affect CSF levels of secreted b-APP. Such findings suggest that phenserine alters the induction of cortical b-APP mRNAs and increased levels of secreted b-APP in the CSF. Phenserine reduces Ab levels by regulating b-APP translation via a recently described iron regulatory element in the 5'-untranslated region of b-APP mRNA that was previously shown to be up-regulated in the presence of interleukin-1. Other dual AChE/A?42 inhibitors include: rivastigmine, ladostigil, asenapine, phenserine, amitriptyline, clomipramine, doxepin and desipramine. Posiphen, the better-tolerated (+) -enantiomer of phenserine, is devoid of anticholinesterase action, but represses translation of neural α- synuclein, a druggable target in the treatment of Parkinson Disease.

InChI:InChI=1/C20H23N3O2/c1-20-11-12-22(2)18(20)23(3)17-10-9-15(13-16(17)20)25-19(24)21-14-7-5-4-6-8-14/h4-10,13,18H,11-12H2,1-3H3,(H,21,24)/t18-,20+/m1/s1

Upstream product

• 103-71-9 phenyl isocyanate 
• 469-22-7 eseroline 
• 153109-52-5 (3S)-(5-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetaldehyde 
• 65166-97-4 (-)-esermethole 
• 799561-30-1 C₂₆H₃₂N₂O₆ 
• 799561-17-4 (3S)-5-methoxy-3-[((4S,5S)-5-{[(3S)-5-methoxy-1,3-dimethyl-2-oxo-1,3-dihydro-2H-indol-3-yl]methyl}-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1,3-dimethyl-1,3-dihydro-2H-indol-2-one 
• 2555-05-7 3-methyl-2-pyrrolidinone 
• 1238046-59-7 C₇H₁₃NO₃ 
• 70354-71-1 (+/-)-eseroline 
• 2731-01-3 (±)-5-methoxy-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indole 
• 1094042-30-4 (S)-3-iodomethyl-5-methoxy-1,3-dimethylindolin-2-one 
• 131101-13-8 (5-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetonitrile 
• 104069-11-6 (3aS,8aR)-5-methoxy-3a,8-dimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole 

Downstream Products

• 1239457-15-8 Br^(1-)*C₂₁H₂₆N₃O₂⁽¹⁺⁾ 

Relevant articles and documents

Nickel-Catalyzed Enantioselective Carbamoyl Iodination: A Surrogate for Carbamoyl Iodides

This work reports the enantioselective formal transfer of a carbamoyl iodide across a 1,1-disubstituted styrene using Ni-catalysis. Employing an air-stable Ni(II) precatalyst and a commercially available chiral ligand ((S)-tBuPHOX), enantioenriched 3,3-disubstituted iodooxindoles were obtained in up to 90% yield and up to 97:3 e.r. This methodology was applied to the total synthesis of (-)-esermethole and (-)-phenserine.

Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities

A series of physostigmine analogues were prepared and evaluated for cholinesterase inhibition activities, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of them showed potent inhibition activities against AChE, in which compound 17 especially exhibited significantly higher selectivity over BChE than phenserine, a compound currently on clinical trial. Discussion about the relationships between structure and activity of these derivatives was also presented.

Method for treating cognitive disorders with phenserine

An improved method of cholinomimetic therapy for cognitive impairments associated with aging and Alzheimer's disease comprising treating a patient with an effective amount of phenserine or a pharmaceutically acceptable salt and derivatives.