164934-44-5

Upstream product

• 7221-33-2 3-(Methylimino-methyl)-phenol 
• 100-83-4 meta-hydroxybenzaldehyde 
• 164934-29-6 3-[3-(benzyl-methyl-amino)-propoxy]-xanthen-9-one 
• 164934-34-3 3-(3-methylamino-propoxy)-xanthen-9-one 
• 164934-24-1 3-(3-chloropropoxy)xanthen-9-one 
• 874-98-6 1-bromomethyl-3-methoxybenzene 
• 41789-95-1 1-(3-methoxyphenyl)-N-methylmethanamine 
• 3722-51-8 3-hydroxyxanthen-9-one 
• 123926-62-5 N-(3-hydroxybenzyl)methylamine 
• 213891-02-2 3-(3-iodopropoxy)xanthen-9-one 
• 164934-39-8 3-{3-[(3-methoxy-benzyl)-methyl-amino]-propoxy}-xanthen-9-one 

Downstream Products

• 164934-16-1 pentyl-carbamic acid 3-({methyl-[3-(9-oxo-9H-xanthen-3-yloxy)-propyl]-amino}-methyl)-phenyl ester 

Relevant academic research and scientific papers

Acetylcholinesterase inhibitors: SAR and kinetic studies on ω-[N-methyl-N-(3-alkylcarbamoyloxyphenyl]methyl] aminoalkoxyaryl derivatives

In this work, we further investigated a class of carbamic cholinesterase inhibitors introduced in a previous paper (Rampa et al. J. Med. Chem. 1998, 41, 3976). Some new ω-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl analogues were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The structure of the lead compound (xanthostigmine) was systematically varied with the aim to optimize the different parts of the molecule. Moreover, such a structure-activity relationships (SAR) study was integrated with a kinetic analysis of the mechanism of AChE inhibition for two representative compounds. The structural modifications lead to a compound (12b) showing an IC50 value for the AChE inhibition of 0.32 ± 0.09 nM and to a group of BuChE inhibitors also active at the nanomolar level, the most potent of which (15d) was characterized by an IC50 value of 3.3 ± 0.4 nM. The kinetic analysis allowed for clarification of the role played by different molecular moieties with regard to the rate of AChE carbamoylation and the duration of inhibition. On the basis of the results presented here, it was concluded that the cholinesterase inhibitors of this class possess promising characteristics in view of a potential development as drugs for the treatment of Alzheimer's disease.

Acetylcholinesterase inhibitors: Synthesis and structure-activity relationships of ω-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives

Acetylcholinesterase (ACHE) inhibitors are one of the most actively investigated classes of compounds in the search for an effective treatment of Alzheimer's disease. This work describes the synthesis, AChE inhibitory activity, and structure-activity relationships of some compounds related to a recently discovered series of AChE inhibitors: the ω-[N-methyl-N-(3- alkylcarbamoyloxyphenyl)methyl]aminoalkoxyxanthen-9-ones. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different parts of the parent molecule, and a theoretical model of the binding of one representative compound to the enzyme was developed. The biological properties of the series were investigated in some detail by considering not only the activity on isolated enzyme but the selectivity with respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on rat cerebral cortex as well. Some of the newly synthesized derivatives, when tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a selective inhibitory activity and were more active than physostigmine. In particular, compound 13, an azaxanthone derivative, displayed the best rat cortex AChE inhibition (190-fold higher than physostigmine), as well as a high degree of enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When tested in the isolated enzyme, compound 13 was less active, suggesting some differences either in drug availability/biotransformation or in the inhibitor-sensitive residues of the enzyme when biologically positioned in rat brain membranes.

Cholinergic Agents. Synthesis and Acetylcholinesterase Inhibitory Activity of Some ω-[N-Methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyxanthen-9-ones

A series of ω-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyxanthen-9-ones was prepared. The alkoxy chain occupies, alternatively, the positions 2, 3 and 4 of the xanthone moiety and has a variable length. The compounds were evaluated for acetylcholinesterase inhibitory activity. Some in this series were revealed to be more potent than physostigmine. Optimum activity was found with the 3 position and with a four or three carbon chain length separating the benzylamino group from the xanthenonyloxy moiety.