923035-06-7Relevant academic research and scientific papers
A karbala sandbank chiral intermediate and its preparation method
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, (2017/04/11)
The invention discloses a chiral intermediate of rivastigmine, and a preparation method thereof. The preparation method comprises the steps of preparing 3-[1-(methyllamino)ethyl]phenol through reacting a raw material of 3-hydroxyacetophenone with an methylamine water solution to form an imine and reducing the imine; carrying out resolution by using a chiral reagent to obtain a novel intermediate of (s)-3-[1-(methyllamino)ethyl]phenol of rivastigmine; and further loading methyl on basis of the intermediate to obtain an important intermediate of (S)-3-[1-(dimethyllamino)ethyl]phenol. Compared with a conventional synthetic method of (s)-rivastigmine, the preparation method provided by the invention has high resolution rate, low cost and small load for treatment of three wastes, has little pollution to an environment, and is beneficial to large-scale production.
Phenyl ether- and aniline-containing 2-aminoquinolines as potent and selective inhibitors of neuronal nitric oxide synthase
Cinelli, Maris A.,Li, Huiying,Pensa, Anthony V.,Kang, Soosung,Roman, Linda J.,Martásek, Pavel,Poulos, Thomas L.,Silverman, Richard B.
, p. 8694 - 8712 (2015/11/25)
Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.
METHOD OF OBTAINING PHENYL CARBAMATES
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Page/Page column 13, (2008/12/06)
The invention relates to a method of obtaining phenyl carbamates (I), wherein R 1 is lower alkyl C 1 -C 5 or benzyl and R 2 is methyl, ethyl or propyl, consisting in reacting L-(S)-3-[(1-methylamino)ethyl]phenol, in the presence of a base, with a carbamoyl halide in order to obtain an intermediate and, subsequently, subjecting said intermediate to a reducing amination reaction or a methylation reaction by reacting same with a methyl halide. The above-mentioned compounds (I) include rivastigmine, a compound that inhibits cholinesterase in the central nervous system, and can be used in the treatment of neurodegenerative diseases (E.g. senile dementia and Alzheimer's disease).
IMPROVED PROCESS FOR THE PREPARATION OF RIVASTIGMINE
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Page/Page column 8, (2008/06/13)
The present invention relates to an improved process for preparation of Rivastigmine of formula (I) or pharmaceutically acceptable salts thereof comprising a step of N-methylation of compound of formula (III), wherein R1 = R2 = H or R1 = H and R2 = CH3 or an acid addition salt thereof, using paraformaldehyde in the presence of Raney Nickel and hydrogen in a suitable solvent to obtain compound of formula (II).
Process for the preparation of Rivastigmine
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Page/Page column 4-5, (2010/11/30)
The present invention relates to an improved process for preparation of Rivastigmine of formula (I) or pharmaceutically acceptable salts thereof comprising a step of N-methylation of compound of formula (III), wherein R1=R2=H or R1=H and R2=CH3 or an acid addition salt thereof, using paraformaldehyde in the presence of Raney Nickel and hydrogen in a suitable solvent to obtain compound of formula (II).
