- Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides
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The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.
- Lebel, Hélène,Mathieu, Gary,Patel, Heena
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p. 2157 - 2168
(2020/11/23)
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- Tetrabenazine intermediate as well as synthesis method and application thereof as, well as intermediate product for synthesis (by machine translation)
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The invention belongs to, the field of drug synthesis, and particularly relates to a butanaphenazine, intermediate and a synthesis method, thereof, as well as a synthesis: method 3,4 - thereof; and, 6,7 . (by machine translation)
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- NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the role of lysosomes in signaling apoptosis and LPS-induced inflammation
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Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH-dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus.
- Blaess, Markus,Bibak, Nelly,Claus, Ralf A.,Kohl, Matthias,Bonaterra, Gabriel A.,Kinscherf, Ralf,Laufer, Stefan,Deigner, Hans-Peter
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- Design, synthesis, and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists
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The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype-selective antagonists for the nAChRs and thereby probe the potential of using these natural products as scaffolds for further ligand optimization. The most selective and potent nAChR ligand to come from the series, 6,7-dimethoxy-2- methyl-1,2,3,4-tetrahydroisoquinoline (3c) (also a natural product by the name of O-methylcorypalline), displayed submicromolar binding affinity toward the α4β2 nAChR with more than 300-fold selectivity over α4β4, α3β4, and α7. Furthermore, this lead structure (which also has inhibitory activity at monoamine oxidases A and B and at the serotonin and norepinephrine transporters) showed antidepressant-like effect in the mouse forced swim test at 30 mg/kg.
- Crestey, Fran?ois,Jensen, Anders A.,Borch, Morten,Andreasen, Jesper Tobias,Andersen, Jacob,Balle, Thomas,Kristensen, Jesper Langgaard
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supporting information
p. 9673 - 9682
(2014/01/06)
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- One-pot anti-markovnikov hydroamination of unactivated alkenes by hydrozirconation and amination
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A one-pot anti-Markovnikov hydroamination of alkenes is reported. The synthesis of primary and secondary amines from unactivated olefins was accomplished in the presence of a variety of functional groups. Hydrozirconation, followed by amination with nitrogen electrophiles, provides exclusive anti-Markovnikov selectivity. Most products are isolated in high yields without the use of column chromatography.
- Strom, Alexandra E.,Hartwig, John F.
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p. 8909 - 8914
(2013/09/24)
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- PROCESS FOR PREPARING N-METHYL-3, 4-DIMETHOXYPHENYLETHYLAMINE
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Provided are intermediates useful for the preparation of verapamil and methods for their preparation.
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Page/Page column 6
(2009/07/17)
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- Amine derivatives, processes for producing them and a use of them as antiarrhythmic drugs
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PCT No. PCT/JP95/01138 Sec. 371 Date May 27, 1997 Sec. 102(e) Date May 27, 1997 PCT Filed Jun. 7, 1995 PCT Pub. No. WO96/04231 PCT Pub. Date Feb. 15, 1996Novel amine derivatives of the following general formula (I): (wherein) A may denote -(CH2)-O-, -(CH2)2-O-, or -(CH2)2-NH-; B may denote -(CH2)2-; R1 may denote a hydrogen atom, a halogen atom, a nitro group, a 1-pyrrolyl group, an acetamido group, an amino group or a dimethylamino group; R2 may denote a hydrogen atom or a nitro group; R3 and R4 may denote a hydrogen atom; R8a and R8b which are the same may denote a chlorine atom or a methoxy group; R9 may denote a hydrogen atom or an amino group; R may denote a methyl group; and X may denote a methanesulfonamido group, a 1-imidazolyl group or a nitro group or a salts thereof are useful as antiarrhythmic drugs.
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- Pharmaceutical piperazine compounds
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A piperazinedione of general formula (I): STR1 wherein R 1 is selected from hydrogen;a group of formula --(NH) t --COR 3 wherein t is 0 or 1 and R 3 is an organic substituent as defined herein;a group of formula (D): STR2 and a group of formula (E): STR3 and the pharmaceutically acceptable salts thereof are useful as modulators of multi-drug resistance.
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- Process for producing N-methyl-2(3,4 dimethoxyphenyl)-ethylamine
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A process for preparing N-methyl-2-(3,4-dimethoxyphenyl)-ethylamine comprises hydrogenating 3,4-dimethoxyphenylacetonitrile with a methylamine of the general formula I STR1 where R1 is hydrogen, benzyl or tert-butyl, and hydrogen in the presence of a supported catalyst which comprises from 0.05 to 50% by weight of copper chromite, copper, silver, gold, iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum or mixtures thereof, in the presence or absence of water at from 20° to 200° C. under from 1 to 300 bar.
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- Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides
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A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the CHRC/5 cell line.Among them the acridone derivatives were the most potent.A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain.Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone.On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy-9-oxo-N-phenyl>-4-acridinecarboxamide (84) has been selected for further development.
- Dodic, Nerina,Dumaitre, Bernard,Daugan, Alain,Pianetti, Pascal
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p. 2418 - 2426
(2007/10/02)
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- SUBSTITUTED 1-(2-THIENYL)CYCLOHEXYLAMINES AND RELATED COMPOUNDS AS POTENTIAL NMDA ANTAGONISTS
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Reactions of bisulfite addition compounds prepared in situ from cyclohexanone or 3,4,5,6-tetrahydro-2H-thiopyran-3-one with potassium cyanide and corresponding amines resulted with high yields in amino nitriles type of V and VI.These compounds were subjected to reactions with 2-thienylmagnesium bromide and in the case of the amino nitriles Vc and Vf with 5-bromo-2-thienylmagnesium bromide.Only in the case of compound Vf, a by-product X was isolated in addition to the desired 1-piperidine (VIIf).Compound VIIf was used for the synthesis of the carboxylic acid XI.The compounds prepared were tested by some methods of biochemical and behavioural pharmacology.
- Sindelar, Karel,Dobrovsky, Karel,Krejci, Ivan,Polivka, Zdenek
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p. 894 - 902
(2007/10/02)
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- Intramolecular Acylolysis of Amide Derivatives of Kemp's Triacid: Strain Effects and Reaction Rates
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Intramolecular acylolysis of comparable secondary and tertiary amide derivatives of Kemp's triacid, 4, and its cis,trans isomer 5 has been examined.For both triacids, the tertiary amide derivatives undergo acylolysis about 1000 times faster than the corresponding secondary amide.Also, amide derivatives of Kemp's triacid undergo acylolysis about 100 times faster than the corresponding amide derivatives of the cis,trans isomer.Thus, acylolysis rates spanning a range of nearly 1E6 are observed.It is proposed that the large rate difference between secondary and tertiary amides in these molecules results from greater pseudoallylic (pseudo-A1,3) strain associated with the tertiary amides.It also is proposed that the slower acylolysis rates observed with amide derivatives of the cis,trans isomer of Kemp's triacid result from greater 1,3-diaxial strain associated with acylolysis of these compounds.The data show that both the structure of the triacid and the structure of the amide have a direct effect on the acylolysis rate.Because previous studies only focused on the structure of the triacid, the proposal that intramolecular acylolysis of amide derivatives of Kemp's triacid is a useful model system for studying enzyme catalysis (Menger, F.M.; Ladika, M.J.Am.Chem.Soc. 1988, 110, 6794.Menger, F.M.Biochemistry 1992, 31, 5368) is reexamined.
- Curran, Timothy P.,Borysenko, Christopher W.,Abelleira, Susan M.,Messier, Renee J.
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p. 3522 - 3529
(2007/10/02)
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- Novel N-[4-(aminosubstituted)phenyl]methanesulfonamides and their use as cardiovascular agents
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Novel N-[4-(aminosubstituted)phenyl]methanesulfonamides and their use as cardiovascular agents, especially as antiarrhythmic agents are described. Pharmaceutical formulations containing such compounds are also discussed.
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- Compounds having calcium blocking activity
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Compound of general formula I STR1 and its addition salts with a pharmaceutically acceptable acid is described. The compound is prepared by reacting bis-(2-(3,4-dimethoxy-phenyl)ethyl)amine with formaldehyde in a reducing medium. The compound is effective in the treatment of cardiovascular diseases and disturbances in cerebral circulation.
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- Effects of 3,4 dimethoxyphenethylamine derivatives on monoamine oxidase
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The cactus alkaloid 3,4 dimethoxyphenethylamine and its naturally occurring N methylated homologs inhibited the deamination of tyramine and tryptamine by rat brain monoamine oxidase. In contrast, the β hydroxylated derivatives of this series failed to inh
- Keller,Ferguson
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p. 1048 - 1050
(2007/10/05)
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