Synthesis and activity of 2-methyl-3-aminopropiophenones as centrally acting muscle relaxants

Shiozawa, Akira; Narita, K.; Izumi, Giichi; Kurashige, Shuji; Sakitama, Katsuhiko; Ishikawa, M.

doi:10.1016/0223-5234(96)88213-4

Cited by 21 publications

(12 citation statements)

References 15 publications

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“…[9] The use of a propiophenone, rather than an acetophenone, ultimately results in the placement of a methyl group at the 3-position of the heterocycle, which is necessary to maintain the axial chirality. [10] Treatment of 2 with of trans-benzylideneacetophenone (2 equiv) in the presence of HBF 4 ·Et 2 O gave pyrylium salt 3 as a racemic mixture, which was obtained as a yellow solid in moderate yield (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

Developing a New Class of Axial Chiral Phosphorus Ligands: Preparation and Characterization of Enantiopure Atropisomeric Phosphinines

Müller

Pidko

Staring

et al. 2008

Chemistry A European J

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Both enantiomers of the first atropisomeric phosphinine (1) have been isolated by using analytical HPLC on a chiral stationary phase. The enrichment of one enantiomer and a subsequent investigation into its racemization kinetics revealed a barrier for internal rotation of DeltaG(298)(double dagger) = (109.5+/-0.5) kJ mol(-1), which is in excellent agreement with the theoretically predicted value of DeltaG(298)(double dagger) =116 kJ mol(-1). Further analysis with UV and circular dichroism spectroscopies and density functional theory calculations led to the determination and assignment of the absolute configurations of both enantiomers. These results are the basis for future investigations into this new class of axially chiral phosphinine-based ligands and their possible applications in asymmetric homogeneous catalysis.

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Section: Resultsmentioning

confidence: 99%

Developing a New Class of Axial Chiral Phosphorus Ligands: Preparation and Characterization of Enantiopure Atropisomeric Phosphinines

Müller

Pidko

Staring

et al. 2008

Chemistry A European J

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“…1), the antidepressant and stop-smoking aid bupropion, antispasmodic agents eperisone and tolperisone, and the anorectic agent diethylpropion. Cathinones with a wide range of activities have been synthesized and some may be useful as new therapeutic agents with improved adverse effect profiles for treating depression, obesity, cocaine and nicotine addiction, and as centrally acting muscle relaxants (Carroll et al, 2009, 2010; Cozzi et al, 2005; Foley and Cozzi, 2003; Lukas et al, 2010; Nisijima et al, 1998; Shiozawa et al, 1995). Identified biological targets for cathinones include acetylcholine, serotonin, dopamine, norepinephrine, histamine, and sigma-1 receptors, voltage-gated sodium and calcium ion channels, plasma membrane transporters for serotonin, norepinephrine, and dopamine (SERT, NET, and DAT, respectively) and the vesicle monoamine transporter 2 (VMAT2) (Baumann et al, 2012; Carroll et al, 2009, 2010; Cozzi and Foley, 2003; Cozzi et al, 1999, 2005, 2007; Foley and Cozzi, 2003; Fujioka and Kuriyama, 1985; Hofer et al, 2006; Kehr et al, 2011; Kocsis et al, 2005; Slemmer et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs

Cozzi

Brandt

Daley³

et al. 2013

European Journal of Pharmacology

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Cathinones are a class of drugs used to treat various medical conditions including depression, obesity, substance abuse, and muscle spasms. Some “designer” cathinones, such as methcathinone, mephedrone, and methylone, are used nonclinically for their stimulant or entactogenic properties. Given the recent rise in nonmedical use of designer cathinones, we aimed to improve understanding of cathinone pharmacology by investigating analogs of methcathinone with a CF3 substituent at the 2-, 3-, or 4-position of the phenyl ring (TFMAPs). We compared the TFMAPs with methcathinone for effects on monoamine uptake transporter function in vitro and in vivo, and for effects on locomotor activity in rats. At the serotonin transporter (SERT), 3-TFMAP and 4–TFMAP were 10-fold more potent than methcathinone as uptake inhibitors and as releasing agents, but 2-TFMAP was both a weak uptake inhibitor and releaser. At the norepinephrine and dopamine transporters (NET and DAT), all TFMAP isomers were less potent than methcathinone as uptake inhibitors and releasers. In vivo, 4-TFMAP released 5-HT, but not dopamine, in rat nucleus accumbens and did not affect locomotor activity, whereas methcathinone increased both 5-HT and dopamine and produced locomotor stimulation. These experiments reveal that TFMAPs are substrates for the monoamine transporters and that phenyl ring substitution at the 3- or 4-position increases potency at SERT but decreases potency at NET and DAT, resulting in selectivity for SERT. The TFMAPs might have a therapeutic value for a variety of medical and psychiatric conditions and may have lower abuse liability compared to methcathinone due to their decreased DAT activity.

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“…It provides β-amino carbonyl compounds and natural products. They possess a wide range of biological applications such as diuretic 4 , antipsychotic 5 , oxytocic 6 , anticonvulsant 7 , muscle relaxant 8 , antimalarial 9,10 , antiviral 11 and anticancer 12 agents. Mannich bases when they form complexes with metal ions exhibit enhanced biological activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterisation and Biological Activity of a New Mannich Base and It’s Metal Complexes

2014

Chem Sci Trans

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Mannich bases play a major role in biological processes. In view of this a new Mannich base 1-(2,5-dioxo pyrolidin-1-yl)(4-methoxy phenyl)(methyl)thiourea (SMBTU) was synthesized using succinimide, methoxybenzaldehyde and thiourea. The complexation behaviour of this ligand with Mn(II), Ni(II), Cu(II) and Zn(II) ions were studied. The structural features of the complexes were analyzed by elemental analysis, IR, UV-Visible, 1 H, 13 C NMR spectra and magnetic susceptibility measurements. The anti microbial activity of the ligand and its complexes has been extensively studied against some of the gram-positive and gram-negative bacterium. The ligand and all the metal complexes showed antimicrobial activity.

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Synthesis and activity of 2-methyl-3-aminopropiophenones as centrally acting muscle relaxants

Cited by 21 publications

References 15 publications

Developing a New Class of Axial Chiral Phosphorus Ligands: Preparation and Characterization of Enantiopure Atropisomeric Phosphinines

Developing a New Class of Axial Chiral Phosphorus Ligands: Preparation and Characterization of Enantiopure Atropisomeric Phosphinines

Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs

Synthesis, Characterisation and Biological Activity of a New Mannich Base and It’s Metal Complexes

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