15639-87-9Relevant academic research and scientific papers
Fluorinated Phenylcyclopropylamines. 1. Synthesis and Effect of Fluorine Substitution at the Cyclopropane Ring on Inhibition of Microbial Tyramine Oxidase
Yoshida, Shinichi,Meyer, Oliver G. J.,Rosen, Thomas C.,Haufe, Günter,Ye, Song,Sloan, Milton J.,Kirk, Kenneth L.
, p. 1796 - 1806 (2004)
Two series of diastereopure phenylcyclopropylamine analogues, 2-fluoro-2-phenylcyclopropylamines and 2-fluoro-2-phenylcyclopropylalkylamines, as well as 2-fluoro-1-phenylcyclopropylamines and 2-fluoro-1-phenylcyclopropylmethylamines, were synthesized in order to study the effects of fluorine substitution on monoamine oxidase inhibition. Inhibitory activity was assayed using commercially available microbial tyramine oxidase. Characterization of tyramine oxidase, carried out prior to the inhibition experiments, confirmed earlier suggestions that this enzyme is a semicarbazide-sensitive copper-containing monoamine oxidase. The most potent competitive inhibitor was trans-2-fluoro-2-phenylcyclopropylamine, which had an IC50 value 10 times lower than that of the nonfluorinated compound, tranylcypromine. 2-Fluoro-1-phenylcyclopropylmethylamine was found to be a weak noncompetitive inhibitor of tyramine oxidase. The presence of a free amino group, directly bonded to the cyclopropane ring, and a fluorine atom in a relationship cis to the amino group were structural features that increased tyramine oxidase inhibition.
Towards nitrile-substituted cyclopropanes-a slow-release protocol for safe and scalable applications of diazo acetonitrile
Hock, Katharina J.,Spitzner, Robin,Koenigs, Rene M.
supporting information, p. 2118 - 2122 (2017/07/24)
Diazo acetonitrile has long been neglected despite its high value in organic synthesis due to a high risk of explosions. Herein, we report our efforts towards the transient and safe generation of this diazo compound, its applications in iron catalyzed cyclopropanation and cyclopropenation reactions and the gram-scale synthesis of cyclopropyl nitriles.
Lewis Basic Sulfide Catalyzed Electrophilic Bromocyclization of Cyclopropylmethyl Amide
Wong, Ying-Chieh,Ke, Zhihai,Yeung, Ying-Yeung
, p. 4944 - 4947 (2015/11/03)
A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.
Selective 5-hydroxytryptamine 2c receptor agonists derived from the lead compound tranylcypromine: Identification of drugs with antidepressant-like action
Sung, Jin Cho,Jensen, Niels H.,Kurome, Toru,Kadari, Sudhakar,Manzano, Michael L.,Malberg, Jessica E.,Caldarone, Barbara,Roth, Bryan L.,Kozikowski, Alan P.
experimental part, p. 1885 - 1902 (2009/12/07)
We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2- phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted be zene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT 2A and 5-HT2B, respectively (EC50) 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.
