928054-81-3Relevant articles and documents
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.
Synthesis of high enantiomeric purity gem-dihalocyclopropane derivatives from biotransformations of nitriles and amides
Wang, Mei-Xiang,Feng, Guo-Qiang,Zheng, Qi-Yu
, p. 347 - 354 (2007/10/03)
Enantioselective biotransformations of geminally dihalogenated cyclopropanecarbonitriles and amides are described. Both the reaction rate and enantioselectivity of the nitrile hydratase and amidase involved in Rhodococcus sp. AJ270 microbial cells are strongly governed by the nature of gem-disubstituents on the cyclopropane ring; the amidase generally exhibits steric dependence on the substituents while both the steric and electronic factors of the substituents may affect the action of the nitrile hydratase. The match of steric bulkiness of the substituents at 2- with that at 3-positions on the cyclopropane ring benefits the efficient and highly enantioselective reaction. Coupled with facile chemical transformations, biocatalytic transformations of nitrile and amide supply an effective synthesis of optically active 2,2-disubstitued-3-phenylcyclopropanecarboxylic acid and amide in both enantiomeric forms.
Enantioselective synthesis of chiral cyclopropane compounds through microbial transformations of trans-2-arylcyclopropanecarbonitriles
Wang,Feng
, p. 6501 - 6505 (2007/10/03)
Enantioselective biotransformations of racemic trans-2-arylcyclopropanecarbonitriles catalyzed by Rhodococcus sp. AJ270 cells proceeded efficiently to give good to excellent optical yields of (-)-(1R,2R)-2-arylcyclopropanecarboxamides and (+)-(1S,2S)-2-arylcyclopropanecarboxylic acids, which were converted into optically active cyclopropylmethylamine and cyclopropylamine derivatives upon reduction and the Curtius rearrangement. (C) 2000 Elsevier Science Ltd.
