939-88-8Relevant 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.
A novel approach to enantiopure cyclopropane compounds from biotransformation of nitriles
Wang, Mei-Xiang,Feng, Guo-Qiang
, p. 1575 - 1583 (2007/10/03)
Rhodococcus sp. AJ270, a powerful and versatile nitrile hydratase/amidase containing microbial whole-cell system, catalyzed the enantioselective hydrolysis of both racemic trans- and cis-2-arylcyclopropanecarbonitriles to afford the corresponding amides and acids with enantiomeric excesses as high as >99%. The reaction rate and enantioselectivity observed for both nitrile hydratase and amidase were also strongly dependent upon the nature of the substituent and substitution pattern on the benzene ring of the substrates. The application of and the advantages of biotransformation of nitriles were demonstrated by preparing (1S,2R)-2-phenylcyclopropylamine and (1R,2R)-2-phenylcyclopropylmethylamine through facile and straightforward chemical manipulations of (1S,2S)-2-phenylcyclopropanecarboxylic acid and (1R,2R)-2-phenylcyclopropanecarboxamide, respectively.
VIBRATIONAL CIRCULAR DICHROISM OF OPTICALLY ACTIVE CYCLOPROPANES. 3. TRANS-2-PHENYLCYCLOPROPANECARBOXYLIC ACID DERIVATIVES AND RELATED COMPOUNDS
Yasui, Sritana C.,Keiderling, Timothy A.
, p. 2311 - 2320 (2007/10/02)
Vibrational circular dichroism (VCD) data are presented for a series of (1R,2R)-trans-2-phenyl-1-(R-substituted)cyclopropanes where R=COOCH3, COOCD3, COOH, CONH2, COCl, CN, CH2OH, CD2OD, CH3, CD3, and NH2 (1S,2R).In addition, VCD for (1S,2S)-1-phenylpropylene oxide is presented for comparison.These data can be correlated to show certain characteristic, structure-indicating transitions common to all of the molecules.This is particularly true in the cyclopropane C-H stretching bands in the near-IR and less so of CH2 deformations and ring modes in the mid-IR.To elucidate these comparisons it is necessary to interpret the frerquency shifts of the characteristic bands as the substituent is varied.The range of compounds studied permits such an analysis for certain characteristic modes.The results for monocarbonyl and-cyano substitution further explain the presence and absence, respectively, of coupled oscillator VCD in the corresponding symmetrically disubstituted cyclopropyl compounds.
