130609-93-7Relevant academic research and scientific papers
NITROGEN-CONTAINING CYCLOHETERO CYCLOALKYLAMINOARYL DERIVATIVES FOR CNS DISORDERS
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, (2008/06/13)
Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychotic disorders, convulsions and parkinsonism. Compounds of particular interest are of the formula STR1 wherein R 1 is selected from hydrido, loweralkyl, cycloalkylalkyl of four to six carbon atoms and loweralkenylloweralkyl; wherein each of R 2 and R 3 is independently selected from hydrido and loweralkyl; wherein each of R 4 through R 7, R 10 and R 11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is a number selected from four through six; wherein p is a number selected from zero through four; wherein q is a number selected from three through five; wherein A is selected from phenyl, naphthyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.
Synthesis and evaluation of N-substituted cis-N-methyl-2-(1-pyrrolidinyl)cyclohexylamines as high affinity σ receptor ligands. Identification of a new class of highly potent and selective σ receptor probes
De Costa,Rice,Bowen,Thurkauf,Rothman,Band,Jacobson,Radesca,Contreras,Gray,Daly,Iyengar,Finn,Vazirani,Walker
, p. 3100 - 3110 (2007/10/02)
Certain benzeneacetamides [(-)- and (+)-cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzenea cetamide] were recently reported to be potent σ receptor ligands. In order to determine whether efficacy for the σ receptor could be improved, a series of compounds related to the benzeneacetamides, N-substituted cis-2-(1-pyrrolidinyl)-N-methylcyclohexylamines, were synthesized and their structure-activity requirements were determined. The compounds were synthesized by starting with the previously reported (±)-, 1S,2R-(+)-, and 1R,2S-(-)-cis-2-(1-pyrrolidinyl)-N-methylcyclohexylamines. Analysis of σ ([3H](+)-3-PPP), κ ([3H]bremazocine and [3H]U69,593), dopamine-d2 ([3H](-)-sulpiride), and phencyclidine (PCP) ([3H]TCP) receptor binding in guinea pig brain revealed a number of highly potent and selective σ receptor ligands. Notably, 1S,2R-cis-(-)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-(2-naphthyl)ac etamide [(-)-29] (K(i) = 8.66 ± 0.35 nM), (±)-cis-2-amino-4,5-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl ]benzeneacetamide [(±)-17] (K(i) = 11 ± 3 nM), 1S,2R-(-)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidin yl)cyclohexylamine [(-)-44] (K(i) = 1.3 ± 0.3 nM), and 1R,2S-(+)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidin yl)cyclohexylamine. [(+)-44] (K(i) = 6 ± 3 nM) exhibited very high affinity at σ receptors, by displacement of [3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H]-(+)-3-PPP). These compounds showed significant affinity for κ, dopamine, or PCP receptors, making them valuable tools for the study of σ receptors. Furthermore, these compounds also exhibited enantioselectivity ranging from 5-fold for (+)- and (-)-44 to 160-fold for (+)- and (-)-29. Several other compounds showed equivalent selectivity but displayed lower σ receptor affinity.
