162732-99-2Relevant articles and documents
Novel 1-Phenylcycloalkanecarboxylic Acid Derivatives Are Potent and Selective ?1 Ligands
Calderon, Silvia N.,Izenwasser, Sari,Heller, Brett,Gutkind, J. Silvio,Mattson, Mariena V.,et al.
, p. 2285 - 2291 (1994)
Carbetapentane (1, 2-ethyl 1-phenyl-1-cyclopentanecarboxylate) binds with high affinity to ? sites and is a potent antitussive, anticonvulsant, and spasmolytic agent.However, carbetapentane interacts at muscarinic binding sites as well, and it is not clear whether either of these receptor systems is involved in the mechanism(s) of action(s) of this drug.In an attempt to determine whether these psychoactivities can be attributed to interaction at ? sites, a series of carbetapentane analogs were prepared.Phenyl ring substitution; contraction expansion, and replacement with a methyl group of the cyclopentyl ring; replacement of the carboxylate function with an amide, methyl ether, and methylamine; and replacement of the N,N-diethyl substituent with a morpholino or piperidino moiety were investigated.All of these novel analogs were evaluated for binding to ?1 and ?2 sites, and comparison of binding at muscarinic m1 and m2 and PCP (1-(1-phenylcyclohexyl)piperidine) receptors was performed.All of the compounds were selective for ?1 over ?2 sites, with the three most selective analogs being compounds 34 (65-fold), 35 (78-fold), and 39 (51-fold).None of the compounds were active at PCP sites, and chemical modification including (1) replacing the ester function, (2) replacing the cyclopentyl ring with a smaller ring system (cyclopropyl) or a methyl group, and (3) replacing the diethylamino moiety with a morpholino group resulted in >220-fold selectivity over muscarinic receptor binding.Therefore, several of these novel compounds are potent, ?1-selective ligands which can now be investigated as potential antitussive, anticonvulsant, and antiischemic agents.These studies may reveal whether ?1 sites play a role in the pharmacological actions of these drugs.
Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor
Shao, Liming,Hewitt, Michael C.,Wang, Fengjiang,Malcolm, Scott C.,Ma, Jianguo,Campbell, John E.,Campbell, Una C.,Engel, Sharon R.,Spicer, Nancy A.,Hardy, Larry W.,Schreiber, Rudy,Spear, Kerry L.,Varney, Mark A.
scheme or table, p. 1438 - 1441 (2011/04/16)
The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC50 = 169, 85, 21 nM) and 42 (SERT, NET, DAT IC50 = 34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants.
PYRROLIDINE TRIPLE REUPTAKE INHIBITORS
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Page/Page column 49; 52, (2010/08/18)
In various embodiments, the present invention provides cycloalkyl pyrrolidine compounds and methods for their use in the treatment and/or prevention of various diseases, conditions and syndromes, including central nervous system (CNS) disorders, such as depression, anxiety, schizophrenia and sleep disorder as well as methods for their synthesis. The invention also relates to pharmaceutical compositions containing the compounds of the invention, as well as methods of inhibiting reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine from the synaptic cleft and methods of modulating one or more monoamine transporter.
