64504-91-2Relevant academic research and scientific papers
Synthesis and pharmacological characterization of bicyclic triple reuptake inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues
Shao, Liming,Hewitt, Michael C.,Malcolm, Scott C.,Wang, Fengjiang,Ma, Jianguo,Campbell, Una C.,Spicer, Nancy A.,Engel, Sharon R.,Hardy, Larry W.,Jiang, Zhi-Dong,Schreiber, Rudy,Spear, Kerry L.,Varney, Mark A.
scheme or table, p. 5283 - 5295 (2011/10/02)
The present work expands the chemical space known to offer potent inhibition of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) and discloses novel bicyclic octahydrocyclopenta[c]pyrrole and octahydro-1H-isoindole scaffolds as potent triple reuptake inhibitors (TRIs) for the potential treatment of depression. Optimized compounds 22a (SERT, NET, DAT, IC50 = 20, 109, 430 nM), 23a (SERT, NET, DAT, IC50 = 29, 85, 168 nM), and 26a (SERT, NET, DAT, IC50 = 53, 150, 140 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 10 and 30 mpk PO, and were not generally motor stimulants at doses ranging from 1 to 30 mpk PO. Moderate in vitro cytochrome P450 (CYP) and potassium ion channel Kv11.1 (hERG) inhibition were uncovered as potential liabilities for the chemical series.
Bond Fixation in Annulenes. 16. Synthesis of the 1,2-Dimethyl-3-phenylcyclooctatetraene ->/<- 1,8-Dimethyl-2-phenylcyclooctatetraene Bond Shift Isomer Pair. Probe of the Relative Size of a Flanking Phenyl Substituent by means of Racemization Kinetics
Paquette, Leo A.,Gardlik, John M.,McCullough, Kevin J.,Samodral, Rodney,DeLucca, George,Ouellette, Robert J.
, p. 7649 - 7655 (2007/10/02)
Two synthetic approaches to the cyclooctatetrene bond shift isomers 3 ->/octadiene to generate the cyclooctatetraene nucleus.Although 3 dominates over 4 in the equilibrium, it is possible to separate these bond shift isomers by cycloaddition with a triazolinedione.When recourse was made to the endo-bornyl-substituted dienophile, it was ultimately possible to obtain (-)-3 and to determine its rate of racemization.The data indicate that the flanking phenyl group in 3 causes significant rate retardation relative to the trimethyl derivative.This finding contrasts with the behavior of 2 which racemizes more rapidly despite an interstitial phenyl substituent.The source of these dissimilar effects has been clarified by MM2 calculations, the details of which are presented.
