121843-50-3Relevant articles and documents
Optimisation of the Anti-Trypanosoma brucei Activity of the Opioid Agonist U50488
Smith, Victoria C.,Cleghorn, Laura A. T.,Woodland, Andrew,Spinks, Daniel,Hallyburton, Irene,Collie, Iain T.,YiMok,Norval, Suzanne,Brenk, Ruth,Fairlamb, Alan H.,Frearson, Julie A.,Read, Kevin D.,Gilbert, Ian H.,Wyatt, Paul G.
, p. 1832 - 1840 (2012/06/18)
Screening of the Sigma-Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)-(1R,2R)-U50488, a weak opioid agonist with an EC50 value of 59nM as determined in our T.brucei invitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure-activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.
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 and convulsions. Compounds of particular interest are of the formula STR1 wherein R1 is selected from hydrido, loweralkyl, cycloalkylalkyl of four to six carbon atoms, and loweralkenylloweralkyl; wherein each of R2 and R3 is independently selected from hydrido and loweralkyl; wherein each of R4 through R7, R10 and R11 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.
A PRACTICAL SYNTHESIS, OPTICAL RESOLUTION AND DETERMINATION OF ABSOLUTE CONFIGURATION OF ENANTIOMERICALLY PURE 1S,2R-(+)- AND 1R,2S-(-)-CIS-2-(1-PYRROLIDINYL)CYCLOHEXYLAMINES: IMPORTANT PRECURSORS FOR A NEW CLASS OF SIGMA-RECEPTOR LIGANDS AND ANTICONVULSANT DRUGS
Costa, Brian R. de,Radesca, Lilian
, p. 1837 - 1846 (2007/10/02)
Enantiomerically pure (+)- and (-)-cis-2-(1-pyrrolidinyl)cylohehexylamines ((+)- and (-)-4) were prepared starting with (+/-)-trans-2-aminocyclohexanol ((+/-)-5).The key step in the generation of the cis stereochemistry of (+)- and (-)-4 empolyed catalytic hydrogenation of the enamine mixture generated from condensation of pyrrolidine with (+/-)-2-(benzamido)cyclohexanone ((+/-)-7).An efficient optical resolution of (+/-)-4 was achieved through two recrystallizations of the mandelate salts.The absolute configuration of (+)- and (-)-4 was assigned as 1S,2R and 1R,2S,respectively, based on conversion of (-)-4 to and comparison with the N-methyl derivative (-)-13 of known 1R,2S absolute configuration.
