1027259-08-0Relevant academic research and scientific papers
In search of novel agents for therapy of tropical diseases and human immunodeficiency virus
Goebel, Tim,Ulmer, Daniela,Projahn, Holger,Kloeckner, Jessica,Heller, Eberhard,Glaser, Melanie,Ponte-Sucre, Alicia,Specht, Sabine,Sarite, Salem Ramadan,Hoerauf, Achim,Kaiser, Annette,Hauber, Ilona,Hauber, Joachim,Holzgrabe, Ulrike
, p. 238 - 250 (2008/09/18)
Malaria, sleeping sickness, Chagas' disease, Aleppo boil, and AIDS are among the tropical diseases causing millions of infections and cases of deaths per year because only inefficient chemotherapy is available. Since the targeting of the enzymes of the polyamine pathway may provide novel therapy options, we aimed to inhibit the deoxyhypusine hydroxylase, which is an important step in the biosynthesis of the eukaryotic initiation factor 5A. In order to identify new lead compounds, piperidines were produced and biologically evaluated. The 3,5-diethyl piperidone-3,5-dicarboxylates 11 and 13 substituted with 4-nitrophenyl rings in the 2 and 6 positions were found to be active against Trypanosoma brucei brucei and Plasmodium falciparum combined with low cytotoxicity against macrophages. The corresponding monocarboxylates are only highly active against the T. brucei brucei. The piperidine oximether 53 demonstrated the highest plasmodicidal activity. Moreover, compounds 11 and 53 were also able to inhibit replication of HIV-1.
Novel piperidine σ receptor ligands as potential antipsychotic drugs
Gilligan,Cain,Christos,Cook,Drummond,Johnson,Kergaye,McElroy,Rohrbach,Schmidt,Tam
, p. 4344 - 4361 (2007/10/02)
σ receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine σ ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for σ sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent. Several of these compounds have good oral potency in some animal models used to evaluate potential antipsychotic drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a, and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not cause catalepsy in the rat, even at very high doses. On the basis of the pharmacology profiles of these σ ligands, we propose these compounds may be effective antipsychotic drugs, which do not induce extrapyramidal side effects or tardive dyskinesia.
