1172142-57-2Relevant academic research and scientific papers
Pro-neurogenic compounds
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Page/Page column 117, (2015/09/22)
This invention relates generally to stimulating neurogenesis (e.g., post-natal neurogenesis, e.g., post-natal hippocampal neurogenesis) and protecting from neuron cell death.
Development of proneurogenic, neuroprotective small molecules
MacMillan, Karen S.,Naidoo, Jacinth,Liang, Jue,Melito, Lisa,Williams, Noelle S.,Morlock, Lorraine,Huntington, Paula J.,Estill, Sandi Jo,Longgood, Jamie,Becker, Ginger L.,McKnight, Steven L.,Pieper, Andrew A.,De Brabander, Jef K.,Ready, Joseph M.
supporting information; experimental part, p. 1428 - 1437 (2011/04/16)
Degeneration of the hippocampus is associated with Alzheimer's disease and occurs very early in the progression of the disease. Current options for treating the cognitive symptoms associated with Alzheimer's are inadequate, giving urgency to the search for novel therapeutic strategies. Pharmacologic agents that safely enhance hippocampal neurogenesis may provide new therapeutic approaches. We discovered the first synthetic molecule, named P7C3, which protects newborn neurons from apopotic cell death, and thus promotes neurogenesis in mice and rats in the subgranular zone of the hippocampal dentate gyrus, the site of normal neurogenesis in adult mammals. We describe the results of a medicinal chemistry campaign to optimize the potency, toxicity profile, and stability of P7C3. Systematic variation of nearly every position of the lead compound revealed elements conducive toward increases in activity and regions subject to modification. We have discovered compounds that are orally available, nontoxic, stable in mice, rats, and cell culture, and capable of penetrating the blood-brain barrier. The most potent compounds are active at nanomolar concentrations. Finally, we have identified derivatives that may facilitate mode-of-action studies through affinity chromatography or photo-cross-linking.
Facile access to bicyclic sultams with methyl 1-sulfonylcyclopropane-l- carboxylate moieties
Rassadin, Valentin A.,Tomashevskiy, Aleksandr A.,Sokolov, Viktor V.,Ringe, Arne,Magull, Joerg,De Meijere, Armin
experimental part, p. 2635 - 2641 (2009/11/30)
N-(2,3-Dibromopropyl)- and N-(3,4-dibromobutyl)(methoxycarbonyl) methanesulfanilides upon treatment with potassium carbonate in DMF furnish, methyl 3-aryl-2,2-dioxo-2thia-3-azabicyclo[n.1.0]alkane-1.-carboxylates in yields ranging from 54 to 84% (10 examples). The starting materials were obtained by sulfonylation of N-alkenylanilines with methyl (chlorosulfonyl) acetate and. subsequent bromination. For the N-alkenylanil.in.es (10 examples, 60-77% yield) an efficient new synthesis employing a 2-nitrophenylsulfonyl substituent as a protective as well as an activating group has been developed. The 4-methoxyphenyl (PMP) group could easily be removed, from, the sultam. nitrogen atom by treatment with cerium(IV) ammonium nitrate.
