1260172-04-0Relevant articles and documents
Pro-neurogenic compounds
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, (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 a scalable synthesis of P7C3-A20, a potent neuroprotective agent
Naidoo, Jacinth,Bemben, Christopher J.,Allwein, Shawn R.,Liang, Jue,Pieper, Andrew A.,Ready, Joseph M.
, p. 4429 - 4431 (2013/07/26)
A scalable synthesis of the neuroprotective agent P7C3-A20 is described. The synthesis has provided hundred-gram batches of the final compound for biological evaluation in rodents primates. The synthesis can be performed without chromatographic purificati
Aminopropyl carbazole analogues as potent enhancers of neurogenesis
Yoon, Hye Jin,Kong, Sun-Young,Park, Min-Hye,Cho, Yongsung,Kim, Sung-Eun,Shin, Jae-Yeon,Jung, Sunghye,Lee, Jiyoun,Farhanullah,Kim, Hyun-Jung,Lee, Jeewoo
, p. 7165 - 7174 (2013/11/06)
Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis.
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.
