Alzheimer therapeutics

The CM reaction between 2-methyl-2-butene (a gera-disubstituted olefin that served in this case also as solvent) and the allylated compound 300, possessing the bicyclo[3.3.1]nonane core of the potential Alzheimer therapeutic garsubellin A (302) [137], underlines the increased activity of the second-generation ruthenium catalysts (Scheme 58). In the presence of 10 mol% of NHC catalyst C, the prenylated compound 301 was formed after only 2 h in 88% yield. 

Walker LC, Rosen RE. Alzheimer therapeutics what after the cholinesterase inhibitors Age Ageing 2006 35 332-5. 

Steele JW, Gandy S (2013) Latrepirdine (Dimebon ), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy 9 617-618... 

Kamal MA, Greig NH, Alhomida AS, Al-Jafari AA (2000) Kinetics of human acetylcholinesterase inhibition by the novel experimental Alzheimer therapeutic agort, tolserine. Biochem Pharmacol 60 561-570... 

Kamal MA, Klein P, Yu QS, Tweedie D, Li Y, Holloway HW, Greig NH (2006) Kinetics of human serum butyrylcholinesterase and its inhibition by a novel experimental Alzheimer therapeutic, bisnorcymserine. J Alzheimers Dis 10 43-51... 

Masters CL Beyreuther K (2006). Alzheimer s centennial legacy prospects for rational therapeutic intervention targeting the AB amyloid pathway. Brain 129 2823-2839... 

Soto C Alzheimer s and prion disease as disorders of protein conformation Implications for the design of novel therapeutic... 

Anatoxin-a has already proven its usefulness as a research tool in our laboratories. It is facilitating the understanding of the biophysical properties of the AChR and of the localization of the AChR in the CNS. The toxin or derivatives of it could be useful therapeutically in diseases of nicotinic receptor pathology (myasthenia gravis or Alzheimer s disease), because as a secondary amine (+)-anatoxin-a can penetrate into the CNS. 

Selkoe, DJ (1999) Translating cell biology into therapeutic advances in Alzheimer s disease. 

Histamine produces its pharmacological actions by three subtypes of receptors the postsynaptic Hi and H2 receptors and the presynaptic H3 receptor. The H3 receptor is mainly located in the central nervous system (CNS), where it acts as an inhibitory autoreceptor in the central histaminergic neuronal pathways [176]. A number of therapeutic applications have been proposed for selective H3 receptor antagonists, including several CNS disorders such as Alzheimer s disease. Attention Deficit Hyperactivity Disorder, Schizophrenia, or for enhancing memory or obesity control. 

It has been revealed that cannabinoids exhibit neuroprotectant activities in both in vitro and in vivo models [249]. The neuroprotective effects are mainly based on regulation of transmitter release, modulation of calcium homeostasis, anti-oxidant properties and modulation of immune responses. A number of neurological disorders, including brain trauma, cerebral ischaemia, Parkinson s disease and Alzheimer s disease represent possible therapeutic areas for cannabinoids with neuroprotective properties. Cannabinoids are also suggested to have potential against glaucoma due to their neuroprotective nature and lowering of intraocular pressure [250]. 

The editors have chosen topics from both important therapeutic areas and from work that advances the discipline of medicinal chemistry. For example, cancer, metabolic syndrome and Alzheimer s disease are fields in which academia and industry are heavily invested to discover new drugs because of their considerable unmet medical need. The editors have therefore prioritized covering new developments in medicinal chemistry in these fields. In addition, important advances in the discipline, such as fragment-based drug design and other aspects of new lead-seeking approaches, are also planned for early volumes in this series. Each volume thus offers a unique opportunity to capture the most up-to-date perspective in an area of medicinal chemistry. 

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

Ibogaine protects the N-methyl-D-aspartate neuron receptors against excessive release of excitatory amino acids and represents, therefore, a potential therapeutic agent for the treatment of Alzheimer s disease, Huntington s chorea, and other... 

Grossberg GT (2003). Cholinesterase inhibitors for the treatment of Alzheimer s disease Getting on and staying on. Current Therapeutic Research, 64, 216-235. 

Cutler NR and Sramek JJ (2001). Review of the next generation of Alzheimer s disease therapeutics Challenges for drug development. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25, 27-57. 

Heiss WD, Kessler J, Slansky I, Mielke R, Szelies B and Herholz K (1993). Activation PET as an instrument to determine therapeutic efficacy in Alzheimer s disease. Annals of the New York Academy of Science, 695, 327-331. 

Pettigrew JW, Levine J and McClure RJ (2000). Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties Relevance for its mode of action in Alzheimer s disease and geriatric depression. Molecular Psychiatry, 5, 626-632. 

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