Anti-Alzheimer’s drug

To test the feasibility of enzyme-catalyzed enantiosective reactions in solid/gas reactors and to evaluate the efficiency of the resolution obtained in the gas phase compared to liquid systems, resolution of racemic 2-pentanol, catalyzed by CALB, through alcoholysis with methyl propanoate as acyl donor has been investigated in both liquid media and the gas phase [24]. As CALB has an enantiopreference for R enantiomers of secondary alcohols, this last reaction leads to S-2-Pentanol. This compound is a chiral intermediate in the synthesis of several potential anti-Alzheimer s drugs that inhibit 3-amyloid peptide release and/or its synthesis [25]. The degree of enantioselectivity was measured by using the enantiomeric ratio E, which is defined as the ratio of the specificity constants kcat/KM for the enantiomers (R/S in this case). E can be determined from the enantiomeric excess of... 

Ethyl-(5)-5-hydroxyhexanoate 68 and (5)-5-hydroxyhexanenitrile 69 (Figure 16.18) are key chiral intermediates in the synthesis of anti-Alzheimer s drugs 70 [95]. 

The chiral intermediates (S)-l-(2 -bromo-4 -fluorophenyl)ethanol 76 and (S)-methyl 4-(2 -acetyl-5 -fluorophenyl)-butanol 77 are potential intermediates for the synthesis of several potential anti-Alzheimer s drugs, such as 78 [97,98], The chiral intermediate (S)-l-(2 -bromo-4 -fluoro phenyl)ethanol 76 (Eigure 16.19A) was prepared by the enantioselective microbial reduction of 2-bromo-4-fluoro acetophenone 79 [99]. Organisms from genuses Candida, Hansenula, Pichia, Rhodotorula, Saccharomyces, and Sphingomonas and baker s yeast reduced 79 to 76 in more than 90% yield and 99% EE. 

FIGURE 16.18 Anti-Alzheimer s drug 70. Enantioselective enzymatic reduction of 5-oxo-hexanoate 71 and 5-oxohexanenitrile 72. 

FIGURE 16.19 Anti-Alzheimer s drug 78. (A) Enantioselective microbial reduction of substituted acetophenone 79. (B) Enantioselective microbial reduction of methyl-4-(2 -acetyl-... 

Pentanol is an intermediate in the synthesis of several potential anti-Alzheimer s drugs, which inhibit a-amyloid peptide release and/or its synthesis (33). The enzymatic resolution of racemic 2-pentanol and 2-heptanol by lipase B from Candida antarctica has been demonstrated (34). 

Nachon, R, Carletti, E., Ronco, C, et al., 2013. Crystal structures of human cholinesterases in complex with huprine W and tacrine elements of specificity for anti-Alzheimer s drugs targeting acetyl- and butyryl-cholinesterase. J. 

Medicinal chemistry has many examples of the development of successful therapeutics based on an exploration of endogenous compounds. The treatment of diabetes mellitus, for example, is based upon the administration of insulin, the hormone that is functionally deficient in this disease. The current treatment of Parkinson s disease is based upon the observation that the symptoms of Parkinson s disease arise from a deficiency of dopamine, an endogenous molecule within the human brain. Since dopamine cannot be given as a drug since it fails to cross the blood-brain barrier and enter the brain, its biosynthetic precursor, L-DOPA, has been successfully developed as an anti-Parkinson s drug. Analogously, the symptoms of Alzheimer s disease arise from a relative deficiency of acetylcholine within the brain. Current therapies for Alzheimer s-type dementia are based upon the administration of cholinesterase... 

Drucker s example uses changes in population (i.e. size/young adults the third world) age structure especially more elderly people distribution between town and country more women in employment more in further/higher education higher disposable income. With little analysis consequences are predictable. For chemistry opportunity lies with medicines for the aged e.g. anti Alzheimer s disease, life style drugs and nutriceuticals. 

The contribution of plants to modern medicine can hardly be overstated. Many plant natural products are used in medicine in their native, undomesticated form and the anti-Alzheimer s alkaloid galanthamine and the anticancer diterpenoid paclitaxel are additions to the inventory of plant-derived drugs obtained by direct isolation.101... 

Central Nervous System Drugs Anti-Parkinson s and Anti-Alzheimer s Agents... 

Vargas, M. G., Havel, J., and Patocka. J. (1998). Determination of the anti-Alzheimer s disea.se drugs tacrine. 7-methoxytacrine, and its metabolites by capillary zone electrophoresis. Am. Clin. Lab. 17(,5), 22-23. 

In addition to discussing possible therapeutic agents, a review of the pharmacology and chemistry of drugs with anti-Alzheimer s disease potential would be incomplete without raising a number of major problems facing research in dementia. We shall therefore examine the clinical symptoms and... 

The use of a glucose/ GDH system for the regeneration of the NADH cofactor also allowed the development of a pH-based screening method for the identification and characterization of novel co-TAs. This three-enzyme cascade found application, for example, in the synthesis of the pharmaceutical intermediate 4-phenylpyrrolidin-2-one [33] and the anti-Alzheimer s disease drug (S)-rivastigmine [34]. As an... 

Allison, A. C. Cacabelos, R. Lombardi, V. R. M. Alveraz, X. A. Vigo, C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer s disease Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2001, 25, 1341-1357. 

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