Amphetamine analogs from

FIGURE 6. Elution pattern of monoamine uptake blockers and amphetamine analogs from reverse-phase HPLC... 

G.K.W. Effects of certain hallucinogenie amphetamine analogs on the release of [ H]serotonin from rat brain synaptosomes. J Med Chem 25 530-535, 1982. 

The amphetamine analog of CPM should be easily made from the alkylation of syringaldehyde with cyclopropyl chloride, followed by conventional reaction of the resulting aldehyde with nitroethane, and finally a reduction step. There is no reason to believe that the resulting compound 3,5-dimethoxy-4-cyclo-propyloxyamphetamine (3C-CPM) would be any shorter acting than CPM. 

The amphetamines were replaced by amphetamine analogs—substances somewhat less potent than amphetamines. Fen-Phen, the combination of fenfluramine and phentermine, was a popular appetite suppressant in the 1990s, but was associated with severe health problems such as pulmonary hypertension, heart valve dysfunction, and nerve damage. As a result, both drugs were withdrawn from the market. 

Nitiyl iodide, from iodine vdth ver nitrite or from NO2 and iodine, adds to alkenes, generally in ether at room temperature, by a radical mechanism. Yields are 50-90%. The products yield nitroalkenes on treatment wiA base, a sequence used recently in the preparation of intermediates (Aidi=CMeN02) for amphetamine analogs. The reaction is also a key step in the a-methylenebuty-lolactone synthesis shown in Scheme 88. ... 

Another Hydrogenation with Platinum Oxide. JACS, 55, 2694. This method is used to reduce those hydrox-mandelonitriles in the amphetamine section. It uses low pressure and can be used on about any reducible compound. It can also use palladium oxide as the catalyst. A solution of 35.8 g of phenyl-2-propanol in 250 ml of 80% ethanol containing 7.3 g of HCl is hydrogenated for 3 hours in a Parr hydrogenation bottle at 3,5kg/cm or 50 p.s.i, over 0,5 g of platinum oxide (or palladium oxide Raney nickel may also work) or an equimolar ratio of analog catalyst for about 3 hours. Filter off the catalyst and rinse with a little water to wash all the product from the catalyst. Dilute the filtrate to 1 liter of volume with water and extract twice with ether to remove any acid insoluble material. The ether extracts do not contain product. The aqueous layer is made alkaline with solid NaHCOs to a pH of 8-9 and the basic oil which separates is extracted with two 300 ml portions of ether. This ether solution is dried over MgS04, and filtered, then evaporated to remove the ether. To convert to the oxalate, add ether to the crude product and add to a solution of 9.6 g of oxalic acid dihydrate in a small volume of methanol. Give ample... 

It is believed that the mechanism of action of amphetamines lies in their ability to release epinephrine (adrenaline) and dopamine from presynaptic nerve endings, which stimulate the corresponding receptors in the CNS. It is also possible that they reduce neuronal uptake of amines as well as inhibit their degradation by monoaminoxidase (MAO). Characteristic of this series of compounds is the effect on the respiratory center, on the satiation center located in the hypothalamus, which leads to suppression of feelings of hunger, thus allowing analog of the examined compounds to be used as anorectics. 

Unexpected neurotoxicity from amphetamine and its analogs (e.g. 3,4 methylenedioxymethamphetamine, also known as ecstasy ) as well as interactions with other drugs subject to CYP2D6 polymorphism would likewise be expected to occur more frequently among Africans and Caucasians than in Asians.(112)... 

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