Amphetamine analogues

How might an aliphatic nitro compound be used in the synthesis of amphetamine analogues such as (5) ... 

This has proved an excellent route to amphetamine analogues. The condensation gives good yields with a... 

Schmidt, C.J. Lynne, W. and Lovenberg, W. Methylenedioxymethamphetamine A potentially neurotoxie amphetamine analogue. Eur J Pharmacol 124 175-178, 1986. 

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

Clinical success with the monoamine oxidase inhibitor and amphetamine analogue tranylcypromine (27) led to... 

Schmidt, C.J., Sullivan, C.K., and Fadayel, G.M., Blockade of striatal 5-hydroxytryptamine2 receptors reduces the increase in extracellular concentrations of dopamine produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine, J. Neurochem. 62(4), 1382-1389, 1994. 

Nichols, D. E., and Kostuba, L. J. (1979) Steric effects of substituents on phenethylamine hallucinogens. 3,4-(Methylenedioxy)amphetamine analogues alkylated on the dioxole ring. J. Med. Chem., 22 1264-1267. 

The three-carbon amphetamine analogue of 2C-F would quite logically be called DOF (2,5-dimethoxy-4-fluoroamphetamine). It has been prepared by reaction of the above benzaldehyde with nitroethane (giving l-(2,5-dimethoxy-4-fluorophenyl)-2-nitropropene, with a melting point of 128-129 °C from ethanol) followed by LAH reduction to DOF (the hydrochloride salt has a melting point of 166-167 °C, after recrystallization from ether/ethyl acetate/ethanol). Animal studies that have compared DOF to the highly potent DOI and DOB imply that the human activity will be some four to six times less than these two heavier halide analogues. As of the present time, no human trials of DOF have been made. 

The extension of the 4-alkoxy-group led to the discovery of the TM A-2 — MEM—MIPM—MPM—MBM series of amphetamine analogues. The 2-carbon counterparts of these would be a fascinating series to explore, I thought, if there was some encouragement to be had from a preliminary try in this field. 

EXTENSIONS AND COMMENTARY Again, as with every other psychedelic amphetamine analogue which has a chiral center and has been explored as the individual optical isomers, it is the R isomer that is the more potent. And again, the other isomer, the S isomer, still shows some activity. The same was true with DOB, and DOM, and MDA. The only exception was MDMA, but then that is more... 

EXTENSIONS AND COMMENTARY And visions of sugar-plums danced through their heads. There are many trisubstituted amphetamine analogues that... 

EXTENSIONS AND COMMENTARY As with the sulfur-free counterpart, the phenethylamine with three ethyl groups hanging out from it is not active in man. It doesn t matter where the sulfur is, since the 3-T-TRIS isomer is also without action. The labor of making the amphetamine analogues of these triethylated things seems hardly worth the effort. 

The use of fiuorescamine for the analysis of primary amines has been discussed for amino acids and biogenic amines. The reaction of this compound with amphetamine analogues is similar. The spray procedure is identical to that described for primary amino acids (Section 4.2.1.1.3). The limit of detection is 100 ng for amphetamine [84]. 

The amphetamine analogue fenfluramine, whose synthesis you designed while you were reading Chapter 31, used to be marketed as an anorectic (appetite-suppressant)—it stimulates the production of the hormone serotonin and makes the body feel satisfied—until it became clear that some undesirable side-effects could be avoided by administering it solely as the (S)-enantiomer. Fenfluramine relaunched as the enantiomerically pure dexfenfluramine, and was reputedly a turning point for your overweight patients —was available in the USA as a component of the slimming pill Redux. 

Tranylcypromine Sulfate, USP. Tranylcypromine sulfate. ( )-(ran.r-2-phcnylcyclopropylamine sulfate (Parnate), was synthesized to be an amphetamine analogue (visualize Ihc nr-mcihyl of amphetamine condensed onto Ihe fi-carbon atom). It d(x .s have. some amphetamine-like proper-lie.s. which may be why it has more immediate CNS stimulant effects than agents that act by MAO inhibition alone. For MAO inhibition, there may be two components to Ihc... 

Cloforex [inn] is an amphetamine analogue which was used as an appetite SUPPRESSANT, clometacin [inn] (C 1656 R 3959) is one of the indoleacetic acid series of cyclooxygenase inhibitors, with... 

Clorprenaline hydrochloride clorprenaline. clorsulon [ban, inn, usan] is an antiparasitic, ANTHELMINTIC and weak CARBONIC anhydrase inhibitor. clortermine [inn] (clortermine hydrochloride [usan]) is an amphetamine analogue with sympathomimetic properties, including CNS stimulation. It has been used as an APPETITE SUPPRESSANT. 

In general, the SARs for amphetamine-like actions of the phenylisopropylamines are quite distinct from those for the DOM-like actions of the phenylisopropylamines, even though both share a common structural skeleton. The SARs for the two actions are summarized in Figure 23.2. The stimulus effects of amphetamine analogues have been reviewed elsewhere (34). 

A logical extension of 2C-T-21 is the three carbon amphetamine analogue which should be, by comparing structures and activities, a very potent and in-teresting material in its own rights. This would be 2,5-dimethoxy-4-(2-fluoroethylthio)amphetamine or, following the nomenclature used... 

---