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Synthesis and dopamine autoreceptor activity of a 5-(methylmercapto)methyl-substituted derivative of (+/-)-3-PPP (3-(3-hydroxyphenyl)-1-n-propylpiperidine). 1985

T R Kelly, and H R Howard, and B K Koe, and R Sarges

In an attempt to enhance the potency of the dopamine autoreceptor agonist 3-PPP, racemic cis-3-(3-hydroxyphenyl)-5-[(methylmercapto)methyl]-N-n-propylpiperidine has been prepared in a stereoselective synthesis. NMR studies of 3 show a diequatorial conformation for the 3- and 5-substituents, which gives compound 3 an intriguing overlap with the ergoline derivative pergolide. Pharmacological testing revealed that 3, which is a 5-(methylmercapto)methyl derivative of racemic 3-PPP does not show the anticipated potency increase as a dopamine autoreceptor agonist. In vitro (inhibition of tyrosine hydroxylation) 3 and 1 have similar potency, and the in vivo potency (inhibition of GBL accelerated dopamine synthesis) of 3 is inferior to that of 1.

UI MeSH Term Description Entries
D010880 Piperidines A family of hexahydropyridines.
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004295 Dihydroxyphenylalanine A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific. Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015107 4-Butyrolactone One of the FURANS with a carbonyl thereby forming a cyclic lactone. It is an endogenous compound made from gamma-aminobutyrate and is the precursor of gamma-hydroxybutyrate. It is also used as a pharmacological agent and solvent. 1,4-Butanolide,4-Hydroxybutyric Acid Lactone,Furanone, tetrahydro-2-,gamma-Butyrolactone,Dihydro-2(3H)-furanone,1,4 Butanolide,4 Butyrolactone,4 Hydroxybutyric Acid Lactone,Furanone, tetrahydro 2,Lactone, 4-Hydroxybutyric Acid,gamma Butyrolactone
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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