Synthesis and dopamine autoreceptor activity of a 5-(methylmercapto)methyl-substituted derivative of (+/-)-3-PPP (3-(3-hydroxyphenyl)-1-n-propylpiperidine)
| Autor: | H. R. Howard, B. K. Koe, R. Sarges, T. R. Kelly |
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| Rok vydání: | 1985 |
| Předmět: |
Agonist
Chemical Phenomena Stereochemistry medicine.drug_class Dopamine Receptors Dopamine Hydroxylation chemistry.chemical_compound Mice Structure-Activity Relationship 4-Butyrolactone Piperidines Drug Discovery medicine Potency Structure–activity relationship Animals Pergolide Chemistry Biological activity Corpus Striatum Dihydroxyphenylalanine Rats Autoreceptor Molecular Medicine medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 28(9) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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