Abstract
5-Methoxy-l-methyl-4-(2-N,N-di-n-propylaminoethyl)indole (12) was synthesized from 5-hydroxyindole by a multistep synthesis. This target compound was designed as a bioisostere of “p-dimethoxy” catechol congeners of dopaminergic agonists derived from a variety of ring systems, in some of which p-dimethoxy-substituted systems are potent, active dopaminergic agonists. To complete the indole series, all possible combinations of N- and O-demethylated derivatives of 12 were prepared and were also evaluated pharmacologically. All members of this indole-derived series showed a low order of cardiovascular activity, which appeared to be independent of dopamine receptors. The lack of dopaminergic activity of 12 is cited as yet another example of the unpredictable effect of replacement of the catechol moiety of a dopaminergic agonist with a p-dimethoxy moiety.
Similar content being viewed by others
REFERENCES
J. G. Cannon. Dopamine agonists: Structure-activity relationships. Prog. Drug Res. 29:303–414 (1985).
S. P. Arneric, J. P. Long, D. B. Goodale, J. Mott, J. M. Laboski, and G. E. Gebhardt. RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane): Central effects of a new dopamine receptor agonist. J. Pharmacol. Exp. Ther. 224:161–170 (1983).
R. D. Sindelar, J. Mott, C. F. Barfknecht, S. P. Arneric, J. R. Flynn, J. P. Long, and R. K. Bhatnagar. 2-Amino-4,7-dimethoxyindan derivatives: Synthesis and assessment of dopaminergic and cardiovascular actions. J. Med. Chem. 25:858–864 (1982).
R. M. De Marinis, D. H. Shah, R. F. Hall, J. P. Hieble, and R. G. Pendleton. α-Adrenergic agents. 2. Synthesis and α1-agonist activity of 2-aminotetralins. J. Med. Chem. 25:136–141 (1982).
J. G. Cannon, V. E. D. Amoo, J. P. Long, R. K. Bhatnagar, and J. R. Flynn. p-Dimethoxy-substituted trans-octa-hydrobenzo[f]-and [g]quinolines: Synthesis and assessment of dopaminergic agonist effects. J. Med. Chem. 29:2529–2534 (1986).
S. P. Arneric, A. Roetker, J. P. Long, J. Mott, and C. F. Barfknecht. Effects of semirigid methoxamine analogs on vascular smooth muscle: Studies of methoxy-2-aminotetralin and 2-aminoindan derivatives. Arch. Int. Pharmacodyn Ther. 257:263–273 (1982).
J. G. Cannon, H. Jackson, J. P. Long, P. Leonard, and R. K. Bhatnagar. 5-HT1A-receptor antagonism: N-Alkyl derivatives of (R)-(−)-8,11-dimethoxynoraporphine. J. Med. Chem. 32:1959–1962 (1989).
J. G. Cannon. The design of potential anti-parkinsonian drugs: What is the dopaminergic pharmacophore in ergot alkaloids? Proc. Iowa Acad. Sci. 93:169–174 (1986).
J. G. Cannon and I. Roufos. Synthetic route to 4-(2-aminoethyl)-5-hydroxyindole derivatives. J. Heterocyc. Chem. 27:2093–2095 (1990).
J. G. Cannon, B. J. Demopoulos, J. P. Long, J. R. Flynn, and F. M. Sharabi. Proposed dopaminergic pharmacophore of lergotrile, pergolide, and related ergot alkaloid derivatives. J. Med. Chem. 24:238–240 (1981).
J. G. Cannon, T. Lee, M. Ilhan, J. Koons, and J. P. Long. 6-Hydroxy-4-[2-(di-n-propylamino)ethyl]indole: Synthesis and dopaminergic actions. J. Med. Chem. 27:386–389 (1984).
Author information
Authors and Affiliations
Additional information
To whom correspondence should be addressed.
Rights and permissions
About this article
Cite this article
Cannon, J.G., Roufos, I., Ma, S.X. et al. Derivatives of 4-(2-N,N-Di-n-propylaminoethyl)-5-hydroxyindole: Synthesis and Pharmacological Effects. Pharm Res 9, 735–738 (1992). https://doi.org/10.1023/A:1015839118825
Issue Date:
DOI: https://doi.org/10.1023/A:1015839118825