Novel dopamine derivatives, processes for their preparation, and

Details Novel dopamine derivatives, processes for their preparation, and Novel dopamine derivatives, processes for their preparation, and

1986-05-30

1990-09-18

Lee, Mary

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

548306, 548332, 548359, C07D23154, C07D23502, C07D24918

Patent

active

049580264

DESCRIPTION:

BRIEF SUMMARY
The invention relates to the subject matter of the claims. One aspect of this invention is to provide dopamine derivatives of general Formula I ##STR7## wherein A represents a substituted phenyl residue of the structure ##STR8## wherein R.sup.1 and R.sup.2, being identical or different, mean hydrogen, C.sub.1-5 -alkyl and allyl, ##STR9## R.sub.4 is hydrogen, C.sub.1 -C.sub.4 -alkyl, CF.sub.3, NH.sub.2 ##STR10## X is OH, NH.sub.2, ##STR11## and NH--SO.sub.2 --CF.sub.3, if Y=OH, Y is OH, NH.sub.2, ##STR12## NH--SO.sub.2 --CF.sub.3 and NH--SO.sub.2 --CH.sub.3, if X=OH, but wherein X and Y do not simultaneously mean OH, with R.sup.3 being hydrogen or C.sub.1-4 -alkyl, and present in the tautomeric basic form, simultaneously OH and NH--SO.sub.2 --CH.sub.3. In Formula I, C.sub.1-4 -and C.sub.1-5 -alkyl mean lower, straight- or branched-chain alkyl of up to five carbon atoms, such as, for example, methyl, ethyl, isopropyl, pentyl, tert-butyl and 2-methylbutyl.
In case Z in the residue A of Formula I means the hydroxy group, this hydroxy group is part of a tautomeric system.
The following tautomeric system is present wherein both tautomeric, interconvertible forms can be stable. ##STR13##
In all benzimidazole and benzotriazole derivatives, two tautomeric forms are possible along the following lines: ##STR14##
Additionally, compounds wherein R.sup.4 =NH.sub.2 and E= ##STR15## possess tautomerizable structures; the following tautomeric, interconvertible forms can be stable:
The natural neurotransmitter dopamine affects various biological processes, such as, for example, in the central nervous system where dopaminergic neurons participate in regulating motor coordination and prolactin secretion. Peripherally, dopamine causes various cardiovascular effects, in that it affects arterial tension, evokes a positive inotropic and positive chronotropic effect on the heart, and promotes renal blood flow. These peripheral effects are based, in part, on dopaminergic mechanisms, i.e. those conveyed by dopamine receptors, in part, on other mechanisms, for example adrenergic mechanisms. Dopamine is usable therapeutically only in a limited way on account of this mechanistic nonuniformity, apart from poor bioavailability upon oral administration. Therefore, it would be desirable to provide active agents exhibiting also peripherally effectiveness mechanisms that are entirely or at least in part dopaminergic. Thus, N,N-dipropyldopamine has been developed, for example [Drugs of the Future 7: 469 (1982)], wherein the therapeutically important antihypertensive action appears and is evoked almost exclusively by way of dopaminergic mechanisms. However, one disadvantage displayed by N,N-dipropyl-dopamine is that it has an only very brief duration of activity.
Furthermore, U.S. Pat. Nos. 3,574,741 and 3,758,692 disclose sulfonamidophenylalkylamines, such as 5'-(2-aminoethyl)-2'-hydroxymethanesulfonanilide which exhibits pronounced vasoconstrictive activity.
The literature contains mentions of attempts to obtain compounds having therapeutically usable properties by arylethylamine analogs with benzimidazole or benzotriazole as the aryl portion.
Thus, the following compounds have been described: ##STR16##
However, these compounds possess hypertensive effects (German Patent No. 294,085).
A similar compound was produced along the same lines with a benzotriazole ring system: ##STR17##
According to data provided by the producers, however, this compound does not display the desired dopaminergic activity [H. Schmidhammer and K. Hohenlohe-Oehringen, Sci. Pharm. 51: 8 (1983)].
It has now been discovered that the dopamine derivatives of Formula I exhibit vasodilatory and antihypertensive activity, the duration of efficacy being substantially prolonged as compared with N,N-dipropyldopamine.
In order to determine the biological efficaciousness of the compounds of this invention, the effect on the blood pressure in dependence on the time was measured on nonanesthetized, spontaneous-hypertensive rats prepared according to the Weeks method.
For this purpose

REFERENCES:
patent: 4314944 (1982-02-01), Huffman
patent: 4554287 (1985-11-01), Stringer et al.
Chem. Abstracts vol. 75(1), Abst. No. 5455k (1971).

Affiliated with

Also associated with

Rating

Novel dopamine derivatives, processes for their preparation, and does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Novel dopamine derivatives, processes for their preparation, and, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Novel dopamine derivatives, processes for their preparation, and will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1573482