Prostaglandin E.sub.1 analogues

Details Prostaglandin E.sub.1 analogues Prostaglandin E.sub.1 analogues

1993-10-19

1997-06-17

Carr, Deborah D.

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

Organic compounds

Fatty compounds having an acid moiety which contains the...

554213, 554214, 554221, 554222, 560121, 562503, C07C 5900

Patent

active

056398999

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP92/00513 filed Apr. 21, 1992, now WO 92-18472 published Oct. 29, 1992.


TECHNICAL FIELD

The present invention relates to novel prostaglandin (hereinafter referred to as PG) E.sub.1 analogues.


BACKGROUND ART

Since PG's exhibit various important biological effects in a trace amount, investigations have been made of the synthesis and biological activity of natural PG's and a large number of PG analogues with the intention of use as medicines.
Especially, PGE.sub.1 is now commercially available as a drug for the improvement of peripheral circulatory disturbances because of having characteristic effects such as blood platelet aggregation inhibiting effect and blood pressure reducing effect, and therefore, a large number of PGE.sub.1 analogues have also been studied. However, the prior art PGE.sub.1 analogues are quickly metabolized in vivo and thereby have drawbacks such as lack of duration of the effect. Furthermore, the prior art PGE.sub.1 analogues cannot be administered orally in a sufficiently high amount to obtain the satisfactory effects because of causing diarrhea as a side-effect.
On the other hand, the known 13, 14-didehydro PGE.sub.1 analogues in which the double bond between the 13- and 14-positions of PGE.sub.1 is replaced by a triple bond include 13,14-didehydro PGE.sub.1 methyl ester and 6-hydroxy-13,14-didehydro PGE.sub.1.
An object of the present invention is to provide novel PGE.sub.1 analogues which have more excellent pharmaceutical effects, longer duration of the effect and less side-effects than the prior art PGE.sub.1 analogues.


DISCLOSURE OF THE INVENTION

As a result of continued extensive research, the present inventors have found that the compounds having a triple bond between the 13- and 14-positions of the PGE.sub.1 analogues, a branch at the 16- or 17-position and a double or triple bond between the 2- and 3-positions can solve the above-mentioned problems, and have accomplished the present invention.
The present invention is directed to a PGE.sub.1 analogue represented by the formula: ##STR2## (wherein A is a vinylene group or an ethynylene group, R.sup.1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an allyl group, R.sup.2 is a hydrocarbon group having 5 to 10 carbon atoms, and n is an integer of 3 to 6), or a salt thereof.
In the present invention, the alkyl group having 1 to 6 carbon atoms refers to a straight or branched chain alkyl group (e.g. a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a t-butyl group, an n-pentyl group and an isopentyl group).
The hydrocarbon group having 5 to 10 carbon atoms refers to an hydrocarbon group having a branch at the .alpha.- or .beta.-position, and particularly, a branched chain alkyl group (e.g. a 1-methylpentyl group, a 2-methylpentyl group, a 1-methylhexyl group, a 2-methylhexyl group, a 2,4-dimethylpentyl group, a 2-ethylpentyl group, a 2-methylheptyl group, a 2-ethylhexyl group, a 2-propylpentyl group and a 2,6-dimethylheptyl group), a cycloalkyl group (e.g. a cyclopentyl group, a cyclohexyl group and a cycloheptyl group), an alkyl group having 1 or 2 carbon atoms substituted by a cycloalkyl group (e.g. a cyclopentylmethyl group, a cyclohexylmethyl group, a cycloheptylmethyl group, a cyclopentylethyl group, a cyclohexylethyl group and a cycloheptylethyl group), a branched chain alkenyl group (e.g. a group which is obtained by converting a single bond at any position of the above-mentioned branched chain alkyl group into a double bond, such as a 2,6-dimethylhept-5-enyl group), a branched chain alkynyl group (e.g. a group which is obtained by converting a single bond at any position of the above-mentioned branched chain alkyl group into a triple bond, such as a 1-methylpent-3-ynyl group, a 1-methylhex-3-ynyl group and a 2-methylhex-3-ynyl group).
The salt of the compound of Formula (I) refers to salts thereof when R.sup.1 is a hydrogen atom, for example, salts with metals (e.g. sodium, potassium and aluminium), or salt

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