6-substituted prostaglandins E.sub.1 and process for producing s

Details 6-substituted prostaglandins E.sub.1 and process for producing s 6-substituted prostaglandins E.sub.1 and process for producing s

1985-10-18

1989-01-10

Gerstl, Robert

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

Organic compounds

Carboxylic acid esters

549422, 549466, 556441, 560 53, 560118, 562463, 562500, 562503, C07D17700

Patent

active

047975067

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

1. Technical Field
The present invention relates to 6-substituted prostaglandins E.sub.1 and a process for producing the same. More specifically, the present invention relates to 6-substituted prostaglandins E.sub.1 such as 6-nitroprostaglandins E.sub.1 and 6-oxoprostaglandins E.sub.1, which are useful as a medicine for the treatment of duodenal ulcers, gastric ulcers, etc., and an industrially advantageous process for producing 6-substituted prostaglandins E.sub.1 wherein organolithium compounds, copper compounds, 4-substituted-2-cyclopentenones, and nitrooelefins are used.
2. Background Art
6-oxoprostaglandin E.sub.1 has a platelet aggregation inhibition effect and a hypertensive effect due to a smooth muscle relaxing effect which are as strong as those of prostacyclin, and is known as an active metabolite of prostacyclin in vivo (C. P. Quilley et al., European Journal of Pharmacology, vol. 57, pp. 273-276, 1979; P. Y. K. Wong et al, European Journal of Pharmacology, vol. 60, pp. 245-248, 1979; C. N. Berry et al., Pharmacology, vol. 26, pp. 324-330, 1983; and R. J. Griffiths et al., British Journal of Pharmacology, vol. 79, pp. 149-155, 1983). It is known that some analogues of 6-oxoprostaglandin E.sub.1 have not only a platelet aggregation inhibition effect and a hypertensive effect but also an excellent antiulcerative effect (Japanese Unexamined Patent Publication Nos. 54-44639 and 55-141465).
On the other hand, prostacyclin exhibits a half-life of activity on the order of several minutes at a physiological pH, and thus, is unstable, as a medicine. However, the above-mentioned 6-oxoprostaglandin E.sub.1 is more stable than prostacyclin (C. P. Quilley et al., European Journal of Pharmacology, vol 57, pp. 273-276, 1979). Thus, there is a desire in the field for the application of 6-oxoprostaglandin E.sub.1 and its analogues as a medicine.
Moreover, 6-nitroprostaglandins E.sub.1 are known and have pharmacological effects such as a platelet aggregation inhibition effect (Japanese Unexamined Patent Publication No. 59-36657).
Conventionally, the above-mentioned 6-oxoprostaglandin E.sub.1 analogues are prepared through prostacyclin by means of several process using, as the starting material, prostaglandin F.sub.2 .alpha. and its analogues, which are obtained through an intermediate referred to as a so-called corey lactone (Japanese Unexamined Patent Publication Nos. 54-44639 and 55-141465). However, this production process not only requires many process to obtain the desired compound but also the resultant derivative is only a compound having a hydroxyl group at the 15-position according to the prostaglandin nomenclature. Therefore, this process is disadvantageous in that it is deficient in general-purpose properties.


DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a novel 15-deoxy-16-hydroxy-6-oxoprostaglandins E.sub.1 and a novel 15-deoxy-16-hydroxy-6-nitroprostaglandins E.sub.1 wherein the hydroxyl group at the 15-position of natural type prostaglandin is shifted to the 16-position.
Another object of the present invention is to provide a novel 6-substituted prostaglandins E.sub.1, such as 15-deoxy-16-hydroxy-6-nitroprostaglandins E.sub.1 and 15-deoxy-16-hydroxy-6-oxoprostaglandins E.sub.1, which are useful for the treatment of digestive organ diseases such as duodenal ulcers and gastric ulcers.
Still another object of the present invention is to provide a process for producing 6-substituted prostaglandins E.sub.1 which is extremely excellent for industrial purposes.
Other objects and advantages of the present invention will be apparent from the following description.
The objects and advantages of the present invention are attained by the following 6-substituted prostaglandins E.sub.1.
That is, the present invention is 6-substituted prostaglandins E.sub.1, which are compounds represented by the following formula [I] or their enantiomers or mixtures thereof in any ratio: ##STR3## wherein R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.10 alkyl group, a substi

REFERENCES:
patent: 4649156 (1987-03-01), Tanaka

Affiliated with

Also associated with

Rating

6-substituted prostaglandins E.sub.1 and process for producing s does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 6-substituted prostaglandins E.sub.1 and process for producing s, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 6-substituted prostaglandins E.sub.1 and process for producing s will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2108622