Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1990-05-18
1992-07-14
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
570075, 568308, C07C23300, C07C 4500
Patent
active
051304830
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The invention relates to novel isoprenoid derivatives and 5-lipoxygenase-inhibitors and anti-ulcer agents containing the same. The isoprenoid derivatives of the invention have an inhibitory activity against 5-lipoxygenase as well as an anti-ulcer activity.
TECHNOLOGICAL BACKGROUND
Leukotrienes such as leukotriene C.sub.4 (LTC.sub.4) and leukotriene D.sub.4 (LTD.sub.4) which participate in the onset mechanism of allergy are biosynthesized from arachidonic acid by the action of 5-lipoxygenase.
It has recently been made evident that leucotrienes relates not only to the onset of allergy, but also to the onset of other pathological conditions including nephritis, hepatis, leumatism and gastric ulcer.
Accordingly, it has been a subject of investigation to find substances inhibiting biosynthesis of leucotrienes thereby being effective in the therapy of these diseases. Discovery of substances having anti-ulcer activities against gastric and other ulcers has also been another subject.
We synthesized a variety of isoprenoid derivatives and made extensive studies on 5-lipoxygenase-inhibiting activities and anti-ulcer activities of these compounds. As a result of these studies we have found that the isoprenoid derivatives according to the present invention possess a high 5-lipoxygenase-inhibiting activity and a potent anti-ulcer activity. The invention has been completed on the basis of the finding. The 5-lipoxygenase inhibitory isoprenoid derivatives of the invention inhibit the biosynthesis of leucotrienes thereby being useful in the therapy of nephritis, hepatitis and rheumatism as well as asthma and rhinitis which are allergic diseases.
Furthermore, the isoprenoid derivatives of the invention which have an anti-ulcer activity are also useful in the therapy of gastric and other ulcers.
It is therefore an object of the invention to provide new isoprenoid derivatives and 5-lipoxygenase inhibitors and anti-ulcer agents containing same.
DISCLOSURE OF THE INVENTION
To meet the above-mentioned object, the invention provides isoprenoid derivatives represented by the general formula (I) ##STR2## wherein R represents a hydrogen atom or a lower alkyl group, X represents --CH.sub.2 --, --O-- or --NH--, n represents number of the double bond in trans-configuration and is 1 or 2 and m is an integer from 0 to 3.
As examples of the above lower alkyl group are mentioned methyl, ethyl, n-propyl, i-propyl, n-butyl and the like. Methyl is most preferable.
The isoprenoid derivatives represented by the formula (I) are prepared selectively by the methods described below depending upon the nature of the group X.
1) The compounds of the formula (I) wherein X is --CH.sub.2 -- are produced by reacting an aldehyde derivative having the formula (II) ##STR3## wherein R.sub.1 represents a group defined above for R or a hydroxy-protecting group, R.sub.2 represents a hydrogen atom or a hydroxy-protecting group and p represents number of the double bond in trans-configuration and is 0 or 1 with an isoprenylacetone having the formula (III) ##STR4## wherein m has the same meaning as defined above followed by a dehydration reaction and a protective group-eliminating reaction.
2) The compounds of the formula (I) wherein X is --O-- are produced by reacting a carboxylic acid derivative having the formula (II)' ##STR5## wherein R.sub.1, R.sub.2 and n have the same meanings as defined above with an isoprenyl alcohol having the formula (III)' ##STR6## wherein m has the same meaning as defined above followed by a protective group-eliminating reaction.
3) The compounds of the formula (I) wherein X is --NH-- are produced by reacting a carboxylic acid derivative having the formula (II)' with an isoprenyl amine having the formula (III)" ##STR7## wherein m has the same meaning as defined above followed by a protective group-eliminating reaction. The isoprenyl amines mentioned above are produced by decomposing a corresponding isoprenyl phthalimide with hydrazine.
As the hydroxy-protecting group in the above reactions is preferably employed
REFERENCES:
patent: 4618627 (1986-10-01), Murase et al.
patent: 4673684 (1987-06-01), Wakabayashi et al.
patent: 4733002 (1988-03-01), Yokoyama et al.
CA108(3):19241z 1987 [Wollenweber, E. et al., Z Naturforsch C:Biosci 42(9-10) 1030-4 1987].
Hashimoto et al., Zeitschrift fur Naturfarsehung 43:470-472 (1988).
Patent Abstracts of Japan, vol. 10, No. 226 (C-364) [2282] (1986).
Patent Abstracts of Japan, vol. 9, No. 309 (C-318) [2032] (1985).
Patent Abstracts of Japan, vol. 13, No. 427 (C-639) [3775] (1989).
Patent Abstracts of Japan, vol. 13, No. 472 (C-647) [3820] (1989).
Koyama Shingo
Masuda Akira
Miyaoka Syozo
Murota Seiitsu
Nanba Ryoichi
Killos Paul J.
Terumo Kabushiki Kaisha
LandOfFree
Isoprenoid derivatives and pharmaceutical preparations containin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Isoprenoid derivatives and pharmaceutical preparations containin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Isoprenoid derivatives and pharmaceutical preparations containin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-336086