Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-06-02
2000-11-21
Lambkin, Deborah C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544347, A61K 31495, C07D24146
Patent
active
061503630
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to dihydrophenazinecarboxylic acid derivatives. More particularly, the invention relates to dihydrophenazinecarboxylic acid derivatives having the below-mentioned formula (I) or (III), and an inhibitory agent of glutamic acid toxicity which contains a dihydrophenazinecarboxylic acid derivative having the below-mentioned formula (I), (III) or (V) as an active ingredient.
BACKGROUND OF THE INVENTION
It is known that glutamic acid which is one of natural amino acids has toxicity to neurocyte (Akaike Akinori, Folia Pharmacol. Jpn. 103, 193-201 (1994), etc.). A substance inhibiting glutamic acid toxicity to neurocyte is employable as a brain metabolism activating agent or a brain metabolism improving agent.
Seto et al. reported that sugar moiety-containing dihydrophenazinecarboxylic acid derivatives represented by the below-mentioned formulas (A) and (B) [aestivophoenins A & B] which were isolated from actinomyces belonging to genus Streptomyces inhibit glutamic acid toxicity and shows antioxidant property: J. Antibiotics, 48, 1378 (1995) and PCT WO96/22996. ##STR2##
Further, a dihydrophenazinecarboxylic acid derivative having no sugar moiety which is represented by the following formula (C): ##STR3## is known {Ann. Chim. [13], 1, 115(1956)].
Also known is a compound of the following formula (D) which has no sugar moiety (benthophoenin): ##STR4## and its methyl ester. These compounds are reported to be employable as a free radical scavenger (anti-oxidant). [J. Nat. Prod., 56, 1255(1993)].
Also known is a compound of the following formula (E) which has no sugar moiety: ##STR5## wherein R represents hydrogen, methyl or nitro [Helv. Chim. Acta, 52, 322(1969)].
Also known is a compound of the following formula (F) which has no sugar moiety: ##STR6## [J. Gen. Microbiol., 104, 299(1978)].
As for the above-mentioned dihydrophenazinecarboxylic acid derivatives having no sugar moiety, the publications give no description concerning inhibition of glutamic acid toxicity.
The compound having the aforementioned formula (D) is obtained only from the mycelium of Streptomyces prunicolor.
The compounds having the aforementioned formulas (A) and (B) which are reported to show inhibition of glutamic acid toxicity are natural products. It is not expected to produce enough amounts of these compounds by culture. Further, it is difficult to prepare these compounds by organic synthetic methods because the compounds have L-rhamnose residue in the molecular structure. Until now, no reports have been given on total synthesis of these compounds or their analogs.
Accordingly, it is desired to provide dihydrophenazinecarboxylic acid derivatives which show inhibition of glutamic acid toxicity and which are easily synthesized.
DISCLOSURE OF THE INVENTION
The inventors studied on compounds showing inhibition of glutamic acid toxicity and discovered that dihydrophenazinecarboxylic acid derivatives having no sugar moiety and being represented by the under-mentioned formula (I), (III) or (V) shows excellent inhibitory activity against glutamic acid toxicity. The present invention has been made on the discovery.
The present invention resides in a dihydrophenazinecarboxylic acid derivative having the formula (I): ##STR7## in which
R.sup.1 represents a hydrogen atom, a linear or branched chain alkyl group, an aralkyl group or an aryl group;
each of R.sup.2 and R.sup.3 is the same or different from each other and represents a hydrogen atom, an alkenyl group having 2 to 5 carbon atoms, an alkyl group, an aralkyl group, an aryl group, or a group represented by the formula (II): ##STR8## wherein each of R.sup.6 and R.sup.7 is the same or different from each other and represents a hydrogen atom, a linear or branched chain alkyl group, an aralkyl group or an aryl group, or R.sup.6 and R.sup.7 are combined together to form a nitrogen atom-containing 5- to 7-membered ring in conjunction with the adjacent nitrogen atom, and m is 2, 3 or 4;
each of R.sup.4 and R.sup.5 is the same or different from each othe
REFERENCES:
patent: 1886365 (1932-11-01), Bayer et al.
patent: 3080283 (1963-03-01), Bijloo et al.
patent: 3752813 (1973-08-01), Shen et al.
patent: 4593097 (1986-06-01), Tomita et al.
Nomura Yutaka
Seto Haruo
Shin-ya Kazuo
Takahashi Toshihiro
Lambkin Deborah C.
Nippon Chemiphar Co., Ltd.
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