Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-09-08
1998-05-05
Robinson, Douglas W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 9, 530317, 530323, 530328, A61K 3815, C07K 1102
Patent
active
057474486
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel derivatives having a cyclo-tetradepsipeptide skeletal structure in common to PF 1022, which is a cyclodepsipeptide and has anthelmintic activities, and having excellent anthelmintic activities; and also to anthelmintic agent containing the derivatives. The novel PF 1022 derivatives according to the present invention show excellent anthelmintic activities against worms parasitic on animals and therefore are useful as anthelmintic agent.
BACKGROUND ART
The PF 1022 substance is a cyclodepsipeptide which was found as a result of Patent Application Laid-Open (Kokai) No. HEI 3-35796, European Patent Application Publication No. 0382173A2 and "J. Antibiotics", 45, 692(1992)!. In addition, the PF 1022 substance is a fermentation product, which is produced by the culture of a filamentous fungus PF1022 strain (deposited under FERM BP-2671 with National Institute of Bioscience and Human-Technology Agency in Tsukuba-shi under the provisions of the Budapest Treaty) belonging to Agonomycetales and is a cyclodepsipeptide represented by the following formula (A): ##STR2##
The PF 1022 substance is a depsipeptide which is formed of ester-bonds and amido-bonds and which can also be represented by the following formula (A'): formula: ##STR3## Lac is a lactic acid residue represented by the following formula: ##STR4## and PhLac is a phenyllactic acid residue represented by the following formula: ##STR5##
By the culture of the above filamentous fungus PF 1022 strain, the PF 1022B substance of the following formula (B), the PF1022C substance of the formula (C), the PF 1022D substance of the formula (D) and the PF 1022E substance of the formula (E) are produced in addition to the above PF 1022 substance. They have anthelmintic activities and were isolated by the Japanese Patent Application Laid-Open (Kokai) No. HEI 5-170749; but concerning PF 1022E, Japanese Patent Application No. HEI 4-279094 (filed Oct. 19, 1992 but not yet laid open)!. ##STR6##
Incidentally, the PF 1022E substance is a novel compound which has not been reported yet.
The above-described PF 1022 substance and PF 1022B to E substances all possess anthelmintic activities and have a marked structural characteristic in that they have a large cyclo-tetradepsipeptide structure as a basic skeleton, and that they have, as side chains, not only four N-methyl groups and four isobutyl groups but also 0-3 methyl group(s) and 1-4 benzyl group(s) and contain eight asymmetric carbon atoms in their molecules. In the skeletal cyclodepsipeptide structure of the group of these PF 1022 substances, a 24-membered ring is formed via 4 ester bonds and 4 amide-bonds. This structure can be presumed to play an important role on the development of biological activities.
So-called helmintic infections cause serious damage to the human and animal health and also to agriculture. There is a steady demand toward novel and useful substances having anthelmintic activities and also advantageous preparation processes for such anthelmintically active substances. Paying attention to such a demand, the present inventors studied with a view toward preparing and providing novel substances related to the PF 1022 substance.
The PF 1022 substance is a fermentation product of the above-described filamentous fungus. Makoto Ohyama et al. proposed, as a process of preparing the PF 1022 substance by total synthesis, a process which Japanese Patent Application No. HEI 4-131139 (filed: May 22, 1992) and Japanese Patent Application Laid-Open No. HEI 5-320148 (laid open: Dec. 31 1993)!. ##STR7##
Incidentally, as one example of hitherto known totally synthetic processes for preparation of cyclodepsipeptides, the process reported in "Agric. Biol. Chem." 43(5), 1079-1083(1979), which is related to total synthesis of enniatin C, can be given.
DISCLOSURE OF THE INVENTION
With a view to providing novel cyclodepsipeptides which have a cyclo-tetradepsipeptide skeletal structure in common to the PF 1022 substance but exhibit anthelmintic activities superior to the
REFERENCES:
patent: 5116815 (1992-05-01), Takagi et al.
patent: 5514773 (1996-05-01), Nishiyama et al.
Kanaoka et al. `Bassianolide, A New Insecticidal Cyclodepsipeptide From Beauveria Bassiana and Verticillium Lecanii`, Agric. Biol. Chem. 42(3) pp. 629-635, 1978.
Isogai et al. `Bassianilide: Syntheses of its Analogs and NMR Studies`, Peptide Chemistry (ed. N. Izumiya), Protein Research Foundation, pp. 167-170, 1979.
Ivanov et al. `Syntheic and Natural Cyclodepsipeptides`, in Peptides pp. 337-350, 1965.
Iinuma Katsuharu
Koyama Masao
Murai Yasushi
Ohishi Maki
Ohyama Makoto
Gupta Anish
Meiji Seika Kaisha Ltd.
Robinson Douglas W.
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