Antibiotics having immunosuppressive activity, delaminomycins an

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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548539, 435121, A61K 3140, C07D20736

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active

055278205

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP93/00845 filed Jun. 22, 1993.


TECHNICAL FIELD

This invention relates to new antibiotics, delaminomycins, which have an immunosuppressive activity and also have an antibacterial activity and an antineoplastic activity. This invention also relates to processes for the production of these antibiotics.
More particularly, this invention relates to delaminomycin A, delaminomycin B, delaminomycin C, delaminomycin A2, delaminomycin B2 and delaminomycin C2 which are the new antibiotics having an immunosuppressive activity, an antibacterial activity to Gram-positive bacteria and an antineoplastic activity, as well as pharmaceutically acceptable salts of the delaminomycins. This inventions also relates to processes for the production of these new antibiotics. Further, this invention relates to a pharmaceutical composition, especially an immunosuppressant composition which comprises the new antibiotic(s) as an active ingredient. Furthermore, this invention relates to sulfuric acid esters of delaminomycins A2, B2 and C2 or salts thereof.
The above-mentioned delaminomycin A, delaminomycin B, delaminomycin C, delaminomycin A2, delaminomycin B2 and delaminomycin C2 are the antibiotics which were named the antibiotics MJ202-72F3-A, MJ202-72F3-B, MJ202-72F3-C, MJ202-72F3-A', MJ202-72F3-B' and MJ202-72F3-C', respectively, at the time which we, the present inventors, initially succeeded in obtaining these new antibiotics. These new antibiotics are described under the laboratory designations, MJ202-72F3, in the specification of Japanese patent application No. 187403/92 (filed 23 Jun. 1992), though the new names of delaminomycins are recently employed by us in stead of the names of MJ202-72F3.


BACKGROUND ART

Hitherto, cyclosporin A, FK506 and spergualins etc., are known as the immunosuppressive substances which are produced by microorganisms. However, these known substances are not fully satisfactory as immunosuppressant.
For many years, there have been demands to provide a new immunosuppressive substance which is useful for transplantation of organs and for therapeutic treatments of immuno-defficiency diseases and local inflammations and is superior to the known immunosuppressants, and to provide a substance which has an excellent antineoplastic activity.


DISCLOSURE OF THE INVENTION

In an attempt to find useful substances having an immunosuppressive activity in the microbial products, we, the present inventors, have isolated a number of microorganisms out of naturally occurring soils and conducted extensive research on the products of these microorganisms. As a result, we have found that three antibiotics, which have an excellent immunosuppressive activity and initially are named as the MJ202-72F3-A, -B and -C substances, are produced and accumulated in a culture broth of a microorganism which we newly have isolated from a soil sample and which belongs to the genus Streptomyces. We have isolated these substances and investigated the biological and physico-chemical properties of these substances. And we have found that these substances have an immunosuppressive activity, an antibacterial activity against Gram-positive bacteria and an anti-neoplastic activity, and that these substances are new compounds as determined through elucidation of their chemical structure formulae and include tautomers.
As mentioned hereinbefore, the substances MJ202-72F3-A, -B and -C substances have recently been re-named as delaminomycin A, delaminomycin B and delaminomycin C, respectively.
Moreover, we have employed each of the above-mentioned delaminomycins A, B and C as a starting material and succeeded in producing delaminomycin A2 from delaminomycin A, delaminomycin B2 from delaminomycin B and delaminomycin C2 from delaminomycin C, respectively, by subjecting the starting materials to a chemical process comprising a ring-closure reaction with accompanying dehydration. We have further investigated biological and physico-chemical properties of delaminomycins A2, B2 and C2 and found that these substances h

REFERENCES:
Ueno et al., J. Antibiotics, (1993), 46(5), 719-27.

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