Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Sanraku-Ocean Co., Ltd.

Akira Takamatsu

Hamao Umezawa

Toshikazu Oki

Masa Hamada

Takaaki Aoyagi

Taiji Inui

Hiroshi Tone

Kenji Kayahara

Rokuro Okamoto

Shunro Mori

Tsumoru Fukumoto

Tomio Takeuchi

Masaaki Ishizuka

Hajime Morishima

Hajime Morishama

New tylosin derivatives having at least one acyl group at the 3- and 4'-positions of tylosin, and the acid addition salts thereof, which inhibit the growth of various microorganisms including drug-resistant bacterial isolants and which produce high blood levels through oral administration are produced by a biochemical reaction using the microorganisms of the genus Streptomyces which are selected for their newly-found ability to acylate at least one of the 3- and 4'-positions of macrolide antibiotics; they are recovered from the reacted mixture by conventional methods for recovering macrolide antibiotics.

Process for manufacturing tylosin derivatives

Tylosin derivatives and their manufacturing process

Compounds having the general formula ##STR1## wherein R.sup.2 is substituted either at the 4'-position or at the 5'-position and is hydrogen, fluoro, bromo, chloro, hydroxy or lower alkyl; R.sup.3 is chloro, bromo or lower alkyl; R.sup.4 is hydroxy, amino or lower alkoxy, and Z is hydrogen or lower alkyl and the nontoxic, pharmaceutically acceptable metal salts of said compounds when Z is hydrogen exhibit strong activities in inhibiting histidine decarboxylase and anthine oxidase.

Treatment of elevated histamine and uric acid levels

Compounds having the formula ##STR1## (the meanings of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are indicated hereinafter) exhibit suppressive activity to various immune responses and can be employed in the therapy of immunological diseases, especially autoimmune diseases. One example is 3',5'-dichloro-2,4'-diacetoxybenzanilide having the formula ##STR2## and another is 3',5'-dichloro-2,4'-dibenzoyloxyanilide having the formula ##STR3##

Pharmaceutical method for the therapy of immune diseases

New antitumor agents named aclacinomycins A and B, which are anthracycline glycosides and inhibit the growth of various microorganisms e.g., Staphylococcus aureus, Micrococcus flavus, Corynebacterium bovis and inhibit the growth of animal tumors such as leukemia L1210 and P388 and lymphoma 6C3HED in mice and hepatomas in rats are produced by the fermentation of a microorganism belonging to the genus Streptomyces which has been designated Streptomyces galilaeus (MA144-M1 and A.T.C.C. 31133); they are recovered from the broth by conventional methods for recovering antibiotics.

Antitumor antibiotics aclacinomycins A and B [RD-9187A]

A novel physiologically active peptide Val-X-Ala-X, in which X is 4-amino-3-hydroxy-6-methylheptanoic acid, which is prepared from R-Val-Val-X-Ala-X by the action of a microbial enzyme, N-acyl derivatives thereof which are produced by acylating said new peptide, and the processes for producing thereof and the microbial enzyme are disclosed.

Novel physiologically active peptide and its n-acyl derivatives and

A novel physiologically active peptide Val--X--Ala--X, in which X is 4-amino-3-hydroxy-6-methylheptanoic acid, which is prepared from R--Val--Val--X--Ala--X by the action of a microbial enzyme, N-acyl derivatives thereof which are produced by acylating said new peptide, and the processes for producing thereof and the microbial enzyme are disclosed.

Processes for producing physiologically active peptide and its N-acyl

Compounds having the formula ##STR1## (the meanings of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are indicated hereinafter) exhibit suppressive activity to various immune responses and can be employed in the therapy of immunological diseases, especially autoimmune diseases. One example is 3',5'-dichloro-2,4'-dihydroxybenzanilide having the formula ##STR2## AND ANOTHER IS 3',5'-DICHLORO-2,2'-DIHYDROXYBENZANILIDE HAVING THE FORMULA ##STR3##

Compounds having the general formula ##STR1## (the meanings of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are indicated hereinafter) and the pharmaceutically acceptable salts and esters thereof exhibit strong activities in inhibiting histidine decarboxylase and xanthine oxidase and are useful for treating elevated histamine and uric acid levels. One example is the compound of the formula ##STR2##

A new antitumor agent named macracidmycin, which is a macromolecular peptide and inhibits the growth of various tumor cells and experimental animal tumors such as Ehrlich ascites carcinoma and Sarcoma 180 is produced by the fermentation of a microorganism belonging to the genus Streptomyces which has been designated Streptomyces atrofaciens (M590-G2 and A.T.C.C. 31104); it is recovered from the broth by conventional methods for recovering antibiotics.

Antitumor antibiotic macracidmycin

Antibiotics aclacinomycins A and B

Compounds having the general formula ##SPC1## (the meanings of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are indicated hereinafter) and the pharmaceutically acceptable salts and esters thereof exhibit strong activities in inhibiting histidine decarboxylase and xanthine oxidase. One example is the compound of the formula ##SPC2##

A process for producing pepstatins by means of a microorganism belonging to Streptomyces and producing pepstatins, wherein at least one amino acid selected from the group consisting of L-leucine, L-valine, L-alanine, L-aspartic acid, L-glutamic acid, and L-lysine is added to the reaction medium, which also contains an energy source.

Growing community of inventors

Yokohama, Japan

Akira Takamatsu