Bristol-myers Company

Bristol-myers Squibb Compnay

Bristol-myers

Masahisa Oka

Takayuki Naito

Jun Okumura

Masataka Konishi

Koji Tomita

Hajime Kamachi

Ken-ichi Numata

Seiji Iimura

Osamu Tenmyo

Keiichi Numata

Hideaki Hoshi

Haruhiro Yamashita

Nobuaki Naruse

Toshikazu Oki

Yosuke Sawada

Masaru Sugawara

Noriyuki Ohkusa

The present invention provides BU-4641V of the formula: ##STR1## This invention also provides a biologically pure culture of BU-4641V producing Arthrinium sp. FA1744. Another aspect of the invention provides a process for preparing BU-4641V. Yet further aspect of the present invention provides a method for treating mammalian tumors and bacterial or viral infections.

BU-4641V, an antibacterial, antiviral and antitumor antibiotic

There is provided a new antiviral antibiotic designated herein as BU-4344V which is produced by fermentation of a BU-4344V-producing strain of a new microorganism, Actinomadura parvosata subsp. kistnae ATCC No. 55076. Antibiotic BU-4344V is recovered and purified from the fermentation broth by use of extraction, chromatography, and crystallization techniques. BU-4344V has been found to have some antibacterial activity and inhibits the growth of viruses, including influenza virus type A.

Antiviral antibiotic BU-4344V

Glidobactin PF-1 of the formula ##STR1## having antitumor activity is prepared by cultivation of Polyangium brachysporum in a nutient medium containing a suitable fatty acid ester, such linolenate, together with other assimilable sources of carbon and nitrogen.

Glidobactin PF-1 peptide antibiotics

Novel peptides of the formula ##STR1## wherein R is CH.sub.3 --(CH.sub.2).sub.6, CH.sub.3 --(CH.sub.2).sub.4 --CH.dbd.CH--(CH.sub.2).sub.2 and CH.sub.3 (CH.sub.2).sub.8 having antibiotic and antitumor activity are prepared by cultivation of the novel microorganism Polyangium brachysporum. Enzymatic hydrolysis of those peptides gives other peptides useful as intermediates in the preparation of peptides having activity as antibiotics and/or antitumor agents.

Peptide antibiotics

Novel peptide antibiotics designated herein as BU-2867T F and G are produced by fermentation of Polyangium brachysporum strain K481-B101 (ATCCC 53080). The new antibiotics are found to have antifungal activity and to inhibit P388 lymphatic leukemia in rodents.

BU-2867T peptide antibiotics

Novel peptides of the formula ##STR1## wherein R is CH.sub.3 --(CH.sub.2).sub.6, CH.sub.3 --(CH.sub.2).sub.4 --CH.dbd.CH--(CH.sub.2).sub.2 and CH.sub.3 (CH.sub.2).sub.8 having antibiotic and antitumor activity are prepared by cultivation of the novel microorganism Polyangium brachysporum. Enzymatic hydrolysis of those peptides gives other peptides usfeul as intermediates in the preparation of peptides having activity as antibiotics and/or antitumor agents.

Peptides of the formula ##STR1## wherein R is CH.sub.3 --(CH.sub.2).sub.6, CH.sub.3 --(CH.sub.2).sub.4 --CH.dbd.CH--(CH.sub.2).sub.2 and CH.sub.3 (CH.sub.2).sub.8 having antibiotic and antitumor activity are prepared by cultivation of the novel microorganism Polyangium brachysporum. Enzymatic hydrolysis of those peptides gives other peptides useful as intermediates in the preparation of peptides having activity as antibiotics and/or antitumor agents.

Semi-synthetic derivatives of the BU-2867T antibiotics are disclosed. These derivatives are active against experimental mammalian tumors, and may be prepared from enzymatic degradation product(s) of BU-2867T A.

Semi-synthetic peptide antibiotics

7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(substituted)-iminoacetamido]-3-[3-( quaternaryammonio)-1-propen-1-yl]-3-cephem-4-carboxylates of the formula ##STR1## in which R.sup.1 and R.sup.2 are defined herein and --.sup..sym. N.tbd.Q is a quaternary ammonio group as defined herein, and salts, solvates, hydrates and esters thereof, are potent antibacterial agents. Processes for their preparation and intermediates in such processes are described.

Cephalosporin derivatives

Semi-synthetic derivatives of the BU-2867T antibotics are disclosed. These derivatives are active against experimental mammalian tumors, and may be prepared from enzymatic degradation product(s) of BU-2867T A.

Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen or a conventional amino-protecting group, R.sup.2 is a straight or branched chain alkyl group containing from 1 to 4 carbon atoms, allyl, 2-butenyl, 3-butenyl, propargyl, 2-butynyl, 3-butynyl, cycloalkyl containing from 3 to 6 carbon atoms or a group of the formula ##STR2## in which R.sup.3 and R.sup.4 each are independently hydrogen, methyl or ethyl, or R.sup.3 and R.sup.4, taken together with the carbon atom to which they are attached, may be a cycloalkylidene ring containing from 3 to 6 carbon atoms or a substituted cyclobutylidene ring of the formula ##STR3## wherein X is halogen, hydroxy or (lower)alkoxy, and R.sup.5 and R.sup.6 each are independently hydrogen, halogen, amino, carbamoyl, acylamino, acyloxy, (lower)alkyl, (lower)alkenyl, (lower)alkoxy, (lower)alkylamino or (lower)alkylthio, in which each (lower)alkyl, (lower)alkoxy, (lower)alkylamino or (lower)alkylthio group may contain 1 or 2 substituents selected from amino, carboxy, halogen and nontoxic pharmaceutically acceptable acid addition salts, physiologically hydrolyzable esters and solvates thereof, as well as processes for their preparation, are disclosed. The compounds in which R.sup.1 is hydrogen are potent antibacterial agents.

Growing community of inventors

Yokohama, Japan

Masahisa Oka