Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Microbial Chemistry Research Foundation

Meiji Seika Pharma Co., Ltd.

Meiji Seika Kaisha, Ltd.

Toshiaki Miyake

Yoshiaki Takahashi

Sumio Umezawa

Masayuki Igarashi

Takeshi Murakami

Masa Hamada

Nobuto Minowa

Daishiro Ikeda

Yoshihiko Kobayashi

Shoichi Murakami

Shigeru Hoshiko

Yoshihisa Akiyama

Mitsuhiro Abe

Kazushige Sasaki

Masaki Tsushima

Yukiko Hiraiwa

Hamao Umezawa

Tsutomu Tsuchiya

Tetsuo Shitara

Tomio Takeuchi

Takeo Yoshioka

Tomohisa Takita

Osamu Tsuchiya

Naoki Matsumoto

Hiroshi Tanaka

Kaichiro Kominato

Shunji Kageyama

Tomo Jikahara

This invention relates to novel aminoglycoside antibiotics, which have potent antimicrobial activity against bacteria, which induce infectious diseases, particularly MRSA, and has no significant nephrotoxicity, and process for producing them. More particularly, the present invention relates to compounds represented by formula (Ia) or their pharmacologically acceptable salts or solvates, or their diastereomer mixtures, antimicrobial agents comprising them, and a process for producing them. 

Aminoglycoside antibiotics

Caprazene is provided which is the compound represented by the following formula (I) wherein Me stands for methyl group, and a 5&#x2033;-N-alkoxycarbonyl or 5&#x2033;-N-aralkyloxycarbonyl derivative thereof, and wherein said compound has theH-NMR andC-NMR data as set forth in Table 15.

Caprazene as a novel compound and derivatives thereof, and caprazol as a novel compound and derivatives thereof

A novel compound that has antimicrobial activity against penicillin-resistant, and an anti-penicillin resistant pneumococci agent that includes the compound as an active ingredient are provided. Thus, an anti-penicillin resistant pneumococci agent is provided that includes as an active ingredient a compound represented by the following formula (I) or a pharmacologically acceptable salt thereof, or hydrates thereof: 

Anti-penicillin resistant pneumococci agent and novel 16-membered macrolide derivative

Caprazene and caprazol could be synthesized by hydrolysis of a caprazamycin. There could be synthesized a caprazene-1'&#x2033;-amide derivative of the formula (II) and a caprazene-1&#x2032;&#x2033;-ester derivative of the formula (III) from caprazene. Further, there could be synthesized a caprazol-1&#x2032;&#x2033;-amide derivative of the formula (V) and a caprazol-1&#x2032;&#x2033;-amide-3&#x2032;&#x2033;-ester derivative and a caprazol-3&#x2032;&#x2033;-ester derivative, etc. from caprazol. Furthermore, an imidazolidinone derivative could be synthesized from the ring-opened product of the 1,4-diazepinone ring of caprazol. The novel caprazene derivative, novel caprazol derivative and novel imidazolidinone derivative now synthesized exhibit excellent antibacterial activities against a variety of bacteria, including acid-fast bacteria.

Caprazene as novel compound and derivatives thereof, and caprazol as novel compound and derivatives thereof

20,23-disubstituted mycaminosyltylonolide derivatives and use of the same in the field of the prophylaxis and treatment of pasteurellosis are disclosed. The di-substituents are peperidino optionally substituted with one or two methyl groups. The derivatives have selective antibacterial activity against Pasteurella.

Macrolide antibiotics and treatment and prophylaxis of pasteurellosis using the same

3,4'-dideoxymycaminosltylonolide derivative and process for producing

3'-Deoxykanamycin B, namely tobramycin is produced in an improved yield with a reduced reaction time under moderate reaction conditions, starting from a penta-N-protected 3'-mono-O-alkyl-, aralkyl- or arylsulfonylated derivative of kanamycin B in which all the 1, 3, 2' and 3'-amino groups and possibly the 6'-amino group have been protected by an arylsulfonyl group, especially tosyl group; the 3'-hydroxyl group of kanamycin B has been alkyl-, aralkyl- or arylsulfonylated; the 4'- and 6'-hydroxyl groups have been blocked with a di-valent hydroxyl-protecting group; and possibly the 4'-hydroxyl group and 6'-amino group have been blocked by being converted into the form of a 4', 6'-cyclic carbamate formed between the 4'-hydroxyl group and the 6'-amino group, by subjecting to a process essentially comprising reaction of said protected kanamycin B derivative with a metal halide for a reaction time of 30 min. to 2 hours at a reaction temperature of 0.degree. C..about.150.degree. C. to produce the corresponding 3'-halo compound, reductive replacement of the 3'-halo group by hydrogen and deprotection.

Process for the production of kanomycin B derivatives and products

3',4'-Dideoxy derivative and 1-N-((S)-.alpha.-hydroxy-.omega.-aminoalkanoyl)-3',4'-dideoxy derivative of kanamycin A are now synthetized from kanamycin A and show a wider and/or higher antibacterial activity than the parent kanamycin A so that they are useful in therapeutic treatment of infections by gram-negative and gram-positive bacteria, including drug-resistant strains thereof. The production of these new derivatives may be made by preparing a protected kanamycin A derivative having its 3'- and 4'-hydroxyl groups unprotected and having its all or substantially all other functional groups protected from the initial material, kanamycin A, sulfonylating the 3'- and 4'-hydroxyl groups, removing the 3'- and 4'-sulfonyloxy groups from the resulting 3',4'-di-sulfonic acid ester product to give a 3'-eno-kanamycin A derivative, hydrogenating the 3'-eno-kanamycin A derivative to saturate the 3',4'-unsaturated bond and to yield a protected 3',4'-dideoxykanamycin A product, followed by removal of the remainiing protective groups, and optionally further followed by 1-N-acylation of the 1-amino group of the resulting 3',4'-dideoxykanamycin A with an (S)-.alpha.-hydroxy-.omega.-aminoalkanoic acid or its reactive equivalent.

3',4'-Dideoxykanamycin A and

Growing community of inventors

Yokohama, Japan

Toshiaki Miyake