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Biomedical subjects

S Umezawa

Publications and source records attributed to S Umezawa.

At least 73 records · Page 4Linked to original sources
PubMed1988

Synthesis of 1-N-(D-threo- and racemic erythro-3-amino-2-hydroxybutanoyl)-2',3'-dideoxykanamycin A.

1-N-(D-Threo-3-amino-2-hydroxybutanoyl)-2',3'-dideoxykanamycin+ ++ A has been prepared by coupling of 3,6'-bis(N-benzyloxycarbonyl)-2',3'-dideoxy-3"-N-(trifluoroacetyl)kanamy cin A with D-threo-3-azido-2-hydroxybutanoic acid. A diastereomeric mixture of the erythro analog has also been prepared by use of racemic erythro-3-azido-2-hydroxybutanoic acid. Synthesis of the D-threo- and racemic erythro-3-amino-2-hydroxybutanoic acids has been described.

Anti-Bacterial Agents↗
PubMed1988

Antitumour activity of new semi-synthetic anthracyclines containing fluorotalopyranose.

The authors have synthesized 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone (FT-ADM) which exhibited strong antitumour activity and weak toxicity. These characteristics of FT-ADM are partly due to the presence of a 2'-fluoro atom which strengthens the glycoside bond. FT-ADM, however, is sparingly soluble in water because of lack of the 3'-amino group of adriamycin. To increase the solubility of FT-ADM, a hydrophilic group was added at the 14-OH group. Then, the 14-hemisuccinate, 14-hemiglutarate, 14-hemiadipiate, 14-hemipimelate and 14-hemisuberate derivatives of FT-ADM were synthesized. Among them, the 14-hemipimelate derivative (FAD-104) was selected for further development because of its potent antitumour activity and weak toxicity. When drugs were injected intraperitoneally every day from day 1 to 9, FAD-104 showed an apparently stronger antitumour effect against mouse L-1210 leukaemia than adriamycin with lower toxicities. FAD-104 was also more effective than adriamycin on L-1210 using other administration schedules. A characteristic feature is that FAD-104 is effective over a very broad range, which will be advantageous for safe clinical use. FAD-104 also showed marked antitumour effect against L-1210 when it was injected intravenously either once on day 1 or three times on days 1, 5 and 9. Thus, FAD-104 may be a more potent antitumour anthracycline than adriamycin.

Animals↗
PubMed1988

Biological properties of ME2303 (FAD-104), a new anthracycline.

ME2303 (FAD-104) is a new anthracycline antibiotic whose structure is characterized by the presence of a 2'-fluoro atom and the lack of a 3'-amino group in the sugar moiety. Its cytocidal activity is superior to or equal to that of adriamycin (ADM). The LD50 value of ME2303 was about 140 mg/kg i.v. in mice and this value was about 7-fold higher than that of ADM. ME2303 was administered intravenously to Golden strain hamsters at doses of 25, 50, 75 and 150 mg/kg and the ECG was examined. From ECG changes, it seems that ME2303 did not show any effect on the heart in acute toxicity. Mutagenicity was recognized as with ADM in the back-mutation test.

Animals↗
PubMed1987

Synthesis of antitumor-active 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)-daunomycinone and -adriamycinone.

The title compounds (17 and 23) were prepared by coupling 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (15) with daunomycinone. The key step in the preparation of 15 was the epoxide-ring opening of methyl 2,3-anhydro-4-O-benzyl-6-deoxy-alpha-L-gulopyranoside with KHF2 in ethylene glycol, whereupon 2-fluoro-alpha-L-idopyranoside was obtained. Compounds 17 and 23 showed strong antitumor activity.

Animals↗
PubMed1987

An attempt to assess the replacement dose of human growth hormone in the treatment of growth hormone deficient children.

In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3-0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900-2100 hours with a dose of 0.46 +/- 0.07 IU/kg/week (equivalent to 14.7 +/- 2.0 IU/m2/week). After 1-3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose.

Adolescent↗
PubMed1987

Syntheses of 23-C-alkylidene, and 23-N-containing derivatives of 5-O-mycaminosyltylonolide.

Several derivatives of 5-O-mycaminosyltylonolide substituted at C-23 have been prepared; these are 23-deoxy-23-C-methylene (3), 23-deoxy-23-C-(methoxycarbonylmethylene) (5), 23-deoxy-23-C-(ethoxycarbonylmethylene) (7), and 23-deoxy-23-C-(butoxycarbonylmethylene) (9), 23-deoxy-23-C-[(2E)-3-(ethoxycarbonyl)-2-propenylene] (11), and 23-deoxy-23-(dimethylaminoimino) (13), and 14-de(hydroxymethyl)-14-nitrile (16) derivatives. The key steps in these syntheses are the reactions of 2',4'-di-O-acetyl-3-O-tert-butyldimethylsilyl-23-deoxy-23-oxo-5-O- mycaminosyltylonolide diethyl acetal (1) with several Wittig reagents, 1,1-dimethylhydrazine and hydroxylamine. Antibacterial activities of these compounds are also described.

Anti-Bacterial Agents↗
PubMed1985

N-Substituted derivatives of 23-amino-4',23-dideoxymycaminosyl tylonolide. Synthesis and antibacterial activity.

23-Amino-4',23-dideoxymycaminosyl tylonolide diethyl acetal (5) has been prepared from 4',23-dideoxy-23-iodomycaminosyl tylonolide diethyl acetal (3) by treatment with sodium azide followed by selective reduction of the resulting azide (4). 23-Acylamino-23-deoxy (6 approximately 8) and 23-deoxy-23-urethane-type compounds (12 approximately 15) were further prepared. Treatment of the 23-alkylamino-4',23-dideoxymycaminosyl tylonolides (9, 10) with chloroformates gave 23-N-alkyl-23-deoxy-23-urethane-type compounds (16 approximately 21, 29, 30). 23-N-Alkyl-23-deoxy-23-(2-hydroxyethalamino and 2-methoxyethylamino)-4',23-dideoxymycaminosyl tylonolides (22 approximately 25, 27, 28) were prepared from 3 and the corresponding amines. Antibacterial activities and toxicities (for 23 and 27) of these compounds are described. toxicities (for 23 and 27) of these compounds are described.

Bacteria↗
PubMed1984

Syntheses of 23-deoxy-23-N-ethyl-23-(2-fluoro-, 2,2-difluoro-, and 2,2,2-trifluoroethyl)amino derivatives of mycaminosyl tylonolide and 4'-deoxymycaminosyl tylonolide.

Derivatives of mycaminosyl tylonolide (1) and 4'-deoxymycaminosyl tylonolide (2) containing N-ethyl-2-fluoro-, 2,2-difluoro- and 2,2,2-trifluoroethylamino groups at their C-23 have been prepared by treating 23-deoxy-23-ethylaminomycaminosyl tylonolide diethyl acetal (14) and its 4'-deoxy analog 15 with 2-fluoro-, 2,2-difluoro- and 2,2,2-trifluoroethyl trifluoromethanesulfonates. The relationship between the antibacterial activity and the numbers of the fluorine atoms introduced in the final products is discussed.

Leucomycins↗