VOL.

45

NO.

7

THE JOURNAL OF ANTIBIOTICS

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7-[2-(2-AMINOOXAZOL4-YL)-(Z)-2-ALKOXYIMINOACETAMIDO] CEPHALOSPORIN ANTIBIOTICS

modification -

in the following

December 27, 1991) having an

derivatives

cephalosporin derivatives,

Fig. 1.

of 3-methoxymethyl

one of which, cefpodo-

xime proxetil (Fig. 1), has been successfully developed as a prodrug for oral use. Our further elaboration for developing orally active cephalo-

sporins has been made in the direction of chemical Scheme

(4a~4e)

activity of the 7-aminooxazolyl is shown in Table

1. These

tested organisms especially against Gram-positive strains. Among them, methoxime (4a) and

In a previous paper3), we reported on the synthesis activity

scheme.

compounds showed fairly good potency against the

aminothiazole-oxime moiety at the C-7 position of the cephem nucleus have been developed for oral use1~3). and the biological

of the

3-methoxymethyl cephalosporin derivatives. 7-[2-(2-Aminooxazol-4-yl)-(Z)-2-alkoxyimino-

The antibacterial

Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140, Japan

In recent years, some cephalosporins

of the C-7 acyl substituent

acetamido] -3-methoxymethyl cephalosporin derivatives (4 and 5) were prepared in a similar manner to that described in previous papers3'40 as illustrated

Eui Nakayama, Koichi Fujimoto, Shigeki Muramatsu and Junya Ide Medicinal Chemistry Research Laboratories, (Received for publication

1193

1.

Structure

of cefpodoxime

2-

and cefpodoxime

THE JOURNAL OF ANTIBIOTICS

1194

Table 1. Antibacterial

activity

Organism

JULY 1992

(MIC, /*g/ml)a of 7-aminooxazolyl

derivatives

(4a~4e).

4d

4e

4a

4b

Staphylococcus aureus 209P JC- 1

0.4

0.2

0.8

0.4

0.1

0.8

S. aureus 56C

0.8

0.8

1.5

0.4

0.8

Escherichia

1.5 3.1

25 3.1

12.5 12.5 12.5

0.4

0.4

6.2 6.2 1.5

0.8 1.5 3.1 0.4

0.4

0.1

0.4

0.1

E. coli

coli NIHJ JC-2

609c

Klebsiella pneumoniae 806 Proteus

vulgaris

Agar dilution

Cefpodoxime.

1420

4c 12.5

CPDXb

0.4

0.1

Synthesis and antibacterial activity of 7-[2-(2-aminooxazol-4-yl)-(Z)-2-alkoxyiminoacetamido]-cephalosporin antibiotics.

VOL. 45 NO. 7 THE JOURNAL OF ANTIBIOTICS SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7-[2-(2-AMINOOXAZOL4-YL)-(Z)-2-ALKOXYIMINOACETAMIDO] CEPHALOSPOR...
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