Akio Hyodo

Synthesis and antibacterial activity of 7-hydrazinoquinolones

A series of new C-7 substituted hydrazino quinolones and naphthyridines were prepared and tested for antibacterial activity. The hydrazine bridge at the C-7 position did not favor the antibacterial activity, whereas the nature of other substituents at N-1, C-5 and C-8 did noticeably influence the antibacterial activity. The 7-(1-aminomorpholino) derivatives exhibited superior antibacterial activity against Gram-positive and inferior activity against Gram-negative bacteria than the 7-(1-aminopiperazinyl) derivatives. Substitution of the quinolone at position-1 with cyclopropyl was the most beneficial for antibacterial activity among the series of compounds prepared.

Studies on monobactams I. Synthesis and β-lactamase inhibitory activity of 4-substituted 3-[(N-methyl-1,2,3-triazol-4-yl)-methylene]-2-azetidinone-1-sulfonates

Two monobactam derivatives, potassium (3Z)-[(N-methyl-1,2,3-triazol-4-yl)methylene]-4-phenylthio-2-azetidinone-1-sulfonate and potassium (3E)-[(N-methyl-1,2,3-triazol-4-yl)methylene]-4-(1,2,3-triazol-1-yl)-2-azetidinone-1-sulfonate, were synthesized and tested for β-lactamase inhibitory activity.

Superior Effect of Tazobactam/ Piperacillin Compared to Piperacillin on β-Lactamase-Producing Pseudomonas aeruginosa

To evaluate the synergistic antimicrobial effects of tazobactam (TAZ), a beta-lactamase inhibitor, and piperacillin (PIPC) on Pseudomonas aeruginosa, we compared the antimicrobial effects of TAZ/PIPC with those of PIPC alone on bacteria inducibly or constitutively producing beta-lactamase. TAZ/PIPC had more potent antimicrobial effects compared with PIPC on clinical isolates producing beta-lactamase. In the treatment of mouse systemic infection, the therapeutic effect of PIPC was markedly decreased by beta-lactamase, but that of TAZ/PIPC was only slightly decreased. In the treatment of local infections in mice, the therapeutic effects of PIPC were decreased due to the induction of beta-lactamase and the emergence of bacterial strains constitutively producing beta-lactamase, while those of TAZ/ PIPC were not affected.

Synthesis and in vitro antimicrobial activity of 3-heteroarylsulphonylmethyl cephems: a new class of cephalosporins

Summary A series of 3-heteroarylsulphonylmethyl and 3-heteroarylsulphenylmethyl cephems were prepared and tested for antimicrobial activities. In contrast to the adverse effect of oxidized ring sulphur of penams and cephems on antimicrobial activities, the oxidized side-chain sulphur of 3-mercaptoheteroaryl cephems retained Gram-negative and slightly decreased Gram-positive activity. The chemical nature of the moieties substituted at C-7 and C-3 positions also influenced the antibacterial activity and spectrum. Compounds with thienyl substitution at C-7 and sulphonylmethylthiazoles or sulphonylmethylthiadiazoles at C-3 exhibited good differentials in antibacterial activity versus their unoxidized counterparts.

Studies on monobactams II. Synthesis and β-lactamase inhibitory activity of 4α-methyl-3-[(thien-2-yl)-methylene]-2-azetidinone-1-sulfonate

Two monobactam derivatives, potassium 4α-methyl-(3E)-[(thien-2-yl)methylene]-2-azetidinone-1-sulfonate and its (3Z)-isomer, were prepared and evaluated for their β-lactamase inhibitory activities. These compounds were devoid of β-lactamase inhibitory activity.