The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform

K. Okonogi - One of the best experts on this subject based on the ideXlab platform.

Liu Mingliang - One of the best experts on this subject based on the ideXlab platform.

  • synthesis of a Cefozopran intermediate z 2 5 amino 1 2 4 thiadiazol 3 yl 2 methoxyiminoacetic acid
    Chinese Journal of Medicinal Chemistry, 2009
    Co-Authors: Liu Mingliang
    Abstract:

    Aim To synthesize(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid,a key intermediate of Cefozopran.Methods The target compound was synthesized from 2-cyanoacetamide via methoxyimination,addition,esterification,reaction with potassium thiocyanate,configuration transformation and then hydrolysis.Results and conclusion The target compound was synthesized with an overall yield of 29.8%,and its structure was identified by 1H-NMR and MS.This procedure can be used in the industrial manufacture due to its advantages of cheap starting material and convenient operation.

Yuji Iizawa - One of the best experts on this subject based on the ideXlab platform.

  • studies on anti mrsa parenteral cephalosporins i synthesis and antibacterial activity of 7β 2 5 amino l52 4 thiadiazol 3 yl 2 z hydroxyiminoacetamido 3 substituted imidazo 1 2 6 pyridazinium 1 yl methyl 3 cephem 4 carboxylates and related compounds
    The Journal of Antibiotics, 2000
    Co-Authors: Tomoyasu Ishikawa, Yuji Iizawa, K. Okonogi, Akio Miyake
    Abstract:

    In an effort to discover a novel Cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1, 2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetamido]-3-(3, 6-diaminoimidazo[1, 2-b]pyridazinium-l-yl)methyl-3-cephem-4-carboxylate (20g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC50=1.6 μg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however, 20g showed activity comparable to that of VCM against MRSA. In addition, 20g showed activity similar or slightly inferior to that of CZOP against Pseudomonas aeruginosa both in vitro and in vivo. Considering its favorable antibacterial activity profile, 20g was considered to be the most promising CZOP derivative for further studies.

  • studies on anti mrsa parenteral cephalosporins iii synthesis and antibacterial activity of 7 beta 2 5 amino 1 2 4 thiadiazol 3 yl 2 z alkoxyiminoacetamido 3 e 2 1 alkylimidazo 1 2 b pyridazinium 6 yl thiovinyl 3 cephem 4 carboxylates and related comp
    The Journal of Antibiotics, 2000
    Co-Authors: Tomoyasu Ishikawa, Yuji Iizawa, K. Okonogi, Keiji Kamiyama, Yutaka Nakayama, Akio Miyake
    Abstract:

    In the course of our exploration for a novel cephalosporin derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we modified the C-3 linked spacers of cephem derivatives bearing a l-methylimidazo[l, 2-b]pyridazinium-6-yl group at the C-3' position and 2-(5-amino-l, 2, 4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetyl group at the C-7 position. The optimal spacers were the (E)-2-vinyl and (E)-2-thiovinyl groups seen in 19a and 29aa, respectively. Their anti-MRSA activity was 16 to 32 times as potent as that of Cefozopran (CZOP). Focusing on the (E)-2-vinyl and (E)-2-thiovinyl spacers, we further modified the alkoxyimino groups in the C-7 acyl moiety and the 1-alkylimidazo[l, 2-b]pyridazinium moieties at the C-3' position and investigated the structureactivity relationships (SAR) of the derivatives. Consequently, we selected 7β-[2-(5-aminol, 2, 4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(l-methylimidazo[l, 2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (29ca) as a new anti-MRSA parenteral cephalosporin candidate for further biological evaluation. The selected 29ca showed anti-MRSA activity comparable to that of vancomycin (VCM) both in vitro and in vivo, high affinity (IC50=2.7 μg/ml) for penicillin binding protein 2' (PBP2') of MRSA and potent activity against Gram-negative bacteria as well.

  • Therapeutic Efficacy of Cefozopran in a Murine Model of Haematogenous Pneumococcal Meningitis
    Chemotherapy, 1998
    Co-Authors: Yuji Iizawa, K. Hiroe, M. Nakao, K. Okonogi
    Abstract:

    Antimicrobial regimens for the treatment of pneumococcal meningitis are not established. We have produced a murine model of haematogenous pneumococcal meningitis and have examined its usefulness for d

  • therapeutic effect of Cefozopran sce 2787 a new parenteral cephalosporin against experimental infections in mice
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Yuji Iizawa, K. Okonogi, Ryogo Hayashi, Tomoyuki Iwahi, Toshiyuki Yamazaki, Akira Imada
    Abstract:

    The therapeutic effect of Cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, Cefozopran was as effective as ceftazidime. The therapeutic effect of Cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, Cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, Cefozopran was the most effective agent. The potent therapeutic effect of Cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans.

Noboru Tsuchimori - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic effects of Cefozopran against experimental mixed urinary tract infection with enterococcus faecalis and pseudomonas aeruginosa in mice
    Journal of Antimicrobial Chemotherapy, 1997
    Co-Authors: Noboru Tsuchimori, Toshiyuki Yamazaki, K. Okonogi
    Abstract:

    The therapeutic activity of Cefozopran, a new semisynthetic parenteral cephalosporin, was compared with those of ceftazidime, ampicillin, imipenem/cilastatin and ofloxacin against an ascending mixed urinary tract infection induced in mice with Enterococcus faecalis TN2005 and Pseudomonas aeruginosa P9. Cefozopran significantly reduced viable cell counts of both organisms in the kidneys. Ceftazidime, imipenem/cilastatin and ofloxacin were active against only P. aeruginosa, and ampicillin was active against only E. faecalis.

  • penicillin binding protein 5 as an inhibitory target of Cefozopran in enterococcus faecalis
    Journal of Antimicrobial Chemotherapy, 1996
    Co-Authors: Noboru Tsuchimori, K. Okonogi
    Abstract:

    The concentration of Cefozopran which inhibits binding of [ 14 C]benzylpenicillin to penicillin-binding protein (PBP) 5 of Enterococcus faecalis TN2005 by 50% was 11 mg/L, and its MIC was 12.5 mg/L. Ceftazidime and cefmenoxime, which were inactive at 100 mg/L, showed no affinity for PBP 5 at this concentration. Ampicillin, benzylpenicillin and imipenem showed higher affinity for PBPs 3/4 and PBP 5 than Cefozopran, and their MICs were lower than that of Cefozopran. No correlation between MICs of the test compounds and the affinity for PBP 1, 2 or 6 was found. These results suggest that Cefozopran exhibits antimicrobial activity against E. faecalis TN2005 by binding to PBP 5.

Tsutomu Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • Cefozopran meropenem or imipenemecilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients a multicenter prospective randomized trial
    2015
    Co-Authors: Takahiko Nakane, Kazuo Tamura, Masayuki Hino, Toshiharu Tamaki, Isao Yoshida, Toshihiro Fukushima, Youichi Tatsumi, Yasuaki Nakagawa, Kazuo Hatanaka, Tsutomu Takahashi
    Abstract:

    We conducted an open-label, randomized study to evaluate the clinical efficacy of Cefozopran, meropenem or imipenemecilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, Cefozopran, meropenem or imipenemecilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in Cefozopran, meropenem or imipenemecilastatin patients compared with cefepime in the per-protocol population (delta ¼ 10%). The response rates for Cefozopran, meropenem and imipenemecilastatin were not significantly different compared with cefepime (Cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p ¼ 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for Cefozopran, meropenem and imipenemecilastatin compared with cefepime were � 5.9% (95% confidence interval (CI): � 20.1 e8.4), � 0.7% (95% CI: � 14.6e13.3), and 5.7% (95% CI: � 8.1e19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3e5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count � 100 � 10 6 /L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3e5, p ¼ 0.006, and 76% versus 48% at day 7, p ¼ 0.002). Our results suggest that the effects of

  • Cefozopran meropenem or imipenem cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients a multicenter prospective randomized trial
    Journal of Infection and Chemotherapy, 2015
    Co-Authors: Takahiko Nakane, Kazuo Tamura, Masayuki Hino, Toshiharu Tamaki, Isao Yoshida, Toshihiro Fukushima, Youichi Tatsumi, Yasuaki Nakagawa, Kazuo Hatanaka, Tsutomu Takahashi
    Abstract:

    We conducted an open-label, randomized study to evaluate the clinical efficacy of Cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, Cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in Cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for Cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (Cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for Cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462).