(Z)-hydroxyimino-(5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-acetic acid methyl ester | 149196-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (Z)-hydroxyimino-(5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-acetic acid methyl ester
• 英文别名: methyl (Z)-2-hydroxyimino-2-(5-methoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate；methyl (2Z)-2-hydroxyimino-2-[5-(methoxycarbonylamino)-1,2,4-thiadiazol-3-yl]acetate
• CAS: 149196-72-5
• 化学式: C₇H₈N₄O₅S
• 分子量: 260.23
• InChiKey: BSIJLEXZAWTUFV-KMKOMSMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  三苯基氯甲烷 、 (Z)-hydroxyimino-(5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-acetic acid methyl ester 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以62%的产率得到(5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-(Z)-trityloxyimino-acetic acid methyl ester
  参考文献：
  名称：

  Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in 3-(heteroarylthio)cephems. Discovery of RWJ-333441 (MC-04,546)

  摘要：

  SAR studies in a series of related 3-(heteroarylthio)cephems determined that a relatively high chemical reactivity of the beta-lactam ring, modulated by electronic effects of substituents at C-3 and C-7, is necessary to achieve high in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA). Such high reactivity results in lowered hydrolytic stability and concomitantly increases susceptibility to beta-lactam ring opening mediated by serum enzymes. Therefore, optimization of anti-MRSA activity versus stability toward serum-mediated degradation required a fine balance of substituent effects. Serum stability studies (measured as percentage of parent drug degraded after 60 min incubation) revealed up to 80-fold difference in degradation rate in a series of closely related (3-heteroarylthio)cephems. Of the compounds evaluated, RWJ-333441 (MC-04,546) possessed the best balance of serum stability (6% degradation after 60 min incubation) and in vitro activity versus MRSA (S. aureus COL MIC-I mug/mL). Accordingly, RWJ-333441 displayed excellent in vivo efficacy versus methicillin-susceptible Staphylococcus aureus (MSSA, ED50=0.39 mg/kg in mouse sepsis model with S. aureus Smith) and good pharmacokinetic properties in the rat (Cl-total=0.39 L/h/kg). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00431-5
• 作为产物：
  描述：

  5-[(甲氧基羰基)氨基]-1,2,4-噻二唑-3-乙酸甲酯 在 吡啶-N-氧化物 、 盐酸羟胺 、 溴 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 17.0h， 生成 (Z)-hydroxyimino-(5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-acetic acid methyl ester
  参考文献：
  名称：

  Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in 3-(heteroarylthio)cephems. Discovery of RWJ-333441 (MC-04,546)

  摘要：

  SAR studies in a series of related 3-(heteroarylthio)cephems determined that a relatively high chemical reactivity of the beta-lactam ring, modulated by electronic effects of substituents at C-3 and C-7, is necessary to achieve high in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA). Such high reactivity results in lowered hydrolytic stability and concomitantly increases susceptibility to beta-lactam ring opening mediated by serum enzymes. Therefore, optimization of anti-MRSA activity versus stability toward serum-mediated degradation required a fine balance of substituent effects. Serum stability studies (measured as percentage of parent drug degraded after 60 min incubation) revealed up to 80-fold difference in degradation rate in a series of closely related (3-heteroarylthio)cephems. Of the compounds evaluated, RWJ-333441 (MC-04,546) possessed the best balance of serum stability (6% degradation after 60 min incubation) and in vitro activity versus MRSA (S. aureus COL MIC-I mug/mL). Accordingly, RWJ-333441 displayed excellent in vivo efficacy versus methicillin-susceptible Staphylococcus aureus (MSSA, ED50=0.39 mg/kg in mouse sepsis model with S. aureus Smith) and good pharmacokinetic properties in the rat (Cl-total=0.39 L/h/kg). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00431-5

文献信息

• Process for preparing 1,2,4-thiadiazole derivatives
  申请人：Katayama Seiyakusyo Co. Ltd.

  公开号：US05585494A1

  公开（公告）日：1996-12-17

  An improved process for the production of 5-amino-1,2,4-thiadiazol-3-yl-(2-(lower)-alkoxyimino)acetic acids starting from 5-substituted- or unsubstituted-3-amino-isoxazole compounds is disclosed herein. The title compounds are useful as acylating agents for the production of 7-acylaminocephalosporins.

  本发明公开了一种改进的制备5-氨基-1,2,4-噻二唑-3-基-(2-(低级)烷氧亚氨基)乙酸的方法，该方法从5-取代或未取代的3-氨基异噁唑化合物开始。标题化合物作为制备7-酰氨基头孢菌素的酰化剂具有实用性。