(R)-benzhydryl 2-((2R,3R)-3-(allyloxycarbonyl)amino-2-(benzo[d]thiazol-2-yldisulfanyl)-4-oxoazetidin-1-yl)-3-methylbut-3-enoate | 211623-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (R)-benzhydryl 2-((2R,3R)-3-(allyloxycarbonyl)amino-2-(benzo[d]thiazol-2-yldisulfanyl)-4-oxoazetidin-1-yl)-3-methylbut-3-enoate
• 英文别名: benzhydryl (2R)-2-[(2R,3R)-2-(1,3-benzothiazol-2-yldisulfanyl)-4-oxo-3-(prop-2-enoxycarbonylamino)azetidin-1-yl]-3-methylbut-3-enoate
• CAS: 211623-25-5
• 化学式: C₃₂H₂₉N₃O₅S₃
• 分子量: 631.797
• InChiKey: MARFHKHQIFYYIS-WWPJHQMMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  177
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (R)-benzhydryl 2-((2R,3R)-3-(allyloxycarbonyl)amino-2-(benzo[d]thiazol-2-yldisulfanyl)-4-oxoazetidin-1-yl)-3-methylbut-3-enoate 在 四(三苯基膦)钯 、 三正丁基氢锡 、 silver(I) acetate 、 碳酸氢钠 、 三乙胺 作用下， 生成 (3R,9R,11R,12S)-9-Methyl-2,6-dioxo-4-phenylacetyl-7-oxa-10-thia-1,4-diaza-tricyclo[7.2.1.03,11]dodecane-12-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  Synthesis of the First 2‘,6 Bridged Penams

  摘要：

  DOI：

  10.1021/ja980195z
• 作为产物：
  描述：

  6-氨基青霉烷酸 在 吡啶 、 过氧乙酸 、 magnesium sulfate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 (R)-benzhydryl 2-((2R,3R)-3-(allyloxycarbonyl)amino-2-(benzo[d]thiazol-2-yldisulfanyl)-4-oxoazetidin-1-yl)-3-methylbut-3-enoate
  参考文献：
  名称：

  6-Arylmethylidene Penicillin-Based Sulfone Inhibitors for Repurposing Antibiotic Efficiency in Priority Pathogens

  摘要：

  The ability of 6-(aryl)methylidene penicillin-based sulfones 1-7 to repurpose beta-lactam antibiotics activity with bacterial species that carry carbapenem-hydrolyzing class D beta-lactamases (OXA-23, OXA-24/40 and OXA-48), as well as with class A (TEM-1, CTX-M-2) and class C (CMY-2, DHA-1) enzymes, is reported. The combinations imipenem/3 and imipenem/4 restored almost completely the antibiotic efficacy in OXA-23 and OXA-24/40 carbapenemase-producing A. baumannii strains (1 mu g mL(-1)) and also provided good results for OXA-48 carbapenemase-producing K. pneumoniae strains (4 mu g mL(-1)). Compounds 2-6 in combinations with ceftazidime and ampicillin were also efficient in restoring antibiotic efficacy in E. coli strains carrying class C (CMY-2 and DHA-1) and class A (TEM-1 and CTX-M-2) beta-lactamase enzymes, respectively. Kinetic and inhibition studies with the OXA-24/40 enzyme, protein mass spectrometry analysis and docking studies allowed us to gain an insight into the inhibition mechanism and the experimentally observed differences between the ligands.

  DOI：

  10.1021/acs.jmedchem.0c00127

文献信息

• The synthesis and evaluation of 6-alkylidene-2'β-substituted penam sulfones as β-lactamase inhibitors
  作者：John D. Buynak、A.Srinivasa Rao、Venkata Ramana Doppalapudi、Greg Adam、Peter J. Petersen、Sirishkumar D. Nidamarthy

  DOI：10.1016/s0960-894x(99)00325-x

  日期：1999.7

  Penicillin sulfones, which structurally incorporate both a 6-position alkylidene substituent and a 2'beta substituent, have been synthesized and evaluated as inhibitors of class C and class A serine beta-lactamases. Incorporation of the 2'beta-substituent generally improves inhibitory activity. Substituents that improve transport across the bacterial cell membrane have also been incorporated.

  已经合成并在结构上结合了6-位亚烷基取代基和2'β取代基的青霉素砜，并被评估为C类和A类丝氨酸β-内酰胺酶的抑制剂。2'β-取代基的掺入通常改善抑制活性。还掺入了改善跨细菌细胞膜运输的取代基。
• BETA-LACTAMASE INHIBITORY COMPOUNDS
  申请人：Buynak John D.

  公开号：US20100009954A1

  公开（公告）日：2010-01-14

  Inhibitors of the enzyme beta-lactamase are provided. The compounds are adapted to inhibit beta-lactamase as produced by beta-lactam resistant bacterial strains. Methods of treatment of beta-lactam resistant bacterial infections in patients are provided.

  提供了抑制酶β-内酰胺酶的抑制剂。这些化合物被改良以抑制由β-内酰胺抗药性细菌株产生的β-内酰胺酶。提供了治疗患者β-内酰胺抗药性细菌感染的方法。
• Design, Synthesis, and Crystal Structures of 6-Alkylidene-2′-Substituted Penicillanic Acid Sulfones as Potent Inhibitors of <i>Acinetobacter baumannii</i> OXA-24 Carbapenemase
  作者：German Bou、Elena Santillana、Anjaneyulu Sheri、Alejandro Beceiro、Jared M. Sampson、Matthew Kalp、Christopher R. Bethel、Anne M. Distler、Sarah M. Drawz、Sundar Ram Reddy Pagadala、Focco van den Akker、Robert A. Bonomo、Antonio Romero、John D. Buynak

  DOI：10.1021/ja104092z

  日期：2010.9.29

  enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel β-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2'-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important β-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play

  D 类 β-内酰胺酶代表了一类不断增长的多样化青霉素失活酶，这些酶通常对商业 β-内酰胺酶抑制剂具有抗性。由于在多重耐药（MDR）鲍曼不动杆菌和铜绿假单胞菌中发现了许多此类酶，因此迫切需要新型β-内酰胺酶抑制剂。合成了五种独特的 6-亚烷基-2'-取代的青霉烯酸砜 (1-5)，并针对 OXA-24 进行了测试，OXA-24 是一种临床上重要的 β-内酰胺酶，可灭活碳青霉烯类，并且存在于鲍曼不动杆菌中。基于 Tyr112 和 Met223 在 OXA-24 β-内酰胺酶中的作用，我们还设计了两种变体（Tyr112Ala 和 Tyr112Ala，Met223Ala）来测试由这些残基形成的疏水隧道影响抑制剂识别的假设。针对 OXA-24 和两种 OXA-24 β-内酰胺酶变体的 IC(50) 值范围为 10 ± 1（4 对 WT）至 338 ± 20 nM（5 对 Tyr112Ala、Met223Ala）。化合物
• US8299051B2
  申请人：——

  公开号：US8299051B2

  公开（公告）日：2012-10-30
• US8575144B2
  申请人：——

  公开号：US8575144B2

  公开（公告）日：2013-11-05