6,7-二氢-4H-吡唑并[5,1-c][1,4]噻嗪-2-甲醛二氧化物 | 623565-07-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6,7-二氢-4H-吡唑并[5,1-c][1,4]噻嗪-2-甲醛二氧化物
• 英文名称: 5,5-dioxo-4,5,6,7-tetrahydro-5λ⁶-pyrazolo[5,1-c][1,4]thiazine-2-carbaldehyde
• 英文别名: 6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]thiazine-2-carbaldehyde 5,5-dioxide；5,5-dioxo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]thiazine-2-carbaldehyde
• CAS: 623565-07-1
• 化学式: C₇H₈N₂O₃S
• 分子量: 200.218
• InChiKey: XHIIEHUJWFAWJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  6,7-二氢-4H-吡唑并[5,1-c][1,4]噻嗪-2-甲醛二氧化物 在 phosphate buffer 、 三乙胺 、 magnesium bromide 、 锌 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 4.5h， 生成 (5R),(6Z)-6-(5,5-dioxo-4,5,6,7-tetrahydro-5λ6-pyrazolo[5,1-c][1,4]thiazin-2-ylmethylene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium salt
  参考文献：
  名称：

  Structure-Activity Relationship of 6-Methylidene Penems Bearing 6,5 Bicyclic Heterocycles as Broad-Spectrum β-Lactamase Inhibitors:  Evidence for 1,4-Thiazepine Intermediates with C7 R Stereochemistry by Computational Methods

  摘要：

  The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.

  DOI：

  10.1021/jm060021p
• 作为产物：
  描述：

  6,7-二氢-4H-吡唑并[5,1-c][1,4]噻嗪-2-羧酸乙酯 在 manganese(IV) oxide 、 锂硼氢 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 22.0h， 生成 6,7-二氢-4H-吡唑并[5,1-c][1,4]噻嗪-2-甲醛二氧化物
  参考文献：
  名称：

  Structure-Activity Relationship of 6-Methylidene Penems Bearing 6,5 Bicyclic Heterocycles as Broad-Spectrum β-Lactamase Inhibitors:  Evidence for 1,4-Thiazepine Intermediates with C7 R Stereochemistry by Computational Methods

  摘要：

  The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.

  DOI：

  10.1021/jm060021p

文献信息

• Bicyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
  申请人：Mansour Suhayl Tarek

  公开号：US20060276445A1

  公开（公告）日：2006-12-07

  This invention relates to certain bicyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. β-Lactamases hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present invention when combined with β-lactam antibiotics will provide an effective treatment against life threatening bacterial infections. In accordance with the present invention there are provided compounds of general formula I or a pharmaceutically acceptable salt or in vivo hydrolyzable ester R 5 thereof: wherein: One of A and B denotes hydrogen and the other an optionally substituted fused bicyclic heteroaryl group; and X═O or S.

  这项发明涉及某些具有双环6-烷基亚烯基青霉素结构的化合物，其作为D类酶的抑制剂。β-内酰胺酶水解β-内酰胺类抗生素，因此是细菌耐药的主要原因。本发明的化合物与β-内酰胺类抗生素结合后，将提供一种有效的治疗方法，用于治疗威胁生命的细菌感染。根据本发明，提供了一般式I的化合物，或其药学上可接受的盐或体内可水解的酯R5：其中：A和B中的一个表示氢，另一个表示可选择取代的融合双环杂环芳基团；X＝O或S。
• [EN] BICYCLIC 6-ALKYLIDENE-PENEMS AS ß-LACTAMASES INHIBITORS<br/>[FR] PENEMES 6-ALKYLIDENE BICYCLIQUES UTILISES EN TANT QU'INHIBITEURS DE ss-LACTAMASES
  申请人：WYETH CORP

  公开号：WO2003093279A1

  公开（公告）日：2003-11-13

  The present invention provides a compound of Formula (I), pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

  本发明提供了一种化合物（I）的配方、药物组合物以及其用于治疗患有细菌感染或疾病的患者的用途。
• Bicyclic 5-alkylidene-penems as beta lactamases inhibitors
  申请人：Wyeth

  公开号：US20040077622A1

  公开（公告）日：2004-04-22

  The present invention provides a compound of formula 1, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof. 1

  本发明提供了一种化合物1，其制备药物组合物并用于治疗需要治疗细菌感染或疾病的患者。
• Bicyclic 6-alkylidene-penems as beta-lactamase inhibitors
  申请人：Venkatesan Mudumbai Aranapakam

  公开号：US20060217361A1

  公开（公告）日：2006-09-28

  The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

  本发明提供了一种I式化合物、制药组合物以及其在治疗需要治疗细菌感染或疾病的患者中的应用。
• Bicyclic 6-alkylidene-penems as β-lactamase inhibitors
  申请人：Wyeth

  公开号：US07112582B2

  公开（公告）日：2006-09-26

  The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof. wherein one of A and B denotes hydrogen and the other an optionally substituted fused bicyclic heteroaryl group; and X is S.

  本发明提供了一种I式化合物，药物组合物及其用途，用于治疗需要治疗细菌感染或疾病的患者。其中A和B中的一个表示氢，另一个表示可选取代的融合双环杂环芳基；X为S。