6-Chlor-2H-1,2,4-benzothiadiazin-7-sulfonylchlorid-1,1-dioxyd | 4194-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 6-Chlor-2H-1,2,4-benzothiadiazin-7-sulfonylchlorid-1,1-dioxyd
• 英文别名: 6-chloro-1,1-dioxo-1,2(4)-dihydro-1λ⁶-benzo[1,2,4]thiadiazine-7-sulfonyl chloride；6-chloro-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazine-7-sulfonyl chloride；6-chloro-1,1-dioxo-4H-1λ6,2,4-benzothiadiazine-7-sulfonyl chloride
• CAS: 4194-47-2
• 化学式: C₇H₄Cl₂N₂O₄S₂
• 分子量: 315.158
• InChiKey: VYMBMYHQAYKSGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N--N'-<(2,2,2-trichloroethoxy)carbonyl>-L-alanyl>-(4S)-4-amino-L-proline ethyl ester 、 6-Chlor-2H-1,2,4-benzothiadiazin-7-sulfonylchlorid-1,1-dioxyd 在 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 20.0h， 以71%的产率得到N--N'-<(2,2,2-trichloroethoxy)carbonyl>-L-alanyl>-(4S)-4-<<<6-chloro-1,2,4-benzothiadiazin-7-yl>sulfonyl>amino>-L-proline ethyl ester S,S-dioxide
  参考文献：
  名称：

  Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives

  摘要：

  Compounds 1a-g consisting of enalaprilat covalently bonded to aryl sulfonamides, including several known thiazide diuretics, were synthesized and tested for ACE inhibitory and diuretic and overall antihypertensive effects. All compounds were potent ACE inhibitors in vitro, with IC50 = 6.5-85 nM. At 10 mg/kg iv or ip in the rat, 1a-g inhibited the AI pressor response by 76-100%; inhibition declined significantly upon oral dosing. Compounds 1a and 1f at 100 mg/kg ip in the sodium-depleted, spontaneously hypertensive rats reduced blood pressure 28-35% and 41-42%, respectively. Compounds 1a and 1f elicited natriuresis and kaliuresis without accompanying volume increases in the rat; 1c at 25 mg/kg iv induced delayed diuresis. Compound 1f has been chosen for further development.

  DOI：

  10.1021/jm00168a013

文献信息

• COMPOUNDS AND THERAPEUTIC USES THEREOF
  申请人：Willardsen J. Adam

  公开号：US20120329786A1

  公开（公告）日：2012-12-27

  The invention relates to compounds, pharmaceutical compositions and methods useful for treating cancer, systemic or chronic inflammation, rheumatoid arthritis, diabetes, obesity, T-cell mediated autoimmune disease, ischemia, and other complications associated with these diseases and disorders.

  本发明涉及化合物、药物组合物和方法，用于治疗癌症、全身或慢性炎症、类风湿性关节炎、糖尿病、肥胖症、T细胞介导的自身免疫性疾病、缺血以及与这些疾病和疾病相关的其他并发症。
• US3960854A
  申请人：——

  公开号：US3960854A

  公开（公告）日：1976-06-01
• US3951967A
  申请人：——

  公开号：US3951967A

  公开（公告）日：1976-04-20
• Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives
  作者：James J. Mencel、John R. Regan、Jeffrey Barton、Paul R. Menard、Joseph G. Bruno、Raul R. Calvo、Brian E. Kornberg、Alfred Schwab、Edward S. Neiss、John T. Suh

  DOI：10.1021/jm00168a013

  日期：1990.6

  Compounds 1a-g consisting of enalaprilat covalently bonded to aryl sulfonamides, including several known thiazide diuretics, were synthesized and tested for ACE inhibitory and diuretic and overall antihypertensive effects. All compounds were potent ACE inhibitors in vitro, with IC50 = 6.5-85 nM. At 10 mg/kg iv or ip in the rat, 1a-g inhibited the AI pressor response by 76-100%; inhibition declined significantly upon oral dosing. Compounds 1a and 1f at 100 mg/kg ip in the sodium-depleted, spontaneously hypertensive rats reduced blood pressure 28-35% and 41-42%, respectively. Compounds 1a and 1f elicited natriuresis and kaliuresis without accompanying volume increases in the rat; 1c at 25 mg/kg iv induced delayed diuresis. Compound 1f has been chosen for further development.