1'--N'-<(2,2,2-trichloroethoxy)carbonyl>-L-alanyl>-5'-(ethoxycarbonyl)-7-(aminosulfonyl)-6-chlorospiro-<2H-1,2,4-benzothiadiazine-3(4H),3'-pyrrolidine> S,S-dioxide | 103632-12-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1'--N'-<(2,2,2-trichloroethoxy)carbonyl>-L-alanyl>-5'-(ethoxycarbonyl)-7-(aminosulfonyl)-6-chlorospiro-<2H-1,2,4-benzothiadiazine-3(4H),3'-pyrrolidine> S,S-dioxide
• 英文别名: ethyl (2'S)-6-chloro-1'-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]-(2,2,2-trichloroethoxycarbonyl)amino]propanoyl]-1,1-dioxo-7-sulfamoylspiro[2,4-dihydro-1λ6,2,4-benzothiadiazine-3,4'-pyrrolidine]-2'-carboxylate
• CAS: 103632-12-8；126373-56-6；126373-57-7
• 化学式: C₃₁H₃₇Cl₄N₅O₁₁S₂
• 分子量: 861.606
• InChiKey: GDHREEKDWPJPAR-KWFLSFFMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  53.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  220.81
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  1'--N'-<(2,2,2-trichloroethoxy)carbonyl>-L-alanyl>-5'-(ethoxycarbonyl)-7-(aminosulfonyl)-6-chlorospiro-<2H-1,2,4-benzothiadiazine-3(4H),3'-pyrrolidine> S,S-dioxide 在 sodium hydroxide 、 溶剂黄146 、 锌 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 1'-[N'-((1S)-1-carboxy-3-phenylpropyl)-L-alanyl]-5'-carboxy-7-(aminosulfonyl)-6-chlorospiro(2H-1,2,4-benzothiadiazine-3(4H),3'-pyrrolidine) 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
• 作为产物：
  描述：

  ethyl (2S)-2-[[(2S)-1-chloro-1-oxopropan-2-yl]-(2,2,2-trichloroethoxycarbonyl)amino]-4-phenylbutanoate 在 盐酸 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 73.5h， 生成 1'--N'-<(2,2,2-trichloroethoxy)carbonyl>-L-alanyl>-5'-(ethoxycarbonyl)-7-(aminosulfonyl)-6-chlorospiro-<2H-1,2,4-benzothiadiazine-3(4H),3'-pyrrolidine> 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

• MENCEL, JAMES J.;REGAN, JOHN R.;BARTON, JEFFREY;MENARD, PAUL R.;BRUNO, JO+, J. MED. CHEM., 33,(1990) N, C. 1606-1615
  作者：MENCEL, JAMES J.、REGAN, JOHN R.、BARTON, JEFFREY、MENARD, PAUL R.、BRUNO, JO+

  DOI：——

  日期：——
• SUH, J. T.;REGAN, J. R.;PIWINSKI, J. J.;MENARD, P.;JONES, H.
  作者：SUH, J. T.、REGAN, J. R.、PIWINSKI, J. J.、MENARD, P.、JONES, H.

  DOI：——

  日期：——
• ——
  作者：SUH J. T.、 REGAN J. R.、 PIWINSKI J. J.、 MENARD P.、 JONES H.

  DOI：——

  日期：——