ethyl 3-amino-4-phenoxy-5-sulfamoylbenzoate | 62273-22-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 3-amino-4-phenoxy-5-sulfamoylbenzoate
• 英文别名: ethyl 3-amino-4-phenoxy-5-sulfamylbenzoate
• CAS: 62273-22-7
• 化学式: C₁₅H₁₆N₂O₅S
• 分子量: 336.368
• InChiKey: YFSHMVPOMPQSJS-UHFFFAOYSA-N

物化性质

• 沸点：
  540.5±60.0 °C(Predicted)
• 密度：
  1.369±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-amino-4-phenoxy-5-sulfamoylbenzoate 在 吡啶 、 chromium(VI) oxide 、 lithium aluminium tetrahydride 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 六甲基磷酰三胺 、 二氯甲烷 、 丙酮 为溶剂， 生成 3-[(But-2-en-1-yl)amino]-5-formyl-2-phenoxybenzene-1-sulfonamide
  参考文献：
  名称：

  DE2630637

  摘要：

  公开号：
• 作为产物：
  描述：

  3-硝基-4-苯氧基-5-磺酰基苯甲酸 、 甲酸铵 在 10 wt% Pd(OH)2 on carbon 、 硫酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 0.5h， 以1.86 g的产率得到ethyl 3-amino-4-phenoxy-5-sulfamoylbenzoate
  参考文献：
  名称：

  Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders

  摘要：

  Aberrant expression ratio of Cl- transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl- transporter NKCC2, creating critical drug compliance issues and health concerns, Here, we report the discovery of a new chemical class of selective NKCC1 inhibitors and the lead drug candidate ARN23746. ARN23746 restores the physiological intracellular Cl- in murine Down syndrome neuronal cultures, has excellent solubility and metabolic stability, and displays no issues with off-target activity vitro. ARN23746 recovers core symptoms in mouse models of Down syndrome and autism, with no diuretic effect, nor overt toxicity upon chronic treatment in adulthood. ARN23746 is ready for advanced preclinical/manufacturing studies toward the first sustainable therapeutics for the neurological conditions characterized by impaired Cl- homeostasis.

  DOI：

  10.1016/j.chempr.2020.06.017

文献信息

• Sulphonamides, compositions containing the same and methods for using
  申请人：Leo Pharmaceutical Products Ltd.

  公开号：US04082851A1

  公开（公告）日：1978-04-04

  The invention relates to a series of new compounds, salts thereof and to methods for the preparation of the compounds which have the general formula ##STR1## in which R.sub.1 stands for an unsubstituted or substituted phenoxy, phenylthio, benzyl, phenylsulfinyl, or anilino radical; R.sub.2 stands for a -YR.sub.2 ' radical, in which Y represents -O-, -S-, or -NH-, and R.sub.2 ' represents C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or -alkynyl; or methyl or ethyl substituted with phenyl, furyl, thienyl or pyridyl; R.sub.3 and R.sub.4 which can be the same or different, and unsubstituted or substituted, stand for hydrogen or for a straight or branched C.sub.1 -C.sub.8 -alkyl, C.sub.2 -C.sub.8 -alkenyl or -alkynyl radical, a C.sub.5 -C.sub.7 -cycloalkyl, a phenyl, or a 5-, 6- or 7-membered heterocyclic ring system containing not more than two hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen, or for a C.sub.1 -C.sub.3 alkyl radical substituted with phenyl or with a 5-, 6- or 7-membered heterocyclic ring system containing not more than two hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen; and R.sub.4 furthermore stands for a lower carbalkoxy radical, a C.sub.1 -C.sub.6 alkanoyl radical, or a benzoyl radical; and Salts thereof with pharmaceutically acceptable acids. The compounds of the invention possess a pronounced diuretic and/or saluretic activity with a very low excretion of potassium ions. The low toxicity also makes the present compounds particularly valuable in human and veterinary practice.

  该发明涉及一系列新化合物，其盐以及制备这些化合物的方法，这些化合物具有一般公式##STR1##其中R.sub.1代表未取代或取代的苯氧基，苯硫基，苄基，苯基亚砜基或苯胺基基团；R.sub.2代表一个-YR.sub.2'基团，其中Y代表-O-，-S-或-NH-，R.sub.2'代表C.sub.1-C.sub.6-烷基，C.sub.2-C.sub.6-烯基或-炔基；或用苯基，呋喃基，噻吩基或吡啶基取代的甲基或乙基；R.sub.3和R.sub.4可以相同也可以不同，并且未取代或取代，代表氢或直链或支链的C.sub.1-C.sub.8-烷基，C.sub.2-C.sub.8-烯基或-炔基基团，C.sub.5-C.sub.7-环烷基，苯基，或者一个含有不超过氧，硫和氮的两个杂原子的5，6或7-成员杂环系统，或者用苯基或含有不超过氧，硫和氮的5，6或7-成员杂环系统取代的C.sub.1-C.sub.3烷基基团；而且R.sub.4还代表一个较低的羧基烷基基团，一个C.sub.1-C.sub.6醇酰基团，或苯甲酰基团；以及与药用酸形成的盐。该发明的化合物具有明显的利尿和/或排盐活性，同时对钾离子的排泄量非常低。低毒性也使得这些化合物在人类和兽医实践中特别有价值。
• Compositions and methods for the treatment of hypertension or oedemas
  申请人：Leo Pharmaceutical Products Ltd. A/S (Lovens Kemiske Fabrik

  公开号：US04247550A1

  公开（公告）日：1981-01-27

  The invention relates to a series of new compounds, salts thereof and to methods for the preparation of the compounds which have the general formula ##STR1## in which R.sub.1 stands for an unsubstituted or substituted phenoxy, phenylthio, benzyl, phenylsulfinyl, or anilino radical; R.sub.2 stands for a --YR.sub.2 ' radical, in which Y represents --O--, --S--, or --NH--, and R.sub.2 ' represents C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or -alkynyl; or methyl or ethyl substituted with phenyl, furyl, thienyl or pyridyl; R.sub.3 and R.sub.4 which can be the same or different, and unsubstituted or substituted, stand for hydrogen or for a straight or branched C.sub.1 -C.sub.8 -alkyl, C.sub.2 -C.sub.8 -alkenyl or -alkynyl radical, a C.sub.5 -C.sub.7 -cycloalkyl, a phenyl, or a 5-, 6- or 7-membered heterocyclic ring system containing not more than two hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen, or for a C.sub.1 -C.sub.3 alkyl radical substituted with phenyl or with a 5-, 6- or 7-membered heterocyclic ring system containing not more than two hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen; and R.sub.4 furthermore stands for a lower carbalkoxy radical, a C.sub.1 -C.sub.6 alkanoyl radical, or a benzoyl radical; and salts thereof with pharmaceutically acceptable acids. The compounds of the invention possess a pronounced diuretic and/or saluretic activity with a very low excretion of potassium ions. The low toxicity also makes the present compounds particularly valuable in human and veterinary practice.

  该发明涉及一系列新化合物、其盐以及制备该化合物的方法，其具有以下通式： ##STR1## 其中，R1代表未取代或取代的苯氧基、苯硫基、苄基、苯基亚磺酰基或苯胺基基团；R2代表--YR2'基团，其中Y代表--O--、--S--或--NH--，R2'代表C1-C6烷基、C2-C6烯基或-炔基；或被苯基、呋喃基、噻吩基或吡啶基取代的甲基或乙基；R3和R4可以相同或不同，未取代或取代，代表氢或直链或支链C1-C8烷基、C2-C8烯基或-炔基、C5-C7环烷基、苯基或含有不超过两个选自氧、硫和氮的杂原子的5、6或7元杂环环系，或被取代为含有不超过两个选自氧、硫和氮的杂原子的5、6或7元杂环环系的C1-C3烷基；R4还代表较低的碳酸烷氧基、C1-C6酰基或苯甲酰基；以及与药用酸盐的盐。该发明的化合物具有显著的利尿和/或盐利尿作用，同时钾离子的排泄非常低。低毒性也使得该化合物在人类和兽医实践中特别有价值。
• US4247550A
  申请人：——

  公开号：US4247550A

  公开（公告）日：1981-01-27
• DE2630637
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders
  作者：Annalisa Savardi、Marco Borgogno、Roberto Narducci、Giuseppina La Sala、Jose Antonio Ortega、Maria Summa、Andrea Armirotti、Rosalia Bertorelli、Andrea Contestabile、Marco De Vivo、Laura Cancedda

  DOI：10.1016/j.chempr.2020.06.017

  日期：2020.8

  Aberrant expression ratio of Cl- transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl- transporter NKCC2, creating critical drug compliance issues and health concerns, Here, we report the discovery of a new chemical class of selective NKCC1 inhibitors and the lead drug candidate ARN23746. ARN23746 restores the physiological intracellular Cl- in murine Down syndrome neuronal cultures, has excellent solubility and metabolic stability, and displays no issues with off-target activity vitro. ARN23746 recovers core symptoms in mouse models of Down syndrome and autism, with no diuretic effect, nor overt toxicity upon chronic treatment in adulthood. ARN23746 is ready for advanced preclinical/manufacturing studies toward the first sustainable therapeutics for the neurological conditions characterized by impaired Cl- homeostasis.