3-[((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butyloxycarbonylamino}-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-yl)oxy]benzoic acid methyl ester | 603122-03-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butyloxycarbonylamino}-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-yl)oxy]benzoic acid methyl ester
• 英文别名: methyl 3-[[(6S)-6-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]oxy]benzoate
• CAS: 603122-03-8
• 化学式: C₃₂H₃₆ClNO₆
• 分子量: 566.094
• InChiKey: HACDNOLBLASFSU-WNJJXGMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butyloxycarbonylamino}-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-yl)oxy]benzoic acid methyl ester 在 盐酸 、 甲醇 、 sodium hydroxide 、 水 作用下， 生成 3-[((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-yl)oxy]benzoic acid hydrochloride
  参考文献：
  名称：

  Discovery of a Novel Series of Benzoic Acid Derivatives as Potent and Selective Human β₃ Adrenergic Receptor Agonists with Good Oral Bioavailability. 3. Phenylethanolaminotetraline (PEAT) Skeleton Containing Biphenyl or Biphenyl Ether Moiety

  摘要：

  We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC(50) = 0.38 nM) for beta(3), high selectivity over beta(1) and beta(2), and good pharmacokinetic properties in rats, dogs, and monkeys.

  DOI：

  10.1021/jm800222k
• 作为产物：
  描述：

  (8S)-8-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-ol 在 copper diacetate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成 3-[((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butyloxycarbonylamino}-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-yl)oxy]benzoic acid methyl ester
  参考文献：
  名称：

  Discovery of a Novel Series of Benzoic Acid Derivatives as Potent and Selective Human β₃ Adrenergic Receptor Agonists with Good Oral Bioavailability. 3. Phenylethanolaminotetraline (PEAT) Skeleton Containing Biphenyl or Biphenyl Ether Moiety

  摘要：

  We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC(50) = 0.38 nM) for beta(3), high selectivity over beta(1) and beta(2), and good pharmacokinetic properties in rats, dogs, and monkeys.

  DOI：

  10.1021/jm800222k

文献信息

• Aminoalcohol derivatives as beta-3 adrenergic receptor agonists
  申请人：Hattori Kouji

  公开号：US20050090669A1

  公开（公告）日：2005-04-28

  The present invention relates to a compound formula [I] wherein R1 and R 5 are each independently hydrogen, halogen, lower alkyl, etc., R 2 is hydrogen or an amino protective group, x is bond, -o-o, —O—CH 2 —, etc., y is in which Z is bond, —O—(CH 2 ) m — (in which m is 1 to 4), etc., R 3 is lower alkanoyl, carboxy, lower alkoxycarbonyl, etc., and R 4 is hydrogen, halogen, hydroxy, phenoxy, lower alkyl, lower alkoxy, etc., and n is 0, 1 or 2, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.

  本发明涉及一种化合物公式[I]，其中R1和R5分别独立地为氢、卤素、较低的烷基等，R2为氢或氨基保护基，x为键，-O-O，—O—CH2—等，y为其中Z为键，—O—( )m—（其中m为1至4），等，R3为较低的烷酰基、羧基、较低的烷氧羰基等，R4为氢、卤素、羟基、苯氧基、较低的烷基、较低的烷氧基等，n为0、1或2，或其盐。本发明的化合物[I]及其药学上可接受的盐对于预防和/或治疗尿频症或尿失禁是有用的。