苄基[(2S)-7-羟基-1,2,3,4-四氢萘-2-基]氨基甲酸酯 | 194785-39-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 苄基[(2S)-7-羟基-1,2,3,4-四氢萘-2-基]氨基甲酸酯
• 英文名称: benzyl [(2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate
• 英文别名: (2S)-2-benzyloxycarbonylamino-7-hydroxy-tetralin；(S)-2-(Benzyloxycarbonylamino)-7-hydroxytetralin；benzyl N-[(2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate
• CAS: 194785-39-2
• 化学式: C₁₈H₁₉NO₃
• 分子量: 297.354
• InChiKey: OQADGPBPEHLXDJ-INIZCTEOSA-N

物化性质

• 沸点：
  517.6±50.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  苄基[(2S)-7-羟基-1,2,3,4-四氢萘-2-基]氨基甲酸酯 在 2,6-二甲基吡啶 、 sodium hydroxide 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 sodium 4-((7S)-7-{[(2R)-2-(3,4-dichlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydro-2-naphthalenyl)benzoate
  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：

  7-甲氧基-2-萘满酮 在 sodium hydroxide 、 dimethyl sulfide borane 、 palladium 10% on activated carbon 、 氢气 、 三溴化硼 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 4.0~60.0 ℃ 、3.04 MPa 条件下， 反应 18.0h， 生成 苄基[(2S)-7-羟基-1,2,3,4-四氢萘-2-基]氨基甲酸酯
  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

• Propanolaminotetralines, preparation thereof and compositions containing same
  申请人：——

  公开号：US20040034070A1

  公开（公告）日：2004-02-19

  The invention relates to phenoxypropanolamines, to pharmaceutical compositions containing them, to processes for preparing them, and to the method of use thereof in the treatment of diseases that are improved by beta-3 agonist action.

  该发明涉及苯氧丙醇胺，含有它们的药物组合物，制备它们的方法，以及在治疗通过β-3激动剂作用改善的疾病中使用它们的方法。
• 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。
• 3,4-disubstituted phenylethanolaminotetralincarboxamide derivatives
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：US06133266A1

  公开（公告）日：2000-10-17

  The present invention relates to 3,4-disubstituted phenylethanolaminotetralincarboxamide derivatives represented by the general formula: ##STR1## (wherein A represents a lower alkylene group; B represents an amino group, a di(lower alkyl)amino group or a 3 to 7-membered alicyclic amino group which may contain an oxygen atom in the ring; n is an integer of 1 or 2; the carbon atom marked with * represents a carbon atom in R configuration, S configuration or a mixture thereof; and the carbon atom marked with (S) represents a carbon atom in S configuration) and pharmaceutically acceptable salts thereof, which have a selective .beta..sub.2 -adrenergic receptor stimulating effect with relieved burdens on the heart such as tachycardia and are useful as an agent for the prevention of threatened abortion and premature labor, a bronchodilator and an agent for pain remission and stone removal in urolithiasis.

  本发明涉及一种以一般式表示的3,4-二取代苯乙醇胺四环酰胺衍生物：##STR1##（其中A表示较低的烷基链；B表示氨基，二（较低烷基）氨基或3到7个成员的脂环氨基，该脂环氨基可以在环中含有一个氧原子；n是1或2的整数；带有*标记的碳原子表示具有R构型、S构型或两者的混合的碳原子；带有（S）标记的碳原子表示具有S构型的碳原子），以及其药学上可接受的盐。该化合物具有选择性β2-肾上腺素能受体刺激作用，减轻心脏负担，如心动过速，并可用作预防威胁性流产和早产、支气管扩张剂以及用于疼痛缓解和尿路结石除石剂的药物。
• 3,4-DISUBSTITUTED PHENYLETHANOLAMINOTETRALINCARBOXAMIDE DERIVATIVES
  申请人：KISSEI PHARMACEUTICAL CO., LTD.

  公开号：EP0882704A1

  公开（公告）日：1998-12-09

  3,4-Disubstituted phenylethanolaminotetralincarboxamide derivatives represented by general formula (1) and their pharmacologically acceptable salts having a selective β2-adrenergic receptor stimulating effect with a relieved burden on the heart such as a frequent pulse. In said formula, A represents lower alkylene; B represents amino, di(lower alkyl)amino or 3- to 7-membered alicyclic amino optionally containing oxygen in the ring; n is an integer of 1 or 2; the carbon atom marked with "*" means a carbon atom or the R- or S- configuration or a mixture thereof; and the carbon atom marked with "(S)" means a carbon atom of the S-configuration. These compounds are useful as a preventive for threatened abortion/premature birth, a bronchodilator and a pain-relieving and lithagogue agent in ureterolithiasis.

  由通式(1)代表的3,4-二取代苯乙醇胺四氢甲酰胺衍生物及其药理上可接受的盐，具有选择性β2-肾上腺素能受体刺激作用，可减轻心脏负担，如频繁脉搏。在所述式中，A 代表低级亚烷基；B 代表氨基、二（低级烷基）氨基或环中任选含氧的 3 至 7 元脂环氨基；n 是 1 或 2 的整数；标有 "*"的碳原子指碳原子或 R 或 S 构型或其混合物；标有"(S) "的碳原子指 S 构型的碳原子。这些化合物可用于预防妊娠流产/早产、支气管扩张剂以及输尿管结石病的止痛和碎石剂。
• US6133266A
  申请人：——

  公开号：US6133266A

  公开（公告）日：2000-10-17