(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxy-propylamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2S)-3-(9H-carbazol-4-yloxy)-2-hydroxy-propylamine
• 英文别名: (2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropylamine；S-desisopropylcarazolol；(2S)-1-amino-3-(9H-carbazol-4-yloxy)-2-propanol；(2S)-1-amino-3-(9H-carbazol-4-yloxy)propan-2-ol
• 化学式: C₁₅H₁₆N₂O₂
• 分子量: 256.304
• InChiKey: UUUATVREIARQHR-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  71.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氟代丙酮 、 (2S)-3-(9H-carbazol-4-yloxy)-2-hydroxy-propylamine 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以62%的产率得到(S)-Fluorocarazolol
  参考文献：
  名称：

  Synthesis, Binding Properties, and 18F Labeling of Fluorocarazolol, a High-Affinity .beta.-Adrenergic Receptor Antagonist

  摘要：

  New beta-adrenergic receptor antagonists, 2-(R)-(+)- and 2-(S)-(-)-1-(9H-earbazol-4-yl-oxy)-3-[[1-(fluoromethyl)ethyl]amino]-2-propanol ((S)- and (R)-fluorocarazolols), were labeled with fluorine-18 at the no-carrier-added level by reductive alkylation of desisopropylcarazolol (4-(2-hydroxy-3-amino-1-propoxy)carbazole) with [F-18]fluoroacetone. The latter was prepared by nucleophilic substitution of fluoride on acetol tosylate and may serve as a useful synthetic precursor for other radiotracers. The radiochemical yield of [F-18]fluorocarazolol (500-1200 Ci/mmol) from [F-18]fluoride was 40 +/- 10% at the end of the 45 min synthesis. Chiral HPLC showed >99% enantiomeric purity of 2-(S)- and 2-(R)- [F-18] fluorocarazolols. The log P of fluorocarazolol was 2.2 at pH 7.4. The in vitro K-D values of(S)- and (R)-fluorocarazolol for the beta-adrenergic receptor were measured in a rat heart preparation to be K-D= 68 and 1128 pM, respectively. Biodistribution experiments in mice demonstrated specific beta-adrenergic receptor binding of (S)-[F-18]fluorocarazolol. (R)-[F-18]fluorocarazolol showed no observable specific binding to beta-receptors in vivo. The uptake of (R)-[F-18]fluorocarazolol may therefore be used as an estimation of nonspecific binding. Positron emission tomography images of pigs showed receptor-specific uptake of(S)-[F-18]fluorocarazolol in the heart and lung. Washout of dissociated ligand from the tissue was observed only after 70 min postinjection. The maximum ratio of specific to nonspecific uptake in pig heart and lung was ca. 10 at 150 min postinjection. Observed levels of fluorocarazolol metabolites in mouse and pig blood were relatively low and remained fairly constant during the period from 10 to 180 min postinjection. These results indicate that (S)-(-)-[F-18]fluorocarazolol is of interest for use as a radiopharmaceutical for estimation of beta-adrenergic receptors with positron tomography.

  DOI：

  10.1021/jm00046a005

文献信息

• Di-substituted aminomethyl-chroman derivative beta-3 adrenoreceptor agonists
  申请人：——

  公开号：US20030078258A1

  公开（公告）日：2003-04-24

  This invention is related to novel di-substituted aminomethyl chroman derivatives which are useful in the treatment of beta-3 receptor-mediated conditions.

  这项发明涉及新型二取代氨甲基色苷衍生物，可用于治疗β-3受体介导的疾病。
• Cyclic amine phenyl beta-3 adrenergic receptor agonists
  申请人：——

  公开号：US20020028835A1

  公开（公告）日：2002-03-07

  This invention provides compounds of Formula I having the structure 1 wherein, R 1 , R 2 , R 3 , R 4 , R 5 , T, T 1 , T 2 , and X are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  本发明提供了具有结构1的化合物，其中R1、R2、R3、R4、R5、T、T1、T2和X如前所定义，或其药学上可接受的盐，其在治疗或抑制与胰岛素抵抗或高血糖有关的代谢紊乱（通常与肥胖或葡萄糖不耐症有关）、动脉粥样硬化、胃肠道疾病、神经遗传性炎症、青光眼、眼压增高和频繁排尿方面非常有用；尤其适用于治疗或抑制2型糖尿病。
• METHODS OF MAKING COMPOUNDS HAVING A BETA-ADRENERGIC INHIBITOR AND A LINKER AND METHODS OF MAKING COMPOUNDS HAVING A BETA-ADRENERGIC INHIBITOR, A LINKER AND A PHOSPHODIESTERASE INHIBITOR
  申请人：Chen Gang

  公开号：US20080262226A1

  公开（公告）日：2008-10-23

  A method is provided for making compounds comprising a beta-adrenergic inhibiting moiety and a linking moiety, the method comprising: a) reacting a compound of formula (A): (R 1 —(CH—O—CH 2 )) with at least one of NH 3 , NH 4 , NH 4 ClNH 3 and R 12′ NH 2 thereby forming a compound of formula (B): (R 1 —CH(OH)—CH 2 —NHR 12′ ); and b) reacting a compound of formula (B) with a compound of formula (C): (R 3 ═O), thereby forming a compound of formula (D): (R 1 —COH—CH 2 —N(R 3 )(R 12′ )), wherein R 1 comprises the beta-adrenergic inhibiting moiety or comprises the beta-adrenergic inhibiting moiety when bonded to —COH—CH 2 —N(R 12′ )— of formula (D); R 3 comprises the linking moiety and is bonded to the =0 of formula (C) via a carbon atom; and R 12′ is selected from hydrogen and a protecting group.

  提供了一种制备含有β-肾上腺素受体抑制基团和连接基团的化合物的方法，该方法包括：a)将式（A）的化合物：（R1-（CH-O-CH2））与NH3、NH4、NH4ClNH3和R12'NH2中的至少一种反应，从而形成式（B）的化合物：（R1-CH（OH）-CH2-NHR12'）；b)将式（B）的化合物与式（C）的化合物反应：（R3═O），从而形成式（D）的化合物：（R1-COH-CH2-N（R3）（R12'）），其中R1包括β-肾上腺素受体抑制基团，或者在与式（D）的—COH-CH2-N（R12'）—结合时包括β-肾上腺素受体抑制基团；R3包括连接基团，并通过碳原子与式（C）的=0结合；R12'选择自氢和保护基团。
• Novel (4-Piperidin-1-yl)-phenyl Sulfonamides as Potent and Selective Human β3 Agonists
  作者：Baihua Hu、John Ellingboe、Stella Han、Elwood Largis、Kitae Lim、Michael Malamas、Ruth Mulvey、Chuansheng Niu、Alexander Oliphant、Jeffrey Pelletier、Thiruvikraman Singanallore、Fuk-Wah Sum、Jeff Tillett、Victoria Wong

  DOI：10.1016/s0968-0896(01)00114-6

  日期：2001.8

  A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta (3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta (3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta (3) agonists with low affinities for beta (1)- and beta (2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta (3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta (3) agonist (EC50 = 0.004 muM, IA = 1.0) with > 500-fold selectivity over beta (1)- and beta (2)-ARs. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Elsinga, Philip H.; Waarde, Aren van; Doze, Petra, Journal of labelled compounds and radiopharmaceuticals, 1997, vol. 40, p. 595 - 597
  作者：Elsinga, Philip H.、Waarde, Aren van、Doze, Petra、Visser, Ton J.、Heldoorn, Marco、et al.

  DOI：——

  日期：——