SKF 77174 | 99447-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: SKF 77174
• 英文别名: 5-Phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol; hydrochloride(SKF 77174)；5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol
• CAS: 99447-34-4
• 化学式: C₁₆H₁₇NO
• 分子量: 239.317
• InChiKey: SNXWZKKKYZCZRK-UHFFFAOYSA-N

物化性质

• 沸点：
  416.7±45.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  SKF 77174 、 3-溴丙烯 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 3-allyl-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  (.+-.)-3-Allyl-7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines as selective high affinity D1 dopamine receptor antagonists: synthesis and structure-activity relationship

  摘要：

  Substituted 1-phenyl-3-benzazepines form a class of compounds possessing potent and selective affinity for the D1 DA receptor. 7,8-Dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 38393) and its 6-halo analogues are potent and selective D1 receptor agonists. Recently, the 3-allyl derivatives of SKF 38393 and its analogues were described as selective D1 agonists with higher D1 efficacy and CNS potency. In order to extend these results to compounds in the 7-halo-8-hydroxy-substituted antagonist series, we have synthesized and pharmacologically characterized 3-allyl analogues of 7-substituted (Cl, Br, H) 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. These 3-allyl derivatives were compared with their 3-methyl and 3-unsubstituted analogues in terms of their D1 receptor affinity and selectivity. The results have been used to generate structure-affinity relationships. The D1 receptor affinity, for 3-substitution, is found to be in the order: methyl > allyl > H. For 7-substitution, the affinity is in the order: Cl = Br > H. The 3-allyl compounds show affinity close to that of the parent (3-methyl) compounds while exhibiting a slightly diminished D1 selectivity. However, the greater lipophilicity of the 3-allyl compounds may enable them to cross the blood-brain barrier more readily and thereby exhibit higher in vivo CNS potency. Thus 3-allylbenzazepines have potential as high affinity selective Dl antagonists.

  DOI：

  10.1021/jm00079a008
• 作为产物：
  描述：

  8-methoxy1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine 在 三溴化硼 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 SKF 77174
  参考文献：
  名称：

  Exploring the Structure−Activity Relationship of the Ethylamine Portion of 3-Iodothyronamine for Rat and Mouse Trace Amine-Associated Receptor 1

  摘要：

  3-Iodothyronamine (1, T(1)AM) is a naturally occurring derivative of thyroid hormone that can potently activate the orphan G protein-coupled receptor (GPCR) known as the trace amine-associated receptor 1 (TAAR(1)). We have previously found that modifying the outer ring of the phenoxyphenethylamine core scaffold of 1 can improve potency and provide potent agonists. In this study, we explored the tolerance of rat and mouse TAAR(1) (rTAAR(1) and mTAAR(1)) for structural modifications in the ethylamine portion of 1. We found that incorporating unsaturated hydrocarbon substituents and polar, hydrogen-bond-accepting groups were beneficial for rTAAR(1) and mTAAR(1), respectively, providing compounds that were equipotent or more potent than 1. Additionally, we have discovered that a naphthyl group is an excellent isosteric replacement for the iodophenyl ring of 1.

  DOI：

  10.1021/jm0700417

文献信息

• Substituted 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines, process for the preparation thereof, and pharmaceutical compositions containing them
  申请人：Technobiotic Ltd.

  公开号：EP0005300A1

  公开（公告）日：1979-11-14

  Disclosed are novel 7-substituted 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines of the general formula wherein X is chloro, bromo or trifluoromethyl, and the pharmaceutically acceptable acid addition salts thereof. The novel compounds may be prepared by methods known per se. Preferably the compounds are prepared by dealkylation of a corresponding 8-alkoxy-1-phenyl-2,3,4,5-tetrahydro-1H-benzazepine at position 8. The novel compounds are useful as intermediates in the preparation of corresponding esters and carbamates and show neuroleptic, antidepressive and antiagressive activity.

  本发明公开了新型 7-取代 8-羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓，通式为 其中 X 为氯、溴或三氟甲基，及其药学上可接受的酸加成盐。 新型化合物可以通过本身已知的方法制备。这些化合物最好是通过相应的 8-烷氧基-1-苯基-2,3,4,5-四氢-1H-苯并氮杂卓在第 8 位的脱烷基化反应来制备。 这些新型化合物可作为制备相应酯类和氨基甲酸酯类化合物的中间体，并具有神经抑制、抗抑郁和抗惊厥活性。
• Esters of substituted 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines, process for the preparation thereof, and pharmaceutical compositions containing them
  申请人：Technobiotic Ltd.

  公开号：EP0005298A1

  公开（公告）日：1979-11-14

  Disclosed are novel esters of substituted 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepines of the general formula I wherein X is chloro, bromo or trifluoromethyl, and the pharmaceutically acceptable acid addition salts thereof. The novel compounds may be prepared by methods known per se. Preferably the compounds are prepared by reacting a 7-X-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine or an alkalimetal salt thereof with an acid R,COOH or a reactive derivative of the acid. The novel compounds show neuroleptic, antidepressive and antiagressive activity.

  本发明公开了通式 I 的取代 8-羟基-1-苯基-2,3,4,5-四氢-1 H-3 苯并氮杂卓的新型酯类，其中 X 为氯代或三氟甲基。 其中 X 为氯、溴或三氟甲基，及其药学上可接受的酸加成盐。 新型化合物可以通过本身已知的方法制备。这些化合物最好是通过 7-X-8- 羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓或其碱金属盐与酸 R,COOH 或该酸的活性衍生物反应制备。 这些新型化合物具有神经安定、抗抑郁和抗惊厥活性。
• Substituted 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines, process for the preparation thereof, and pharmaceutical compositions containing them
  申请人：Technobiotic Ltd.

  公开号：EP0005299A1

  公开（公告）日：1979-11-14

  Disclosed are novel 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines of the general formula I wherein X is fluoro, chloro, bromo, trifluoromethyl or methyl and the pharmaceutically acceptable acid addition salts thereof. The novel compounds may be prepared by methods known per se. Preferably the compounds are prepared by reacting a 7-X-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine with a mono- or disubstituted amine whereby at least one of the reactants is in the form of a reactive derivative and one of the reactants provides the carbonyl group contained in the compound of formula I between the R,R2N-group and the oxygen at position 8. The novel compounds show neuroleptic, antidepressive and antiagressive activity.

  公开了通式 I 的新型 1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓 其中 X 为氟、氯、溴、三氟甲基或甲基及其药学上可接受的酸加成盐。 新型化合物可以通过本身已知的方法制备。这些化合物最好是通过 7-X-8-羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓与一元胺或二取代胺反应制备的。 其中至少一种反应物为活性衍生物形式，一种反应物提供式 I 化合物中 R、R2N-基团与第 8 位氧之间所含的羰基。这些新型化合物具有神经安定、抗抑郁和抗攻击活性。
• 7,8-Amino, hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines, process for their preparation and pharmaceutical compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0033632A2

  公开（公告）日：1981-08-12

  A group of 1-phenyl-2,3,4,5-tetrahydro-1H-3-benz- azepines having structures with amino, hydroxy substituents at the 7,8-positions of the benzazepine nucleus is disclosed. Also described are pharmacodynamic pharmaceutical compositions containing them and processes for their preparation.

  本研究公开了一组 1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓，其结构在苯并氮杂卓核的 7、8 位上具有氨基和羟基取代基。还描述了含有它们的药效学药物组合物及其制备工艺。
• ECOPIPAM FOR TREATMENT OF TOURETTES SYNDROME
  申请人：Emalex Biosciences, Inc.

  公开号：EP3919060A1

  公开（公告）日：2021-12-08

  The present invention encompasses methods of treating a subject who has been diagnosed as having a tic disorder or a movement disorder. The tic disorder can be Tourette's Syndrome, and the methods can include the steps of: (a) identifying a subject in need of treatment; and (b) administering to the subject a therapeutically effective amount of composition comprising a D1/D5 receptor antagonist, a D1/D5 receptor partial agonist, or a mixture thereof. For example, the D1/D5 receptor antagonist can be ecopipam or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, structural analog, metabolite, or polymorph thereof.

  本发明包括治疗被诊断为抽动障碍或运动障碍的受试者的方法。抽动障碍可以是抽动秽语综合征，方法可以包括以下步骤(a) 确定需要治疗的受试者；以及 (b) 向受试者施用治疗有效量的组合物，该组合物包含 D1/D5 受体拮抗剂、D1/D5 受体部分激动剂或其混合物。例如，D1/D5受体拮抗剂可以是依可比泮或其药学上可接受的盐、溶液剂、水合物、原药、结构类似物、代谢物或多晶型物。