SCH 23390 | 87075-17-0

• 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: SCH 23390
• 英文别名: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride；N-methyl-R(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8-ol；(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine；(R)-(1)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine；R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine；(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol；(5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol
• CAS: 87075-17-0
• 化学式: C₁₇H₁₈ClNO
• 分子量: 287.789
• InChiKey: GOTMKOSCLKVOGG-OAHLLOKOSA-N

物化性质

• 沸点：
  414.7±45.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  SCH 23390 在 4-二甲氨基吡啶 、 ammonium acetate 、 吡啶盐酸盐 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 间二甲苯 为溶剂， 反应 138.0h， 生成 (10R)-4-chloro-8-methyl-10-phenyl-6,7,9,10-tetrahydro-3H-pyrazolo[3,4-i][3]benzazepine
  参考文献：
  名称：

  具有改善的药代动力学的多巴胺D1 / D5受体拮抗剂：苯并ze庚因D1 / D5拮抗剂的酚类生物立体异构体的设计，合成和生物学评估。

  摘要：

  苯并ze庚因1和2（分别为SCH 23390和SCH 39166）是两种经典的苯并ze庚因D1 / D5拮抗剂，Ki值分别为1.4和1.2 nM。化合物2已在人类临床试验中用于多种疾病，包括精神分裂症，可卡因添加和肥胖。由于苯酚部分的快速首过代谢，因此1和2均显示出较低的血浆水平和较差的口服生物利用度。合成了几个含有NH氢键供体的杂环系统，并将其评估为苯酚等排物。通过比较含有不同NH载体的类似物来确定氢键的优先取向。用吲哚环取代2的酚基团产生第一个有效的D1 / D5拮抗剂11b。进一步的优化导致合成了非常有效的苯并咪唑酮类化合物19，20和苯并噻唑酮类似物28、29。这些化合物对D2-D4受体，α2a受体和5-HT转运蛋白具有极好的选择性。与2相比，这些杂环苯酚等排物显示出更好的药代动力学特性，如大鼠血浆水平所证实。与之形成鲜明对比的是，1中类似的酚类取代基显着降低了结合亲和力，这大概是

  DOI：

  10.1021/jm030614p
• 作为产物：
  描述：

  normethyl-SCH 23390*HCl 在 硫酸氢铵 、 lithium aluminium tetrahydride 作用下， 反应 0.17h， 生成 SCH 23390
  参考文献：
  名称：

  Ram, Siya; Spicer, Leonard D., Synthetic Communications, 1989, vol. 19, # 20, p. 3561 - 3572

  摘要：

  DOI：

文献信息

• [EN] SELECTIVE D1/D5 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OBESITY AND CNS DISORDERS<br/>[FR] ANTAGONISTES SELECTIFS DU RECEPTEUR D1/D5 POUR LE TRAITEMENT DE L'OBESITE ET DE TROUBLES SNC
  申请人：SCHERING CORP

  公开号：WO2004020442A1

  公开（公告）日：2004-03-11

  The present invention provides compounds, which, are novel antagonists for D1/D5 receptors as well as methods for preparing such compounds. In another embodiment, the invention provides pharmaceutical compositions comprising such D1/D5 receptor antagonists as well as methods of using them to treat CNS disorders, obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

  本发明提供了一种新型D1/D5受体拮抗剂化合物，以及制备这种化合物的方法。在另一实施方式中，本发明提供了包含这种D1/D5受体拮抗剂的药物组合物，以及使用它们治疗中枢神经系统疾病、肥胖症、代谢性疾病、食欲障碍（如过度进食）和糖尿病的方法。
• Pharmaceutical dopamine glycoconjugate compositions and methods of their preparation and use
  申请人：christian T. Samuel

  公开号：US20050250739A1

  公开（公告）日：2005-11-10

  Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use, wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”; each of X and Y is optional; X, when present is either —C(R 1 ) 2 — or —C(R 1 ) 2 —; Y, when present, is either —CH 2 — or —CH 2 —CH 2 —; z, R 5 and R 5′ . are optional, and when present z, R 5 and R 5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof; R 1 and R 4 are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl; R 2 and R 3 are hydroxyl; R 5 and R 6 , when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and, R 6 and R 6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

  根据FORMULA V，水亲性可运输的N-连接糖基的多巴胺前药化合物及其使用方法，其中，环1包括一个芳基或杂环芳基环，其中含有4至8个碳原子，其中原子被计为“X”和“Y”；X和Y各自是可选的；当存在X时，它是- C（R1）2-或-C（R1）2-；当存在Y时，它是-CH2-或-CH2-CH2-；z，R5和R5'是可选的，当存在z，R5和R5'时，它们共同形成较低的烷基或取代较低的烷基基团；N是氨基或酰胺连接的一部分；E是一个糖类，通过其碳或氧原子之一的单键与N形成连接；R1和R4从选组中选择，包括氢，羟基，卤素，卤代较低烷基，烷氧基，烷氧基较低烷基，卤代烷氧基，硫酰胺基，氨基磺酰基，烷氧羰基，羧酰胺，氨基羰基和烷基氨基羰基；R2和R3是羟基；当存在时，R5和R6从选组中选择，包括氢，羟基，烷氧基，羰基，烷氧基羰基，氨基羰基，烷基氨基羰基和二烷基氨基羰基；而R6和R6'从选组中选择，包括氢，羟基，烷氧基，羧基，烷氧基羰基，氨基羰基，烷基氨基羰基和二烷基氨基羰基，但前提是环1能够与以下任何一个结合：从选组中选择的多巴胺能感受器，包括D1受体和D5受体；DAT转运体；VMAT转运体；前提是E能够与以下从选组中选择的GLUT转运体结合：GLUT1受体和GLUT3受体。
• Method of identifying transmembrane protein-interacting compounds
  申请人：O'Dowd F. Brian

  公开号：US20050287602A1

  公开（公告）日：2005-12-29

  A method for screening compounds for their ability to interact with transmembrane proteins is provided. Also provided is a method for determining whether proteins such as transmembrane proteins are able to oligomerise.

  提供了一种筛选化合物与跨膜蛋白相互作用能力的方法。还提供了一种确定蛋白质（如跨膜蛋白）是否能够寡聚的方法。
• Substituted 2-aminotetralins
  申请人：Whitby Research, Inc.

  公开号：US05274003A1

  公开（公告）日：1993-12-28

  Optically active or racemic compounds are provided having the formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H and OH with the provision that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that R.sub.2 and R.sub.4 are not both OH; X is oxygen; and R.sub.1 is selected from the group consisting of ##STR2## wherein Z is oxygen, nitrogen or sulfur, wherein Y is selected from the group consisting of hydroxy, nitro, cyano, azido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido, halogen, hydrocarbyl and heteroatom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12 carbon atoms, and a is an integer of from zero to 3. These compounds are capable of binding selectivity of one or more dopamine D.sub.2 receptors, for instance, in humans. They are useful in treatment of disorders of the central nervous, cardiovascular, and endocrine systems, such as elevated intraocular pressure, schizophrenia and Parkinsonism, and for inducing anorexia and weight loss in humans and other mammals.

  提供具有以下式子的旋光性或外消旋化合物：##STR1## 其中R.sub.2、R.sub.3和R.sub.4分别选择自H和OH的组，但至少其中一个为H，且R.sub.2和R.sub.4不同时为OH；X为氧；R.sub.1选择自下列组：##STR2## 其中Z为氧、氮或硫，Y选择自羟基、硝基、氰基、叠氮基、氨基、酰胺基、羧酸胺基、三氟甲基、硫酸酯、磺酰胺基、卤素、烃基和取代烃基基团，其中所述的杂原子选择自卤素、氮、氧、硫和磷的组，所述的烃基基团包含1至12个碳原子，且a为0至3的整数。这些化合物能够选择性地结合一种或多种多巴胺D.sub.2受体，例如在人体中。它们在治疗中枢神经、心血管和内分泌系统的疾病方面有用，例如高眼压、精神分裂症和帕金森病，并可诱导人类和其他哺乳动物的厌食和减重。
• PHARMACEUTICAL DOPAMINE GLYCOCONJUGATE COMPOSITIONS AND METHODS OF THEIR PREPARATION AND USE
  申请人：Christian Samuel T.

  公开号：US20080194802A1

  公开（公告）日：2008-08-14

  Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use, wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”; each of X and Y is optional; X, when present is either —C(R 1 ) 2 — or —C(R) 2 —; Y, when present, is either —CH 2 — or —CH 2 —CH 2 —; z, R 5 and R 5′ are optional, and when present z, R 5 and R 5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof; R 1 and R 4 are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl; R 2 and R 3 are hydroxyl; R 5 and R 6 , when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and, R 6 and R 6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

  根据公式V及其使用方法，水亲和性可转运的N-连接糖基多巴胺前药化合物，其中，环1包括4至8个碳原子的芳基或杂芳基环，其中原子计算为“X”和“Y”；X和Y各自是可选的；当存在X时，它是—C（R1）2—或—C（R）2—；当存在Y时，它是—CH2—或—CH2—CH2—；z，R5和R5'是可选的，当存在时，z，R5和R5'共同形成较低的烷基或取代较低的烷基基团；N是胺或酰胺连接的一部分；E是一种糖，通过其碳或氧原子中的单键与N形成连接；R1和R4从氢、羟基、卤素、卤素较低烷基、烷氧基、烷氧基较低烷基、卤素烷氧基、硫酰胺、氨基磺酰、烷氧基羰基、羧酰胺、氨基羰基和烷基氨基羰基中选择；R2和R3是羟基；当存在R5和R6时，它们从氢、羟基、烷氧基、羰基、烷氧基羰基、氨基羰基、烷基氨基羰基和二烷基氨基羰基中选择；R6和R6'从氢、羟基、烷氧基、羧基、烷氧基羰基、氨基羰基、烷基氨基羰基和二烷基氨基羰基中选择，但环1能够与以下任意一种结合：D1受体和D5受体中选择的多巴胺能受体；DAT转运体；VMAT转运体；并且，E能够与GLUT1受体和GLUT3受体中选择的GLUT转运体结合。