trans-(4-amino)-cyclohexylacetic acid hydrogen sulfate | 61502-37-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-(4-amino)-cyclohexylacetic acid hydrogen sulfate
• CAS: 61502-37-2
• 化学式: C₈H₁₅NO₂*H₂O₄S
• 分子量: 255.292
• InChiKey: MEBHRCYQCWYWQK-MEZFUOHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.33
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  137.92
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  trans-(4-amino)-cyclohexylacetic acid hydrogen sulfate 在 硫酸 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 41.3h， 生成 2-(2-((trans)-4-aminocyclohexyl)ethyl)-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile
  参考文献：
  名称：

  Design and Synthesis of trans-N-[4-[2-(6-Cyano-1,2,3,4-tetrahydroisoquinolin-2- yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011):  A Potent and Selective Dopamine D₃ Receptor Antagonist with High Oral Bioavailability and CNS Penetration in the Rat

  摘要：

  A selective dopamine D-3 receptor antagonist offers the potential for an effective antipsychotic therapy, free of the serious side effects of currently available drugs. Using clearance and brain penetration studies as a screen, a series of 1,2,3,4-tetrahydroisoquinolines, exemplified by 13, was identified with high D-3 affinity and selectivity against the D-2 receptor. Following examination of molecular models, the flexible butyl linker present in 13 was replaced by a more conformationally constrained cyclohexylethyl Linker, leading to compounds with improved oral bioavailability and selectivity over other receptors. Subsequent optimization of this new series to improve the cytochrome P450 inhibitory profile and CNS penetration gave trans-N-[4-[2-(6-cyano -1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (24, SB-277011). This compound is a potent and selective dopamine D-3 receptor antagonist with high oral bioavailability and brain penetration in the rat and represents an excellent new chemical tool for the investigation of the role of the dopamine D-3 receptor in the CNS.

  DOI：

  10.1021/jm000090i

文献信息

• [EN] M3 MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR D'ACETYLCHOLINE MUSCARINIQUE M3
  申请人：GLAXO GROUP LTD

  公开号：WO2005094835A1

  公开（公告）日：2005-10-13

  Muscarinic Acetylcholine receptor antagonists and methods of using them are provided.

  提供了肌氨酸乙酰胆碱受体拮抗剂及其使用方法。
• Tetrahydroisoquinoline derivatives as modulators of dopamine D3 receptors
  申请人：SmithKline Beecham, p.l.c.

  公开号：US20030191314A1

  公开（公告）日：2003-10-09

  Compounds of formula (I): 1 wherein: R 1 represents a substituent selected from: a hydrogen or halogen atom; a hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, pentafluoroethyl, C 1-4 alkyl, C 1-4 alkoxy, arylC 1-4 alkoxy, C 1-4 alkylthio, C 1-4 alkoxyC 1-4 alkyl, C 3-6 cycloalkylC 1-4 alkoxy, C 1-4 alkanoyl, C 1-4 alkoxycarbonyl, C 1-4 alkylsulfonyl, C 1-4 alkylsulfonyloxy, C 1-4 alkylsulfonylC 1-4 alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC 1-4 alkyl, C 1-4 alkylsulfonamido, C 1-4 alkylamido, C 1-4 alkylsulfonamidoC 1-4 alkyl, C 1-4 alkylamidoC 1-4 alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC 1-4 alkyl, arylcarboxamidoC 1-4 alkyl, aroyl, aroylC 1-4 alkyl, or arylC 1-4 alkanoyl group; a group R 3 OCO(CH 2 ) p , R 3 CON(R 4 )(CH 2 ) p , R 3 R 4 NCO(CH 2 ) p or R 3 R 4 NSO 2 (CH 2 ) p where each of R 3 and R 4 independently represents a hydrogen atom or a C 1-4 alkyl group or R 3 R 4 forms part of a C 3-6 azacyloalkane or C 3-6 (2-oxo)azacycloalkane ring and p represents zero or an integer from 1 to 4; or a group Ar 1 —Z, wherein Ar 1 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring and Z represents a bond, O, S , or CH 2 ; R 2 represents a hydrogen atom or a C 1-4 alkyl group; q is 1 or 2; A represents a group of formula (a) or (b) 2 wherein T, U, V and Y independently represent CH or a nitrogen atom; R 5 is a group selected from: a hydrogen or halogen atom, cyano, C 1-4 alkyl or C 1-4 alkoxy group s is 1 or 2. Ar 2 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring; and salts thereof. The compounds are useful for the treatment of conditions which require modulaton of a dopamine receptor such as schizophrenia.

  式(I)的化合物：其中：R1代表从中选择的取代基：氢或卤素原子；羟基、氰基、硝基、三氟甲基、三氟甲氧基、三氟甲磺酰氧基、五氟乙基、C1-4烷基、C1-4烷氧基、芳基C1-4烷氧基、C1-4烷硫基、C1-4烷氧基C1-4烷基、C3-6环烷基C1-4烷氧基、C1-4烷酰基、C1-4烷氧羰基、C1-4烷基磺基、C1-4烷基磺酰氧基、C1-4烷基磺基C1-4烷基、芳基磺基、芳基磺酰氧基、芳基磺基C1-4烷基、C1-4烷基磺酰胺基、C1-4烷基酰胺基、C1-4烷基磺酰胺基C1-4烷基、C1-4烷基酰胺基C1-4烷基、芳基磺酰胺基、芳基羧酰胺基、芳基磺酰胺基C1-4烷基、芳基羧酰胺基C1-4烷基、芰基、芰基C1-4烷基或芳基C1-4烷酰基；R3OCO(CH2)p、R3CON(R4)( )p、R3R4NCO( )p或R3R4NSO2( )p中的一种，其中R3和R4各自独立地代表氢原子或C1-4烷基或R3R4构成C3-6氮代环烷烃或C3-6(2-氧代)氮代环烷烃环的一部分，p表示零或1至4之间的整数；或Ar1—Z中的一种，其中Ar1代表可选择取代的苯环或可选择取代的5-或6-成员芳香杂环环，Z代表键，O，S或 ；R2代表氢原子或C1-4烷基；q为1或2；A代表式(a)或(b)的基团，其中T、U、V和Y分别独立地表示CH或氮原子；R5是从中选择的基团：氢或卤素原子、氰基、C1-4烷基或C1-4烷氧基；Ar2代表可选择取代的苯环或可选择取代的5-或6-成员芳香杂环环；及其盐。这些化合物可用于治疗需要调节多巴胺受体的疾病，如精神分裂症。
• 2-3-dihydro-1H-isoindole derivatives useful as modulators of dopamine D3 receptors (an-tipsychotic agents)
  申请人：SmithKline Beecham p.l.c.

  公开号：US20030158222A1

  公开（公告）日：2003-08-21

  Oompounds of formula (I), wherein R 2 represents a hydrogen atom or a C 1-4 alkyl group; q is 1 or 2; A represents a group of formula (a), (b), (c) or (d), wherein Ar represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring; or an optionally substituted bicyclic ring system; Ar 1 and Ar 2 each independently represent an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring; and Y represents a bond, —NHCO—, —CONH—, —CH 2 —, or —(CH 2 ) m Y 1 (CH 2 ) n —, wherein Y 1 represents O, S, SO 2 or CO and m and n each represent zero or (I) such that the sum of m+n is zero or 1; providing that when A represents a group of formula (a), any substituent present in Ar ortho to the carboxamide moiety is necessarily a hydrogen or methoxy group; r and s independently represent an integer from zero to 3 such that the sum of r and s is equal to an integer from 1 to 4; V represents a bond, O or S; and salts thereof. Compounds of formula (I) and their salts have affinity for dopamine receptors, in particular the D 3 receptor, and thus potential in the treatment of conditions wherein modulation of the D 3 receptor is beneficial, e.g. as antipsychotic agents.

  式(I)的化合物，其中R2代表氢原子或C1-4烷基；q为1或2；A代表公式(a)、(b)、(c)或(d)的基团，其中Ar代表可选取代的苯环或可选取代的5-或6-成员芳香杂环环；或可选取代的双环环系；Ar1和Ar2分别独立地代表可选取代的苯环或可选取代的5-或6-成员芳香杂环环；Y代表键，—NHCO—，—CONH—，—CH2—或—( )mY1( )n—，其中Y1代表O、S、SO2或CO，m和n分别代表零或(I)，使得m+n的和为零或1；但当A代表公式(a)的基团时，Ar中与羧酰胺基团相对的任何取代基必须是氢或甲氧基；r和s独立地表示从零到3的整数，使得r和s的和等于从1到4的整数；V代表键、O或S；以及它们的盐。式(I)的化合物及其盐具有亲和力，特别是对D3受体，因此在调节D3受体有益的情况下具有潜在的治疗作用，例如作为抗精神病药物。
• M3 muscarinic acetylchoine receptor antagonists
  申请人：Busch-Petersen Jakob

  公开号：US20070185088A1

  公开（公告）日：2007-08-09

  Muscarinic Acetylcholine receptor antagonists and methods of using them are provided.

  本发明提供了肌肉型乙酰胆碱受体拮抗剂及其使用方法。
• TETRAHYDROISOQUINOLINE DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS
  申请人：SmithKline Beecham plc

  公开号：EP1086095B1

  公开（公告）日：2002-10-23