6-氰基-1,2,3,4-四氢异喹啉盐酸盐 | 171084-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 6-氰基-1,2,3,4-四氢异喹啉盐酸盐
• 中文别名: 1,2,3,4-四氢异喹啉-6-氰基盐酸盐；1,2,3,4-四氢-6-异喹啉甲腈盐酸盐；1,2,3,4-四氢异喹啉-6-甲腈盐酸盐；6-腈基-1,2,3,4-四氢异喹啉盐酸盐;；6-氰基-1,2,3,4-四氢喹啉盐酸盐；6-腈基-1,2,3,4-四氢异喹啉盐酸盐
• 英文名称: 6-cyano-1,2,3,4-tetrahydroisoquinoline hydrochloride
• 英文别名: 1,2,3,4-tetrahydroisoquinoline-6-carbonitrile hydrochloride；1,2,3,4-tetrahydro-isoquinolin-6-carbonitrile hydrochloride；1,2,3,4-tetrahydroisoquinoline-6-carbonitrile;hydrochloride
• CAS: 171084-93-8
• 化学式: C₁₀H₁₀N₂*ClH
• 分子量: 194.664
• InChiKey: FYJDPVBTMLJVDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.63
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  35.8
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  | 温度范围：2-8℃ |

反应信息

• 作为反应物：
  描述：

  6-氰基-1,2,3,4-四氢异喹啉盐酸盐 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 74.0h， 生成 2-(2-Methyloxirane-2-carbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile
  参考文献：
  名称：

  1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators

  摘要：

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.

  DOI：

  10.1021/jm401625b
• 作为产物：
  描述：

  N-BOC-6-羟基-3,4-二氢异喹啉 在 盐酸 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.16h， 生成 6-氰基-1,2,3,4-四氢异喹啉盐酸盐
  参考文献：
  名称：

  1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators

  摘要：

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.

  DOI：

  10.1021/jm401625b

文献信息

• [EN] BICYCLIC BENZAMIDE COMPOUNDS AS HISTAMINE H3 RECEPTOR LIGAND USEFUL IN THE TREATMENT OF NEUROLOGICAL DISEASES<br/>[FR] COMPOSES BENZAMIDE BICYCLIQUES TENANT LIEU DE LIGANDS DU RECEPTEUR H3 DE L'HISTAMINE, UTILES DANS LE TRAITEMENT DES MALADIES NEUROLOGIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2004037788A1

  公开（公告）日：2004-05-06

  The present invention relates to novel bicyclic benzamide derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

  本发明涉及具有药理活性的新型双环苯甲酰胺衍生物，其制备方法，含有它们的组合物以及它们在治疗神经系统和精神疾病中的应用。
• 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)(CH2)p、R3R4NCO(CH2)p或R3R4NSO2(CH2)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CH2；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。
• [EN] TETRAHYDROISOQUINOLINE DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS<br/>[FR] DERIVES DE TETRAHYDROISOQUINOLINE COMME MODULATEURS DES RECEPTEURS D3 DE LA DOPAMINE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1998050364A1

  公开（公告）日：1998-11-12

  (EN) Compounds of formula (I) wherein: R represents a substituent selected from: a hydrogen or a substituent as defined in the claims; R2 represents a hydrogen atom or a C1-4alkyl group; q is 1 or 2; A represents a group of formula (a), (b) or (c) 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; Ar1 and Ar2 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-, -CH2-, or -(CH2)mY1(CH2)n-, wherein Y1 represents O, S, SO2, or CO and m and n each represent zero or 1 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 $i(ortho) to the carboxamide moiety is necessarily a hydrogen or a methoxy group; and salts thereof. Compounds of formula (I) and their salts have affinity for dopamine receptors, in particular the D3 receptor, and thus potential in the treatment of conditions wherein modulation of the D3 receptor is beneficial, e.g. as antipsychotic agents.(FR) L'invention concerne des composés de la formule (I), dans laquelle R représente un substituant sélectionné parmi un hydrogène ou un substituant tel que défini dans les revendications. R2 représente un atome d'hydrogène ou un groupe alkyle C1-4; q est égal à 1 ou 2; A représente un groupe de la formule (a), (b) ou (c) où Ar représente une chaîne phényle éventuellement substituée ou une chaîne hétérocyclique aromatique à 5 ou 6 éléments, éventuellement substituées; ou une chaîne bicyclique éventuellement substituée; Ar1 et Ar2 représentent, chacun, indépendamment, une chaîne phényle éventuellement substituée ou une chaîne hétérocyclique aromatique à 5 ou 6 éléments, éventuellement substituée; et Y représente une liaison, -NHCO-, -CONH-, -CH2-, ou -(CH2)mY1(CH2)n-, où Y1 représente O, S, SO2 ou CO et m et n représentent chacun zéro ou 1 de telle sorte que la somme m+n est égale à zéro ou 1; à condition que A représente un groupe de la formule (a). Selon l'invention, tout substituant présent dans Ar en position ortho par rapport à la fraction de carboxamide est nécessairement un groupe hydrogène ou méthoxy; et l'invention concerne ausii des sels de ces derniers. Les composés de la formule (I) et leurs sels présentent une affinité pour les récepteurs de la dopamine, en particulier le récepteur D3, et ainsi offrent une utilité pour traiter les états dans lequels il est souhaitable de moduler le récepteur D3, par exemple, comme agents antipsychotiques.

  化合物的公式(I)中，其中：R代表从氢或定义在权利要求中的取代基中选择的取代基；R2代表氢原子或C1-4烷基基团；q为1或2；A代表公式(a)、(b)或(c)的基团，其中：Ar代表选择性取代的苯环或选择性取代的5-或6元杂环芳香环；或选择性取代的双环环系统；Ar1和Ar2各自独立地代表选择性取代的苯环或选择性取代的5-或6元杂环芳香环；Y代表键合、-NHCO-、-CONH-、-CH2-或-(CH2)mY1(CH2)n-，其中Y1代表O、S、SO2或CO，而m和n分别表示零或1，使得m+n的总和为零或1；但当A代表公式(a)的基团时，Ar中存在于羧酰胺基团的正位上的任何取代基必须是氢或甲氧基；以及它们的盐。公式(I)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治疗作用，例如作为抗精神病药物。
• Tetraisoquinoline derivatives as modulators of dopamine D3 receptors
  申请人：SmithKline Beecham p.l.c.

  公开号：US06414154B1

  公开（公告）日：2002-07-02

  Compounds of formula (I), wherein: R1 represents a substituent selected from: a hydrogen or halogen atom; a hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, pentafluoroethyl, C1-4alkyl, C1-4alkoxy, arylC1-4alkoxy, C1-4alkylthio, C1-4alkoxyC1-4alkyl, C3-6cycloalkylC1-4alkoxy, C1-4alkanoyl, C1-4alkoxycarbonyl, C1-4alkylsulfonyl, C1-4alkylsulfonyloxy, C1-4alkylsulfonylC1-4alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC1-4alkyl, C1-4alkylsulfonamido, C1-4alkylamido, C1-4alkylsulfonamidoC1-4alkyl, C1-4alkylamidoC1-4alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC1-4alkyl, arylcarboxamidoC1-4alkyl, aroyl, aroylC1-4alkyl, or arylC1-4alkanoyl group; a group R3OCO(CH2)p, R3CON(R4)(CH2)p, R3R4NCO(CH2)p or R3R4NSO2(CH2)p where each of R3 and R4 independently represents a hydrogen atom or a C1-4alkyl group or R3R4 forms part of a C3-6azacyloalkane or C3-6(2-oxo)azacycloalkane ring and p represents zero or an integer from 1 to 4; or a group Ar1—Z, wherein Ar1 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 CH2; R2 represents a hydrogen atom or a C1-4alkyl group; q is 1 or 2; A represents a group of formula —(CH2)r—V—CH2)s—Ar wherein 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; 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; and salts thereof. The compounds are useful for the treatment of conditions which require modulation of a dopanine receptor such as schizophrenia.

  式(I)的化合物，其中：R1代表从氢或卤素原子；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烷基硫醚、C1-4烷氧基C1-4烷基、C3-6环烷基C1-4烷氧基、C1-4酰基、C1-4烷氧羰基、C1-4烷基磺酰基、C1-4烷基磺酰氧基、C1-4烷基磺酰基C1-4烷基、芳基磺酰基、芳基磺酰氧基、芳基磺酰基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、芳酰基、芳酰基C1-4烷基或芳基C1-4烷酰基；R3OCO（CH2）p，R3CON（R4）（CH2）p，R3R4NCO（CH2）p或R3R4NSO2（CH2）p的基团，其中R3和R4各自独立地代表氢原子或C1-4烷基团，或R3R4是C3-6氮杂环烷或C3-6（2-氧代）氮杂环烷环的一部分，p代表零或1到4的整数；或Ar1—Z的基团，其中Ar1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，Z代表键，O，S或CH2；R2代表氢原子或C1-4烷基团；q为1或2；A代表公式—（CH2）r—V—CH2）s—Ar的基团，其中r和s各自独立地表示从零到3的整数，使得r和s的和等于1到4的整数；V代表键，O或S；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统；及其盐。这些化合物对于需要调节多巴胺受体的疾病，如精神分裂症的治疗非常有用。
• Bicyclic Benzamide Compoundssa as Histamine H3 Receptor Ligand Useful in the Treatment of Neurological Diseases
  申请人：Best John Desmond

  公开号：US20070105838A1

  公开（公告）日：2007-05-10

  The present invention relates to novel bicyclic benzamide derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

  本发明涉及具有药理活性的新型双环苯甲酰胺衍生物，其制备方法，包含它们的组合物以及它们在治疗神经和精神障碍方面的应用。