(S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid | 75493-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid
• 英文别名: (S)-1-benzyloxycarbonyl-1,2,3,4-tetrahydro-quinoline-2-carboxylic acid；(S)-1-((Benzyloxy)carbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid；(2S)-1-phenylmethoxycarbonyl-3,4-dihydro-2H-quinoline-2-carboxylic acid
• CAS: 75493-94-6
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: SUWSCDKXOAADST-INIZCTEOSA-N

物化性质

• 沸点：
  513.2±50.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid 在 四溴化碳 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 27.0h， 生成 (S)-(-)-N-(4-(4-m-tolylpiperazin-1-yl)butyl)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxamide
  参考文献：
  名称：

  Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies

  摘要：

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

  DOI：

  10.1021/jm501119j
• 作为产物：
  描述：

  (S)-1,2,3,4-四氢喹啉-2-羧酸甲酯 在 碳酸氢钠 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 生成 (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid
  参考文献：
  名称：

  Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies

  摘要：

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

  DOI：

  10.1021/jm501119j

文献信息

• Novel Aryl Piperazine Derivatives With Medical Utility
  申请人：Campiani Giuseppe

  公开号：US20090238761A1

  公开（公告）日：2009-09-24

  This invention provides novel aryl piperazine derivatives having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D 3 , D 2 -like and 5-HT 2 receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders incl. schizophrenia.

  这项发明提供了具有医疗效用的新型芳基哌嗪衍生物，特别是作为多巴胺和5-羟色胺受体的调节剂，优选为D3、D2样和5-HT2受体亚型，特别适用于治疗包括精神分裂症在内的神经精神障碍。
• Caspase inhibtors and uses thereof
  申请人：——

  公开号：US20020061853A1

  公开（公告）日：2002-05-23

  This invention provides caspase inhibitors having the formula 1 wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group, or an heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; Ar is an optionally substituted aryl group; and R 3 is hydrogen, an optionally substituted C 1-6 alkyl, F 2 , CN, aryl or R 3 is attached to Ar to form an unsaturated or partially saturated five or six membered fused ring having 0-2 heteroatoms. The compounds are useful for treating caspase-mediated diseases in mammals.

  这项发明提供了具有以下结构的caspase抑制剂： 其中Ring A是可选择取代的哌啶、四氢喹啉或四氢异喹啉环；R1是氢、CHN2、R或—CH2Y；R是从脂肪基、芳基、芳基烷基、杂环基或杂环烷基中选择的可选择取代基；Y是电负离子离去基团；R2是CO2H、CH2CO2H或它们的酯、酰胺或同分异构体；Ar是可选择取代的芳基；R3是氢、可选择取代的C1-6烷基、F2、CN、芳基或R3连接到Ar以形成具有0-2个杂原子的不饱和或部分饱和的五元或六元融合环。这些化合物可用于治疗哺乳动物中的caspase介导的疾病。
• Synthesis of benzo-fused, 7,5- and 7,6-fused azepinones as conformationally restricted dipeptide mimetics
  作者：Jeffrey A. Robl、Donald S. Karanewsky、Magdi M. Asaad

  DOI：10.1016/0040-4039(95)00096-u

  日期：1995.3

  generation of novel conformationally restricted dipeptide mimetics 9 and 16 has been developed. The key step involved intramolecular addition of an oxonium ion to the proximal indoline/tetrahydroquinoline aromatic ring. A dramatic difference in reactivity was observed in the formation of the 7,5- versus the 7,6-fused azepinone nuclei. Application of these mimetics in the synthesis of dual-acting ACE/NEP

  已经开发了用于产生新的构象受限的二肽模拟物9和16的方法。关键步骤涉及在近端二氢吲哚/四氢喹啉芳族环中分子内添加氧鎓离子。在7，5-与7，6-融合的氮杂pin酮核的形成中观察到反应性的显着差异。描述了这些模拟物在合成双作用ACE / NEP抑制剂1和2中的应用。
• 1-[Acylthio) and
  申请人：Norwich Eaton Pharmaceuticals, Inc.

  公开号：US04461896A1

  公开（公告）日：1984-07-24

  A series of 1-[acylthio) and (mercapto)-1-oxoalkyl]-1,2,3,4-tetrahydroquinoline-2-carboxylic acids and salts thereof are useful as Angiotensin I converting enzyme inhibitors.

  一系列1-[酰硫)和(巯基)-1-氧代烷基]-1,2,3,4-四氢喹啉-2-羧酸及其盐对于作为血管紧张素I转换酶抑制剂是有用的。
• Benzo-fused lactams
  申请人：Bristol-Myers Squibb Co.

  公开号：US05504080A1

  公开（公告）日：1996-04-02

  Compounds of the formula ##STR1## wherein A is ##STR2## are useful as ACE and NEP inhibitors and those wherein A is ##STR3## are useful as ACE inhibitors. Methods of preparation and intermediates are also disclosed.

  公式为##STR1##的化合物，其中A为##STR2##的化合物可用作ACE和NEP抑制剂，其中A为##STR3##的化合物可用作ACE抑制剂。还披露了制备方法和中间体。