N-(4-bromophenyl)carbamic acid quinuclidin-3-yl ester | 195190-96-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-bromophenyl)carbamic acid quinuclidin-3-yl ester
• 英文别名: N-(4-Bromophenyl)carbamic Acid 1-azabicyclo[2.2.2]octan-3-yl Ester；1-azabicyclo[2.2.2]octan-3-yl N-(4-bromophenyl)carbamate
• CAS: 195190-96-6
• 化学式: C₁₄H₁₇BrN₂O₂
• 分子量: 325.205
• InChiKey: SLJMPDGIEKZJAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴异氰酸苯酯 、 奎宁环-3-醇 以 四氢呋喃 为溶剂， 反应 0.33h， 以81%的产率得到N-(4-bromophenyl)carbamic acid quinuclidin-3-yl ester
  参考文献：
  名称：

  Synthesis and preliminary evaluation of a carbon-11-labelled agonist of the?7 nicotinic acetylcholine receptor

  摘要：

  一种由Astra实验室描述的新系列氮杂双环碳酸酯的领先化合物，即N-(4-溴苯基)碳酸奎尼克林-3-基酯，已通过无载体添加的[11C]氯化碳和异氰酸酯途径标记了碳-11。通常，在放射合成的30分钟内（包括HPLC纯化），可获得25–35 mCi（0.92–1.29 GBq）的示踪剂，其特定放射活性范围为500至800 mCi/µmol（18.5–29.6 GBq/µmol）。生物分布研究表明该化合物在脑中的摄取相对较好（在不同脑区为0.8–1.2% I.D./g组织），但在富含α7亚型烟碱受体的脑区（如海马、脑桥和上丘）没有 preferential concentration。通过冷化合物和尼古丁进行的预饱和研究未能证明特定结合。因此，该配体不适合在PET成像中进一步探索。版权所有 © 2001 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.504

文献信息

• Syntheses of²H-labelled dihydropyrimidinediones and their metabolites
  作者：Georg Heinkele、Ute Hofmann、Joachim Opitz、Thomas E. Mürdter

  DOI：10.1002/jlcr.426

  日期：2001.1

  Starting with uracil or thymine, [5,5,6,6-2H4]-dihydrouracil and [5,6,6,α,α,α,-2H6]-dihydrothymine were synthesised in high yields by catalytic deuteriation. Subsequent hydrolyses resulted in the corresponding β-ureidoalkanoic acids and β-aminoacids. Copyright © 2001 John Wiley & Sons, Ltd.

  从尿嘧啶或胸腺嘧啶出发，通过催化去uteration合成了高产率的[5,5,6,6-2H4]-二氢尿嘧啶和[5,6,6,α,α,α,-2H6]-二氢胸腺嘧啶。随后水解反应产生了相应的β-脲基烷酸和β-氨基酸。版权 © 2001 John Wiley & Sons, Ltd.
• 3-Substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof
  申请人：——

  公开号：US20040002513A1

  公开（公告）日：2004-01-01

  The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C 1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the &agr;7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

  本发明涉及3-取代-2-(芳基烷基)-1-氮杂双环烷类化合物，制备这些化合物的方法以及使用这些化合物进行治疗的方法。这些氮杂双环烷通常是氮杂双环庚烷、氮杂双环辛烷或氮杂双环壬烷。芳基烷基中的芳基是一个5-或6-成员环杂芳基，优选是3-吡啶基和5-嘧啶基，烷基通常是C1-4烷基。1-氮杂双环烷的3-位取代基是一个含有羰基的基团，例如酰胺、碳酸酯、脲、硫代酰胺、硫代碳酸酯、硫脲或类似功能基团。这些化合物在尼古丁型乙酰胆碱受体(nAChRs)上表现出活性，特别是α7 nAChR亚型，并且对调节神经递质传递和与神经递质有关的配体释放具有用处。还公开了用于预防或治疗中枢神经系统（CNS）疾病等疾病和疾病的方法，这些疾病和疾病以正常神经递质传递的改变为特征。还公开了用于治疗炎症、自身免疫疾病、疼痛和过度新生血管化的方法，例如与肿瘤生长相关的新生血管化。
• Azabicyclic esters of carbamic acids useful in therapy
  申请人：Astra AB

  公开号：US05998429A1

  公开（公告）日：1999-12-07

  A compound of formula ##STR1## wherein: A is ##STR2## X is O or S; Y is O or S; G and D are independently nitrogen or carbon with the proviso that no more than one of G, D, or E is nitrogen; E is N or C-R.sub.4 ; R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen or fluoro; R.sub.3 is hydrogen, halogen, C.sub.1 to C.sub.3 alkyl, --OR.sub.5, --CN, --CONH.sub.2, --CO.sub.2 R.sub.5, --NR.sub.5 R.sub.6 or phenyl optionally substituted with one to three of the following substituents: halogen, C.sub.1 to C.sub.3 alkyl, --NO.sub.2, --CN, or --OCH.sub.3 ; R.sub.4 is hydrogen, halogen, C.sub.1 to C.sub.3 alkyl, --OR.sub.5, --CN, --CONH.sub.2, --CO.sub.2 R.sub.5, --NR.sub.5 R.sub.6 or phenyl optionally substituted with one to three of the following substituents: halogen, C.sub.1 to C.sub.3 alkyl, --NO.sub.2, --CN, or --OCH.sub.3 ; or R.sub.2 and R.sub.3 or R.sub.4 may together represent a fused phenyl ring optionally substituted with one or two of the following substituents: halogen, C.sub.1 to C.sub.3 alkyl, --NO.sub.2, --CN, or --OCH.sub.3 ; R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1 to C.sub.3 alkyl; or an enantiomer thereof, and pharmaceutically acceptable salts thereof, processes for preparing them, compositions containing them, and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders, as well as intermediates and use of intermediates in synthesis.

  化合物的化学式为##STR1##其中：A为##STR2##X为O或S; Y为O或S; G和D独立地为氮或碳，但须注意G、D或E中最多只有一个为氮; E为N或C-R.sub.4; R.sub.1为氢或甲基; R.sub.2为氢或氟; R.sub.3为氢、卤素、C.sub.1到C.sub.3烷基、--OR.sub.5、--CN、--CONH.sub.2、--CO.sub.2R.sub.5、--NR.sub.5R.sub.6或苯基，可选地取代有以下一到三个取代基：卤素、C.sub.1到C.sub.3烷基、--NO.sub.2、--CN或--OCH.sub.3; R.sub.4为氢、卤素、C.sub.1到C.sub.3烷基、--OR.sub.5、--CN、--CONH.sub.2、--CO.sub.2R.sub.5、--NR.sub.5R.sub.6或苯基，可选地取代有以下一到三个取代基：卤素、C.sub.1到C.sub.3烷基、--NO.sub.2、--CN或--OCH.sub.3; 或者R.sub.2和R.sub.3或R.sub.4可以共同表示一个融合的苯环，可选地取代有以下一或两个取代基：卤素、C.sub.1到C.sub.3烷基、--NO.sub.2、--CN或--OCH.sub.3; R.sub.5和R.sub.6独立地为氢或C.sub.1到C.sub.3烷基; 或其对映体，以及其药学上可接受的盐，制备它们的方法，包含它们的组合物，以及它们在治疗中的使用，特别是在治疗或预防精神障碍和智力障碍方面的使用，以及中间体和中间体在合成中的使用。
• 3-SUBSTITUTED-2(ARYLALKYL)-1- AZABICYCLOALKANES AND METHODS OF USE THEREOF
  申请人：Mazurov Anatoly A.

  公开号：US20080138287A1

  公开（公告）日：2008-06-12

  The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds, and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C 1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

  本发明涉及3-取代-2-(芳基烷基)-1-氮杂双环烷类化合物、制备该类化合物的方法以及使用该类化合物的治疗方法。氮杂双环烷通常是氮杂双环庚烷、氮杂双环辛烷或氮杂双环壬烷。芳基烷基中的芳基是一个5-或6-成员环杂芳基，优选是3-吡啶基和5-嘧啶基，烷基通常是C1-4烷基。1-氮杂双环烷的3-位取代基是一种含有羰基基团的基团，例如酰胺、氨基甲酸酯、脲、硫酰胺、硫代氨基甲酸酯、硫脲或类似的官能团。该化合物在尼古丁乙酰胆碱受体(nAChRs)上表现出活性，特别是α7 nAChR亚型，并且对于调节神经递质和神经递质参与的配体的释放是有用的。还公开了预防或治疗条件和疾病的方法，包括中枢神经系统(CNS)疾病，这些疾病的特征是正常神经递质的改变。还公开了治疗炎症、自身免疫性疾病、疼痛和过度新血管生成的方法，例如与肿瘤生长相关的新血管生成。
• 3-SUBSTITUTED-2(ARYLALKYL)-1-AZABICYCLOALKANES AND METHODS OF USE THEREOF
  申请人：Mazurov Anatoly A.

  公开号：US20110071187A1

  公开（公告）日：2011-03-24

  The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C 1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

  本发明涉及3-取代-2-(芳基烷基)-1-氮杂双环烷化合物，制备该化合物的方法以及使用该化合物的治疗方法。氮杂双环烷通常是氮杂双环庚烷，氮杂双环辛烷或氮杂双环壬烷。芳基烷基中的芳基基团是一个5-或6-成员环的杂芳基，优选为3-吡啶基和5-嘧啶基团，而烷基通常是C1-4烷基。在1-氮杂双环烷的3位取代基是含有羰基的基团，例如酰胺，氨基甲酸酯，脲，硫酰胺，硫代氨基甲酸酯，硫脲或类似的官能团。该化合物在尼古丁乙酰胆碱受体(nAChRs)上表现出活性，特别是α7 nAChR亚型，并且对调节神经递质和参与神经递质释放的配体具有用处。还公开了预防或治疗包括中枢神经系统(CNS)疾病在内的疾病和障碍的方法，这些疾病和障碍的特征是正常神经递质发生改变。还公开了治疗炎症、自身免疫性疾病、疼痛和过度新生血管化的方法，例如与肿瘤生长相关的新生血管化。