O-吡喃鼠李糖基-(1-3)-O-吡喃木糖基-(1-2)-O-吡喃鼠李糖基-(1-4)-O-吡喃葡萄糖基-(1-1)-2-N-二十四烷酰(神经)鞘氨醇 | 128200-13-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: O-吡喃鼠李糖基-(1-3)-O-吡喃木糖基-(1-2)-O-吡喃鼠李糖基-(1-4)-O-吡喃葡萄糖基-(1-1)-2-N-二十四烷酰(神经)鞘氨醇
• 英文名称: 3-Aminomethyl-3-hydroxyquinuclidine
• 英文别名: 3-(aminomethyl)-3-hydroxy-1-azabicyclo<2.2.2>octane；3-aminomethyl-3-hydroxy-1-azabicyclo[2.2.2]octane；3-aminomethyl-1-azabicyclo[2.2.2]octan-3-ol；3-aminomethylquinuclidin-3-ol；3-(Aminomethyl)quinuclidin-3-ol；3-(aminomethyl)-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 128200-13-5
• 化学式: C₈H₁₆N₂O
• mdl: MFCD12407453
• 分子量: 156.228
• InChiKey: UONKGCZCROZZCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  49.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  O-吡喃鼠李糖基-(1-3)-O-吡喃木糖基-(1-2)-O-吡喃鼠李糖基-(1-4)-O-吡喃葡萄糖基-(1-1)-2-N-二十四烷酰(神经)鞘氨醇 以 5,5-dimethyl-1,3-cyclohexadiene 、 溶剂黄146 为溶剂， 生成 AF 125
  参考文献：
  名称：

  Spiro nitrogen-bridged heterocyclic compounds

  摘要：

  该发明涉及用于治疗中枢神经系统和外周神经系统疾病的新化合物（I）：##STR1## 包括对映体、消旋体和其酸加合物及季铵盐，其中X和Y中的一个为O，另一个为N；Q为（CH.sub.2）.sub.n或C(CH.sub.3).sub.2，其中n为1、2或3，桥-Q-的一端连接到位置1，另一端连接到位置4或5，R.degree.为氢、甲基或羟基；在基团##STR2## 中，连接Z和Y的线表示当X-Z为O-C-R且Y为N时为双键，当X-Z为N.dbd.C-R且Y为O时为单键；Z为C-R，其中R从氢、NH.sub.2、NH-R"（R"=C.sub.1-6-烷基）、N(R").sub.2、R"、C.sub.2-6-烯基、C.sub.2-6-炔基、C.sub.3-7-环烷基、R"被羟基或1-6个卤原子取代、R"O-C.sub.1-6-烷基、羧基-C.sub.1-6-烷基、R"OCO-C.sub.1-6-烷基、氨基-C.sub.1-6-烷基、R""NH-C.sub.1-6-烷基、（R"）.sub.2N-C.sub.1-6-烷基、2-氧代吡咯烷-1-基甲基、芳基、二芳基甲醇和R"被一个或两个芳基取代，其中芳基表示苯基，可选择地被1-3个卤原子取代，R"、R"O和（或）CF.sub.3。还声明了其中连接Z和Y的线表示没有键的化合物，X为O，Z为H，Y为NH.sub.2，NO.sub.2或N.sub.3。

  公开号：

  US05053412A1
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 硼烷 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 15.0h， 生成 O-吡喃鼠李糖基-(1-3)-O-吡喃木糖基-(1-2)-O-吡喃鼠李糖基-(1-4)-O-吡喃葡萄糖基-(1-1)-2-N-二十四烷酰(神经)鞘氨醇
  参考文献：
  名称：

  Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)oxazoles)

  摘要：

  The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.

  DOI：

  10.1021/jm00084a007
• 作为试剂：
  描述：

  3-吲哚甲酸 、 tetrahydrofuran N,N-dimethylformamide 、 N,N'-羰基二咪唑 、 富马酸 在 氮 、 O-吡喃鼠李糖基-(1-3)-O-吡喃木糖基-(1-2)-O-吡喃鼠李糖基-(1-4)-O-吡喃葡萄糖基-(1-1)-2-N-二十四烷酰(神经)鞘氨醇 、 四氢呋喃 、 disodium;carbonate 、 甲苯 、 异丙醇 、 Sodium sulfate-III 、 水 、 乙醚 、 乙腈 、 乙酸乙酯 、 title compound 作用下， 以 甲醇 为溶剂， 反应 24.5h， 生成 N-(3-Hydroxy-1-azabicyclo[2.2.2]oct-3-ylmethyl)-1H-indole-3-carboxamide fumarate hydrate
  参考文献：
  名称：

  3-[N-aroyl(or thioaroyl)aminomethyl]-3-quinuclidinols

  摘要：

  3-[N-Aroyl（或thioaryol）aminoalkyl]-3-quinuclidinols对应的公式如下：##STR1##其中X为O或S，Ar为苯基，取代苯基，吲哚，吲哚咪唑或嘧啶；其光学异构体和药学上可接受的酸盐和溶剂化物。这些化合物具有胃排空、抗恶心、抗焦虑和选择性血清素调节或抑制活性。

  公开号：

  US05137895A1

文献信息

• [EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉ DE QUINUCLIDINE COMME LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011053292A1

  公开（公告）日：2011-05-05

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic 7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  该披露提供了公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是烟碱7受体的配体，可能对治疗中枢神经系统的各种紊乱，特别是情感和神经退行性疾病有用。
• QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  申请人：Cook, II James H.

  公开号：US20090270405A1

  公开（公告）日：2009-10-29

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  该披露提供了公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是烟碱性α7受体的配体，可能对治疗中枢神经系统的各种疾病，特别是情感和神经退行性疾病，有用。
• Spirocyclic compounds incorporating five-membered rings with two
  申请人：Merck Sharp & Dohme Limited

  公开号：US04940703A1

  公开（公告）日：1990-07-10

  The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted line represents an optional chemical bond in one of the two possible positions; A represents a group of formula II: ##STR2## in which R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, benzyloxy, hydroxy (C.sub.1-6)alkyl, halogen, amino, cyano, nitro, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, halogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarbonyl; V represents nitrogen, --CH or --C--; and W represents oxygen, sulphur or --NR.sup.8, in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; two of X, Y and Z are the same or different and each represents oxygen, sulphur or nitrogen; and the remaining group X, Y or Z is carbon, or Y is carbonyl (C=O); and Q is the residue of an azacyclic or azabicyclic ring system; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal or dependence; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; movement disorders; and presenile and senile dementia.

  本发明提供了公式I的化合物或其盐或前药：其中虚线表示两种可能位置中的一个可选化学键；A代表公式II的一个基团：其中R.sup.1代表氢、羟基、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基、C.sub.1-6烷氧基、苄氧基、羟基(C.sub.1-6)烷基、卤素、氨基、氰基、硝基、-CONR.sup.6 R.sup.7或-SO.sub.2 NR.sup.6 R.sup.7，其中R.sup.6和R.sup.7独立地代表氢、卤素、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；R.sup.2代表氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-6烷基羰基；V代表氮、-CH或-C-；W代表氧、硫或-NR.sup.8，其中R.sup.8代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；X、Y和Z中的两个相同或不同，每个代表氧、硫或氮；剩余的X、Y或Z是碳，或Y是羰基(C=O)；Q是氮杂环或氮杂双环环系统的残基；这些化合物在治疗精神分裂症（如精神分裂症和狂躁症）；焦虑症；酒精或药物戒断或依赖；疼痛；胃排空延迟；胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）；偏头痛、恶心和呕吐；运动障碍；以及老年性痴呆症和老年性痴呆症方面具有用处。
• Quinuclidine Compounds as Alpha-7 Nicotinic Acetylcholine Receptor Ligands
  申请人：Cook, II James H.

  公开号：US20100099684A1

  公开（公告）日：2010-04-22

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  本公开提供公式I的化合物，包括其盐，以及使用这些化合物的组合物和方法。这些化合物是尼古丁α7受体的配体，可能对中枢神经系统的各种疾病，特别是情感和神经退行性疾病的治疗有用。
• Spirocyclic compounds incorporating five-membered rings with two heteroatoms
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0337547A1

  公开（公告）日：1989-10-18

  The present invention provides a compound of formula I or a salt or prodrug thereof: wherein the dotted line represents an optional chemical bond in one of the two possible positions; A represents a group of formula II: in which R1 represents hydrogen, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, benzyloxy, hydroxy(C1-6)alkyl, halogen, amino, cyano, nitro, -CONR6R7 or -S02NR6R7, in which R6 and R7 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R2 represents hydrogen, halogen, C1 -6 alkyl, C1 -6 alkoxy or C1-6 alkylcarbonyl; V represents nitrogen, -CH or -C-; and W represents oxygen, sulphur or -NR8, in which R8 represents hydrogen, C, -6 alkyl, C2-6 alkenyl or C2-6 alkynyl; two of X, Y and Z are the same or different and each represents oxygen, sulphur or nitrogen; and the remaining group X, Y or Z is carbon, or Y is carbonyl (C = 0); and Q is the residue of an azacyclic or azabicyclic ring system; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal or,dependence; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; moyement disorders; and presenile and senile dementia,

  本发明提供一种式 I 的化合物或其盐或原药： 其中虚线代表两个可能位置之一的任选化学键；A 代表式 II 的基团： 其中 R1 代表氢、羟基、C1-6 烷基、C2-6 烯基、C2-6 烷炔基、C1-6 烷氧基、苄氧基、羟基（C1-6）烷基、卤素、氨基、氰基、硝基、-CONR6R7 或 -S02NR6R7，其中 R6 和 R7 独立地代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； R2 代表氢、卤素、C1-6 烷基、C1-6 烷氧基或 C1-6 烷基羰基； V 代表氮、-CH 或-C-；以及 W 代表氧、硫或-NR8，其中 R8 代表氢、C, -6 烷基、C2-6 烯基或 C2-6 烷炔基； X、Y 和 Z 中的两个相同或不同，各自代表氧、硫或氮；其余基团 X、Y 或 Z 为碳，或 Y 为羰基（C = 0）；以及 Q 是氮杂环或氮双环环系统的残基；这些化合物可用于治疗精神病（如精神分裂症和躁狂症）、焦虑症、酒精或药物戒断或依赖症、疼痛、胃淤血、胃功能障碍（如消化不良、消化性溃疡、反流性食管炎和胀气）、偏头痛、恶心和呕吐、精神错乱以及先天性和老年性痴呆症、