3-Hydroxy-3-methoxycarbonylmethyl-chinuclidin | 178419-56-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-Hydroxy-3-methoxycarbonylmethyl-chinuclidin
• 英文别名: (3-hydroxy-1-aza-bicyclo[2.2.2]oct-3-yl)-acetic acid methyl ester；2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetic acid methyl ester；methyl 2-(3-hydroxy-1-azabicyclo[2.2.2]octan-3-yl)acetate
• CAS: 178419-56-2
• 化学式: C₁₀H₁₇NO₃
• mdl: MFCD09029613
• 分子量: 199.25
• InChiKey: YKBWECLSUPRXOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Hydroxy-3-methoxycarbonylmethyl-chinuclidin 在 肼 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以63%的产率得到2-(3-Hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetic acid hydrazide
  参考文献：
  名称：

  (−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘-oxazolidin-2‘-one], a Conformationally Restricted Analogue of Acetylcholine, Is a Highly Selective Full Agonist at the α7 Nicotinic Acetylcholine Receptor

  摘要：

  Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha7 nicotinic receptor, which is highly selective for the rat alpha7 nicotinic receptor over the alpha4 beta2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha7 nicotinic receptor affinity.

  DOI：

  10.1021/jm000249r
• 作为产物：
  描述：

  2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetic acid t-butyl ester 在 硫酸 、 三氟乙酸 作用下， 以 甲醇 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 二氯甲烷 为溶剂， 生成 3-Hydroxy-3-methoxycarbonylmethyl-chinuclidin
  参考文献：
  名称：

  Spiroazabicyclic heterocyclic compounds

  摘要：

  式为##STR1##的化合物，其中n为0或1；m为0或1；p为0或1；X为氧或硫；Y为CH、N或NO；W为氧、H.sub.2或F.sub.2；A为N或C(R.sup.2)；G为N或C(R.sup.3)；D为N或C(R.sup.4)；但A、G和D中不超过一个是氮，但Y、A、G和D中至少一个是氮或NO；R.sup.1为氢或C.sub.1至C.sub.4烷基；R.sup.2、R.sup.3和R.sup.4分别独立地为氢、卤素、C.sub.1-C.sub.4烷基、C.sub.2-C.sub.4烯基、C.sub.2-C.sub.4炔基、芳基、杂芳基、OH、OC.sub.1-C.sub.4烷基、CO.sub.2R.sup.1、--CN、--NO.sub.2、--NR.sup.5R.sup.6、--CF.sub.3、--OSO.sub.2CF.sub.3或R.sup.2和R.sup.3，或R.sup.3和R.sup.4，可以共同形成另一个六元芳香或杂芳环，其中共享A和G，或G和D，分别含有零到两个氮原子，并且取代为以下取代基之一或两个：独立地氢、卤素、C.sub.1-C.sub.4烷基、C.sub.2-C.sub.4烯基、C.sub.2-C.sub.4炔基、芳基、杂芳基、OH、OC.sub.1-C.sub.4烷基、CO.sub.2R.sup.1、--CN、--NO.sub.2、--NR.sup.5R.sup.6、--CF.sub.3、--OSO.sub.2CF.sub.3；R.sup.5和R.sup.6独立地为氢、C.sub.1-C.sub.4烷基、C(O)R.sup.7、C(O)NHR.sup.8、C(O)OR.sup.9、SO.sub.2R.sup.10或共同为(CH.sub.2).sub.jQ(CH.sub.2).sub.k，其中Q为O、S、NR.sup.11或键；j为2至7，k为0至2；R.sup.7、R.sup.8、R.sup.9、R.sup.10和R.sup.11独立地为C.sub.1-C.sub.4烷基、芳基或杂芳基，或其对映异构体，以及其药学上可接受的盐，制备它们的方法，含有它们的组合物，以及它们在疗法中的使用，特别是在治疗或预防精神障碍和智力障碍方面。

  公开号：

  US06110914A1

文献信息

• New compounds
  申请人：——

  公开号：US20020187994A1

  公开（公告）日：2002-12-12

  A compound of formula 1 wherein n is 0 or 1; m is 0 or 1; p is 0 or 1; X is oxygen or sulfur; Y is CH, N or NO; W is oxygen, H 2 or F 2 ; A is N or C(R 2 ); G is N or C(R 3 ); D is N or C(R 4 ); with the proviso that no more than one of A, G, and D is nitrogen, but at least one of Y, A, G, and D is nitrogen or NO; R 1 is hydrogen or C 1 to C 4 alkyl; R 2 , R 3 , and R 4 are independently hydrogen, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, aryl, heteroaryl, OH, OC 1 -C 4 alkyl, CO 2 R 1 , —CN, —NO 2 , —NR 5 R 6 , —CF 3 , —OSO 2 CF 3 or R 2 and R 3 , or R 3 and R 4 respectively, may together form another six membered aromatic or heteroaromatic ring sharing A and G, or G and D, respectively, containing between zero and two nitrogen atoms, and substituted with one to two of the following substituents: independently hydrogen, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, aryl, heteroaryl, OH, OC 1 -C 4 alkyl, CO 2 R 1 , —CN, —NO 2 , —NR 5 R 6 , —CF 3 , —OSO 2 CF 3 ; R 5 and R 6 are independently hydrogen, C 1 -C 4 alkyl, C(O)R 7 , C(O)NHR 8 , C(O)OR 9 , SO 2 R 10 or may together be (CH 2 ) j Q(CH 2 ) k where Q is O, S, NR 11 , or a bond; j is 2 to 7, k is 0 to 2; R 7 , R 8 , R 9 , R 10 , and R 11 are independently C 1 -C 4 alkyl, aryl, or heteroaryl, or an enantiomer thereof, and the pharmaceutically acceptable salts thereof, processes for preparing them, composition containing them, and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders.

  化合物的化学式为1，其中n为0或1；m为0或1；p为0或1；X为氧或硫；Y为CH、N或NO；W为氧、H2或F2；A为N或C（R2）；G为N或C（R3）；D为N或C（R4）；但是A、G和D中最多只有一个是氮，但Y、A、G和D中至少有一个是氮或NO；R1为氢或C1到C4烷基；R2、R3和R4独立地为氢、卤素、C1-C4烷基、C2-C4烯基、C2-C4炔基、芳基、杂环芳基、OH、OC1-C4烷基、CO2R1、-CN、-NO2、-NR5R6、-CF3、-OSO2CF3或R2和R3，或R3和R4可以分别形成另一个共用A和G或G和D的六元芳香或杂芳香环，其中包含零到两个氮原子，并且取代有以下一个或两个取代基：独立地为氢、卤素、C1-C4烷基、C2-C4烯基、C2-C4炔基、芳基、杂环芳基、OH、OC1-C4烷基、CO2R1、-CN、-NO2、-NR5R6、-CF3、-OSO2CF3；R5和R6独立地为氢、C1-C4烷基、C（O）R7、C（O）NHR8、C（O）OR9、SO2R10或可以共同为（CH2）jQ（CH2）k，其中Q为O、S、NR11或键；j为2到7，k为0到2；R7、R8、R9、R10和R11独立地为C1-C4烷基、芳基或杂环芳基，或其对映体，以及其药学上可接受的盐，制备它们的过程，包含它们的组合物以及它们在治疗中的应用，特别是在治疗或预防精神障碍和智力障碍方面。
• Spiroazabicyclic Heterocyclic Compounds
  申请人：Phillips Eifion

  公开号：US20080153864A1

  公开（公告）日：2008-06-26

  A compound of formula wherein n, m, p, X, Y, W, A, G and D are as defined in the specification, enantiomers thereof, pharmaceutical compositions containing said compound, pharmaceutically acceptable salts thereof, its use in therapy, especially in the treatment of psychotic disorders and intellectual impairment disorders.

  一种化合物的化学式为式中n，m，p，X，Y，W，A，G和D在规范中定义，其对映异构体，含有该化合物的制药组合物，其药学上可接受的盐，其在治疗中的用途，特别是用于治疗精神疾病和智力障碍。
• Spiroazo bicyclic heterocyclic
  申请人：AstraZeneca AB

  公开号：US06703502B2

  公开（公告）日：2004-03-09

  A compound of formula wherein n is 0 or 1; m is 0 or 1; p is 0 or 1; X is oxygen or sulfur; Y is CH, N or NO; W is oxygen, H2 or F2; A is N or C(R2); G is N or C(R3); D is N or C(R4); with the proviso that no more than one of A, G, and D is nitrogen, but at least one of Y, A, G, and D is nitrogen or NO; R1 is hydrogen or C1 to C4 alkyl; R2, R3, and R4 are independently hydrogen, halogen, C1, C4 alkyl, C2, C4 alkenyl, C2-C4 alkynyl, aryl, heteroaryl, OH, OC1, C4 alkyl, CO2R1, —CN, —NO2, —NR5R6, —CF3, —OSO2CF3 or R2 and R3, or R3 and R4, respectively, may together form another six membered aromatic or heteroaromatic ring sharing A and G, or G and D, respectively, containing between zero and two nitrogen atoms, and substituted with one to two of the following substituents: independently hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, heteroaryl, OH, OC1-C4 alkyl, CO2R1, —CN, —NO2, —NR5R6, —CF3, —OSO2CF3; R5 and R6 are independently hydrogen, C1-C4 alkyl, C(O)R7, C(O)NHR8, C(O)OR9, SO2R10 or may together be (CH2)jQ(CH2)k where Q is O, S, NR11, or a bond; j is 2 to 7, k is 0 to 2; R7, R8, R9, R10, and R11 are independently C1-C4 alkyl, aryl, or heteroaryl, or an enantiomer thereof, and the pharmaceutically acceptable salts thereof, processes for preparing them, composition containing them, and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders.

  一种化合物的公式，其中n为0或1；m为0或1；p为0或1；X为氧或硫；Y为CH、N或NO；W为氧、H2或F2；A为N或C（R2）；G为N或C（R3）；D为N或C（R4）；但前提是A、G和D中最多只有一个是氮，但Y、A、G和D中至少有一个是氮或NO；R1为氢或C1至C4烷基；R2、R3和R4分别独立地为氢、卤素、C1、C4烷基、C2、C4烯基、C2-C4炔基、芳基、杂环芳基、OH、OC1、C4烷基、CO2R1、—CN、—NO2、—NR5R6、—CF3、—OSO2CF3或R2和R3或R3和R4可共同形成另一个六元芳香或杂芳环，共享A和G或G和D，其中含有零到两个氮原子，并置换有以下一到两个取代基：独立的氢、卤素、C1-C4烷基、C2-C4烯基、C2-C4炔基、芳基、杂环芳基、OH、OC1-C4烷基、CO2R1、—CN、—NO2、—NR5R6、—CF3、—OSO2CF3；R5和R6独立地为氢、C1-C4烷基、C（O）R7、C（O）NHR8、C（O）OR9、SO2R10或可共同为（CH2）jQ（CH2）k，其中Q为O、S、NR11或键；j为2至7，k为0至2；R7、R8、R9、R10和R11独立地为C1-C4烷基、芳基或杂环芳基或其对映异构体，以及其药学上可接受的盐，制备它们的过程，含有它们的组合物以及它们在治疗中的用途，特别是在治疗或预防精神障碍和智力障碍方面。
• Compounds
  申请人：Astra Zeneca AB

  公开号：US06369224B1

  公开（公告）日：2002-04-09

  A compound of formula wherein n is 0 or 1; m is 0 or 1; p is 0 or 1; X is oxygen or sulfur; Y is CH, N or NO; W is oxygen, H2 or F2; A is N or C(R2); G is N or C(R3); D is N or C(R4); with the proviso that no more than one of A, G, and D is nitrogen, but at least one of Y, A, G, and D is nitrogen or NO; R1 is hydrogen or C1 to C4 alkyl; R2, R3, and R4 are independently hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, heteroaryl, OH, OC1-C4 alkyl, CO2R1, —CN, —NO2, —NR5R6, —CF3, —OSO2CF3 or R2 and R3, or R3 and R4, respectively, may together form another six membered aromatic or heteroaromatic ring sharing A and G, or G and D, respectively, containing between zero and two nitrogen atoms, and substituted with one to two of the following substituents: independently hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, heteroaryl, OH, OC1-C4 alkyl, CO2R1, —CN, —NO2, —NR5R6, —CF3, —OSO2CF3; R5 and R6 are independently hydrogen, C1-C4 alkyl, C(O)R7, C(O)NHR8, C(O)OR9, SO2R10 or may together be (CH2)jQ(CH2)k where Q is O, S, NR11, or a bond; j is 2 to 7, k is 0 to 2; R7, R8, R9, R10, and R11 are independently C1-C4 alkyl, aryl, or heteroaryl, or an enantiomer thereof, and the pharmaceutically acceptable salts thereof, processes for preparing them, composition containing them, and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders.

  该化合物的化学式为n为0或1；m为0或1；p为0或1；X为氧或硫；Y为CH，N或NO；W为氧，H2或F2；A为N或C（R2）；G为N或C（R3）；D为N或C（R4）；但是A，G和D中最多只有一个是氮，但Y，A，G和D中至少有一个是氮或NO；R1为氢或C1至C4烷基；R2，R3和R4分别独立地为氢，卤素，C1-C4烷基，C2-C4烯基，C2-C4炔基，芳基，杂环芳基，OH，OC1-C4烷基，CO2R1，-CN，-NO2，-NR5R6，-CF3，-OSO2CF3或R2和R3，或R3和R4共同形成另一个共用A和G或G和D的六元芳香或杂芳香环，其中含有零到两个氮原子，并用以下取代基之一或两个取代：独立的氢，卤素，C1-C4烷基，C2-C4烯基，C2-C4炔基，芳基，杂环芳基，OH，OC1-C4烷基，CO2R1，-CN，-NO2，-NR5R6，-CF3，-OSO2CF3；R5和R6独立地为氢，C1-C4烷基，C（O）R7，C（O）NHR8，C（O）OR9，SO2R10或共同为（CH2）jQ（CH2）k，其中Q为O，S，NR11或键；j为2到7，k为0到2；R7，R8，R9，R10和R11独立地为C1-C4烷基，芳基或杂环芳基，或其对映异构体，以及其药学上可接受的盐，制备它们的过程，包含它们的组合物，以及它们在治疗中的用途，特别是在治疗或预防精神障碍和智力障碍方面。
• Spiro [1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine for use in the treatment of psychotic and intellectual impairment disorders
  申请人：AstraZeneca AB

  公开号：EP1213291A1

  公开（公告）日：2002-06-12

  A compound spiro[1-azabicyclo[2.2.2]octane-3,2'-(3'H)-furo[2,3-b]pyridine] or an enantiomer thereof, and pharmaceutically acceptable salts thereof, processes for preparing them, composition containing them, and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders.

  一种化合物螺[1-氮杂双环[2.2.2]辛烷-3,2'-(3'H)-呋喃并[2,3-b]吡啶]或其对映体，及其药学上可接受的盐、制备工艺、含有它们的组合物，以及它们在治疗中的用途，特别是在治疗或预防精神障碍和智力障碍方面的用途。