3-Hydroxy-3-vinyl-chinuclidin | 90608-28-9

• 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-vinyl-chinuclidin
• 英文别名: 3-Ethenyl-3-hydroxy-1-azabicyclo[2.2.2]octane；3-ethenyl-3-hydroxyquinuclidine；3-vinyl-1-aza-bicyclo[2.2.2]octan-3-ol；3-vinyl-quinuclidin-3-ol；3-Vinyl-chinuclidin-3-ol；3-ethenyl-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 90608-28-9
• 化学式: C₉H₁₅NO
• 分子量: 153.224
• InChiKey: LJLUTMJIZANZQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Hydroxy-3-vinyl-chinuclidin 、 4-(4-溴苯氧基)苯甲酸甲酯 在 四丁基氯化铵 、 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以59%的产率得到methyl 4-(4-(2-(3-hydroxyquinuclidin-3-yl)vinyl)phenoxy)benzoate
  参考文献：
  名称：

  Selective non zinc binding inhibitors of MMP13

  摘要：

  Directed screening has identified a novel series of MMP13 inhibitors that possess good levels of activity whilst possessing excellent selectivity over related MMPs. The binding mode of the series has been solved by co-crystallisation and demonstrates an interesting mode of inhibition without interaction with the catalytic zinc atom. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.075
• 作为产物：
  描述：

  3-乙炔基奎宁环-3-醇 在 钯 氢气 作用下， 以 乙醇 为溶剂， 生成 3-Hydroxy-3-vinyl-chinuclidin
  参考文献：
  名称：

  Quinuclidine derivatives as squalene synthase inhibitors

  摘要：

  化合物的化学式（I）及其药用盐，其中R.sup.1为氢或羟基；R.sup.2为氢；或R.sup.1和R.sup.2结合在一起，使得CR.sup.1 -CR.sup.2为双键；X从--CH.sub.2 CH.sub.2 --，--CH.dbd.CH--，--C.tbd.C--，--CH.sub.2 O--，--CH.sub.2 NH--，--NHCH.sub.2 --，--CH.sub.2 CO--，--COCH.sub.2 --，--CH.sub.2 S--和--SCH.sub.2 --中选择；Ar.sup.1为苯基；Ar.sup.2为杂环芳基；其中Ar.sup.1和Ar.sup.2中的一个或两个可以选择性地带有一个或多个取代基，取代基独立地从卤素，羟基，氨基，硝基，氰基，羧基，氨基甲酰基，烷基，烯基，炔基，烷氧基，烷基氨基，二烷基氨基，N-烷基氨基甲酰基，二N,N-烷基氨基甲酰基，烷氧羰基，烷基硫醚，烷基砜基，卤代烷基，羧基烷基和烷酰胺基中独立选择；但当R.sup.1为羟基时，X不可从--NHCH.sub.2 --和--SCH.sub.2 --中选择；是皂化酶的抑制剂，因此在治疗降低胆固醇有益的医疗状况中有用，如高胆固醇血症和动脉粥样硬化。还描述了制备这些衍生物的方法，含有它们的药物组合物以及它们在医学中的用途。

  公开号：

  US05714496A1

文献信息

• Quinclidine derivatives as squalene synthase inhibitors
  申请人：Zeneca Limited

  公开号：US05691349A1

  公开（公告）日：1997-11-25

  Quinuclidine derivatives of formula, and their pharmaceutically acceptable salts, in which: R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; pr R.sup.1 and R.sup.2 are joined together so that CR.sup.1 -CR.sup.2 is a double bond; X is selected from --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.dbd.C--, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 NH--, NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S(O).sub.n -- and --S(O).sub.n CH.sub.2 -- wherein n is 0, 1 or 2; and AR is phenyl which may be optionally unsubstituted or substituted by one or more substituents such as halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, N-alkylcarbamoyl, N,N-di-alkylcarbamoyl, alkoxycarbonyl, alkythio, alkylsulphinyl, alkylsulphonyl, halogeno alkyl, alkanoylamino, alkylenedioxy, alkanoyl and oxime derivatives thereof and O-alkyl ethers of said oximes; provided that when X is selected from --OCH.sub.2 --, --NHCH.sub.2 --, and SCH.sub.2 --, R.sup.1 is not hydroxy; inhibit squalene synthase and are useful in treating diseases or medical conditions in which inhibition of squalene synthase is desirable. The use of such heterocyclic derivatives in treating conditions such as hypercholesterolemia, and atherosclerosis is referred to as well as novel compounds, processes for their preparation and pharmaceutical compositions containing them.

  喹诺克林衍生物的公式，以及它们的药用可接受盐，其中：R.sup.1是氢或羟基；R.sup.2是氢；或者R.sup.1和R.sup.2连接在一起，使得CR.sup.1-CR.sup.2是一个双键；X选自--CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.dbd.C--, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 NH--, NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S(O).sub.n --和--S(O).sub.n CH.sub.2 --，其中n为0、1或2；AR是苯基，它可以是未取代的，也可以是取代的，取代基可以是卤素、羟基、氨基、硝基、氰基、羧基、氨基甲酰基、烷基、烯基、炔基、烷氧基、烷基氨基、二烷基氨基、N-烷基氨基甲酰基、N，N-二烷基氨基甲酰基、烷氧基羰基、烷基硫、烷基亚磺酰基、烷基亚磺酰基、卤代烷基、烷酰氨基、烷二氧基、烷酰和肟衍生物以及所述肟的O-烷基醚；当X选自--OCH.sub.2 --, --NHCH.sub.2 --和--SCH.sub.2 --时，R.sup.1不是羟基；抑制角鲨烯合酶，在抑制角鲨烯合酶是可取的情况下，用于治疗疾病或医疗状况。此类杂环衍生物在治疗高胆固醇血症和动脉粥样硬化等状况中的应用，以及新的化合物、它们的制备过程和含有它们的药物组合物。
• Spiroazabicyclic heterocyclic compounds
  申请人：Astra Aktiebolag

  公开号：US06110914A1

  公开（公告）日：2000-08-29

  A compound of formula ##STR1## 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.sub.2 or F.sub.2 ; A is N or C(R.sup.2); G is N or C(R.sup.3); D is N or C(R.sup.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.sup.1 is hydrogen or C.sub.1 to C.sub.4 alkyl; R.sup.2, R.sup.3, and R.sup.4 are independently hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, aryl, heteroaryl, OH, OC.sub.1 -C.sub.4 alkyl, CO.sub.2 R.sup.1, --CN, --NO.sub.2, --NR.sup.5 R.sup.6, --CF.sub.3, --OSO.sub.2 CF.sub.3 or R.sup.2 and R.sup.3, or R.sup.3 and R.sup.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.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, aryl, heteroaryl, OH, OC.sub.1 -C.sub.4 alkyl, CO.sub.2 R.sup.1, --CN, --NO.sub.2, --NR.sup.5 R.sup.6, --CF.sub.3, --OSO.sub.2 CF.sub.3 ; R.sup.5 and R.sup.6 are independently hydrogen, C.sub.1 -C.sub.4 alkyl, C(O)R.sup.7, C(O)NHR.sup.8, C(O)OR.sup.9, SO.sub.2 R.sup.10 or may together be (CH.sub.2).sub.j Q(CH.sub.2).sub.k where Q is O, S, NR.sup.11, or a bond; j is 2 to 7, k is 0 to 2; R.sup.7, R.sup.8, R.sup.9, R.sup.10, and R.sup.11 are independently C.sub.1 -C.sub.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.

  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。
• 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。