(3-(biphenyl-4-yl)quinuclidine)-3-hydroxyquinuclidine | 136562-09-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3-(biphenyl-4-yl)quinuclidine)-3-hydroxyquinuclidine
• 英文别名: BPH-651；3-(biphenyl-4-yl)-3-hydroxyquinuclidine；3-(4-phenylphenyl)-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 136562-09-9
• 化学式: C₁₉H₂₁NO
• 分子量: 279.382
• InChiKey: WPCQYFUQHBLGAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 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-(biphenyl-4-yl)quinuclidine)-3-hydroxyquinuclidine 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 3-Biphenyl-4-yl-1-aza-bicyclo[2.2.2]oct-2-ene
  参考文献：
  名称：

  一系列新的3-联芳基奎宁环烯角鲨烯合酶抑制剂的合成和活性。

  摘要：

  具有3-联芳基取代基的喹核苷是一类新的有效的，口服活性的角鲨烯合酶（SQS）抑制剂。这些刚性结构周围的变化指示出阳离子SQS抑制剂的关键结构要求。因此，暗示了带有3个取代基的喹核苷的体外效价较低，该奎尼啶没有覆盖3-（联苯基-4-基）-3-羟基喹核苷（2）的联苯基团（IC50 = 16 nM，大鼠微粒体SQS）。 3取代基的方向性要求。类似地，3-三联苯类似物6的较低效能（IC50 = 370 nM）表明该取代基的尺寸受到限制。在具有奎宁环和联苯环之间连接基团的化合物中，亲脂性较低的连接基团的耐受性较差（例如，17，CH2CH2，IC50 = 5 nM与19，NHCO，IC50 = 1.2 microM）。用更具极性的吡啶杂环取代2的远端苯环会导致体外效能降低。通常，大鼠体内的良好体内活性仅限于3-羟基类似物，其中3- [4-（吡啶-4-基）苯基]衍生物39（IC50 = 161 nM）显示出最佳的抑制作用（口服给药后）

  DOI：

  10.1021/jm950907l
• 作为产物：
  描述：

  3-奎宁环酮 在 仲丁基锂 作用下， 反应 2.58h， 生成 (3-(biphenyl-4-yl)quinuclidine)-3-hydroxyquinuclidine
  参考文献：
  名称：

  一系列新的3-联芳基奎宁环烯角鲨烯合酶抑制剂的合成和活性。

  摘要：

  具有3-联芳基取代基的喹核苷是一类新的有效的，口服活性的角鲨烯合酶（SQS）抑制剂。这些刚性结构周围的变化指示出阳离子SQS抑制剂的关键结构要求。因此，暗示了带有3个取代基的喹核苷的体外效价较低，该奎尼啶没有覆盖3-（联苯基-4-基）-3-羟基喹核苷（2）的联苯基团（IC50 = 16 nM，大鼠微粒体SQS）。 3取代基的方向性要求。类似地，3-三联苯类似物6的较低效能（IC50 = 370 nM）表明该取代基的尺寸受到限制。在具有奎宁环和联苯环之间连接基团的化合物中，亲脂性较低的连接基团的耐受性较差（例如，17，CH2CH2，IC50 = 5 nM与19，NHCO，IC50 = 1.2 microM）。用更具极性的吡啶杂环取代2的远端苯环会导致体外效能降低。通常，大鼠体内的良好体内活性仅限于3-羟基类似物，其中3- [4-（吡啶-4-基）苯基]衍生物39（IC50 = 161 nM）显示出最佳的抑制作用（口服给药后）

  DOI：

  10.1021/jm950907l

文献信息

• Biphenyl quinuclidines
  申请人：Zeneca Limited

  公开号：US05792777A1

  公开（公告）日：1998-08-11

  Biphenylylquinuclidine compounds of the formula I: ##STR1## and pharmaceutically-acceptable salts thereof; wherein R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 -CR.sup.2 is a double bond; and one or both ring A and ring B may be optionally unsubstituted or independently substituted by one or more substituents selected from halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino, di-\x9b(1-6C)alkyl!amino, N-\x9b(1-6C)alkyl!carbamoyl, N,N-di-\x9b(1-6C)alkyl!carbamoyl, (1-6C)alkoxycarbonyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl and halogeno-(1-6C)alkyl; are inhibitors of squalene synthase and are hence useful in treating diseases or medical conditions such as hypercholesterolemia, atherosclerosis and fungal diseases. Methods of using these compounds to treat such conditions, novel compounds, processes for making these compounds and pharmaceutical compositions containing them are claimed.

  苯基喹啉化合物的化学式 I：##STR1## 及其药用可接受的盐；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；环 A 和/或环 B 可能是未取代的，也可以独立地被一个或多个卤素、羟基、氨基、硝基、氰基、羧基、氨甲酰基、(1-6C)烷基、(1-6C)烷氧基、(1-6C)烷基氨基、二-(1-6C)烷基氨基、N-(1-6C)烷基)氨甲酰基、N,N-二-(1-6C)烷基)氨甲酰基、(1-6C)烷氧羰基、(1-6C)烷基硫醚基、(1-6C)烷基磺氧基、(1-6C)烷基磺酰基和卤素-(1-6C)烷基取代；这些化合物是角鲨烯合成酶的抑制剂，因此在治疗高胆固醇血症、动脉粥样硬化和真菌病等疾病或医疗状况中有用。声明了使用这些化合物治疗这些疾病的方法、新化合物、制备这些化合物的方法以及含有它们的药物组合物。
• Biphenylquinuclidines as inhibitors of squalene synthase and growth of parasitic protozoa
  作者：Silvia Orenes Lorente、Rosario Gómez、Carmen Jiménez、Simon Cammerer、Vanessa Yardley、Kate de Luca-Fradley、Simon L. Croft、Luis M. Ruiz Perez、Julio Urbina、Dolores Gonzalez Pacanowska、Ian H. Gilbert

  DOI：10.1016/j.bmc.2005.02.060

  日期：2005.5

  In this paper we describe the preparation of some biphenylquinuclidine derivatives and their evaluation as inhibitors of squalene synthase in order to explore their potential in the treatment of the parasitic diseases leishmaniasis and Chagas disease. The compounds were screened against recombinant Leishmania major squalene synthase and against Leishmania mexicana promastigotes, Leishmania donovani intracellular amastigotes and Trypanosoma cruzi intracellular amastigotes. Compounds that inhibited the enzyme, also reduced the levels of steroids and caused growth inhibition of L. mexicana promastigotes. However there was a lower correlation between inhibition of the enzyme and growth inhibition of the intracellular parasites, possibly due to delivery problems. Some compounds also showed growth inhibition of T brucei rhodesiense trypomastigotes, although in this case alternative modes of action other than inhibition of SQS are probably involved. (c) 2005 Elsevier Ltd. All rights reserved.
• BIPHENYLYLQUINUCLIDINES, USEFUL AS SQUALENE SYNTHETASE INHIBITORS
  申请人：ZENECA LIMITED

  公开号：EP0569564B1

  公开（公告）日：1997-12-29
• COMPOSITIONS AND METHODS FOR INHIBITING PROTOZOAN GROWTH
  申请人：Beverley Stephen M.

  公开号：US20080119483A1

  公开（公告）日：2008-05-22

  The present invention provides compositions and methods for inhibiting protozoan growth comprising a synergistic combination of lipid synthesis inhibitors. In addition, the invention provides compositions and methods that are useful for the treatment of protozoan infections and the identification of potential new drugs for the treatment of protozoan infections.
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT NEUROINFLAMMATORY DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160303146A1

  公开（公告）日：2016-10-20

  This invention provides methods and pharmaceutical compositions that can treat neuroinflammatory disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.