(-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine | 142035-23-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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: (-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine
• 英文别名: diphenylmethyl-1-azabicyclo[3.2.2]octan-3-amine；(2S,3S)-2-diphenylmethylquinuclidin-3-amine；(2S,3S)-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine；(-)-(2S,3S)-cis-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine；(2S,3S)-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine；(2S,3S)-3-Amino-2-diphenylmethyl-1-azabicyclo[2.2.2]octane；(2S,3S)-2-Diphenylmethyl-1-azabicyclo[2.2.2]octan-3-amine；(2S,3S)-2-benzhydryl-1-azabicyclo[2.2.2]octan-3-amine
• CAS: 142035-23-2
• 化学式: C₂₀H₂₄N₂
• 分子量: 292.424
• InChiKey: MECDCHFRZHLREI-PMACEKPBSA-N

物化性质

• 沸点：
  420.5±28.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine 在 dimethyl sulfide borane 、 硫酸 、 尿素 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 97.92h， 生成 (-)-diphenylmethyl-3-((2-methoxy-5-azidophenyl)methylamino)-1-azabicyclo[3.2.2]octane
  参考文献：
  名称：

  Macdonald, Douglas; Silberman, Stephen C.; Lowe III, John A., Molecular Pharmacology, 1996, vol. 49, # 5, p. 808 - 813

  摘要：

  DOI：
• 作为产物：
  描述：

  (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine 在 palladium dihydroxide 盐酸 、 氢气 作用下， 以 methanol (MeOH) 为溶剂， 以96%的产率得到(-)-(2S,3S)-cis-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octane-3-amine
  参考文献：
  名称：

  Substituted benzylamino nitrogen containing non-aromatic heterocycles

  摘要：

  本发明涉及新型取代苄胺基氮含非芳香杂环化合物，具体而言，涉及式##STR1##的化合物，其中W、R.sup.1、R.sup.2、R.sup.3和A如规范中定义，并且涉及用于合成这类化合物的中间体。式I的新型化合物在治疗炎症和中枢神经系统疾病以及其他疾病中有用。

  公开号：

  US05721255A1

文献信息

• Substituted benzylaminoquinuclidines as substance P antagonists
  申请人：Pfizer Inc.

  公开号：US05604241A1

  公开（公告）日：1997-02-18

  Compounds useful in the treatment of inflammatory disorders, central nervous system disorders and other disorders of the formula I ##STR1## and the pharmaceutically-acceptable salts thereof, wherein Ar.sup.1 and Ar.sup.2 are each independently aryl or substituted aryl; R.sup.1 is alkyl having from 1 to 6 carbon atoms; R.sup.2 is hydrogen or alkyl having from 1 to 6 carbon atoms; and either X and Y are taken separately and they are each, independently, hydrogen, dialkylphosphoryl having 2 to carbon atoms, alkyl having from 1 to 6 carbon atoms, alkenyl having from 2 to 6 carbon atoms or alkynyl having from 2 to 6 carbon atoms; or X and Y are taken together and they represent a hydrocarbon chain having 3, 4, or 5 carbon atoms, optionally containing up to 2 double bonds and optionally having 1 or 2 substituents selected from oxo, hydroxy and alkyl having from 1 to 6 carbon atoms; or Y is methoxy when X is ethyl; provided that when X and Y are taken together they are attached to adjacent carbon atoms; and provided that if either X or Y is hydrogen, then the other one must be alkenyl or alkynyl; and provided that when Y is methoxy and X is ethyl, then Y is at the 4-position and X is at the 5-position, Ar.sup.1 or Ar.sup.2 must each be phenyl, R.sup.1 is methyl and R.sup.2 is hydrogen.

  用于治疗炎症性疾病、中枢神经系统疾病和其他公式I的化合物##STR1##及其药用盐，其中Ar.sup.1和Ar.sup.2分别独立地为芳基或取代芳基；R.sup.1为具有1至6个碳原子的烷基；R.sup.2为氢或具有1至6个碳原子的烷基；X和Y分别取，并且它们分别独立地为氢、具有2至碳原子的二烷基磷酰基、具有1至6个碳原子的烷基、具有2至6个碳原子的烯基或具有2至6个碳原子的炔基；或者X和Y一起取，并且它们代表具有3、4或5个碳原子的碳氢链，可选地含有最多2个双键，并且可选地具有1或2个从氧代、羟基和具有1至6个碳原子的烷基中选择的取代基；或者当X为乙基时，Y为甲氧基；前提是当X和Y一起取时，它们连接到相邻的碳原子上；并且如果X或Y中的任一个为氢，则另一个必须为烯基或炔基；并且当Y为甲氧基且X为乙基时，Y位于4位，X位于5位，Ar.sup.1或Ar.sup.2必须为苯基，R.sup.1为甲基，R.sup.2为氢。
• The discovery of (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine as a novel, nonpeptide substance P antagonist
  作者：John A. Lowe、Susan E. Drozda、R. Michael Snider、Kelly P. Longo、Stevin H. Zorn、Jean Morrone、Elisa R. Jackson、Stafford McLean、Dianne K. Bryce

  DOI：10.1021/jm00092a009

  日期：1992.7

  describe the structure-activity relationship development of a series of quinuclidines which culminated in the first potent, selective, nonpeptide substance P (SP) antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxy-phenyl)methyl]-1- azabicyclo[2.2.2]octan-3-amine, 3 (CP-96,345). Compound 3 is a potent displacer of [3H]SP binding in human IM-9 cells and blocks SP-induced and capsaicin-induced plasma

  我们描述了一系列喹啉核苷的结构-活性关系发展，该喹啉核苷在第一个有效的，选择性的，非肽类物质P（SP）拮抗剂，（2S，3S）-顺-2-（二苯基甲基）-N-[（2-甲氧基-苯基）甲基] -1-氮杂双环[2.2.2]辛-3-胺，（CP-96,345）3。化合物3是人IM-9细胞中[3H] SP结合的有效置换剂，并在体内阻断了SP诱导的和辣椒素诱导的血浆外渗以及SP诱导的唾液分泌。这种化合物既可以帮助我们进一步了解小分子与肽受体的相互作用，又可以评估SP拮抗剂的治疗潜力。
• Heteroatom substituted alkyl benzylaminoquinuclidines
  申请人：PFizer Inc.

  公开号：US05741797A1

  公开（公告）日：1998-04-21

  Compounds useful in the treatment of inflammatory disorders, central nervous system disorders and other disorders of the formula I and the pharmaceutically-acceptable salts thereof; ##STR1## wherein R is C.sub.1 -C.sub.6 alkyl; X is C.sub.1 -C.sub.6 alkyl having one or more substituents which include at least one heteroatom; Ar.sup.1 and Ar.sup.2 are each, independently, aryl optionally substituted by one C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, halogen, cyano, nitro, phenoxy, mono C.sub.1 -C.sub.6 alkylamino, di C.sub.1 -C.sub.6 alkylamino, halosubstituted C.sub.1 -C.sub.6 alkyl, or halosubstituted C.sub.1 -C.sub.6 alkoxy; Y is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, Z--(CH.sub.2).sub.p --, or W--(CH.sub.2).sub.m --CHR.sup.2 --(CH.sub.2).sub.n --NR.sup.1 CO-- wherein Y is at the 4-, 5- or 6-position on the quinuclidine ring; R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, benzyl or --(CH.sub.2).sub.r --W; R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl which may be substituted by one hydroxy, amino, methylthio, methylmercapto, benzyl, 4-hydroxybenzyl, 3-indolylmethyl or --(CH.sub.2).sub.r --W; R.sup.1 may form a ring with R.sup.2 ; Z is C.sub.1 -C.sub.6 alkoxy, --CONR.sup.4 R.sup.5, --CO.sub.2 R.sup.4, --CHR.sup.4 OR.sup.5, --CHR.sup.4 NR.sup.5 R.sup.6, --COR.sup.4, --CONR.sup.4 OR.sup.5 or optionally substituted aryl; each W is independently cyano, hydroxymethyl, C.sub.2 -C.sub.6 alkoxymethyl, aminomethyl, mono C.sub.1 -C.sub.6 alkylaminomethyl, di C.sub.1 -C.sub.6 alkylaminomethyl, carboxyl, carbamoyl or C.sub.1 -C.sub.6 alkoxycarbonyl; R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.8 cycloalkyl or an optionally substituted aryl or heterocyclic group; p is 0 to 6; and m, n and r are each, independently, 0 to 3.

  这是有关治疗炎症性疾病、中枢神经系统疾病和其他公式I及其药用盐的化合物的信息；其中R为C.sub.1 -C.sub.6烷基；X为具有一个或多个取代基的C.sub.1 -C.sub.6烷基，其中取代基至少包括一个杂原子；Ar.sup.1和Ar.sup.2各自独立地为芳基，可选择地被一个C.sub.1 -C.sub.6烷基、C.sub.1 -C.sub.6烷氧基、C.sub.1 -C.sub.6烷硫基、卤素、氰基、硝基、苯氧基、单C.sub.1 -C.sub.6烷基氨基、双C.sub.1 -C.sub.6烷基氨基、卤素取代的C.sub.1 -C.sub.6烷基或卤素取代的C.sub.1 -C.sub.6烷氧基取代；Y为氢、C.sub.1 -C.sub.6烷基、C.sub.2 -C.sub.6烯基、C.sub.3 -C.sub.8环烷基、Z--(CH.sub.2).sub.p --、或W--(CH.sub.2).sub.m --CHR.sup.2 --(CH.sub.2).sub.n --NR.sup.1 CO--，其中Y在喹啉环上的4、5或6位；R.sup.1为氢、C.sub.1 -C.sub.6烷基、苄基或--(CH.sub.2).sub.r --W；R.sup.2为氢或C.sub.1 -C.sub.6烷基，可以被一个羟基、氨基、甲硫基、甲硫醇基、苄基、4-羟基苄基、3-吲哚甲基或--(CH.sub.2).sub.r --W取代；R.sup.1可以与R.sup.2形成环；Z为C.sub.1 -C.sub.6烷氧基、--CONR.sup.4 R.sup.5、--CO.sub.2 R.sup.4、--CHR.sup.4 OR.sup.5、--CHR.sup.4 NR.sup.5 R.sup.6、--COR.sup.4、--CONR.sup.4 OR.sup.5或可选择地取代的芳基；每个W分别为氰基、羟甲基、C.sub.2 -C.sub.6烷氧基甲基、氨基甲基、单C.sub.1 -C.sub.6烷基氨基甲基、双C.sub.1 -C.sub.6烷基氨基甲基、羧基、氨甲酰基或C.sub.1 -C.sub.6烷氧羰基；R.sup.4、R.sup.5和R.sup.6各自独立地为氢、C.sub.1 -C.sub.6烷基、C.sub.1 -C.sub.6烷氧基、C.sub.3 -C.sub.8环烷基或可选择地取代的芳基或杂环基；p为0至6；m、n和r各自独立地为0至3。
• Substituted benzolactam compounds
  申请人：——

  公开号：US20030105124A1

  公开（公告）日：2003-06-05

  This invention relates to compounds of the general formula (1): 1 or a pharmaceutically acceptable salt thereof, W, T, Y, X, Q, R 1 , R 2 , and R 3 are defined herein. This invention also relates to compounds of the formula I, depicted above, wherein Y is —NH—; T is (2S,3S)-2-phenylpiperidin-3-yl, where the phenyl group of said (2S, 3S)-2-phenylpiperidine-3-yl may optionally be substituted with fluoro; Q is oxygen and is double bonded to the carbon atom to which it is attached, X is methoxy or ethoxy, R 1 is hydrogen, methyl or halo-C 1 -C 2 alkyl, W is methylene, ethylene or vinylene; R 2 and R 3 are independently hydrogen or methyl, or one of R 2 or R 3 may be hydroxy, when W is ethylene, R 2 and R 3 are both methyl, when W is methylene, and R 2 and R 3 are both hydrogen, when W is vinylene. The invention is further directed to methods of treating various CNS and other disorders using said compounds and pharmaceutical compositions thereof.

  这项发明涉及通式（1）：1的化合物或其药学上可接受的盐，其中W、T、Y、X、Q、R1、R2和R3的定义如本文所述。本发明还涉及上述示出的通式I的化合物，其中Y为—NH—；T为（2S,3S）-2-苯基哌啶-3-基，其中所述（2S,3S）-2-苯基哌啶-3-基的苯基可以选择地被氟取代；Q为氧并与其连接的碳原子双键结合，X为甲氧基或乙氧基，R1为氢、甲基或卤代-C1-C2烷基，W为亚甲基、乙烯基或乙烯基；R2和R3独立地为氢或甲基，或R2或R3中的一个可能为羟基，当W为乙烯基时，R2和R3均为甲基，当W为亚甲基时，R2和R3均为氢，当W为乙烯基时，R2和R3均为氢。该发明进一步涉及使用上述化合物及其药物组成物治疗各种中枢神经系统和其他疾病的方法。
• 制备马罗匹坦游离碱的方法
  申请人：海门慧聚药业有限公司

  公开号：CN106977512B

  公开（公告）日：2019-01-01

  本发明涉及马罗匹坦游离碱的制备方法,反应式如下：。