N,N-dimethyl-1-(3-oxatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),7,9,11,14,16-hexaen-4-yl)methanamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: N,N-dimethyl-1-(3-oxatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),7,9,11,14,16-hexaen-4-yl)methanamine
• 化学式: C₂₀H₂₃NO
• 分子量: 293.4
• InChiKey: ACTVOFFLDWZANE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

文献信息

• [EN] SUBSTITUTED TETRACYCLIC TETRAHYDROFURAN DERIVATIVES<br/>[FR] DERIVES TETRAHYDROFURANES TETRACYCLIQUES SUBSTITUES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1997038991A1

  公开（公告）日：1997-10-23

  (EN) This invention concerns the compounds of formula (I), the $i(N)-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, wherein n is zero to 6; p and q are zero to 4; r is zero to 5; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; halomethylcarbonyl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; each R3 and R4 independently are halo, cyano, hydroxy, halomethyl, halomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or halomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; aryl is optionally substituted phenyl; provided that the compound is other than (±)-3,3a,8,12b-tetrahydro-$i(N)-methyl-2$i(H)-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-furan-2-methanamine oxalic acid. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.(FR) L'invention concerne des composés de la formule (I), des formes $i(N)-oxyde, des sels d'addition acceptables sur le plan pharmacologique et des formes isomères sur le plan stéréochimique de ces composés. Dans cette formule, n vaut zéro à 6, p et q valent de zéro à 4, r vaut zéro à 5, R1 et R2 représentent chacun indépendamment hydrogène, sont éventuellement substitués par alkyle C1-6, alkylcarbonyle C1-6, halométhylcarbonyle, ou bien R1 et R2 pris ensemble avec l'atome d'azote auquel ils sont attachés peuvent former un noyau morpholinyle ou un hétérocycle éventuellement substitué, R3 et R4 représentent chacun indépendamment halo, cyano, hydroxy, halométhyle, halométhoxy, carboxyle, nitro, amino, mono- ou di(alkyle C1-6)amino, alkylcarbonylamino C1-6, aminosulfonyle, mono- ou di(alkyle C1-6)aminosulfonyle, alkyle C1-6, alkyloxy C1-6, alkylcarbonyle C1-6 ou alkyloxycarbonyle C1-6, chaque R5 représente indépendamment alkyle C1-6, cyano ou halométhyle, X représente CR6R7, NR8, O, S, S(=O) ou S(=O)2, aryle représente phényle éventuellement substitué, à condition que le composé soit autre que l'acide oxalique de (±)-3,3a,8,12b-tétrahydro-$i(N)-méthyl-2$i(H)-dibenzo(3,4:6,7)-cyclohepta(1,2-b)-furan-2-méthanamine. On peut utiliser les composés de la formule (I) en tant qu'agents thérapeutiques dans le traitement ou la prévention de troubles du système nerveux central, de troubles cardio-vasculaires ou gastro-intestinaux.

  本发明涉及公式（I）化合物，其$i(N)-氧化物形式，药学上可接受的加成盐及其立体异构体形式，其中n为0至6；p和q为0至4；r为0至5；R1和R2各自独立地为氢；可选取代的C1-6烷基；C1-6烷基羰基；卤代甲基羰基；或R1和R2与它们附着的氮原子一起可以形成吗啡啶环或可选取代的杂环；每个R3和R4各自独立地为卤素，氰基，羟基，卤代甲基，卤代甲氧基，羧基，硝基，氨基，单或双（C1-6烷基）氨基，C1-6烷基羰基氨基，氨基磺酰基，单或双（C1-6烷基）氨基磺酰基，C1-6烷基，C1-6烷氧基，C1-6烷基羰基，C1-6烷氧羰基；每个R5独立地为C1-6烷基，氰基或卤代甲基；X为CR6R7，NR8，O，S，S（=O）或S（=O）2；芳基为可选取代的苯基；前提是该化合物不是（±）-3,3a,8,12b-四氢-$i(N)-甲基-2$i(H)-二苯并[3,4:6,7]-环庚[1,2-b]-呋喃-2-甲酸。公式（I）化合物可用于治疗或预防中枢神经系统疾病，心血管疾病或胃肠疾病的治疗剂。
• Novel mandelates salts of substituted tetracyclic tetrahydrofuran derivatives
  申请人：Medaer Bart Petrus Anna Maria Jozef

  公开号：US20050085533A1

  公开（公告）日：2005-04-21

  The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R 1 and R 2 each independently are hydrogen or C 1-6 alkyl and R 3 and R 4 each independently are hydrogen or halogen. In the foregoing definitions C 1-6 alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media. Also disclosed are pharmaceutical compositions comprising mandelate salts according to the invention, mandelate salts according to the invention for use as a medicine, a process for preparing the mandelate salts according to the invention and the use of the mandelate salts and pharmaceutical compositions comprising mandelate salts according to the invention for the treatment or the prevention of CNS disorders, cardiovascular disorders and gastrointestinal disorders.

  本发明的对象是一种按照公式（I）定义的取代四环四氢呋喃衍生物的新型曼德酸盐，其中N-氧化物形式和立体化学异构体形式，其中R1和R2各自独立地为氢或C1-6烷基，R3和R4各自独立地为氢或卤素。在上述定义中，C1-6烷基定义为具有1至6个碳原子的直链和支链饱和碳氢基基团，例如甲基，乙基，丙基，丁基，1-甲基丙基，1,1-二甲基乙基，戊基或己基。新型曼德酸盐不敏感于光，并且比先前的盐在室温，升高温度和相对高湿度以及在水介质中更加稳定。还披露了包括根据本发明的曼德酸盐的制药组合物，根据本发明的曼德酸盐作为药物的用途，制备根据本发明的曼德酸盐的过程以及用于治疗或预防中枢神经系统疾病，心血管疾病和胃肠疾病的曼德酸盐和包含曼德酸盐的制药组合物的用途。
• SUBSTITUTED TETRACYCLIC TETRAHYDROFURAN DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0892793A1

  公开（公告）日：1999-01-27
• NOVEL MANDELATE SALTS OF SUBSTITUTED TETRACYCLIC TETRAHYDROFURAN DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1446397A1

  公开（公告）日：2004-08-18
• US6057441A
  申请人：——

  公开号：US6057441A

  公开（公告）日：2000-05-02