(+/-)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-furan-2-methanamine oxalic acid | 41921-08-8

• 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: (+/-)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-furan-2-methanamine oxalic acid
• 英文别名: N-methyl-1-(3-oxatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),7,9,11,14,16-hexaen-4-yl)methanamine;oxalic acid
• CAS: 41921-08-8
• 化学式: C₂H₂O₄*C₁₉H₂₁NO
• 分子量: 369.417
• InChiKey: LQQNWXFPFJQTAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.58
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  6

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。
• Halogen substituted tetracyclic tetrahydrofuran derivatives
  申请人：——

  公开号：US20030134852A1

  公开（公告）日：2003-07-17

  This invention concerns the compounds of formula (I), 1 the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X is CH 2 or O; R 1 and R 2 each independently are hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, halomethylcarbonyl or C 1-6 alkyl substituted with hydroxy, C 1-6 alkyloxy, carboxyl, C 1-6 alkylcarbonyloxy, C 1-6 alkyloxycarbonyl or aryl; or R 1 and R 2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R 3 and R 4 are both halogen; or R 3 is halogen and R 4 is hydrogen; or R 3 is hydrogen and R 4 is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C 1-6 alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.

  该发明涉及公式（I）的化合物，其N-氧化物形式，药学上可接受的加成盐和立体化学异构体形式，其中n为零，1，2，3，4，5或6; X为CH2或O; R1和R2各自独立地为氢，C1-6烷基，C1-6烷基羰基，卤甲基羰基或C1-6烷基取代羟基，C1-6烷氧基，羧基，C1-6烷基羰氧基，C1-6烷氧羰酰基或芳基; 或R1和R2与它们所附着的氮原子一起可以形成吗啡啶环或可选取代的杂环; R3和R4均为卤素; 或R3为卤素且R4为氢; 或R3为氢且R4为卤素; 而芳基为苯基或取代有1、2或3个卤、羟基、C1-6烷基和卤甲基的苯基。公式（I）的化合物可以用作治疗剂。
• Preparation of trans-fused 3,3a,8,12b-tetrahydro-2h-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan derivatives
  申请人：Lang Lydia Yolande

  公开号：US20050014820A1

  公开（公告）日：2005-01-20

  The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

  本发明涉及式 (I) 的 4 种非对映异构体中每一种的立体化学纯形式的制备工艺。 立体化学纯度的 4 种非对映异构体。在酸催化的环化反应中形成具有反式融合的五元环和七元环的四环环系统。本发明还涉及由此获得的顺式融合的四环醇中间体、甲胺终产物，甲胺终产物可用作药物，特别是中枢神经系统活性药物。
• Preparation of cis-fused 3,3a,8,12b-tetrahydro-2h-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan derivatives
  申请人：Hua Mao

  公开号：US20050033067A1

  公开（公告）日：2005-02-10

  The present invention concerns a process for preparing each of the 4 individual diastereomers of formula (I) in stereochemically pure form from a single enantiomerically pure precursor. The tetracyclic ringsystem having cis-fused five and seven membered rings is formed in a base-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates and methanamine end-products, and the methanamine end-products for use as a medicine, in particular as CNS active medicines.

  本发明涉及一种从单一对映体纯的前体制备立体化学纯的式（I）的 4 种非对映异构体的工艺。在碱催化的环化反应中形成了具有顺式融合的 5 个和 7 个成员环的四环环系统。本发明进一步涉及由此获得的顺式融合四环醇中间体和甲胺终产物，以及用作药物，特别是用作中枢神经系统活性药物的甲胺终产物。
• SUBSTITUTED TETRACYCLIC TETRAHYDROFURAN DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0892793A1

  公开（公告）日：1999-01-27