(-)-6-methylergolin-8-one | 58155-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (-)-6-methylergolin-8-one
• 英文别名: 6-methyl-ergolin-8-one；6-methyl-8-oxo-ergoline；(6aR,10aR)-7-methyl-4,6,6a,8,10,10a-hexahydroindolo[4,3-fg]quinolin-9-one
• CAS: 58155-79-6
• 化学式: C₁₅H₁₆N₂O
• 分子量: 240.305
• InChiKey: WZWHHCYTJDBJPY-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-6-methylergolin-8-one 在 盐酸 、 sodium hydroxide 、 叠氮磷酸二苯酯 、 氧气 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 3.17h， 生成 <4α,5β>-1,3,4,5-tetrahydro-4-methylamino-5-aminomethylbenzindole
  参考文献：
  名称：

  7-甲基-4,6,6a，7,10,10a-六氢吲哚并[4,3- fg ]喹唑啉衍生物的合成

  摘要：

  报道了与麦角灵有关的一系列化合物吲哚[4,3- fg ]喹唑啉（indolo [4,3- fg ]喹啉）的合成。合成序列的关键步骤是酮IV的环裂解。手性中心的立体化学是由二氢麦角酸I的手性建立的。

  DOI：

  10.1002/jhet.5570290227
• 作为产物：
  描述：

  (+)-9,10-didehydro-6-methylergoline-8-one 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以50%的产率得到(-)-6-methylergolin-8-one
  参考文献：
  名称：

  New Routes to Clavine-type Ergot Alkaloids. Part 1. First Total Synthesis of Three Natural Products: (+)-Setoclavine, (+)-Isosetoclavine, (-)-9,10-Dihydroisosetoclavine, and Structure Correction of the Latter

  摘要：

  The double bond in ring D of (+)-9,10-didehydro-6-methylergolin-8-one (2) was reduced selectively by catalytic hydrogenation to yield (-)-6-methylergolin-8-one (6). Grignard reaction of 6 has been performed with methylmagnesium iodide to afford two isomers (5 and 7). The main isomer having an 8 alpha-methyl group at C8 with a C/D-trans junction (5; (-)-dihydroisosetoclavine) proved to be identical with the natural product, hence its name and structure should be corrected. As a minor isomer (7) a C/D-cis clavine derivative was also isolated which can be regarded as unnatural (+)-8 alpha-hydroxy-costaclavine. (+)-Setoclavine (8) and (+)-isosetoclavine (9) have also been prepared from 2, thus achieving the first total synthesis of these natural products. Detailed structure elucidation of 5-9 has been carried out as well.

  DOI：

  10.3987/com-05-s(t)26

文献信息

• 3-Pyridylamine substituted ergolines
  申请人：Sandoz Ltd.

  公开号：US04004011A1

  公开（公告）日：1977-01-18

  This invention provides new compounds of formula I, ##STR1## wherein R is 3-pyridyl or 3-pyridyl mono- or polysubstituted BY LOWER ALKYL, LOWER ALKOXY, LOWER ALKYLTHIO, PHENOXY, HALOGEN, HYDROXY, OR THE GROUP ##STR2## wherein each of R.sub.1 and R.sub.2 is, independently, hydrogen or lower alkyl, Useful as prolactin secretion inhibitors for the treatment of galactorrhea.

  这项发明提供了新的化合物，其化学式为I，##STR1## 其中R是3-吡啶基或3-吡啶基单烷基或多取代物，通过LOWER ALKYL，LOWER ALKOXY，LOWER ALKYLTHIO，PHENOXY，HALOGEN，HYDROXY或GROUP ##STR2## 进行取代，其中R.sub.1和R.sub.2各自独立地为氢或低烷基。这些化合物可用作催乳素分泌抑制剂，用于治疗泌乳素过多症。
• Ergoline compounds useful as antiparkinson agents
  申请人：Farmitalia Carlo Erba S.p.A.

  公开号：US04746666A1

  公开（公告）日：1988-05-24

  Ergoline derivatives of the formula I ##STR1## wherein R.sub.1 =H,CH.sub.3 ; R.sub.2 =H, halogen, CH.sub.3, CN, C.sub.1 -C.sub.4 alkylthio or phenylthio; R.sub.3 =C.sub.1 -C.sub.4 hydrocarbon; R.sub.4 =H, OCH.sub.3 ; R.sub.5 =H and R.sub.6 =--CH.dbd.CH--CONHR.sub.7 or R.sub.5 and R.sub.6 =.dbd.CH--CONHR.sub.7 ; R.sub.7 =2-thiazolyl, 3-pyridazinyl, 1,3,4-thiadiazol-2-yl or 4-pyrimidinyl group optionally substituted, and pharmaceutically acceptable salts thereof, display activity on the Central Nervous System and are useful as antiprolactinic agents. Their preparation and pharmaceutical compositions containing them are also described.

  化学式为I的Ergoline衍生物： 其中，R.sub.1 = H，CH.sub.3；R.sub.2 = H，卤素，CH.sub.3，CN，C.sub.1-C.sub.4烷基硫或苯基硫；R.sub.3 = C.sub.1-C.sub.4碳氢化合物；R.sub.4 = H，OCH.sub.3；R.sub.5 = H，R.sub.6 = --CH.dbd.CH--CONHR.sub.7或R.sub.5和R.sub.6 = .dbd.CH--CONHR.sub.7；R.sub.7 = 2-噻唑基，3-吡啶嗪基，1,3,4-噻二唑-2-基或4-嘧啶基，可选地被取代，以及其药学上可接受的盐，在中枢神经系统上具有活性，并且可用作抗催乳素剂。还描述了它们的制备和含有它们的制药组合物。
• Ergolin-Derivate, Verfahren zu ihrer Herstellung, diese enthaltende pharmazeutische Zusammensetzungen und ihre Anwendung bei therapeutischen Behandlungen
  申请人：SANDOZ AG

  公开号：EP0001062A1

  公开（公告）日：1979-03-21

  Ergolin-Derivate der Formel I mit zentral-dopaminerg stimulierenden Eigenschaften, worin R1 Wasserstoff oder niederea Alkyl bedeutet, R2, R3 und R4 unabhängig voneinander für Wasserstoff, Halogen, niederes Alkoxy, niederes Alkyl oder (worin R5 und R6 je Wasserstoff oder niederes Alkyl bedeuten), für die Bindung -CH2CH= oder-CH=C= stehen. Die Verbindungen werden hergestellt durch Reduktion eines 8-oxo-Ergolin- Derivates in Gegenwart eines Amins der Formel

  具有中枢多巴胺能刺激特性的式 I 的麦角啉衍生物、 其中 R1 是氢或低级烷基，R2、R3 和 R4 相互独立地是氢、卤素、低级烷氧基、低级烷基或 (其中 R5 和 R6 各自为氢或低级烷基），代表键 -CH2CH= 或-CH=C=。 这些化合物是通过 8-氧代麦角啉衍生物在以下式子的胺存在下被还原而制备的
• Ergoline derivatives, process for preparing them, pharmaceutical composition and use
  申请人：FARMITALIA CARLO ERBA S.r.l.

  公开号：EP0206206A1

  公开（公告）日：1986-12-30

  Ergoline derivatives of the formula I wherein R1=H, CH3; R2=H, halogen, CH3, CN, C1-C4 alkylthio or phenylthio; R3=C1-C4 hydrocarbon; R4=H, OCH3; R5=H and R6=-CH=CH-CONHR7 or R5 + R6= =CH-CONHR7; R7= 2-thiazolyl, 3-pyridazinyl, 1,3,4-thiadiazol-2-yl or 4-pyrimidinyl group optionally substituted, and pharmaceutically acceptable salts thereof, display activity on the Central Nervous System and are useful as antiprolactinic agents. Their preparation, pharmaceutical compositions containing them, and their use in the preparation of a medicament for the treatment of Parkinson's disease are also described.

  式 I 的麦角啉衍生物 其中 R1=H, CH3; R2=H, 卤素, CH3, CN, C1-C4 烷硫基或苯硫基; R3=C1-C4 碳氢化合物; R4=H, OCH3; R5=H 和 R6=-CH=CH-CONHR7 或 R5 + R6= =CH-CONHR7；R7= 2-噻唑基、3-哒嗪基、1,3,4-噻二唑-2-基或任选取代的 4-嘧啶基，以及它们的药学上可接受的盐，对中枢神经系统具有活性，可用作抗催乳素药。此外，还介绍了它们的制备方法、含有它们的药物组合物以及它们在制备治疗帕金森病的药物中的用途。
• Synthesis and in vitro and in vivo evaluation of dopaminergic ergoline derivatives
  作者：Sergio Mantegani、Enzo Brambilla、Carla Caccia、Enrico Di Salle、Maria Antonietta Cervini、Robert A. McArthur、Gabriella Traquandi、Mario Varasi

  DOI：10.1016/s0014-827x(97)00009-8

  日期：1998.1

  A series of ergoline-amides was synthesised in the discovery of new dopaminomimetic agents. Several compounds exhibited in vivo high prolactin lowering activity (indirectly measured by the nidation test) in rats. For the most active, the potential anti-Parkinson activity was evaluated by observation of the contralateral turning behaviour in 6-OH-DA lesioned rats. The acute toxicity by oral route in mice was also studied. (C) 1998 Elsevier Science S.A.