N-[[(6aR,9S,10aR)-2-tert-butyl-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinolin-9-yl]methyl]-5-bromopyridine-3-carboxamide

• 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: N-[[(6aR,9S,10aR)-2-tert-butyl-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinolin-9-yl]methyl]-5-bromopyridine-3-carboxamide
• 化学式: C₂₆H₃₁BrN₄O
• 分子量: 495.462
• InChiKey: XOJPSABQGLYGIG-UYGSHGSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  61
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9,10-dihydrolysergic acid methyl ester 在 镍 sodium tetrahydroborate 、 磺酰氯 、 一水合肼 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 三氟乙酸 为溶剂， 反应 11.42h， 生成 N-[[(6aR,9S,10aR)-2-tert-butyl-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinolin-9-yl]methyl]-5-bromopyridine-3-carboxamide
  参考文献：
  名称：

  Synthesis and in vitro structure-activity relationship of 13-tert-butyl-ergoline derivatives as 5-HT1A receptor ligands

  摘要：

  A series of novel 13-tert-butyl-ergoline derivatives was prepared and evaluated for affinity to adrenergic, dopaminergic and serotonergic receptor sites. Selectivity for 5-HT1A receptors versus alpha(1), alpha(2), D-1, D-2, and 5-HT2 appears to be influenced by the presence of the tert-butyl moiety at position 13 of the ergoline skeleton. Some compounds within this series display nanomolar 5-HT1A affinity and hundred-fold selectivity versus the other receptors considered.

  DOI：

  10.1016/s0223-5234(99)80065-8

文献信息

• SEROTONINERGIC ERGOLINE DERIVATIVES
  申请人：PHARMACIA & UPJOHN S.p.A.

  公开号：EP0628042B1

  公开（公告）日：2001-08-16
• US5430031A
  申请人：——

  公开号：US5430031A

  公开（公告）日：1995-07-04
• [EN] SEROTONINERGIC ERGOLINE DERIVATIVES<br/>[FR] DERIVES D'ERGOLINIE SEROTONINERGIQUES
  申请人：FARMITALIA CARLO ERBA S.R.L.

  公开号：WO1994014806A1

  公开（公告）日：1994-07-07

  (EN) The present invention provides compounds of formula (I) wherein A represents OH, NH2, COOR3', OCONHR4, CONHR4, NHCOR4, NHCO2R4, NHC(X)NHR4, NHC(X)NHCOR4, (a) or (b), R1 is hydrogen or C1-4 linear or branched alkyl; R2 is hydrogen, chlorine, bromine or an S-C1-4 alkyl group; R3 and R3' are, independently, C1-5 alkyl or hydrogen, n is 0,1 or 2, m is 1 or 2; R4 is hydrogen, C1-7 alkyl, C3-7 cycloalkyl, adamantidyl (tricyclo 3.3.1.1.3,7) decan-1-yl, C1-5 alkylphenyl, C2 alkenylphenyl; C2 alkynylphenyl, phenyl optionally substituted by one or more groups selected from C1-4 alkyl, C1-3 alkoxy, methylendioxy, cyano, trifluoromethyl, hydroxy, nitro and acetyl; an optionally substituted naphthyl ring or phenyl condensed with a heterocyclic ring system having 5- or 6- ring members including 1 to 4 heteroatoms selected from nitrogen, oxygen and sulphur; a heterocyclic ring having 5 or 6 ring members including 1 or 2 heteroatoms selected from nitrogen, oxygen and sulphur which is optionally substituted by a group selected from C1-4 alkyl, phenyl optionally substituted as defined above, C1-3 alkoxy and halogen; R5 is hydrogen, C1-4 alkyl or a phenyl group and X is NH, O, S; or a pharmaceutically acceptable salt thereof. A process for their preparation and the pharmaceutical compositions comprising them are also provided.(FR) Composés répondant à la formule (I), dans laquelle A représente OH, NH2, COOR3', OCONHR4, CONHR4, NHCOR4, NHCO2R4, NHC(X)NHR4, NHC(X)NHCOR4, (a) ou (b); R1 représente hydrogène ou alkyle C1-4 linéaire ou ramifié; R2 représente hydrogène, chlore, brome ou un groupe alkyle S-C1-4; R3 et R3', indépendamment l'un de l'autre, représentent alkyle C1-5 ou hydrogène; n vaut 0, 1 ou 2; m vaut 1 ou 2; R4 représente hydrogène, alkyle C1-7, cycloalkyle C3-7, adamantidyle (tricyclo 3,3,1,1,3,7) décan-1-yle), alkylphényl C1-5, alcénylphényle C2; alcynylphényle C2, phényle éventuellement substitué par un ou plusieurs groupes sélectionnés parmi alkyle C1-4, alcoxy C1-3, méthylèndioxy, cyano, trifluorométhyle, hydroxy, nitro et acétyle, un cycle naphtyle éventuellement substitué ou phényle condensé avec un système cyclique hétérocyclique penta- ou hexagonal comprenant de 1 à 4 hétéroatomes sélectionnés parmi l'azote, l'oxygène et le soufre; un cycle hétérocyclique penta- ou hexagonal comprenant 1 ou 2 hétéroatomes sélectionnés parmi l'azote, l'oxygène et le soufre, éventuellement substitué par un groupe sélectionné parmi alkyle C1-4, phényle éventuellement substitué de la manière précitée, alcoxy C1-3 et halogène; R5 représente hydrogène, alkyle C1-4 ou un groupe phényle; et X représente NH, O ou S; ou leur sel pharmaceutiquement acceptable. On a également prévu leur procédé de préparation, et des compositions pharmaceutiques les contenant.
• Synthesis and in vitro structure-activity relationship of 13-tert-butyl-ergoline derivatives as 5-HT1A receptor ligands
  作者：S Mantegani、E Brambilla、C Caccia、MG Fornaretto、RA Mc Arthur、M Varasi

  DOI：10.1016/s0223-5234(99)80065-8

  日期：1997.10

  A series of novel 13-tert-butyl-ergoline derivatives was prepared and evaluated for affinity to adrenergic, dopaminergic and serotonergic receptor sites. Selectivity for 5-HT1A receptors versus alpha(1), alpha(2), D-1, D-2, and 5-HT2 appears to be influenced by the presence of the tert-butyl moiety at position 13 of the ergoline skeleton. Some compounds within this series display nanomolar 5-HT1A affinity and hundred-fold selectivity versus the other receptors considered.