6-<2-(dimethylamino)ethoxy>-5-methoxy-1H-indole | 170691-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-<2-(dimethylamino)ethoxy>-5-methoxy-1H-indole
• 英文别名: 6-(2-dimethylaminoethoxy)-5-methoxy-1H-indole；2-[(5-methoxy-1H-indol-6-yl)oxy]-N,N-dimethylethanamine
• CAS: 170691-25-5
• 化学式: C₁₃H₁₈N₂O₂
• 分子量: 234.298
• InChiKey: MFCOZZVJQJYWJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  37.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-<2-(dimethylamino)ethoxy>-5-methoxy-1H-indole 在 sodium hydroxide 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 20.0h， 生成 2,3-Dihydro-6-(2-dimethylaminoethoxy)-5-methoxy-1-[4-(2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)benzoyl]-1H-indole
  参考文献：
  名称：

  The Selective 5-HT_1B Receptor Inverse Agonist 1‘-Methyl-5-[[2‘-methyl-4‘- (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4‘-piperidine] (SB-224289) Potently Blocks Terminal 5-HT Autoreceptor Function Both in Vitro and in Vivo

  摘要：

  5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively Linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1D beta and 5-HT1D alpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

  DOI：

  10.1021/jm970457s
• 作为产物：
  描述：

  3-[2-(dimethylamino)ethoxy]-4-methoxyaniline 在 palladium on activated charcoal 氢气 、 三氟乙酸 、 三氟乙酸酐 作用下， 反应 30.0h， 生成 6-<2-(dimethylamino)ethoxy>-5-methoxy-1H-indole
  参考文献：
  名称：

  The Selective 5-HT_1B Receptor Inverse Agonist 1‘-Methyl-5-[[2‘-methyl-4‘- (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4‘-piperidine] (SB-224289) Potently Blocks Terminal 5-HT Autoreceptor Function Both in Vitro and in Vivo

  摘要：

  5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively Linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1D beta and 5-HT1D alpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

  DOI：

  10.1021/jm970457s

文献信息

• Indole, indoline and quinoline derivatives with 5HT.sub.1D
  申请人：SmithKline Beecham, p.l.c.

  公开号：US05889022A1

  公开（公告）日：1999-03-30

  Novel indole, indoline and quinoline derivatives of formula (I) processes for their preparation, pharmaceutical compositions containing them, and their use in medicine is disclosed. A structurally distinct class of compounds have now been discovered and have been found to exhibit 5HT.sub.1-D antagonist activity. In a first aspect, the present invention therefore provides a compound of formula (I) or a salt thereof, in which P is a 5-7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, A, B, m, R.sup.1 -R.sup.8 are defined in the application.

  披露了公式(I)的吲哚、吲哚啉和喹啉衍生物及其制备过程，含有它们的药物组合物及其在医学上的用途。现已发现了一个结构上明显不同的化合物类别，并发现这些化合物具有5HT.sub.1-D拮抗剂活性。因此，在一个方面，本发明提供了一种公式(I)的化合物或其盐，其中P是一个含有1到3个氧、氮或硫杂原子的5-7成员杂环，A、B、m、R.sup.1 -R.sup.8在申请中定义。
• Biphenylamide compounds as 5HT.sub.1D Antagonists
  申请人：SmithKline Beecham p.l.c.

  公开号：US05817833A1

  公开（公告）日：1998-10-06

  Compounds of formula (I) or a salt thereof: ##STR1## R.sup.1 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, COC.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, hydroxyC.sub.1-6 alkyl, hydroxyC.sub.1-6 alkoxy, C.sub.1-6 alkoxyC.sub.1-6 alkoxy, acyl, nitro, trifluoromethyl, cyano, CHO, SR.sup.9, SOR.sup.9, SO.sub.2 R.sup.9, SO.sub.2 NR.sup.10 R.sup.11, CO.sub.2 R.sup.10, NR.sup.10 SO.sub.2 R.sup.11, CONR.sup.10 R.sup.11, CO.sub.2 NR.sup.10 R.sup.11, CONR.sup.10 (CH.sub.2).sub.p CO.sub.2 R.sup.11, (CH.sub.2).sub.p NR.sup.10 R.sup.11, (CH.sub.2).sub.p CONR.sup.10 R.sup.11, (CH.sub.2).sub.p NR.sup.10 COR.sup.11, (CH.sub.2).sub.p CO.sub.2 C.sub.1-6 alkyl, CO.sub.2 (CH.sub.2).sub.p OR.sup.10, CONHNR.sup.10 R.sup.11, NR.sup.10 R.sup.11, NR.sup.10 CO.sub.2 R.sup.11, NR.sup.10 CONR.sup.10 R.sup.11, CR.sup.10 .dbd.NOR.sup.11, CNR.sup.10 .dbd.NOR.sup.11, where R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl and p is 1 to 4; R.sup.2 and R.sup.3 are independently hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, CO.sub.2 R.sup.10, CONR.sup.10 R.sup.11, NR.sup.10 R.sup.11 where R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl; R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl; R.sup.6 is hydrogen, halogen, hydroxy, C.sub.1-6 alkyl or C.sub.1-6 alkoxy; R.sup.7 and R.sup.8 are independently hydrogen, C.sub.1-6 alkyl, aralkyl, or together with the nitrogen atom to which they are attached form an optionally substituted 5-7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur; A is oxygen, S(O).sub.q where q is 0, 1 or 2, CR.sup.4 .dbd.CR.sup.5 or CR.sup.4 R.sup.5 where R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl, or A is NR.sup.12 where R.sup.12 is hydrogen or C.sub.1-6 alkyl; B is (CR.sup.13 R.sup.14).sub.q where q is 2, 3 or 4 and R.sup.13 and R.sup.14 are independently hydrogen or C.sub.1-6 alkyl or B is (CR.sup.13 R.sup.14).sub.r --D where r is 0, 1, 2 or 3 and D is oxygen, sulphur or CR.sup.13 .dbd.CR.sup.14 ; m is 1 to 4; and n is 1 or 2, exhibit 5HT.sub.1D antagonist activity.

  化合物的公式(I)或其盐：##STR1##其中，R.sup.1是氢、卤素、C.sub.1-6烷基、C.sub.3-6环烷基、COC.sub.1-6烷基、C.sub.1-6烷氧基、羟基、羟基C.sub.1-6烷基、羟基C.sub.1-6烷氧基、C.sub.1-6烷氧基C.sub.1-6烷氧基、酰基、硝基、三氟甲基、氰基、CHO、SR.sup.9、SOR.sup.9、SO.sub.2R.sup.9、SO.sub.2NR.sup.10R.sup.11、CO.sub.2R.sup.10、NR.sup.10SO.sub.2R.sup.11、CONR.sup.10R.sup.11、CO.sub.2NR.sup.10R.sup.11、CONR.sup.10(CH.sub.2).sub.pCO.sub.2R.sup.11、(CH.sub.2).sub.pNR.sup.10R.sup.11、(CH.sub.2).sub.pCONR.sup.10R.sup.11、(CH.sub.2).sub.pNR.sup.10COR.sup.11、(CH.sub.2).sub.pCO.sub.2C.sub.1-6烷基、CO.sub.2(CH.sub.2).sub.pOR.sup.10、CONHNR.sup.10R.sup.11、NR.sup.10R.sup.11、NR.sup.10CO.sub.2R.sup.11、NR.sup.10CONR.sup.10R.sup.11、CR.sup.10.dbd.NOR.sup.11、CNR.sup.10.dbd.NOR.sup.11，其中R.sup.10和R.sup.11独立地为氢或C.sub.1-6烷基，p为1至4；R.sup.2和R.sup.3独立地为氢、卤素、C.sub.1-6烷基、C.sub.3-6环烷基、C.sub.3-6环烯基、C.sub.1-6烷氧基、酰基、芳基、酰氧基、羟基、硝基、三氟甲基、氰基、羟基C.sub.1-6烷基、C.sub.1-6烷氧基C.sub.1-6烷基、CO.sub.2R.sup.10、CONR.sup.10R.sup.11、NR.sup.10R.sup.11，其中R.sup.10和R.sup.11独立地为氢或C.sub.1-6烷基；R.sup.4和R.sup.5独立地为氢或C.sub.1-6烷基；R.sup.6为氢、卤素、羟基、C.sub.1-6烷基或C.sub.1-6烷氧基；R.sup.7和R.sup.8独立地为氢、C.sub.1-6烷基、芳基烷基，或与它们连接的氮原子一起形成一个可选择性取代的5-7元杂环环，其中包含从氧、氮或硫中选择的一个或两个杂原子；A为氧、S（O）.sub.q，其中q为0、1或2，CR.sup.4.dbd.CR.sup.5或CR.sup.4R.sup.5，其中R.sup.4和R.sup.5独立地为氢或C.sub.1-6烷基，或A为NR.sup.12，其中R.sup.12为氢或C.sub.1-6烷基；B为（CR.sup.13R.sup.14）.sub.q，其中q为2、3或4，R.sup.13和R.sup.14独立地为氢或C.sub.1-6烷基，或B为（CR.sup.13R.sup.14）.sub.r-D，其中r为0、1、2或3，D为氧、硫或CR.sup.13.dbd.CR.sup.14；m为1至4；n为1或2，具有5HT.sub.1D拮抗活性。
• INDOLE, INDOLINE AND QUINOLINE DERIVATIVES WITH 5HT 1D? (ANTI-DEPRESSIVE) ACTIVITY
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0736023A1

  公开（公告）日：1996-10-09
• EP0736023B1
  申请人：——

  公开号：EP0736023B1

  公开（公告）日：1998-07-08
• BIPHENYLAMIDE DERIVATIVES AS 5HT 1D ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0777650B1

  公开（公告）日：2001-03-07