N-<3-<2-(dimethylamino)ethoxy>-4-methoxyphenyl>aminoacetaldehyde dimethyl acetal | 170691-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-<3-<2-(dimethylamino)ethoxy>-4-methoxyphenyl>aminoacetaldehyde dimethyl acetal
• 英文别名: N-[3-(2-dimethylaminoethoxy)4-methoxyphenyl]aminoacetaldehyde dimethyl acetal；N-(2,2-dimethoxyethyl)-3-[2-(dimethylamino)ethoxy]-4-methoxyaniline
• CAS: 170691-24-4
• 化学式: C₁₅H₂₆N₂O₄
• 分子量: 298.382
• InChiKey: UVGZICDQIIPZSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  52.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-<3-<2-(dimethylamino)ethoxy>-4-methoxyphenyl>aminoacetaldehyde dimethyl acetal 在 三氟乙酸 、 三氟乙酸酐 作用下， 反应 7.0h， 以83%的产率得到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
• 作为产物：
  描述：

  3-<2-(dimethylamino)ethoxy>-4-nitroanisole 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 23.0h， 生成 N-<3-<2-(dimethylamino)ethoxy>-4-methoxyphenyl>aminoacetaldehyde dimethyl acetal
  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

• 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独立地是氢或C.sub.1-6烷基，p为1到4；R.sup.2和R.sup.3独立地是氢，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独立地是氢或C.sub.1-6烷基；R.sup.4和R.sup.5独立地是氢或C.sub.1-6烷基；R.sup.6是氢，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独立地是氢，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的含有一个或两个来自氧，氮或硫的杂原子的取代的5-7元杂环；A是氧，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独立地是氢或C.sub.1-6烷基，或A是NR.sup.12，其中R.sup.12是氢或C.sub.1-6烷基；B是（CR.sup.13R.sup.14）.sub.q，其中q为2，3或4，R.sup.13和R.sup.14独立地是氢或C.sub.1-6烷基，或B是（CR.sup.13R.sup.14）.sub.r--D，其中r为0，1，2或3，D是氧，硫或CR.sup.13.dbd.CR.sup.14；m为1到4；n为1或2，具有5HT.sub.1D拮抗活性。
• 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.

  本发明揭示了一种新的吲哚、吲哚啉和喹啉衍生物的化合物(I)及其制备方法、含有它们的制药组合物以及它们在医学上的应用。现在已经发现了一类结构上独特的化合物，并发现它们表现出5HT.sub.1-D拮抗剂活性。因此，在第一方面，本发明提供了一种化合物(I)或其盐，其中P是一个5-7元杂环环，包含1至3个从氧、氮或硫中选择的杂原子，A、B、m、R.sup.1-R.sup.8在申请中有定义。
• 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