N,N-dimethyl-N'-(2-methoxy-5-nitrophenyl)ethylenediamine | 170229-84-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N-dimethyl-N'-(2-methoxy-5-nitrophenyl)ethylenediamine
• 英文别名: N-(2-methoxy-5-nitrophenyl)-N',N'-dimethylethane-1,2-diamine
• CAS: 170229-84-2
• 化学式: C₁₁H₁₇N₃O₃
• 分子量: 239.274
• InChiKey: CPNDBGRHFXBBET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-N'-(2-methoxy-5-nitrophenyl)ethylenediamine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 N,N-dimethyl-N'-(tert-butyloxycarbonyl)-N'-(5-amino-2-methoxyphenyl)ethylenediamine
  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：

  N,N-dimethyl-N'-(2-methoxyphenyl)ethylenediamine 在 硫酸 、 potassium nitrate 作用下， 以 水 为溶剂， 反应 4.0h， 以49%的产率得到N,N-dimethyl-N'-(2-methoxy-5-nitrophenyl)ethylenediamine
  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

• Heterocyclic biphenylylamides useful as 5HT1D antagonists
  申请人：SmithKline Beecham plc

  公开号：US05801170A1

  公开（公告）日：1998-09-01

  A compound of formula (I) or a salt thereof: ##STR1## wherein P is a 5 to 7 membered heterocyclic ring selected from the group consisting of thienyl, furyl, pyrrolyl, triazolyl, diazolyl, tetrazolyl, imidazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimdyl and pyrazinyl; R.sup.1, 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, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, alkanoyl, optionally substituted phenyl, alkanoyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.9,CONR.sup.10 R.sup.11 where R.sup.9, 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, a optionally substituted phenylalkyl or together with the nitrogen atom to which they are attached form an optionally substituted 5- to 7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur; A is CONH or NHCO; B is oxygen, S(O)p where p is 0, 1 or 2, NR.sup.12 where R.sup.12 is hydrogen, C.sub.1-6 alkyl or phenylC.sub.1-6 alkyl, or B is 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; m is 1 to 4; and n is 1 or 2.

  化合物的式(I)或其盐：##STR1## 其中P是从噻吩基、呋喃基、吡咯基、三唑基、二唑基、四唑基、咪唑基、噁二唑基、异噻唑基、异恶唑基、噻二唑基、吡啶基、嘧啶基和吡嗪基中选择的5至7元杂环；R.sup.1、R.sup.2和R.sup.3独立地表示氢、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、羟基C.sub.1-6烷基、C.sub.1-6烷氧基C.sub.1-6烷基、酰基、可选取代的苯基、酰氧基、羟基、硝基、三氟甲基、氰基、CO.sub.2R.sup.9、CONR.sup.10R.sup.11，其中R.sup.9、R.sup.10和R.sup.11独立地表示氢或C.sub.1-6烷基；R.sup.4和R.sup.5独立地表示氢或C.sub.1-6烷基；R.sup.6表示氢、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独立地表示氢、C.sub.1-6烷基、可选取代的苯基烷基，或者与它们所连接的氮原子一起形成一个选自氧、氮或硫的一个或两个杂原子的可选取代的5至7元杂环；A是CONH或NHCO；B是氧、S(O)p，其中p为0、1或2，NR.sup.12，其中R.sup.12表示氢、C.sub.1-6烷基或苯基C.sub.1-6烷基，或者B是CR.sup.4.dbd.CR.sup.5或CR.sup.4R.sup.5，其中R.sup.4和R.sup.5独立地表示氢或C.sub.1-6烷基；m为1至4；n为1或2。
• HETEROCYCLIC BIPHENYLYLAMIDES USEFUL AS 5HT1D ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0733048A1

  公开（公告）日：1996-09-25
• US5801170A
  申请人：——

  公开号：US5801170A

  公开（公告）日：1998-09-01
• [EN] HETEROCYCLIC BIPHENYLYLAMIDES USEFUL AS 5HT1D ANTAGONISTS<br/>[FR] BIPHENYLYLAMIDES HETEROCYCLIQUES UTILISABLES COMME ANTAGONISTES DU 5HT1D
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1995015954A1

  公开（公告）日：1995-06-15

  (EN) A compound of formula (I) or a salt thereof, wherein P is a 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; A is CONH or NHCO; B is oxygen, S(O)p where p is O, 1 or 2, or NR12; m is 1 to 4; and the R's are hydrogen or substituents, is useful as a 5HT1D receptor antagonist in the treatment of CNS disorders.(FR) La présente invention concerne un composé selon la formule générale (I) ou l'un de ses sels. P est un anneau hétérocyclique de 5 à 7 segments comportant 1 à 3 hétéro-atomes sélectionnés dans le groupe oxygène, azote ou soufre. A est CONH ou NHCO. B est ou bien hydrogène, ou bien S(O)p, p valant 0, 1 ou 2, ou bien encore NR12. m vaut de 1 à 4. Les R sont hydrogène ou des substituants. Ce composé est utilisé comme antagoniste du récepteur 5HT1D pour le traitement des troubles du système nerveux central.
• 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-<i>f</i>]indole-3,4‘-piperidine] (SB-224289) Potently Blocks Terminal 5-HT Autoreceptor Function Both in Vitro and in Vivo
  作者：Laramie M. Gaster、Frank E. Blaney、Susannah Davies、D. Malcolm Duckworth、Peter Ham、Sarah Jenkins、Andrew J. Jennings、Graham F. Joiner、Frank D. King、Keith R. Mulholland、Paul A. Wyman、Jim J. Hagan、Jon Hatcher、Brian J. Jones、Derek N. Middlemiss、Gary W. Price、Graham Riley、Claire Roberts、Carol Routledge、Julie Selkirk、Paula D. Slade

  DOI：10.1021/jm970457s

  日期：1998.4.1

  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.