4-(6-chloro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester | 345235-81-6

• 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: 4-(6-chloro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(6-chloro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate；6-chloro-3-(1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole；3-[1-(t-butoxycarbonyl)-1,2,3,6-tetrahydro-4-pyridinyl]-6-chloroindole；tert-butyl 4-(6-chloro-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 345235-81-6
• 化学式: C₁₈H₂₁ClN₂O₂
• 分子量: 332.83
• InChiKey: RHNDGCMQLNVDHP-UHFFFAOYSA-N

物化性质

• 沸点：
  490.9±45.0 °C(Predicted)
• 密度：
  1.258±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(6-chloro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester 在 palladium on activated charcoal potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists

  摘要：

  A series of Ni-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)indole derivatives was designed and synthesized. These compounds were shown to have high affinity for the 5-HT6 receptor. Two analogs, 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-1-sulfonyl]-phenylamine 15g and 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-5-methoxy-1H-indole-1-sulfonyl]-phenylamine 15y, had 0.4 and 3.0nM affinity, respectively, and antagonized the production of adenylate cyclase at sub-nanomolar concentrations. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.064
• 作为产物：
  描述：

  6-氯吲哚 、 N-叔丁氧羰基-4-哌啶酮 以 甲醇 为溶剂， 反应 12.0h， 生成 4-(6-chloro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties

  摘要：

  A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT6 receptor ligands. The study allowed for the identification of 25 (4-{[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT6 receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10-30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity.

  DOI：

  10.1021/acsmedchemlett.6b00056

文献信息

• Antipsychotic heterocycle compounds
  申请人：——

  公开号：US20020072611A1

  公开（公告）日：2002-06-13

  Compounds of Formula I are useful antipsychotic and antidepressant agents demonstrating potent inhibition of 5-HT reuptake and dopamine D2 receptor antagonism. Ar—Y—(CH 2 ) m —Z   I In Formula I: Ar is selected from 1 Z is II or III; 2 Y is sulfur or oxygen; R 1 and R 4 are independently selected from H and lower alkyl; R 2 , R 3 , R 6 and R 7 are independently selected from H, halogen, and lower alkoxy; R 5 is selected from H, halogen, lower alkoxy and cyano; m is an integer from 2-6; n is zero or the integer 1 or 2; and a dotted line represents an optional double bond.

  式I的化合物是有用的抗精神病和抗抑郁药物，表现出对5-HT再摄取和多巴胺D2受体的强效抑制作用。Ar—Y—(CH2)m—Z 在式I中：Ar从1中选择Z为II或III；2Y为硫或氧；R1和R4分别选择自H和较低的烷基；R2、R3、R6和R7分别选择自H、卤素和较低的烷氧基；R5从H、卤素、较低的烷氧基和氰基中选择；m为2-6之间的整数；n为零或整数1或2；虚线代表可选的双键。
• Inhibition of serotonin reuptake
  申请人：Eli Lilly and Company

  公开号：US05846982A1

  公开（公告）日：1998-12-08

  This invention provides compounds and a method for the inhibition of serotonin reuptake in mammals.

  这项发明提供了一种用于抑制哺乳动物中5-羟色胺再摄取的化合物和方法。
• 1H-indole and benzo(b)thiophene derivatives with 4-(1,2,3,6-tetra:hydro:pyridinyl)- and 4-piperidinyl-groups bound to the heterocyclic ring as inhibitors of serotonin reuptake
  申请人：ELI LILLY AND COMPANY

  公开号：EP0812826A1

  公开（公告）日：1997-12-17

  The pharmaceutical use of novel compounds of formula I: where Z is a structure of formula A-B is -C=CH- or -C(R5)-CH2-; X is S or NR4; R1 is H, halo, formyl, C1-C4 alkyl, C1-C4 alkoxy, thienylmethyloxy, 4,5-dihydrothiazol-2-yl, cyano, nitro, carboxamido, trifluoromethyl or hydroxy; R2 is H or halo; R3 is H, C1-C4 alkyl, (C1-C4 alkylene)-aryl, or -CH2-Y-NR7R8; R4 is H, C1-C4 alkyl, C1-C5 acyl, or phenylsulfonyl; R5 is H or OH; R6 is H or methyl; Y is -CH2- or -C(O)-; R7 is pyridinyl; and R8 is H or -C(O)-(C3-C6 cycloalkyl); and pharmaceutically acceptable salts thereof.

  化合物的药用途：其中Z是formulaA-B结构，-C=CH-或-C(R5)-CH2-；X是S或NR4；R1是H、卤素、甲酰基、C1-C4烷基、C1-C4烷氧基、噻吩甲氧基、4,5-二氢噻唑-2-基、氰基、硝基、羧酰胺基、三氟甲基或羟基；R2是H或卤素；R3是H、C1-C4烷基、(C1-C4烷基)-芳基，或-CH2-Y-NR7R8；R4是H、C1-C4烷基、C1-C5酰基，或苯基磺酰基；R5是H或OH；R6是H或甲基；Y是-CH2-或-C(O)-；R7是吡啶基；R8是H或-C(O)-(C3-C6环烷基)；以及其药用上可接受的盐。
• Pyrazole-based cathepsin S inhibitors with improved cellular potency
  作者：Jianmei Wei、Barbara A. Pio、Hui Cai、Steven P. Meduna、Siquan Sun、Yin Gu、Wen Jiang、Robin L. Thurmond、Lars Karlsson、James P. Edwards

  DOI：10.1016/j.bmcl.2007.08.038

  日期：2007.10

  High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of Cats inhibitors. Although substitutions on this heterocyclic framework had a moderate impact on enzymatic potency, dramatic effects on cellular activity were observed. Optimization afforded indole- and benzothiophene-derived analogues that were high affinity Cats inhibitors (IC50 = 20-40 nM) with good cellular potency (IC50 = 30-340 nM). (c) 2007 Elsevier Ltd. All rights reserved.
• EP1242072A4
  申请人：——

  公开号：EP1242072A4

  公开（公告）日：2004-02-04