1',2',3',4',5',6'-hexahydro[2,4']bipyridinyl 1-oxide hydrochloride

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1',2',3',4',5',6'-hexahydro[2,4']bipyridinyl 1-oxide hydrochloride
• 英文别名: 1',2',3',4',5',6'-hexahydro-2'H-[2,4'-bipyridine] N-oxide hydrochloride；2-piperidin-4-ylpyridinium N-oxide hydrochloride；1',2',3',4',5',6'-hexahydro-[2,4']bipyridinyl 1-oxide hydrochloride salt；1-Oxido-2-piperidin-4-ylpyridin-1-ium;hydrochloride
• 化学式: C₁₀H₁₄N₂O*ClH
• 分子量: 214.695
• InChiKey: XSJLMRDFMAEYFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.21
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1',2',3',4',5',6'-hexahydro[2,4']bipyridinyl 1-oxide hydrochloride 在 吡啶 作用下， 以 甲苯 为溶剂， 生成 2-{1-[(3Z)-3-(4-chlorophenyl)-3-(methoxyimino)propyl]piperidin-4-yl}pyridinium N-oxide
  参考文献：
  名称：

  1-Aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one Oximes as Potent Dopamine D₄ Receptor Agonists for the Treatment of Erectile Dysfunction

  摘要：

  A new series of dopamine D-4 receptor agonists, 1-aryl-3-(4-pyridinepiperazin-1-yl) propanone oximes, was designed through the modification of known dopamine D4 receptor agonist PD 168077. Replacement of the amide group with a methylene-oxime moiety produced compounds with improved stability and efficacy. Structure-activity relationsips (SAR) of the aromatic ring linked to the N-4-piperazine ring confirmed the superiority of 2-pyridine as a core for D4 agonist activity. A two-methylene linker between the oxime group and the N-1-piperazine ring displayed the best profile. New dopamine D4 receptor agonists, exemplified by (E)-1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (59a) and (E)-1-(3-chloro- 4-fluorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (64a), exhibited favorable pharmacokinetic profiles and showed oral bioavailability in rat and dog. Subsequent evaluation of 59a in the rat penile erection model revealed in vivo activity, comparable in efficacy to apomorphine. Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists.

  DOI：

  10.1021/jm060279f
• 作为产物：
  描述：

  3,6-二氢-4-[[(三氟甲基)磺酰]氧基]-1(2H)-吡啶甲酸叔丁酯 在 palladium on activated charcoal 盐酸 、 四(三苯基膦)钯 、 氢气 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， -78.0~60.0 ℃ 、413.68 kPa 条件下， 反应 5.75h， 生成 1',2',3',4',5',6'-hexahydro[2,4']bipyridinyl 1-oxide hydrochloride
  参考文献：
  名称：

  Discovery of 3-Methyl-N-(1-oxy-3‘,4‘,5‘,6‘-tetrahydro-2‘H-[2,4‘-bipyridine]-1‘-ylmethyl)benzamide (ABT-670), an Orally Bioavailable Dopamine D₄ Agonist for the Treatment of Erectile Dysfunction

  摘要：

  The goal of this study was to identify a structurally distinct D-4-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl) piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl) piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein.

  DOI：

  10.1021/jm060662k

文献信息

• Acetamides and benzamides that are useful in treating sexual dysfunction
  申请人：——

  公开号：US20040029887A1

  公开（公告）日：2004-02-12

  The present invention relates to the use of compounds of formula (I) 1 for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

  本发明涉及使用式(I)的化合物治疗性功能障碍，以及含有式(I)化合物的组合物用于治疗性功能障碍。
• Fused bicyclic aromatic compounds that are useful in treating sexual dysfunction
  申请人：Cowart D. Marlon

  公开号：US20060172995A1

  公开（公告）日：2006-08-03

  The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction, wherein A, L, D and B, are as described in the specification.

  本发明涉及使用公式(I)化合物的用途，用于治疗性功能障碍，以及包含用于治疗性功能障碍的公式(I)化合物的组合物，其中A、L、D和B如说明书中所述。
• [EN] FUSED BICYCLIC AROMATIC COMPOUNDS THAT ARE USEFUL IN TREATING SEXUAL DYSFUNCTION<br/>[FR] COMPOSES AROMATIQUES BICYCLIQUES CONDENSES UTILES DANS LE TRAITEMENT DE DYSFONCTIONNEMENT SEXUEL
  申请人：ABBOTT LAB

  公开号：WO2003101994A1

  公开（公告）日：2003-12-11

  The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

  本发明涉及使用化合物(I)的治疗性功能障碍，并涉及含有化合物(I)的组合物用于治疗性功能障碍。
• J. Med. Chem. 2006, 49, 7450-7465
  作者：

  DOI：——

  日期：——
• US7528134B2
  申请人：——

  公开号：US7528134B2

  公开（公告）日：2009-05-05