(4S)-1-(4-methoxybenzyl)-4-methyl-3,4-dihydropyridin-2-one | 234447-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4S)-1-(4-methoxybenzyl)-4-methyl-3,4-dihydropyridin-2-one
• 英文别名: (4S)-1-(4-methoxybenzyl)-4-methyl-5,6-dehydro-2-piperidone；(4S)-1-[(4-methoxyphenyl)methyl]-4-methyl-3,4-dihydropyridin-2-one
• CAS: 234447-82-6
• 化学式: C₁₄H₁₇NO₂
• 分子量: 231.294
• InChiKey: BWEFNFZSJFYSAP-LLVKDONJSA-N

物化性质

• 沸点：
  404.4±34.0 °C(Predicted)
• 密度：
  1.103±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4S)-1-(4-methoxybenzyl)-4-methyl-3,4-dihydropyridin-2-one 在 palladium on activated charcoal sodium hydroxide 、 正丁基锂 、 三氟化硼乙醚 、 potassium tert-butylate 、 triethyloxonium fluoroborate 、 甲基三辛基氯化铵 、 乙酸乙酯 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 苯甲醚 为溶剂， 反应 47.5h， 生成 (1R,5S,6S,7R)-5,7-dimethyl-2-azabicyclo[4.1.0]hept-2-en-3-amine
  参考文献：
  名称：

  Design and Synthesis of Orally Bioavailable Inhibitors of Inducible Nitric Oxide Synthase. Identification of 2-Azabicyclo[4.1.0]heptan-3-imines

  摘要：

  Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00034-8
• 作为产物：
  描述：

  methyl 3-(R)-methyl-5-hydroxypentanoate 在 三氧化硫吡啶 、 对甲苯磺酸 、 三乙胺 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 9.0h， 生成 (4S)-1-(4-methoxybenzyl)-4-methyl-3,4-dihydropyridin-2-one
  参考文献：
  名称：

  Design and Synthesis of Orally Bioavailable Inhibitors of Inducible Nitric Oxide Synthase. Identification of 2-Azabicyclo[4.1.0]heptan-3-imines

  摘要：

  Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00034-8

文献信息

• PROCESS FOR THE PREPARATION OF INTERMEDIATE COMPOUNDS OF DRUGS
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1188749A1

  公开（公告）日：2002-03-20

  The present invention relates to a process for preparing selectively compound (I), (1S, 5S, 6R, 7R)-2-aza-7-chloro-5-methyl-3-oxobicyclo[4.1.0]heptane, by preparing compound (II) from compound (V) through compound (III) via a series of reactions, and by crystallizing the obtained compound (II); and the novel intermediate compound represented by the structural formula (III) and hydrate salts thereof.

  本发明涉及一种通过从化合物（V）经过一系列反应制备化合物（II）并通过结晶得到的化合物（II），来选择性制备化合物（I）（1S，5S，6R，7R）-2-aza-7-chloro-5-methyl-3-oxobicyclo[4.1.0]heptane的方法；以及由结构式（III）表示的新型中间体化合物及其水合盐。
• Condensed piperidine compound
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06110930A1

  公开（公告）日：2000-08-29

  A compound represented by formula (I): ##STR1## wherein all symbols are defined in the specification, or an acid addition salt thereof or a hydrate thereof; a process for preparing the same; and a nitrogen monoxide synthase inhibitor comprising the same as an active ingredient.

  化合物由式(I)表示：##STR1## 其中所有符号在规范中定义，或其酸加盐或水合物；制备该化合物的方法；以及以该化合物作为活性成分的一氧化氮合酶抑制剂。
• Design and Synthesis of Orally Bioavailable Inhibitors of Inducible Nitric Oxide Synthase. Identification of 2-Azabicyclo[4.1.0]heptan-3-imines
  作者：Yasufumi Kawanaka、Kaoru Kobayashi、Shinya Kusuda、Tadashi Tatsumi、Masayuki Murota、Toshihiko Nishiyama、Katsuya Hisaichi、Atsuko Fujii、Keisuke Hirai、Masao Naka、Masaharu Komeno、Yshihiko Odagaki、Hisao Nakai、Masaaki Toda

  DOI：10.1016/s0968-0896(03)00034-8

  日期：2003.4

  Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported. (C) 2003 Elsevier Science Ltd. All rights reserved.