5-Benzyl-3-ethoxycarbonylpyridine-2-carboxylic acid | 675616-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-Benzyl-3-ethoxycarbonylpyridine-2-carboxylic acid
• CAS: 675616-25-8
• 化学式: C₁₆H₁₅NO₄
• 分子量: 285.299
• InChiKey: XUOGPKWRPDXPOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  76.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  乙醇 、 3-Benzylfuro[3,4-b]pyridine-5,7-dione 生成 2-[(ethoxy)carbonyl]-5-(phenylmethyl)-3-pyridinecarboxylic acid 、 5-Benzyl-3-ethoxycarbonylpyridine-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and Antiviral Activity of 7-Benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV Integrase Inhibitors

  摘要：

  The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naphthyridinone ring system. Low nanomolar IC50 values were achieved in an HIV-integrase strand transfer assay with both carboxylic ester and carboxamide groups at C-3. More importantly, several carboxamide congeners showed potent antiviral activity in cellular assays. A 7-benzyl substituent was found to be critical for potent enzyme inhibition, and an N-(2-methoxyethyl)-carboxamide moiety at C-3 significantly reduced plasma protein binding effects in vitro. Pharmacokinetic data in rats for one carboxamide analogue demonstrated oral bioavailability and reasonable in vivo clearance.

  DOI：

  10.1021/jm801404b

文献信息

• Heterocyclic compounds having inhibitory activity against HIV integrase
  申请人：Murai Hitoshi

  公开号：US20090118233A1

  公开（公告）日：2009-05-07

  A heterocyclic compound of the formula (I): wherein B 1 is —C(R 2 )═ or —N═; R 1′ is H, etc.; one of R 1 and R 2 is -Z 1 -Z 2 -Z 3 -R 5 wherein Z 1 and Z 3 are independently single bond, optionally substituted alkylene, etc.; Z 2 is single bond, optionally substituted alkylene, etc.; R 5 is optionally substituted aryl, optionally substituted heteroaryl, etc., and the other of R 1 and R 2 is H; -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, etc. wherein Y is OH, etc.; R A is —COR 7 wherein R 7 is OH, etc.; one of R 3 and R 4 is carboxy, etc., and the other of R 1 and R 2 is H, etc, a prodrug thereof, a pharmaceutically acceptable salt thereof, and a solvate thereof, having an antiviral activity, more particularly, an inhibitory activity against HIV integrase, and a pharmaceutical composition containing the same, especially an anti-HIV drug.

  一种具有以下式（I）的杂环化合物：其中B1为—C（R2）═或—N═；R1'为H等；R1和R2中的一个为-Z1-Z2-Z3-R5，其中Z1和Z3分别为单键，可选择性地取代的烷基等；Z2为单键，可选择性地取代的烷基等；R5为可选择性取代的芳基，可选择性取代的杂环芳基等；R1和R2中的另一个为H；-A1-为—C（—Y）═C（—RA）—C（—R3）═C（—R4）—等，其中Y为OH等；RA为—COR7，其中R7为OH等；R3和R4中的一个为羧基等，另一个为H等。该化合物的前药、其药学上可接受的盐和溶剂化物具有抗病毒活性，尤其是对HIV整合酶的抑制活性，并且包含该化合物的药物组合物，特别是一种抗HIV药物。
• US7358249B2
  申请人：——

  公开号：US7358249B2

  公开（公告）日：2008-04-15
• Synthesis and Antiviral Activity of 7-Benzyl-4-hydroxy-1,5-naphthyridin-2(1<i>H</i>)-one HIV Integrase Inhibitors
  作者：Eric E. Boros、Cynthia E. Edwards、Scott A. Foster、Masahiro Fuji、Tamio Fujiwara、Edward P. Garvey、Pamela L. Golden、Richard J. Hazen、Jerry L. Jeffrey、Brian A. Johns、Takashi Kawasuji、Ryuichi Kiyama、Cecilia S. Koble、Noriyuki Kurose、Wayne H. Miller、Angela L. Mote、Hitoshi Murai、Akihiko Sato、James B. Thompson、Mark C. Woodward、Tomokazu Yoshinaga

  DOI：10.1021/jm801404b

  日期：2009.5.14

  The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naphthyridinone ring system. Low nanomolar IC50 values were achieved in an HIV-integrase strand transfer assay with both carboxylic ester and carboxamide groups at C-3. More importantly, several carboxamide congeners showed potent antiviral activity in cellular assays. A 7-benzyl substituent was found to be critical for potent enzyme inhibition, and an N-(2-methoxyethyl)-carboxamide moiety at C-3 significantly reduced plasma protein binding effects in vitro. Pharmacokinetic data in rats for one carboxamide analogue demonstrated oral bioavailability and reasonable in vivo clearance.