2-{[(phenylmethyl)oxy]amino}-3-pyridinecarboxylic acid | 1312356-01-6

• 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: 2-{[(phenylmethyl)oxy]amino}-3-pyridinecarboxylic acid
• 英文别名: 2-(Phenylmethoxyamino)pyridine-3-carboxylic acid；2-(phenylmethoxyamino)pyridine-3-carboxylic acid
• CAS: 1312356-01-6
• 化学式: C₁₃H₁₂N₂O₃
• 分子量: 244.25
• InChiKey: SCNRTIXEZXTQOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{[(phenylmethyl)oxy]amino}-3-pyridinecarboxylic acid 在 ammonium cerium (IV) nitrate 、 sodium methylate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醚 、 正己烷 、 水 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 2.91h， 生成 4-chloro-1-[(phenylmethyl)oxy]pyrido[2,3-d]pyrimidin-2(1H)-one
  参考文献：
  名称：

  Pyridopyrimidinone inhibitors of HIV-1 RNase H

  摘要：

  Using a structure based pharmacophore design, a weak inhibitor of RNase H, identified from a small library of two metal binding HIV-1 integrase inhibitors, was optimized for potency and physicochemical properties. This manuscript describes the SAR and in vivo DMPK for the pyridopyrimidinone class of inhibitors.

  DOI：

  10.1016/j.ejmech.2014.06.061
• 作为产物：
  描述：

  O-苄基羟胺 、 2-氟烟酸 在 N,N-二异丙基乙胺 作用下， 反应 0.67h， 以69%的产率得到2-{[(phenylmethyl)oxy]amino}-3-pyridinecarboxylic acid
  参考文献：
  名称：

  Pyridopyrimidinone inhibitors of HIV-1 RNase H

  摘要：

  Using a structure based pharmacophore design, a weak inhibitor of RNase H, identified from a small library of two metal binding HIV-1 integrase inhibitors, was optimized for potency and physicochemical properties. This manuscript describes the SAR and in vivo DMPK for the pyridopyrimidinone class of inhibitors.

  DOI：

  10.1016/j.ejmech.2014.06.061

文献信息

• [EN] COMPOUNDS FOR INHIBITING DRUG-RESISTANT STRAINS OF HIV-1 INTEGRASE<br/>[FR] COMPOSÉS POUR INHIBER DES SOUCHES RÉSISTANTES AUX MÉDICAMENTS D'INTÉGRASE DE VIH-1
  申请人：US HEALTH

  公开号：WO2014186398A1

  公开（公告）日：2014-11-20

  A method of inhibiting drug -resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally- substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen to which R8 and R9 are attached form an optionally-substituted heterocycle.

  在需要的患者中给予一种化合物（公式I）的治疗有效量，或其药用盐或酯，以抑制患者体内的耐药HIV-1整合酶。该化合物的结构为：其中X为N、C（OH）或CH；Y为H或OH；Z1-Z5中的每一个独立地为H或卤素；R4为H、OH、NH2、NHR8、NR8R9或R8；R5、R6和R7每一个独立地为H、卤素、OR8、R8、NHR8、NR8R9、CO2R8、CONR8R9、SO2NR8R9，或者R5和R6与其连接的碳原子形成一个可选择取代的碳环或可选择取代的杂环；R8和R9每一个独立地为H、可选择取代的烷基、可选择取代的烯基、可选择取代的炔基、可选择取代的芳基、可选择取代的环烷基、可选择取代的环烷基烯、可选择取代的杂环、可选择取代的酰胺、可选择取代的酯，或者R8和R9与其连接的氮原子形成一个可选择取代的杂环。
• COMPOUNDS FOR INHIBITING DRUG-RESISTANT STRAINS OF HIV-1 INTEGRASE
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SEC., DEPT. OF HEALTH AND HUMAN SERVICES

  公开号：US20160083382A1

  公开（公告）日：2016-03-24

  A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z 1 -Z 5 is independently H or halogen; R 4 is H, OH, NH 2 , NHR 8 , NR 8 R 9 or R 8 ; R 5 , R 6 , and R 7 is each independently H, halogen, OR 8 , R 8 , NHR 8 , NR 8 R 9 , CO 2 R 8 , CONR 8 R 9 , SO 2 NR 8 R 9 , or R 5 and R 6 together with the carbon atoms to which R 5 and R 6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R 8 and R 9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R 8 and R 9 together with the nitrogen to which R 8 and R 9 are attached form an optionally-substituted heterocycle.

  本方法涉及在需要抑制药物耐药性HIV-1整合酶的主体中向其施用公式I的化合物的治疗有效量，或其药学上可接受的盐或酯，其结构为：其中X为N，C（OH）或CH；Y为H或OH；Z1-Z5中的每一个独立为H或卤素；R4为H，OH，NH2，NHR8，NR8R9或R8；R5、R6和R7各自独立为H，卤素，OR8，R8，NHR8，NR8R9，CO2R8，CONR8R9，SO2NR8R9或R5和R6与R5和R6附着的碳原子一起形成可选地取代的碳环或可选地取代的杂环；R8和R9各自独立为H，可选地取代的烷基，可选地取代的烯基，可选地取代的炔基，可选地取代的芳基，可选地取代的环烷基，可选地取代的环烷基，可选地取代的杂环，可选地取代的酰胺，可选地取代的酯，或R8和R9与R8和R9附着的氮一起形成可选地取代的杂环。
• Compounds for inhibiting drug-resistant strains of HIV-1 integrase
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：US10208035B2

  公开（公告）日：2019-02-19

  A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen to which R8 and R9 are attached form an optionally-substituted heterocycle.

  一种抑制受试者体内耐药 HIV-1 整合酶的方法，包括向有需要的受试者施用治疗有效量的式 I 化合物或其药学上可接受的盐或酯，其结构为： 其中 X 是 N、C(OH)或 CH； Y 是 H 或 OH； Z1-Z5 各自独立地为 H 或卤素； R4 是 H、OH、NH2、NHR8、NR8R9 或 R8； R5、R6 和 R7 各自独立地为 H、卤素、OR8、R8、NHR8、NR8R9、CO2R8、CONR8R9、SO2NR8R9，或 R5 和 R6 与 R5 和 R6 所连接的碳原子一起形成任选取代的碳环或任选取代的杂环；以及 R8 和 R9 各自独立地为 H、任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的芳基、任选取代的环烷基、任选取代的环亚烷基、任选取代的杂环、任选取代的酰胺、任选取代的酯，或 R8 和 R9 与 R8 和 R9 所连接的氮一起形成任选取代的杂环。
• US9676771B2
  申请人：——

  公开号：US9676771B2

  公开（公告）日：2017-06-13
• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011075747A1

  公开（公告）日：2011-06-23

  1-hydroxypyrido[2,3-c/]pyrimidin-2(1 H)-one compounds that inhibit reverse transcriptase, particularly 1-hydroxypyrido[2,3-d]pyrimidin-2(1 H)-one compounds that inhibit the RNase H domain of a human HIV reverse transcriptase, and solvates, hydrates and pharmaceutically acceptable salts thereof, and methods of using same.