2-甲基-1-氧代-吡啶-1-鎓-3-羧酸 | 177785-13-6

• 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
• 中文名称: 2-甲基-1-氧代-吡啶-1-鎓-3-羧酸
• 英文名称: 2-methylnicotinic acid N-oxide
• 英文别名: 2-Methyl-1-oxo-1lambda~5~-pyridine-3-carboxylic acid；2-methyl-1-oxidopyridin-1-ium-3-carboxylic acid
• CAS: 177785-13-6
• 化学式: C₇H₇NO₃
• 分子量: 153.137
• InChiKey: QKKZCIBRTCZSHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  62.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1-(4-methyl-4-piperidinyl)-piperidine 、 2-甲基-1-氧代-吡啶-1-鎓-3-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 [4-[4-[(Z)-C-(4-bromophenyl)-N-ethoxy-carbonimidoyl]-1-piperidyl]-4-methyl-1-piperidyl]-(2-methyl-1-oxido-pyridin-1-ium-3-yl)methanone
  参考文献：
  名称：

  Synthesis, SAR, and Biological Evaluation of Oximino-Piperidino-Piperidine Amides. 1. Orally Bioavailable CCR5 Receptor Antagonists with Potent Anti-HIV Activity

  摘要：

  We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl] -4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our initial lead compound as well as the synthesis and SAR studies directed toward optimization of substitution at the phenyl, oxime, and right-hand side amide groups in the oximino-piperidino-piperidine series. Substitutions (4-Br, 4-CF3, 4-OCF3, 4-SO2Me, and 4-Cl) at the phenyl group are well-tolerated, and small alkyl substitutions (Me, Et, Pr-n, Pr-i, and cyclopropyl methyl) at the oxime moiety are preferred for CCR5 antagonism. The 2,6-dimethylnicotinamide N-oxide moiety is the optimal choice for the right-hand side. Several compounds in this series, including compound 1, exhibited excellent antiviral activity in vitro. Compound 1, which has a favorable pharmacokinetic profile in rodents and primates, excellent oral bioavailability, and potent antiviral activity against a wide range of primary HIV-1 isolates, is a potentially promising new candidate for treatment of HIV-1 infection.

  DOI：

  10.1021/jm0200815

文献信息

• Benzodiazepine derivatives
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05763437A1

  公开（公告）日：1998-06-09

  Benzodiazepine derivatives of formula (I) wherein R.sup.1 is aryl which may have one or more suitable substituent(s), R.sup.2 is C.sub.3 -C.sub.8 cycloalkyl which may have one or more suitable substituent(s), A is lower alkylene, R.sup.3 is a heterocyclic group selected from the group consisting of tetrahydrofuryl, dioxolanyl, filryl, thienyl, isoxazolyl, pyridyl, benzimidazolyl, benzotiazolyl, benzoxazolyl, benzopyrany, quinolyl, isoquinolyl, tetrahydroisoquinolyl, benzothienyl and benzofuryl, each of which may have one or more suitable substituent(s), or a pharmaceutically acceptable salt thereof, which are useful as a medicament.

  公式（I）中的苯二氮平衍生物，其中R.sup.1是芳基，可以有一个或多个合适的取代基，R.sup.2是C.sub.3-C.sub.8环烷基，可以有一个或多个合适的取代基，A是较低的烷基，R.sup.3是从四氢呋喃基，二氧杂环戊烷基，噻吩基，异恶唑基，吡啶基，苯并咪唑基，苯并噻唑基，苯并噁唑基，苯并吡喃基，喹啉基，异喹啉基，四氢异喹啉基，苯并噻吩基和苯并呋喃基中选择的杂环基，每个基可以有一个或多个合适的取代基，或其药学上可接受的盐，用作药物。
• BENZODIAZEPINE DERIVATIVES
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0804425A2

  公开（公告）日：1997-11-05
• US5763437A
  申请人：——

  公开号：US5763437A

  公开（公告）日：1998-06-09
• [EN] BENZODIAZEPINE DERIVATIVES<br/>[FR] DERIVES DE BENZODIAZEPINE
  申请人：——

  公开号：WO1996004254A2

  公开（公告）日：1996-02-15

  [EN] Benzodiazepine derivatives of formula (I) wherein R<1> is aryl which may have one or more suitable substituent(s), R<2> is C3-C8 cycloalkyl which may have one or more suitable substituent(s), A is lower alkylene, R<3> is a heterocyclic group selected from the group consisting of tetrahydrofuryl, dioxolanyl, furyl, thienyl, isoxazolyl, pyridyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzopyranyl, quinolyl, isoquinolyl, tetrahydroisoquinolyl, benzothienyl and benzofuryl, each of which may have one or more suitable substituent(s), or a pharmaceutically acceptable salt thereof, which are useful as a medicament.
  [FR] L'invention se rapporte à des dérivés de benzodiazépine de la formule (I) dans laquelle R<1> représente un aryle pouvant avoir un ou plusieurs substituants appropriés, R<2> représente cycloalkyle en C3-C8 pouvant avoir un ou plusieurs substituants appropriés, A représente alkylène inférieur, R<3> représente un groupe hétérocyclique sélectionné dans le groupe constitué par tétrahydrofuryle, dioxolanyle, furyle, thiényle, isoxazolyle, pyridyle, benzimidazolyle, benzothiazolyle, benzoxazolyle, benzopyranyle, quinolyle, isoquinolyle, tétrahydroisoquinolyle, benzothiényle et benzofuryle, chacun d'eux pouvant avoir un ou plusieurs substituants appropriés, ou à un sel pharmaceutiquement acceptable de ces dérivés, lesquels sont utilisés comme médicaments.