2-甲氧基-6-苯基异烟酸 | 1041204-92-5

• 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-甲氧基-6-苯基异烟酸
• 英文名称: 2-methoxy-6-phenylisonicotinic acid
• 英文别名: 2-methoxy-6-phenyl-isonicotinic acid；2-methoxy-6-phenylpyridine-4-carboxylic acid
• CAS: 1041204-92-5
• 化学式: C₁₃H₁₁NO₃
• 分子量: 229.235
• InChiKey: BEIOKBBXZRBYHA-UHFFFAOYSA-N

物化性质

• 沸点：
  469.9±45.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-甲氧基-6-苯基异烟酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.67h， 生成 (S)-N-(3-(2-ethyl-4-(5-(2-methoxy-6-phenylpyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)-2-hydroxypropyl)-2-hydroxyacetamide
  参考文献：
  名称：

  Novel S1P1 receptor agonists – Part 5: From amino-to alkoxy-pyridines

  摘要：

  In a previous communication we reported on the discovery of aminopyridine 1 as a potent, selective and orally active S1P(1) receptor agonist. More detailed studies revealed that this compound is phototoxic in vitro. As a result of efforts aiming at eliminating this undesired property, a series of alkoxy substituted pyridine derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy pyridines was significantly lower than the one of aminopyridine 1 and most compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4-pyridine derivatives delivered highly potent S1P(1) receptor agonists. While the 2-pyridines were clearly more selective against S1PR(3), the corresponding 3- or 4 pyridine analogues showed significantly longer oral half-lives and as a consequence longer pharmacological duration of action after oral administration. One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed EC50 values of 0.7 and 140 nM on S1PR(1) and S1PR(3), respectively, and maximally reduced the blood lymphocyte count for at least 24 h after oral administration of 10 mg/kg to Wistar rats. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.020
• 作为产物：
  描述：

  柠嗪酸 在 四(三苯基膦)钯 、 sodium carbonate 、 三溴氧磷 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 50.33h， 生成 2-甲氧基-6-苯基异烟酸
  参考文献：
  名称：

  Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections

  摘要：

  We report novel polymyxin analogues with improved antibacterial in vitro potency against polymprin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.

  DOI：

  10.1021/jm400416u

文献信息

• SPIROCHROMANON DERIVATIVES
  申请人：Iino Tomoharu

  公开号：US20090270436A1

  公开（公告）日：2009-10-29

  The invention relates to a compound of a general formula (I): wherein Ar1 represents a group formed from an aromatic ring selected from a group consisting of benzene, pyrazole, isoxazole, pyridine, indole, 1H-indazole, 1H-furo[2,3-c]pyrazole, 1H-thieno[2,3-c]pyrazole, benzimidazole, 1,2-benzisoxazole, imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine and 1H-pyrazolo[3,4-b]pyridine, having Ar2, and optionally having one or two or more substituents selected from R3: R1 and R2 each independently represent a hydrogen atom, a halogen atom, a cyano group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, a C2-C7 alkanoyl group, a C2-C7 alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-C1-C6 alkoxy group, a carboxy-C2-C6 alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb; or a C1-C6 alkyl group optionally having a substituent; or an aryl or heterocyclic group optionally having a substituent; or a C1-C6 alkyl group or a C2-C6 alkenyl group having the aryl or heterocyclic group; T and U each independently represent a nitrogen atom or a machine group; and V represents an oxygen atom or a sulfur atom. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.

  本发明涉及一种通式（I）的化合物：其中Ar1代表从苯，吡唑，异噁唑，吡啶，吲哚，1H-吲唑，1H-呋喃[2,3-c]吡唑，1H-噻吩[2,3-c]吡唑，苯并咪唑，1,2-苯并异噁唑，咪唑并[1,2-a]吡啶，咪唑并[1,5-a]吡啶和1H-吡唑并[3,4-b]吡啶中选择的芳香环形成的基团，具有Ar2，并且可选地具有一个、两个或更多从R3中选择的取代基：R1和R2各自独立地表示氢原子，卤素原子，氰基，C2-C6烯基基团，C1-C6烷氧基团，C2-C7烷酰基基团，C2-C7烷氧羰基基团，芳基烷氧羰基基团，氨基-C1-C6烷氧基团，羧基-C2-C6烯基基团或-Q1-N（Ra）-Q2-Rb基团；或者是一个可选具有取代基的C1-C6烷基基团；或者是一个可选具有取代基的芳基或杂环基团；或者是一个具有芳基或杂环基团的C1-C6烷基或C2-C6烯基基团；T和U各自独立地表示氮原子或机器基团；V表示氧原子或硫原子。本发明的化合物可用作治疗各种ACC相关疾病的治疗剂。
• Polymyxin Derivates Useful As Antibacterial Agents
  申请人：Magee Thomas Victor

  公开号：US20120316105A1

  公开（公告）日：2012-12-13

  The present invention provides a new class of polymyxin derivates useful for treating bacterial infections, especially Gram-negative infections, that have reduced renal cytotoxicity.

  本发明提供了一种新的聚霉素衍生物类别，用于治疗细菌感染，特别是革兰氏阴性菌感染，并且具有降低肾细胞毒性的特性。
• Spirochromanon derivatives
  申请人：MSD K.K.

  公开号：US08138197B2

  公开（公告）日：2012-03-20

  The invention relates to a compound of a general formula (I): wherein Ar1 represents a group formed from an aromatic ring selected from a group consisting of benzene, pyrazole, isoxazole, pyridine, indole, 1H-indazole, 1H-furo[2,3-c]pyrazole, 1H-thieno[2,3-c]pyrazole, benzimidazole, 1,2-benzisoxazole, imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine and 1H-pyrazolo[3,4-a]pyridine, having Ar2, and optionally having one or two or more substituents selected from R3; R1 and R2 each independently represent a hydrogen atom, a halogen atom, a cyano group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, a C2-C7 alkanoyl group, a C2-C7 alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-C1-C6 alkoxy group, a carboxy-C2-C6 alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb; or a C1-C6 alkyl group optionally having a substituent; or an aryl or heterocyclic group optionally having a substituent; or a C1-C6 alkyl group or a C2-C6 alkenyl group having the aryl or heterocyclic group; T and U each independently represent a nitrogen atom or a methine group; and V represents an oxygen atom or a sulfur atom. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.

  本发明涉及一种通式(I)的化合物： 其中Ar1代表由苯、吡唑、异氧唑、吡啶、吲哚、1H-吲唑、1H-呋喃[2,3-c]吡唑、1H-噻吩[2,3-c]吡唑、苯并咪唑、1,2-苯并异氧唑、咪唑并[1,2-a]吡啶、咪唑并[1,5-a]吡啶和1H-吡唑并[3,4-a]吡啶中选取的芳香环组成的基团，具有Ar2，并可选地具有一个或两个或更多的取代基，所述取代基选自R3；R1和R2各自独立地代表氢原子、卤素原子、氰基、C2-C6烯基基团、C1-C6烷氧基团、C2-C7烷酰基基团、C2-C7烷氧羰基基团、芳基烷氧羰基基团、氨基-C1-C6烷氧基团、羧基-C2-C6烯基基团，或-Q1-N(Ra)-Q2-Rb的基团；或者是具有取代基的C1-C6烷基基团；或者是具有取代基的芳基或杂环基团；或者是具有芳基或杂环基团的C1-C6烷基或C2-C6烯基基团；T和U各自独立地代表氮原子或甲基基团；V代表氧原子或硫原子。本发明的化合物可用作治疗各种与ACC相关的疾病的治疗剂。
• WO2008/88692
  申请人：——

  公开号：——

  公开（公告）日：——
• US8138197B2
  申请人：——

  公开号：US8138197B2

  公开（公告）日：2012-03-20