3-溴-5-甲基吡啶甲酸甲酯 | 1228880-68-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 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: 3-溴-5-甲基吡啶甲酸甲酯
• 英文名称: methyl 3-bromo-5-methylpicolinate
• 英文别名: methyl 3-bromo-5-methylpyridine-2-carboxylate
• CAS: 1228880-68-9
• 化学式: C₈H₈BrNO₂
• 分子量: 230.061
• InChiKey: WBEKRCUPWRCRGA-UHFFFAOYSA-N

物化性质

• 沸点：
  292.5±35.0 °C(Predicted)
• 密度：
  1.503±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P305+P351+P338,P280
• 危险性描述：
  H319,H317
• 储存条件：
  室温

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  3-溴-5-甲基吡啶甲酸	3-bromo-5-methyl-pyridine-2-carboxylic acid	1211515-68-2	C7H6BrNO2	216.034

反应信息

• 作为反应物：
  描述：

  3-溴-5-甲基吡啶甲酸甲酯 在 三乙烯二胺 、 copper(l) iodide 、 2,2,6,6-四甲基-3,5-庚二酮 、 乙酸酐 、 三溴化硼 、 二异丁基氢化铝 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 41.5h， 生成 8-(4-fluoro-2-hydroxyphenoxy)-6-methylindolizine-2-carbonitrile
  参考文献：
  名称：

  Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group

  摘要：

  Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 Å resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ~40 μg/mL, which is similar to that for the approved drug efavirenz and ~1000-fold greater than for rilpivirine.

  DOI：

  10.1021/ja408917n
• 作为产物：
  描述：

  甲醇 、 3-溴-5-甲基吡啶甲酸 在 氯化亚砜 作用下， 以69 %的产率得到3-溴-5-甲基吡啶甲酸甲酯
  参考文献：
  名称：

  Synthesis and Evaluation of Benzylamine Inhibitors of Neuropathogenic Naegleria fowleri “Brain-Eating” Amoeba

  摘要：

  DOI：

  10.1021/acsmedchemlett.3c00440

文献信息

• SUBSTITUTED 7-AZABICYCLES AND THEIR USE AS OREXIN RECEPTOR MODULATORS
  申请人：COATE Heather R.

  公开号：US20160046640A1

  公开（公告）日：2016-02-18

  The present invention is directed to compounds of Formula I: wherein ring A is phenyl, naphihalenyl, pyridyl, quinolinyl, isoquinolinyl, imidazopyridyl, furanyi, tlisazolyl, isoxazolvl, pyrazolyl, imidazothiazolyi, benzimidazolyl, or indazolyi; R 1 is H, alky], aikoxy, hydroxyalkylene, OH, halo, phenyl, triazolyl, oxazolyl, isoxazofyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazmyl, piperazinyl, pyrazolyl, oxadiazolvl, pyrrolidinyl, thiophenyi, morpholinyl, or dialkyiamino; R 2 is H, alkyl, aikoxy, hydroxyalkylene, or halo; Z is NH, N-alkyl, or O; R 5 is pyridyl, pyrimidinyl, pyrazinyl, pyridazmyl, qumazolinyi, quinoxalinyl, pyrazolyl, benzoxazolyl, imidazopyrazinyl, triazolopyrazinyl, optionally substituted with a one or two substituents independently selected from the group consisting of alkyl, aikoxy, or halo; and n is 0 or 1, Methods of making the compounds of Formula 1 are also described. The invention also relates to pharmaceutical compositions comprising compounds of Formula I. Methods of using the compounds of the invention are also within the scope of the invention.

  本发明涉及式I的化合物：其中环A为苯基、萘基、吡啶基、喹啉基、异喹啉基、咪唑吡啉基、呋喃基、噻唑基、异噁唑基、吡唑基、咪唑噻唑基、苯并咪唑基或吲哚基；R1为H、烷基、烷氧基、羟基烷基、OH、卤素、苯基、三唑基、噁唑基、异噁唑基、吡啶基、嘧啶基、吡嗪基、吡啶并嗪基、哌嗪基、吡唑基、噁二唑基、吡咯烷基、噻吩基、吗啉基或二烷氨基；R2为H、烷基、烷氧基、羟基烷基或卤素；Z为NH、N-烷基或O；R5为吡啶基、嘧啶基、吡嗪基、吡啶并嗪基、喹唑啉基、喹喹啉基、吡唑基、苯并噁唑基、咪唑吡嗪基、三唑咪唑基，可选地取代一个或两个独立选择自烷基、烷氧基或卤素的基团；n为0或1，还描述了制备式I化合物的方法。本发明还涉及包含式I化合物的药物组合物。本发明还涉及使用该化合物的方法。
• [EN] SPIRO-OXAZOLONES<br/>[FR] SPIRO-OXAZOLONES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015091411A1

  公开（公告）日：2015-06-25

  The present invention provides spiro-oxazolones, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The present compounds are useful as therapeutics acting peripherally and centrally in the conditions of inappropriate secretion of vasopressin, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, aggressive behavior and phase shift sleep disorders, in particular jetlag.

  本发明提供了螺环噁唑酮，其作为V1a受体调节剂，特别是作为V1a受体拮抗剂，其制备方法，含有它们的药物组合物以及它们作为药物的用途。本化合物在外周和中枢作用下，对于不当分泌加压素、焦虑、抑郁症、强迫症、自闭症谱系障碍、精神分裂症、攻击性行为和相位转移性睡眠障碍，特别是时差反应等症状的治疗具有用处。
• [EN] DISUBSTITUTED HETEROARYL-FUSED PYRIDINES<br/>[FR] PYRIDINES ACCOLÉES À DI-SUBSTITUTION HÉTÉROARYLE
  申请人：NOVARTIS AG

  公开号：WO2011076744A1

  公开（公告）日：2011-06-30

  The invention relates to compound of the formula (I') in which the substituents are as defined in the specification; in free form or in salt form; to its preparation, to its use as medicament and to medicaments comprising it.

  这项发明涉及公式(I')的化合物，其中取代基如规范中所定义；以自由形式或盐形式存在；其制备方法，其作为药物的用途以及包含它的药物。
• DISUBSTITUTED HETEROARYL-FUSED PYRIDINES
  申请人：Babiger Sangamesh

  公开号：US20120258973A1

  公开（公告）日：2012-10-11

  The invention relates to compound of the formula (I′) in which the substituents are as defined in the specification; in free form or in salt form; to its preparation, to its use as medicament and to medicaments comprising it.

  这项发明涉及式(I′)的化合物，其中取代基如规范中所定义；以自由形式或盐形式存在；其制备，其作为药物的用途以及包含它的药物。
• COMPOUNDS AND METHODS FOR TREATING HIV INFECTIONS
  申请人：YALE UNIVERSITY

  公开号：US20150105351A1

  公开（公告）日：2015-04-16

  The present invention is directed to novel nanomolar and picomolar inhibitors of HIV reverse transcriptase, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV-1 and HIV-2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.

  本发明涉及新型纳摩尔和皮摩尔HIV逆转录酶抑制剂，以及由此制备的药物组合物和用于抑制逆转录酶和治疗HIV感染的方法，特别包括对HIV-1和HIV-2的耐药菌株以及作为HIV感染后果发生的次生疾病状态和/或条件。