methyl 5-(chlorocarbonyl)pyridine-2-carboxylate | 43083-20-1

• 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: methyl 5-(chlorocarbonyl)pyridine-2-carboxylate
• 英文别名: methyl 5-(carbonochloridoyl)pyridine-2-carboxylate；5-chlorocarbonyl-pyridine-2-carboxylic acid methyl ester；2-methoxycarbonylpyridine-5-carbonyl chloride；6-carbomethoxy-nicotinoyl chloride；methyl 5-carbonochloridoylpyridine-2-carboxylate
• CAS: 43083-20-1
• 化学式: C₈H₆ClNO₃
• 分子量: 199.594
• InChiKey: QVFSHDSAXZCIMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  327.6±27.0 °C(Predicted)
• 密度：
  1.358±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-(chlorocarbonyl)pyridine-2-carboxylate 在 silver(l) oxide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 3.0h， 生成 (2-carboxy-5-pyridyl)acetic acid dimethyl ester
  参考文献：
  名称：

  Novel inhibitors of prolyl 4-hydroxylase

  摘要：

  A series of 5-acyl sulfonamides derived from pyridine-2,5-dicarboxylic acid (15) has been prepared and several members of this series have been shown to be more potent, in vitro, as inhibitors of prolyl 4-hydroxylase than 15. Several chain-extended pyridinedicarboxylic acids have also been prepared and shown to be potent inhibitors of prolyl 4-hydroxylase. The structure-activity in both these series is discussed. The results indicate that the 5-carboxylic acid binding site, in the enzyme, can accept a carboxylic acid or an acyl sulfonamide equally well. This indicates a much greater degree of freedom in this distal carboxylic acid binding site than is predicted by the current theorical model of the active site.

  DOI：

  10.1021/jm00083a001
• 作为产物：
  描述：

  2-甲基氢吡啶-2,5-二羧酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 为溶剂， 反应 3.0h， 生成 methyl 5-(chlorocarbonyl)pyridine-2-carboxylate
  参考文献：
  名称：

  用于酮合成的镍介导的羧酸衍生物光还原交叉偶联**

  摘要：

  介导合成：提出了一种使用可见光和两种羧酸衍生底物镍催化合成酮的策略。不需要昂贵的铱催化剂，环保的 Hantzsch 酯既充当光敏剂又充当光还原剂。介绍了广泛的合成酮以及不同反应物作用的光谱和计算研究。

  DOI：

  10.1002/chem.202103486

文献信息

• Retinoidal Pyrimidinecarboxylic Acids. Unexpected Diaza-Substituent Effects in Retinobenzoic Acids.
  作者：Kiminori OHTA、Emiko KAWACHI、Noriko INOUE、Hiroshi FUKASAWA、Yuichi HASHIMOTO、Akiko ITAI、Hiroyuki KAGECHIKA

  DOI：10.1248/cpb.48.1504

  日期：——

  Several pyridine-and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid (2b) and 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)amino]pyrimidene-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.

  几种吡啶和嘧啶羧酸被合成为视黄酸核受体、视黄酸受体（RARs）和视黄酸X受体（RXRs）的配体候选物。虽然吡啶衍生物，6-[(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)氨基甲酰]吡啶-3-羧酸（2b）和6-[(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)羧酰胺]吡啶-3-羧酸（5b）比相应的苯甲酸型视黄酸更有效，如Am80（2a）和Am580（5a），但将Am580（5a）、Am555（6a）或Am55（7a）的苯环替换为嘧啶环会导致视黄酸活性在HL-60细胞分化试验和使用COS-1细胞的RAR转录激活试验中丧失。另一方面，具有二苯胺骨架（DA系列，8和9）的强效RXR激动剂（视黄酸协同剂）的嘧啶类似物（PA系列，10和11）在HL-60细胞分化试验中表现出强效的视黄酸协同活性并激活RXRs。在合成的化合物中，2-[N-正丙基-N-(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)氨基]嘧啶-5-羧酸（PA013，10e）在HL-60试验中是最活跃的视黄酸协同剂。
• [EN] NOVEL BEXAROTENE ANALOGS<br/>[FR] ANALOGUES INÉDITS DU BEXAROTÈNE
  申请人：UNIV ARIZONA

  公开号：WO2011103321A1

  公开（公告）日：2011-08-25

  The present invention relates to analogs of bexarotene and methods of use thereof.

  本发明涉及贝沙罗汀的类似物及其使用方法。
• 4-Mercaptopyrrolidine derivatives as farnesyl transferase inhibitors
  申请人：Zeneca Limited

  公开号：US06232338B1

  公开（公告）日：2001-05-15

  Pharmaceutical compositions comprising an inhibitor of ras farnesylation of formula (I) wherein, R1 is for example H and further values as defined in the specification; R2 is for example H and further values as defined in the specification; R3 is for example H or a substituent having values as defined in the specification; p is 0-3 in which R3 values can be the same or different; L is a linking moiety for example —CO—NH2— and further values as defined in the specification; A is selected from phenyl; naphthyl; a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms where the heteroatoms are independently selected from O, N and S; or a —S—S— dimer thereof when R2=H; or an enantiomer, diastereoisomer, pharmaceutically acceptable salt, prodrug or solvate thereof together with a pharmaceutically acceptable diluent or carrier. A particular use is cancer therapy.

  药物组合物包括式(I)的ras法尼酰化抑制剂，其中，R1例如为H，进一步的值如规范中定义；R2例如为H，进一步的值如规范中定义；R3例如为H或具有规范中定义的值的取代基；p为0-3，其中R3的值可以相同也可以不同；L是一个连接基团，例如—CO—NH2—和规范中定义的进一步值；A从苯基；萘基；一个含有最多5个杂原子的5-10元单环或双环杂芳基环中选择，其中杂原子独立地从O、N和S中选择；或者当R2=H时的—S—S—二聚体；或其对映体、非对映异构体、药学上可接受的盐、前药或溶剂化合物，连同药学上可接受的稀释剂或载体。一个特定用途是癌症治疗。
• Characterization and Insulin‐Mimetic Potential of Oxidovanadium(IV) Complexes Derived from Monoesters and ‐carboxylates of 2,5‐Dipicolinic Acid
  作者：Jessica Gätjens、Beate Meier、Yusuke Adachi、Hiromu Sakurai、Dieter Rehder

  DOI：10.1002/ejic.200600130

  日期：2006.9

  and3 with VOSO4 afforded the complexes [VO(H2O)(5ROdipic)2](4a–d) and [VO(H2O)(5R′NHdipic)2], 5a–d, respectively. [Mg(H2O)6](2MeOdipic)2·4H2O, 2b, 3a and 4a·0.5H2O were characterized by single-crystal X-ray diffraction analysis. Selected type 4 and 5 complexes were submitted to in vitro tests (fibroblasts, SV 3T3 mice fibroblasts) for their uptake kinetics and insulin-mimetic behavior. The compounds were

  2,5-吡啶二羧酸的单甲酯 2MeOdipicH (1)，以其镁盐 [Mg(H2O)6](2MeOdipic)2 为特征，通过二酯 2MeO-5ROdipic 和铜配合物 [Cu(5ROdipic) 2]，配体 5ROdipicH (R = iPr 2a, (S)-2-Bu 2b)。前配体 2MeO-5ROdipic（R = 二异丙基-D-半乳糖 2c，肌醇原甲酸酯 2d）和 2MeO-5R'NHdipic（其中 R' 代表乙基保护的 L-氨基酸残基 Gly 3a、Ala 3b、Val 3c和Phe 3d)是从2-MeO-5Cldipic和氨基酸乙酯获得的。2 和 3 与 VOSO4 反应得到复合物 [VO(H2O)(5ROdipic)2](4a-d) 和 [VO(H2O)(5R'NHdipic)2], 5a-d。[Mg(H2O)6](2MeOdipic)2·4H2O、2b、3a和4a·0
• ARYL HYDROCARBON RECEPTOR MODULATOR
  申请人：Ariagen, Inc.

  公开号：US20190307731A1

  公开（公告）日：2019-10-10

  Disclosed is an aryl hydrocarbon receptor modulator of formula (I), and a pharmaceutically acceptable salt thereof, wherein R′ is H, CN, CH 2 (OH)R 0 , C m H 2m+1 , C n H 2n-1 , C n H 2n-3 , two R a are independently H or two R a together form ═O or ═N—W 3 —R 1 ; A is a C 6 to C 10 aromatic ring unsubstituted or substituted with 1 to 3 R, or a C 2 -C 10 heteroaromatic ring interrupted by 1 to 5 heteroatoms selected from N, O, and S or a 4 to 7 membered nonaromatic heterocyclic ring containing C═N and interrupted by 1 to 3 heteroatoms selected from N, O, and S, with either one unsubstituted or substituted with 1 to 3 R; Q is R, or is a C 6 to C 10 aromatic ring or a C 2 to C 10 heteroaromatic ring unsubstituted or substituted with 1 to 3 R and interrupted by 1 to 5 heteroatoms selected from N, O, and S; and R is R c which is C-attached or R N which is N-attached. The compounds of formula (I) of the present invention can regulate AhR activity, and can be used to inhibit the growth of cancer cells and inhibit the metastasis and invasion of tumor cells.

  本发明揭示了一种化学式（I）的芳香烃受体调节剂及其药用可接受盐，其中R′为H、CN、CH2（OH）R0、CmH2m+1、CnH2n-1、CnH2n-3，两个Ra独立地为H或两个Ra共同形成═O或═N—W3—R1；A为未取代或取代1至3个R的C6至C10芳香环，或由N、O和S中选择的1至5个杂原子中断的C2-C10杂芳环，或含有C═N并由N、O和S中选择的1至3个杂原子中断的4至7个成员的非芳杂环，其中一个未取代或取代1至3个R；Q为R，或者是未取代或取代1至3个R并由N、O和S中断的C6至C10芳香环或C2至C10杂芳环；R为C-连接的Rc或N-连接的RN。本发明的化合物可以调节AhR活性，可用于抑制癌细胞的生长，以及抑制肿瘤细胞的转移和侵袭。