2-(3,4-methylenedioxybenzoyl)-3-carboxypyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 2-(3,4-methylenedioxybenzoyl)-3-carboxypyridine
• 英文别名: 2-(1,3-Benzodioxole-5-carbonyl)pyridine-3-carboxylic acid
• 化学式: C₁₄H₉NO₅
• 分子量: 271.229
• InChiKey: IXCHBOBUGSJEBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  85.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3,4-methylenedioxybenzoyl)-3-carboxypyridine 在 palladium on activated charcoal 氯化亚砜 、 硫酸 、 氢气 、 magnesium 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives

  摘要：

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00122-0
• 作为产物：
  描述：

  2,3-吡啶二羧酸酐 、 4-溴-1,2-亚甲二氧基苯 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 生成 2-(3,4-methylenedioxybenzoyl)-3-carboxypyridine 、 3-(3,4-methylenedioxyphenylcarbonyl)pyridine-2-carboxylic acid
  参考文献：
  名称：

  6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives

  摘要：

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00122-0

文献信息

• BENZO AND PYRIDO PYRIDAZINONE AND PYRIDAZINTHIONE COMPOUNDS WITH PDE IV INHIBITING ACTIVITY
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0612321A1

  公开（公告）日：1994-08-31
• US5716954A
  申请人：——

  公开号：US5716954A

  公开（公告）日：1998-02-10
• [EN] BENZO AND PYRIDO PYRIDAZINONE AND PYRIDAZINTHIONE COMPOUNDS WITH PDE IV INHIBITING ACTIVITY
  申请人：SYNTEX (U.S.A.) INC.

  公开号：WO1993007146A1

  公开（公告）日：1993-04-15

  (EN) Benzo or pyridopyridazinones and pyridazinthiones of formula (I) wherein: X and Y are nitrogen or carbon, provided that at least one is carbon, and Z is oxygen or sulfur; R1 is hydrogen, lower alkyl, aryl, heteroaryl, or heterocycle lower alkylene; R2, R3, R4, R5 and R6 are independently selected from hydrogen, lower alkyl, halo, carboxy, alkoxycarbonyl, carbamoyl, acyl, acyl halide, thiomethyl, trifluoromethyl, cyano or nitro; or a pharmaceutically acceptable ester, ether or salt thereof, have been found to be useful as an anti-inflammatory, antiasthmatic, immunosuppressive, anti-allograft rejection, anti-graft-vs-host rejection, autoimmune disease or analgetic agent(s).(FR) Benzo ou pyrido pyridazinones et pyridazinthiones de la formule (I) dans laquelle X et Y représentent azote ou carbone, à condition qu'au moins l'un des deux représente du carbone, et Z représente oxygène ou soufre; R1 représente hydrogène, alkyle inférieur, aryle, hétéroaryle ou alkylène inférieur à hétérocycles; R2, R3, R4, R5 et R6 sont sélectionnés indépendamment parmi hydrogène, alkyle inférieur, halo, carboxy, alcoxycarbonyle, carbamoyle, acyle, halogénure d'acyle, thiométhyle, trifluorométhyle, cyano ou nitro; ou un ester, éther ou sel pharmaceutiquement acceptable desdits composés. On a découvert que les composés de l'invention sont utiles comme agents anti-inflammatoires, anti-asthmatiques, immunosuppresseurs, anti-rejet d'halogreffes, anti-rejet de greffes par un hôte, contre les maladies auto-immunes ou analgésiques.
• 6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives
  作者：Kenji Niiyama、Toshiaki Mase、Hirobumi Takahashi、Akira Naya、Kasumi Katsuki、Toshio Nagase、Satoshi Ito、Takashi Hayama、Akihiro Hisaka、Satoshi Ozaki、Masaki Ihara、Mitsuo Yano、Takahiro Fukuroda、Kazuhito Noguchi、Masaru Nishikibe、Kiyofumi Ishikawa

  DOI：10.1016/s0968-0896(02)00122-0

  日期：2002.8

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.