4-羟基-2-吡啶羧酸乙酯 | 53764-72-0

• 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: 4-羟基-2-吡啶羧酸乙酯
• 中文别名: 4-羟基-2-吡啶甲酸乙酯
• 英文名称: ethyl 4-hydroxypicolinate
• 英文别名: ethyl 4-oxo-1H-pyridine-2-carboxylate
• CAS: 53764-72-0
• 化学式: C₈H₉NO₃
• mdl: MFCD09834737
• 分子量: 167.164
• InChiKey: NXYYJUMPOIFBFP-UHFFFAOYSA-N

物化性质

• 沸点：
  411.5±25.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P330,P362,P403+P233,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-羟基-2-吡啶羧酸乙酯 在 palladium on activated charcoal 、 Rh/Al₂O₃ 甲酸 、 4 A molecular sieve 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 、 pyridinium chlorochromate 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 25.0~100.0 ℃ 、6.89 MPa 条件下， 反应 22.0h， 生成 ethyl 4-(cyanomethyl)-N-methylpiperidine-2-carboxylate
  参考文献：
  名称：

  4-(Tetrazolylalkyl)piperidine-2-carboxylic acids. Potent and selective N-methyl-D-aspartic acid receptor antagonists with a short duration of action

  摘要：

  We have prepared a series of cis-4-(tetrazolylalkyl)piperidine-2-carboxylic acids as potent and selective N-methyl-D-aspartic acid (NMDA) receptor antagonists. NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia. The compounds prepared were evaluated in vitro in both receptor binding assays ([H-3]CGS-19755, [H-3]AMPA, and [H-3]kainic acid) and in a cortical-wedge preparation (versus NMDA, quisqualic acid, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced convulsions in neonatal rats and NMDA-induced lethality in mice. The most potent compound of this series, 15 (LY233053), selectively displaced [H-3]CGS-19755 binding with an IC50 of 107 +/- 7 nM and selectively antagonized responses due to NMDA in a cortical-wedge preparation with an IC50 of 4.2 +/- 0.4-mu-M. Compound 15 blocked both NMDA-induced convulsions in neonatal rats (minimum effective dose (MED) = 20 mg/kg ip) and NMDA-induced lethality in mice (MED = 5 mg/kg ip). This is the first example of an NMDA receptor antagonist that incorporates a tetrazole moiety as an omega-acid bioisostere. These amino acid antagonists are also unique from their phosphonic acid counterparts in that they have a shorter duration of action in vivo. For the treatment of acute disorders such as stroke, where an NMDA antagonist would be administered parenterally, the shorter duration of action may be beneficial, e.g., allowing for better dosage control. The combination of potent NMDA receptor antagonism and a short duration of action may make these compounds useful therapeutic agents in the treatment of a variety of neurological disorders.

  DOI：

  10.1021/jm00105a016
• 作为产物：
  描述：

  4-甲氧基吡啶-2-甲腈 在 盐酸 、 氢溴酸 作用下， 反应 72.0h， 生成 4-羟基-2-吡啶羧酸乙酯
  参考文献：
  名称：

  4-(Tetrazolylalkyl)piperidine-2-carboxylic acids. Potent and selective N-methyl-D-aspartic acid receptor antagonists with a short duration of action

  摘要：

  We have prepared a series of cis-4-(tetrazolylalkyl)piperidine-2-carboxylic acids as potent and selective N-methyl-D-aspartic acid (NMDA) receptor antagonists. NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia. The compounds prepared were evaluated in vitro in both receptor binding assays ([H-3]CGS-19755, [H-3]AMPA, and [H-3]kainic acid) and in a cortical-wedge preparation (versus NMDA, quisqualic acid, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced convulsions in neonatal rats and NMDA-induced lethality in mice. The most potent compound of this series, 15 (LY233053), selectively displaced [H-3]CGS-19755 binding with an IC50 of 107 +/- 7 nM and selectively antagonized responses due to NMDA in a cortical-wedge preparation with an IC50 of 4.2 +/- 0.4-mu-M. Compound 15 blocked both NMDA-induced convulsions in neonatal rats (minimum effective dose (MED) = 20 mg/kg ip) and NMDA-induced lethality in mice (MED = 5 mg/kg ip). This is the first example of an NMDA receptor antagonist that incorporates a tetrazole moiety as an omega-acid bioisostere. These amino acid antagonists are also unique from their phosphonic acid counterparts in that they have a shorter duration of action in vivo. For the treatment of acute disorders such as stroke, where an NMDA antagonist would be administered parenterally, the shorter duration of action may be beneficial, e.g., allowing for better dosage control. The combination of potent NMDA receptor antagonism and a short duration of action may make these compounds useful therapeutic agents in the treatment of a variety of neurological disorders.

  DOI：

  10.1021/jm00105a016

文献信息

• Drug efflux pump inhibitor
  申请人：DAIICHI PHARMACEUTICAL CO., LTD

  公开号：US20030092720A1

  公开（公告）日：2003-05-15

  A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): 1 wherein, R 1 and R 2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W 1 represents —CH═CH—, —CH 2 O—, —CH 2 CH 2 — or the like; R 3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R 4 represents hydrogen atom, a group of —OZ 0-4 R 5 (Z 0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R 5 represents a cyclic alkyl group, an aryl group or the like); W 2 represents a single bond or —C(R 8 )═C(R 9 )— (R 8 and R 9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W 2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

  一种用于预防和/或治疗微生物感染的药物，其活性成分表示为以下一般式(I)的化合物： 其中，R1和R2代表氢原子、卤素原子、羟基或类似物，W1代表—CH═CH—、—CH2O—、—CH2CH2—或类似物；R3代表氢原子、卤素原子、羟基或氨基；R4代表氢原子、—OZ0-4R5（Z0-4代表烷基链、氟取代的烷基链或单键，R5代表环烷基、芳基或类似物）；W2代表单键或—C(R8)═C(R9)—（R8和R9代表氢原子、卤素原子、较低烷基或类似物，Q代表酸性基团，但W2和Q可以共同形成乙烯基噻唑二酮或等效的杂环环；m和n代表0到2的整数，q代表0到3的整数。
• [EN] TETRAZOLE CONTAINING APOPTOSIS SIGNAL-REGULATING KINASE 1 INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE LA KINASE 1 RÉGULANT LE SIGNAL D'APOPTOSE CONTENANT DES TÉTRAZOLES ET LEURS MÉTHODES D'UTILISATION
  申请人：ENANTA PHARM INC

  公开号：WO2019213244A1

  公开（公告）日：2019-11-07

  The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof: (I) which inhibit the Apoptosis signal-regulating kinase 1 (ASK-l), which is associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-l related disease. The invention also relates to methods of treating an ASK-l related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-l associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

  本发明揭示了化合物的结构式（I），以及其药学上可接受的盐和酯：（I），这些化合物抑制凋亡信号调节激酶1（ASK-l），该激酶与自身免疫性疾病、神经退行性疾病、炎症性疾病、慢性肾脏疾病、心血管疾病有关。本发明还涉及包含上述化合物的药物组合物，用于给患有与ASK-l相关疾病的受试者使用。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的ASK-l相关疾病的方法。本发明具体涉及治疗与肝脂肪变性相关的ASK-l的方法，包括非酒精性脂肪肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）。
• Medicine for inhibiting drug elimination pump
  申请人：Nakayama Kiyoshi

  公开号：US20050009843A1

  公开（公告）日：2005-01-13

  A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R 1 and R 2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W 1 represents —CH═CH—, —CH 2 O—, —CH 2 CH 2 — or the like; R 3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R 4 represents hydrogen atom, a group of —OZ 0-4 R 5 (Z 0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R 5 represents a cyclic alkyl group, an aryl group or the like); W 2 represents a single bond or —C(R 8 )═C(R 9 )—(R 8 and R 9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W 2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

  预防和/或治疗微生物感染的药物，其活性成分为以下通用式（I）所表示的化合物：其中，R1和R2表示氢原子、卤原子、羟基或类似物，W1表示—CH═CH—、—CH2O—、—CH2CH2—或类似物；R3表示氢原子、卤原子、羟基或氨基；R4表示氢原子、—OZ0-4R5（Z0-4表示烷基、氟代烷基或单键，R5表示环烷基、芳基或类似物）；W2表示单键或—C（R8）═C（R9）—（R8和R9表示氢原子、卤原子、低烷基或类似物，Q表示酸性基团，但W2和Q可以共同形成乙烯基噻唑烷二酮或等效的杂环环；m和n表示0至2的整数，q表示0至3的整数。
• Tetrazole excitatory amino acid receptor antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0330353A1

  公开（公告）日：1989-08-30

  The present invention provides novel tetrazole derivatives useful as excitatory amino acid receptor antagonists and in treating a variety of associated nervous system disorders.

  本发明提供了可用作兴奋性氨基酸受体拮抗剂和治疗各种相关神经系统疾病的新型四氮唑衍生物。
• MEDICINE FOR INHIBITING DRUG ELIMINATION PUMP
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1389463A1

  公开（公告）日：2004-02-18

  A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R1 and R2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W1 represents -CH=CH-, -CH2O-, -CH2CH2- or the like; R3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R4 represents hydrogen atom, a group of -OZ0-4R5 (Z0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R5 represents a cyclic alkyl group, an aryl group or the like); W2 represents a single bond or -C(R8)=C(R9)- (R8 and R9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

  一种用于预防和/或治疗微生物感染的药物，其活性成分包括由以下通式(I)代表的化合物： 其中，R1 和 R2 代表氢原子、卤素原子、羟基或类似基团；W1 代表-CH=CH-、-CH2O-、-CH2CH2-或类似基团；R3 代表氢原子、卤素原子、羟基或氨基；R4 代表氢原子、-OZ0-4R5 的基团（Z0-4 代表亚烷基、氟取代的亚烷基或单键，R5 代表环状烷基、芳基或类似基团）；W2 代表单键或-C(R8)＝C(R9)-（R8 和 R9 代表氢原子、卤素原子、低级烷基或类似基团，Q 代表酸性基团，但 W2 和 Q 可共同形成亚乙烯基噻唑烷二酮或等效的杂环；m 和 n 代表 0 至 2 的整数，q 代表 0 至 3 的整数。