喹唑啉-2-羧酸乙酯 | 869299-42-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 喹唑啉-2-羧酸乙酯
• 英文名称: ethyl quinazoline-2-carboxylate
• CAS: 869299-42-3
• 化学式: C₁₁H₁₀N₂O₂
• 分子量: 202.213
• InChiKey: QFABTMLXPTVXSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  喹唑啉-2-羧酸乙酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(4-quinazoline-2-carboxamido)morphinan
  参考文献：
  名称：

  Structure activity relationship studies of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan (NAQ) analogues as potent opioid receptor ligands: Preliminary results on the role of electronic characteristics for affinity and function

  摘要：

  17-Cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3'-carboxamido)morphinan (NAQ) was previously designed following the 'message-address' concept and was identified as a potent and highly selective mu opioid receptor (MOR) ligand based on its pharmacological profile. We here report the preliminary structure activity relationship (SAR) studies of this novel lead compound. For the new ligands synthesized as NAQ analogues, their binding assay results showed that a longer spacer and a saturated ring system of the side chain were unfavorable for their MOR selectivity over the kappa and delta opioid receptors. In contrast, substitutions with different electronic properties at either 1'- or 4'-position of the isoquinoline ring of the side chain were generally acceptable for reasonable MOR selectivity. The majority of NAQanalogues retained low efficacy at the MOR compared to NAQin the S-35-GTP[gamma S] binding assays while electron-withdrawing groups at 1'-position of the isoquinoline ring induced higher MOR stimulation than electron-donating groups did. In summary, the electronic characteristics of substituents at 1'- or 4'-position of the isoquinoline ring in NAQ seem to be critical and need to be further tuned up to achieve higher MOR selectivity and lower MOR stimulation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.07.043
• 作为产物：
  描述：

  4-喹唑啉酮-2-甲酸乙酯 在 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 氯仿 为溶剂， 20.0 ℃ 、103.42 kPa 条件下， 反应 11.5h， 生成 喹唑啉-2-羧酸乙酯
  参考文献：
  名称：

  Structure activity relationship studies of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan (NAQ) analogues as potent opioid receptor ligands: Preliminary results on the role of electronic characteristics for affinity and function

  摘要：

  17-Cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3'-carboxamido)morphinan (NAQ) was previously designed following the 'message-address' concept and was identified as a potent and highly selective mu opioid receptor (MOR) ligand based on its pharmacological profile. We here report the preliminary structure activity relationship (SAR) studies of this novel lead compound. For the new ligands synthesized as NAQ analogues, their binding assay results showed that a longer spacer and a saturated ring system of the side chain were unfavorable for their MOR selectivity over the kappa and delta opioid receptors. In contrast, substitutions with different electronic properties at either 1'- or 4'-position of the isoquinoline ring of the side chain were generally acceptable for reasonable MOR selectivity. The majority of NAQanalogues retained low efficacy at the MOR compared to NAQin the S-35-GTP[gamma S] binding assays while electron-withdrawing groups at 1'-position of the isoquinoline ring induced higher MOR stimulation than electron-donating groups did. In summary, the electronic characteristics of substituents at 1'- or 4'-position of the isoquinoline ring in NAQ seem to be critical and need to be further tuned up to achieve higher MOR selectivity and lower MOR stimulation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.07.043

文献信息

• SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150329556A1

  公开（公告）日：2015-11-19

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR 1 (R 1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R 2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH 2 ), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是一个具有1到6个原子的可选择取代的间隔物，环C是（1）一个可选择取代的同核环或（2）一个除了由（II）表示的环之外的可选择取代的杂环（X′是S、O、SO或CH2），并且环B和环C中至少有一个有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]2-羟基丙基}5,6-二甲基-4-氧代-1,4-二氢噻唑并[2,3-d]嘧啶-2-羧酰胺，或其盐。
• [EN] NOVEL OXIME DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS D'OXIMES ET LEUR UTILISATION COMME MODULATEURS ALLOSTÉRIQUES DE RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE
  申请人：DOMAIN THERAPEUTICS

  公开号：WO2011051478A1

  公开（公告）日：2011-05-05

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGiuR4.

  本发明提供了一般式（I）的新羟肟衍生物，包含它们的药物组合物以及它们用于治疗和/或预防与改变的谷氨酸信号和/或功能有关的疾病，和/或在哺乳动物中改变谷氨酸水平或信号会影响的疾病。本发明进一步提供了一般式（I）的新羟肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新羟肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向变构调节剂，更具体地说是mGluR4的正向变构调节剂。
• [EN] HETEROCYCLIC AMIDE COMPOUND AND USE THEREOF AS AN MMP-13 INHIBITOR<br/>[FR] COMPOSÉ AMIDE HETEROCYCLIQUE ET UTILISATION DE CELUI-CI EN TANT QU'INHIBITEUR MMP-13
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005105760A1

  公开（公告）日：2005-11-10

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen-containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR1 (R1 is a hydrogen atom or an optionally substituted hydrocarbon group), - - - is a single bond or a double bond, R2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionnally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X’ is S, O, SO, or CH2), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5,6-dimethyl-4-oxo-1,4-dihadrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），- - - 是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是具有1到6个原子的可选择取代的间隔物，环C是(1)一个可选择取代的同核环或(2)除了由(II)表示的环之外的可选择取代的杂环（X'是S、O、SO或CH2），并且环B和环C中至少有一个具有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]-2-羟基丙基}-5,6-二甲基-4-氧代-1,4-二氢噻吩[2,3-d]嘧啶-2-羧酰胺或其盐。
• A Cooperative Catalytic System of Platinum/Iridium Alloyed Nanoclusters and a Dimeric Catechol Derivative: An Efficient Synthesis of Quinazolines Through a Sequential Aerobic Oxidative Process
  作者：Hao Yuan、Woo-Jin Yoo、Hiroyuki Miyamura、Shū Kobayashi

  DOI：10.1002/adsc.201200880

  日期：2012.11.12

  A cooperative catalytic system of heterogeneous polymer-supported bi-metallic platinum/iridium (Pt/Ir) alloyed nanoclusters and 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spiro-bisindane (TTSBI) enabled the facile preparation of quinazoline derivatives with low catalyst loadings and broad substrate scope under mild aerobic oxidative conditions. The ability to perform the reaction in gram-scale

  多相聚合物负载的双金属铂/铱（Pt / Ir）合金纳米簇与5,5'，6,6'-四羟基-3,3,3'，3'-四甲基-1,1的协同催化体系′-螺双茚满（TTSBI）在温和的需氧氧化条件下，可轻松制备具有低催化剂负载量和宽底物范围的喹唑啉衍生物。在克规模和露天条件下进行反应的能力突显了这种协同催化系统的合成应用。
• Novel Oxime Derivatives and Their Use As Allosteric Modulators of Metabotropic Glutamate Receptors
  申请人：Schann Stephan

  公开号：US20120277212A1

  公开（公告）日：2012-11-01

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

  本发明提供了一般式（I）的新的肟衍生物，以及包含它们的制药组合物，以及它们用于治疗和/或预防与改变谷氨酸信号和/或功能相关的疾病和/或与哺乳动物中谷氨酸水平或信号改变有关的疾病的用途。本发明还提供了一般式（I）的新的肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新的肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向异构调节剂，更具体地说是mGluR4的正向异构调节剂。