α-[(dimethylamino)methylene]-β-oxo-2-thiophenepropanenitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-[(dimethylamino)methylene]-β-oxo-2-thiophenepropanenitrile
• 英文别名: 3-dimethylamino-2-(thiophene-2-carbonyl)acrylonitrile；1-thien-2-yl-2-cyano-3-dimethylaminopropen-1one；2-[(Dimethylamino)methylene]-3-oxo-3-(2-thienyl)propanenitrile；(E)-3-(dimethylamino)-2-(thiophene-2-carbonyl)prop-2-enenitrile
• 化学式: C₁₀H₁₀N₂OS
• 分子量: 206.268
• InChiKey: JQZFGDHPUCKBHT-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-[(dimethylamino)methylene]-β-oxo-2-thiophenepropanenitrile 在 铁粉 、 氯化铵 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 [7-(3-aminophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-thien-2-yl-methanone
  参考文献：
  名称：

  Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents: parallel synthesis for lead optimization of amide region

  摘要：

  A novel series of p21 chemoselective agents containing a pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides were identified by high throughput screening. Optimization of the amide region by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described. The isopropyl carbamate derivative 34 was identified as a highly chemoselective agent displaying a potency of 51 nM in the p21 deficient cell line. © 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.066
• 作为产物：
  描述：

  2-乙酰基噻吩 反应 36.0h， 生成 α-[(dimethylamino)methylene]-β-oxo-2-thiophenepropanenitrile
  参考文献：
  名称：

  Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: Exploration of core and headpiece structure–activity relationships

  摘要：

  A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides, selective for p21-deficient cells, were identified by high-throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece is described. Strict steric, positional, and electronic requirements were observed, with a clear preference for both core nitrogens, a thienoyl headpiece, and meta substituted tailpiece. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.116

文献信息

• Salts And Co-Crystals of Pyrazolopyrimidine Compounds, Compositions Thereof And Methods For Their Production And Use
  申请人：LIPPA S. Arnold

  公开号：US20080045547A1

  公开（公告）日：2008-02-21

  The invention provides pharmaceutically acceptable salts and co-crystals of pyrazolopyrimidine compounds such as zaleplon, indiplon and ocinaplon, processes for their preparation, compositions comprising such salts and co-crystals and methods of using such salts and co-crystals for treating various diseases and conditions.

  这项发明提供了吡唑基嘧啶化合物的药用可接受盐和共晶体，例如扎来普隆、印地普隆和奥西那普隆，以及它们的制备方法、包含这些盐和共晶体的组合物，以及利用这些盐和共晶体治疗各种疾病和症状的方法。
• 5-cyano-2-aminopyrimidine derivatives
  申请人：——

  公开号：US20020147339A1

  公开（公告）日：2002-10-10

  Pyrimidines of formula (1) are described 1 wherein Ar is an optionally substituted aromatic or heteroaromatic group; R 1 is a hydrogen atom or a straight or branched chain alkyl group; R 2 is a —X 1 —R 3 group where X 1 is a direct bond or a linker atom or group, and R 3 is an optionally substituted aliphatic, cycloaliphatic, heteroaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are selective KDR Kinase and/or FGFr Kinase inhibitors and are of use in the prophylaxis and treatment of disease states associated with angiogenesis.

  公式（1）中描述了嘧啶类化合物，其中Ar是可选择取代的芳香或杂芳基团；R1是氢原子或直链或支链烷基基团；R2是一个—X1—R3基团，其中X1是直接键或连接原子或基团，而R3是可选择取代的脂肪、环脂肪、杂原子脂肪、杂环脂肪、芳香或杂芳基团；以及它们的盐、溶剂合物、水合物和N-氧化物。这些化合物是选择性的KDR激酶和/或FGFr激酶抑制剂，并可用于预防和治疗与血管生成相关的疾病状态。
• Novel 3-aroylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides 8-substituted, ligands at GABAA/benzodiazepine receptor complex: Synthesis, pharmacological and molecular modeling studies
  作者：Gabriella Guerrini、Giovanna Ciciani、Giovanni Cambi、Fabrizio Bruni、Silvia Selleri、Fabrizio Melani、Marina Montali、Claudia Martini、Carla Ghelardini、Monica Norcini、Annarella Costanzo

  DOI：10.1016/j.bmc.2008.02.058

  日期：2008.4

  The synthesis and binding studies of a series of 3-acylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA(A) receptor complex (GABA(A)/BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3

  报道了一系列3-取代的3-酰基吡唑并[5,1-c] [1,2,4]苯并三嗪5-氧化物的合成和结合研究。当3-芳酰基取代基由五元杂芳酰基环（呋喃酰基-，壬酰基-和吡咯酰基-）代表时，获得了GABA（A）受体复合物（GABA（A）/ BzR复合物）上苯并二氮杂位处的高亲和力配体。 ）。此外，位置3上的杂芳酰基环的类型会影响位置8上的取代基的特性，从而获得高亲和力的配体：位置3上的“氢键受体环”与位置8上的电子给体取代基具有协同作用，而“氢键供体环与抽出取代基协同作用。考虑到六种潜在的苯二氮卓类药物的作用，对化合物8a，9b和11的药理作用进行了体内深入研究：运动协调，抗惊厥作用，自发运动和探索活动，抗焦虑作用，小鼠学习和记忆调节以及乙醇增强作用。为了合理化和定性地解释化合物8a和11的GABA（A）/ Bz结合亲和力，进行了动态分子建模研究，目的是评估蛋白质-配体复合物的优选几何形状。
• [EN] 5-CYANO-2-AMINOPYRIMIDINE DERIVATIVES<br/>[FR] DERIVES DE 5-CYANO-2-AMINOPYRIMIDINE
  申请人：CELLTECH CHIROSCIENCE LTD

  公开号：WO2000078731A1

  公开（公告）日：2000-12-28

  Pyrimidines of formula (1) are described wherein Ar is an optionally substituted aromatic or heteroaromatic group; R1 is a hydrogen atom or a straight or branched chain alkyl group; R2 is a -X1-R3 group where X1 is a direct bond or a linker atom or group, and R3 is an optionally substituted aliphatic, cycloaliphatic, heteroaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are selective KDR Kinase and/or FGFr Kinase inhibitors and are of use in the prophylaxis and treatment of disease states associated with angiogenesis.

  描述了式（1）的嘧啶类化合物，其中Ar是可选择的取代芳香族或杂环芳香族基团；R1是氢原子或直链或支链烷基；R2是-X1-R3基团，其中X1是直接键或连接原子或基团，R3是可选择的取代脂肪族、环状脂肪族、杂原子脂肪族、杂环脂肪族、芳香族或杂环芳香族基团；以及其盐、溶剂合物、水合物和N-氧化物。这些化合物是选择性的KDR激酶和/或FGFr激酶抑制剂，可用于预防和治疗与血管生成相关的疾病状态。
• Controlled-release sedative-hypnotic compositions and methods related thereto
  申请人：Campbell Bruce D.

  公开号：US20050244496A1

  公开（公告）日：2005-11-03

  Controlled-release formulations providing a “pulsed” plasma profile of a sedative-hypnotic compounds having a particularly short half-life are provided. The formulation contains a sedative-hypnotic compound or precursor thereof that is metabolized to generate a sedative-hypnotic compound in vivo, wherein the compound has a mean plasma half life ranging from 0.1 to 2 hours; and at least one release retardant such that, following administration of the formulation to a patient, the patient has specified pulsed plasma profile for the sedative-hypnotic compound as disclosed herein. In a preferred embodiment, the sedative-hypnotic compound is NBI-34060.

  提供了一种受控释放的配方，可以提供具有特别短半衰期的镇静催眠化合物的“脉冲”血浆剖面。该配方包含一种在体内代谢产生镇静催眠化合物的镇静催眠化合物或其前体，其中该化合物的平均血浆半衰期范围为0.1至2小时；以及至少一种释放延迟剂，使得在给患者注射该配方后，患者具有所述镇静催眠化合物的特定脉冲血浆剖面。在优选实施例中，镇静催眠化合物为NBI-34060。