2-(异氰酰基甲基)噻吩 | 71189-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 中文名称: 2-(异氰酰基甲基)噻吩
• 英文名称: 2-thienylmethyl isocyanate
• 英文别名: 2-(isocyanatomethyl)thiophene
• CAS: 71189-20-3
• 化学式: C₆H₅NOS
• mdl: MFCD08060606
• 分子量: 139.178
• InChiKey: CDDYYRHLZPJLPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-(异氰酰基甲基)噻吩 在 4-二甲氨基吡啶 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 4-{3,3-Diethyl-4-oxo-1-[(thiophen-2-ylmethyl)-carbamoyl]-azetidin-2-yloxy}-benzoic acid
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003
• 作为产物：
  描述：

  2-噻吩乙酸 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 3.5h， 以12%的产率得到2-(异氰酰基甲基)噻吩
  参考文献：
  名称：

  [EN] 3-SUBSTITUTED-4-0X0-3, 4-DIHYDRO-IMIDAZO- [5, 1-D] [1,2,3,5] -TETRAZINE-8-CARBOXYLIC ACID AMIDES AS ANTICANCER AGENTS
  [FR] AMIDES D'ACIDES 4-OXO-3,4-DIHYDROIMIDAZO[5,1-D][1,2,3,5-TÉTRAZINE-8-CARBOXYLIQUES SUBSTITUÉS EN POSITION 3 ET LEUR UTILISATION

  摘要：

  公开号：

  WO2009077741A3

文献信息

• Substituted pyrimid-2-ones, the salts thereof, processes for their
  申请人：Nyegaard & Co. A/S

  公开号：US04478839A1

  公开（公告）日：1984-10-23

  Compounds of general formula: ##STR1## (wherein X represents a halogen atom or a trifluoromethyl group; R.sup.1 and R.sup.2, which may be the same or different, each represents a hydrogen atom, or a C.sub.1-4 alkyl group, and R.sup.3 represents a hydrogen atom or a C.sub.1-5 saturated or unsaturated, straight or branched acyclic aliphatic group; a C.sub.3-8 saturated or unsaturated cyclic aliphatic group; a heterocyclic substituted aliphatic group; an araliphatic group; or a heterocyclic or carbocyclic aryl group; any of said groups optionally carrying one or more substituents selected from halogen, oxo, hydroxy, mercapto, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkanoyloxy and amino) and, where an acidic or basic group is present, physiologically compatible salts thereof have been found to be of use in combating abnormal cell proliferation. The compounds of formula I may be prepared by reaction of a 5-halo- or 5-trifluoromethyl-pyrimidin-2-one with an appropriate isocyanate.

  通用公式化合物：##STR1##（其中X代表卤素原子或三氟甲基基团；R.sup.1和R.sup.2，可以相同也可以不同，每个代表氢原子，或C.sub.1-4烷基基团，R.sup.3代表氢原子或C.sub.1-5饱和或不饱和，直链或支链脂肪族基团；C.sub.3-8饱和或不饱和环状脂肪族基团；杂环取代脂肪族基团；芳基脂肪族基团；或杂环或碳环芳基基团；所述基团中的任何一个可选地携带来自卤素、氧代、羟基、巯基、C.sub.1-4烷基、C.sub.1-4烷氧基、C.sub.1-4酰氧基和氨基的一个或多个取代基），并且，在存在酸性或碱性基团时，已发现其生理相容盐可用于对抗异常细胞增殖。公式I的化合物可通过5-卤或5-三氟甲基嘧啶-2-酮与适当异氰酸酯的反应制备。
• Imidazole derivatives as histamine receptor H3 (ANT) agonists
  申请人：Institut National de la Sante et de la Recherche Medical

  公开号：US06248765B1

  公开（公告）日：2001-06-19

  Novel imidazole derivatives as histamine receptor H3 antagonists and/or agonists, preparation thereof and therapeutical uses thereof. Chemical compounds for use as histamine receptor H3 agonists, partial agonists or antagonists, having general formula (Ia) or (Ib), the use thereof for making drugs, and methods for revealing the agonist, partial agonist or antagonist activity of such compounds in vivo, are disclosed.

  新型咪唑衍生物作为组胺受体H3拮抗剂和/或激动剂，其制备和治疗用途。用作组胺受体H3激动剂、部分激动剂或拮抗剂的化合物，具有通式(Ia)或(Ib)，其用于制备药物的用途，并公开了在体内揭示这类化合物的激动剂、部分激动剂或拮抗剂活性的方法。
• Novel Carbamates as Potent Histamine H₃ Receptor Antagonists with High <i>in Vitro</i> and Oral <i>in Vivo</i> Activity^,
  作者：Holger Stark、Katja Purand、Xavier Ligneau、Agnès Rouleau、Jean-Michel Arrang、Monique Garbarg、Jean-Charles Schwartz、Walter Schunack

  DOI：10.1021/jm9507688

  日期：1996.1.1

  their H3 receptor antagonist activity. Different chain lengths and various substituents possessing different electronic and steric parameters were introduced and structure-activity relationships established. In different functional tests, the new antagonists showed high H3 receptor antagonist potencies in vitro (-log Ki values of 6.4-8.4) at synaptosomes of rat cerebral cortex and low activities at histamine

  已知的组胺H3受体拮抗剂burimamide，thioperamide，clobenpropit和相关的homogenamine thioamide衍生物被用作模板，以寻找新的线索。通过用相应的异氰酸酯或氨基甲酰氯处理醇，以高收率制备了结构上被描述为3-（1H-咪唑-4-基）丙醇的氨基甲酸酯衍生物的新型组胺H3受体拮抗剂，并研究了它们的H3受体拮抗剂活性。介绍了不同的链长和具有不同的电子和空间参数的各种取代基，并建立了结构-活性关系。在不同的功能测试中，新的拮抗剂在体外显示出较高的H3受体拮抗剂效价（对数Ki值为6.4-8。4）在大鼠大脑皮层的突触小体，组胺H1和H2受体亚型的活性低。口服给药后，还筛选了它们在小鼠中的中心体内活性。最有前途的化合物（2、16、19）的ED（50）值约为1-2 mg / kg，因此是治疗H3受体依赖性疾病的潜在药物。一些新颖的氨基甲酸酯衍生物是具有高体外和体内活性的H
• Hyperconjugation effect on diene reactivity in 1-methyltetrazolo[5,1-a]isoindole-derived amides and thioamides
  作者：Tatyana V. Yegorova、Svitlana V. Shishkina、Roman I. Zubatyuk、Magdalina D. Tsapko、Oleg V. Shishkin、Zoia V. Voitenko

  DOI：10.1016/j.tet.2019.02.025

  日期：2019.3

  Optimized synthesis of 1-methyltetrazolo[5,1-a]isoindole-derived amides and thioamides was elaborated. Based on 13C NMR spectroscopy and X-Ray diffraction studies data, it was proposed that zwitterionic resonance structures contributed significantly to the structure of these compounds. Geometry optimization was performed in vacuo using m06-2x/cc-pvtz method taking into account polarizing effect of

  阐述了1-甲基四唑并[5,1- a ]异吲哚衍生的酰胺和硫代酰胺的最佳合成方法。基于13 C NMR光谱和X射线衍射研究数据，提出两性离子共振结构对这些化合物的结构起了重要作用。考虑到环境的偏振效应（PCM模型）和特定的分子间相互作用，使用m06-2x / cc-pvtz方法在真空中进行几何优化。使用NBO方法分析这些分子中的电子密度分布。使用Δ（HOMO二烯-LUMO亲双烯体在酰胺和硫代酰胺）真空并在质子溶剂中评估了Diels–Alder反应的可能性。在真空，非质子传递和质子传递溶剂中估算了酰胺衍生物的π-π共轭和n→σ*超共轭的能量。
• Antagonists of the human adenosine A2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d]pyrimidines and 6-arylpurines
  作者：Roger J. Gillespie、Ian A. Cliffe、Claire E. Dawson、Colin T. Dourish、Suneel Gaur、Allan M. Jordan、Antony R. Knight、Joanne Lerpiniere、Anil Misra、Robert M. Pratt、Jonathan Roffey、Gemma C. Stratton、Rebecca Upton、Scott M. Weiss、Douglas S. Williamson

  DOI：10.1016/j.bmcl.2008.03.072

  日期：2008.5

  A series of pyrazolo[3,4-d]pyrimidine, pyrrolo[2,3-d]pyrimidine and 6-arylpurine adenosine A(2A) antagonists is described. Many examples were highly selective against the human A(1) receptor sub-type and were active in an in vivo model of Parkinson's disease.

  描述了一系列的吡唑并[3,4-d]嘧啶，吡咯并[2,3-d]嘧啶和6-芳基嘌呤腺苷A（2A）拮抗剂。许多示例对人类A（1）受体亚型具有高度选择性，并且在帕金森氏病的体内模型中具有活性。