3-hydroxy-2-butyl-4(1H)-quinolone | 70111-44-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-hydroxy-2-butyl-4(1H)-quinolone
• 英文别名: N-pentanoylanthranilic acid；2-(N-Valerylamino)-benzoic Acid；2-(pentanoylamino)benzoic acid
• CAS: 70111-44-3
• 化学式: C₁₂H₁₅NO₃
• mdl: MFCD00448093
• 分子量: 221.256
• InChiKey: FNXYKRJGWPQPIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-2-butyl-4(1H)-quinolone 在 ammonium hydroxide 、 sodium hydroxide 作用下， 生成 2-butylquinazolin-4(3H)-one
  参考文献：
  名称：

  Phosphodiesterase inhibitory properties of losartan. design and synthesis of new lead compounds

  摘要：

  A 4-centre PDE 4 pharmacophore search has been carried out in several 3D-databases containing compounds belonging to different therapeutic areas. Losartan, an angiotensin-II antagonist, has been identified as a new lead compound for developping PDE 4 inhibitors. New families of compounds derived from losartan has been synthesized and their PDE inhibition has been measured. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00058-4
• 作为产物：
  描述：

  2-butyl-3-hydroxy-4(1H)-quinoline 在 HodC-W₁₆₀A protein, HodC: 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase C₆₉S mutant 、 氧气 作用下， 生成 3-hydroxy-2-butyl-4(1H)-quinolone
  参考文献：
  名称：

  Substrate-Assisted O2 Activation in a Cofactor-Independent Dioxygenase

  摘要：

  In contrast to the majority of O-2-activating enzymes, which depend on an organic cofactor or a metal ion for catalysis, a particular group of structurally unrelated oxygenases is functional without any cofactor. In this study, we characterized the mechanism of O-2 activation in the reaction pathway of a cofactor-independent dioxygenase with an alpha/beta-hydrolase fold, which catalyzes the oxygenolytic cleavage of 2-alkyl-3-hydroxy-4(1H)-quinolones. Chemical analysis and electron paramagnetic resonance spectroscopic data revealed that O-2 activation in the enzyme's active site is substrate-assisted, relying on single electron transfer from the bound substrate anion to Ow(2) to form a radical pair, which recombines to a C2-peroxide intermediate. Thus, an oxygenase can function without a cofactor, if the organic substrate itself, after activation to a (carb) anion by an active-site base, is intrinsically reactive toward molecular oxygen.

  DOI：

  10.1016/j.chembiol.2013.11.013

文献信息

• Benzimidazole derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0425921A1

  公开（公告）日：1991-05-08

  Novel imidazole derivatives of the formula (I): wherein R¹ is an optionally substituted alkyl group, R² and R³ are independently a group capable of forming anion or a group which can be changed thereinto, ring A is benzene ring optionally having, besides the group shown by R², further substituents, and X shows linkage of phenylene group and phenyl group directly or through a spacer whose atomic chain is not more than 2 and a salt thereof, show antagonistic actions to angiotensin II, thus being useful as therapeutics for cardiovascular diseases.

  式(I)的新型咪唑衍生物： 其中，R¹为任选取代的烷基，R²和R³分别为可形成阴离子的基团或可改变其性质的基团，环A为苯环，除R²所示基团外，还可任选具有其他取代基，X为亚苯基和苯基直接连接或通过原子链不超过2的间隔物连接及其盐，这些衍生物具有拮抗血管紧张素II的作用，因此可作为心血管疾病的治疗药物。
• Catalytic Mechanism of Cofactor-Free Dioxygenases and How They Circumvent Spin-Forbidden Oxygenation of Their Substrates
  作者：Aitor Hernández-Ortega、Matthew G. Quesne、Soi Bui、Derren J. Heyes、Roberto A. Steiner、Nigel S. Scrutton、Sam P. de Visser

  DOI：10.1021/jacs.5b03836

  日期：2015.6.17

  Dioxygenases catalyze a diverse range of biological reactions by incorporating molecular oxygen into organic substrates. Typically, they use transition metals or organic cofactors for catalysis. Bacterial 1-H-3-hydroxy-4-oxoquinaldine-2,4-dioxygenase (HOD) catalyzes the spin-forbidden transfer of dioxygen to its N-heteroaromatic substrate in the absence of any cofactor. We combined kinetics, spectroscopic and computational approaches to establish a novel reaction mechanism. The present work gives insight lotto the rate limiting steps in the reaction mechanism, the effect of first-coordination sphere amino acids as well as electron-donating/electron-withdrawing,substituents on the substrate. We highlight the role of active site residues Ser(101)/Trp(160)/His(251) and their involvement in the reaction mechanism. The work shows, for the first time, that the reaction is initiated by triplet dioxygen and its binding to deprotonated substrate and only thereafter a spin state crossing to the singlet spin state occurs. As revealed by steady- and transient-state kinetics the oxygen-dependent steps are rate-limiting, whereas Trp(160) and His(251) are essential residues for catalysis and contribute to substrate positioning and activation, respectively. Computational modeling further confirms the experimental observations and rationalizes the electron transfer pathways, and the effect of substrate and substrate binding pocket residues. Finally, we make a direct comparison with iron-based dioxygenases and explain the mechanistic and electronic differences with cofactor-free dioxygenases. Our multidisciplinary study confirms that the oxygenation reaction can take place in absence of any cofactor by a unique mechanism in which the specially designed fit-for-purpose active-site architecture modulates substrate reactivity toward oxygen.
• SUBSTITUTED BENZIMIDAZOLES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0525129A1

  公开（公告）日：1993-02-03
• EP0525129A4
  申请人：——

  公开号：EP0525129A4

  公开（公告）日：1993-03-24
• [EN] SUBSTITUTED BENZIMIDAZOLES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1991016313A1

  公开（公告）日：1991-10-31

  (EN) Angiotensin II receptor antagonists having formula (I), which are useful in regulating hypertension and in the treatment of congestive heart failure, renal failure, and glaucoma, pharmaceutical compositions including these antagonists, and methods of using these compounds to produce angiotensin II receptor antagonism in mammals.(FR) Antagonistes des récepteurs à l'angiotensine II de formule (I) qui sont utiles pour le traitement de l'hypertension ainsi que pour le traitement de défaillances cardiaques congestives, de défaillance rénales et de glaucomes. Compositions pharmaceutiques comprenant ces antagonistes et procédés d'utilisation de ces composés pour provoquer l'antagonisme aux récepteurs de l'angiotensine II chez des mammifères.