Fenamic acid
(Synonyms: 甲芬那酸; N-苯基邻氨基苯甲酸; N-Phenylanthranilic acid) 目录号 : GC60834
Fenamic acid (N-Phenylanthranilic acid, 2-(Phenylamino)benzoic acid, 2-Anilinobenzoic acid, Diphenylamine-2-carboxylic acid) serves as a parent structure for several nonsteroidal anti-inflammatory drugs (NSAIDs), including mefenamic acid, tolfenamic acid, flufenamic acid, and meclofenamic acid.
Cas No.:91-40-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fenamic acid (N-Phenylanthranilic acid, 2-(Phenylamino)benzoic acid, 2-Anilinobenzoic acid, Diphenylamine-2-carboxylic acid) serves as a parent structure for several nonsteroidal anti-inflammatory drugs (NSAIDs), including mefenamic acid, tolfenamic acid, flufenamic acid, and meclofenamic acid.
| Cas No. | 91-40-7 | SDF | |
| 别名 | 甲芬那酸; N-苯基邻氨基苯甲酸; N-Phenylanthranilic acid | ||
| Canonical SMILES | O=C(O)C1=CC=CC=C1NC2=CC=CC=C2 | ||
| 分子式 | C13H11NO2 | 分子量 | 213.23 |
| 溶解度 | DMSO: 125 mg/mL (586.22 mM) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 4.6898 mL | 23.4489 mL | 46.8977 mL |
| 5 mM | 0.938 mL | 4.6898 mL | 9.3795 mL |
| 10 mM | 0.469 mL | 2.3449 mL | 4.6898 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Repurposing Fenamic acid Drugs To Combat Multidrug-Resistant Neisseria gonorrhoeae
Antimicrob Agents Chemother 2020 Jun 23;64(7):e02206-19.PMID:32393483DOI:10.1128/AAC.02206-19.
The rise of extensively drug-resistant and multidrug-resistant strains of Neisseria gonorrhoeae has occurred in parallel with the increasing demand for new drugs. However, the current methods of drug discovery are burdened with rigorous assessments and require more time than can be spared until gonococcal infections become difficult to control. To address this urgency, we utilized a drug-repurposing strategy and identified three clinically approved anthranilic acid drugs (tolfenamic acid, flufenamic acid, and meclofenamic acid) with potent antigonococcal activity, inhibiting 50% of the strains (MIC50) from 4 to 16 μg/ml. Furthermore, tolfenamic acid showed indifferent activity with antibiotics of choice for gonococcal infections, azithromycin and ceftriaxone, in checkerboard assays with a fractional inhibitory concentration index ranging from 0.75 to 1.5. Fenamic acids reduced a high inoculum of N. gonorrhoeae below the limit of detection within 12 h and exhibited a low frequency of resistance. Interestingly, the fenamic acids did not inhibit the growth of commensal Lactobacillus spp. that comprise the healthy female genital microbiota. Fenamic acids were also superior to ceftriaxone in reducing the burden of intracellular N. gonorrhoeae within infected endocervical cells by 99%. Furthermore, all three fenamic acids significantly reduced the expression of proinflammatory cytokines by infected endocervical cells. Finally, fenamic acids and other structurally related anthranilic acid derivatives were evaluated to ascertain a more in-depth structure-activity relationship (SAR) that revealed N-phenylanthranilic acid as a novel antigonorrheal scaffold. This SAR study will pave the road to repositioning more potent fenamic acids analogues against N. gonorrhoeae.
Substrate-selective Inhibition of Cyclooxygeanse-2 by Fenamic acid Derivatives Is Dependent on Peroxide Tone
J Biol Chem 2016 Jul 15;291(29):15069-81.PMID:27226593DOI:10.1074/jbc.M116.725713.
Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid (AA) and endocannabinoid substrates, placing the enzyme at a unique junction between the eicosanoid and endocannabinoid signaling pathways. COX-2 is a sequence homodimer, but the enzyme displays half-of-site reactivity, such that only one monomer of the dimer is active at a given time. Certain rapid reversible, competitive nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit COX-2 in a substrate-selective manner, with the binding of inhibitor to a single monomer sufficient to inhibit the oxygenation of endocannabinoids but not arachidonic acid. The underlying mechanism responsible for substrate-selective inhibition has remained elusive. We utilized structural and biophysical methods to evaluate flufenamic acid, meclofenamic acid, mefenamic acid, and tolfenamic acid for their ability to act as substrate-selective inhibitors. Crystal structures of each drug in complex with human COX-2 revealed that the inhibitor binds within the cyclooxygenase channel in an inverted orientation, with the carboxylate group interacting with Tyr-385 and Ser-530 at the top of the channel. Tryptophan fluorescence quenching, continuous-wave electron spin resonance, and UV-visible spectroscopy demonstrate that flufenamic acid, mefenamic acid, and tolfenamic acid are substrate-selective inhibitors that bind rapidly to COX-2, quench tyrosyl radicals, and reduce higher oxidation states of the heme moiety. Substrate-selective inhibition was attenuated by the addition of the lipid peroxide 15-hydroperoxyeicosatertaenoic acid. Collectively, these studies implicate peroxide tone as an important mechanistic component of substrate-selective inhibition by flufenamic acid, mefenamic acid, and tolfenamic acid.
Conformational Heterogeneity and Self-Assembly of α,β,γ-Hybrid Peptides Containing Fenamic acid: Multistimuli-Responsive Phase-Selective Gelation
ACS Omega 2020 Jan 30;5(5):2287-2294.PMID:32064390DOI:10.1021/acsomega.9b03532.
The effect of fenamic acid-α-aminoisobutyric acid corner motif in α,β,γ-hybrid peptides has been reported. From X-ray single-crystal diffraction studies, it is observed that Phe-containing peptide 1 has an "S"-shaped conformation that is stabilized by two consecutive intramolecular N-H···N hydrogen bonds. However, the tyrosine analogue peptide 2 has an "S"-shaped conformation, which is stabilized by consecutive intramolecular six-member N-H···N and seven-member N-H···O hydrogen bonds. The asymmetric unit of peptide 3 containing m-aminobenzoic acid has two molecules which are stabilized by multiple intermolecular hydrogen-bonding interactions. There are also π-π stacking interactions between the aromatic rings of Fenamic acid. The peptides 1 and 2 have a polydisperse microsphere morphology, but peptide 3 has an entangled fiber-like morphology. Peptides 1-3 do not form organogels. However, in the presence of water, the peptide 3 forms a phase-selective instant gel in xylene. The gel exhibits high stability and thermal reversibility. The phase-selective gel of peptide 3 is highly responsive to H2SO4.
Aqueous chlorination of fenamic acids: Kinetic study, transformation products identification and toxicity prediction
Chemosphere 2017 May;175:114-122.PMID:28211324DOI:10.1016/j.chemosphere.2017.02.045.
Fenamic acids, one important type of non-steroidal anti-inflammatory drugs, are ubiquitous in environmental matrices. Thus it is of high significance to know the fate of them during chlorination disinfection considering their potential toxicity to the environment and humans. In the present study, the chlorination kinetics of three fenamic acids, i.e. mefenamic acid (MEF), tolfenamic acid (TOL) and clofenamic acid (CLO), were examined at different pHs, which followed second-order reaction under studied conditions. The studied fenamic acids degraded fast, with the largest apparent second-order rate coefficient (kapp) values of 446.7 M-1 s-1 (pH 7), 393.3 M-1 s-1 (pH 8) and 360.0 M-1 s-1 (pH 6) for MEF, TOL and CLO, respectively. The transformation products (TPs) were identified by solid-phase extraction-liquid chromatography-mass spectrometer and ion-pair liquid-liquid extraction and injection port derivatization-gas chromatography-mass spectrometer. Despite different numbers of TPs were detected for each studied Fenamic acid through these two analytical methods, the types of TPs were almost the same; chlorine substitution, oxidation and the joint oxidation with chlorine substitution are transformation reactions involved in chlorination. Moreover, the total toxicity of the TPs was assayed based on luminescent bacteria. Under different pHs, the different types of TPs might form, resulting in the varied total toxicity. The toxicity of all three fenamic acids chlorinated at pH of 8 was greater than those at pHs of 6 and 7. This study provided the information about the kinetics, transformation and toxicity of three fenamic acids during water chlorination, which is important to the drinking water safety.
Application of engineered cytochrome P450 mutants as biocatalysts for the synthesis of benzylic and aromatic metabolites of Fenamic acid NSAIDs
Bioorg Med Chem 2014 Oct 15;22(20):5613-20.PMID:24999003DOI:10.1016/j.bmc.2014.06.022.
Cytochrome P450 BM3 mutants are promising biocatalysts for the production of drug metabolites. In the present study, the ability of cytochrome P450 BM3 mutants to produce oxidative metabolites of structurally related NSAIDs meclofenamic acid, mefenamic acid and tolfenamic acid was investigated. A library of engineered P450 BM3 mutants was screened with meclofenamic acid (1) to identify catalytically active and selective mutants. Three mono-hydroxylated metabolites were identified for 1. The hydroxylated products were confirmed by NMR analysis to be 3'-OH-methyl-meclofenamic acid (1a), 5-OH-meclofenamic acid (1b) and 4'-OH-meclofenamic acid (1c) which are human relevant metabolites. P450 BM3 variants containing V87I and V87F mutation showed high selectivity for benzylic and aromatic hydroxylation of 1 respectively. The applicability of these mutants to selectively hydroxylate structurally similar drugs such as mefenamic acid (2) and tolfenamic acid (3) was also investigated. The tested variants showed high total turnover numbers in the order of 4000-6000 and can be used as biocatalysts for preparative scale synthesis. Both 1 and 2 could undergo benzylic and aromatic hydroxylation by the P450 BM3 mutants, whereas 3 was hydroxylated only on aromatic rings. The P450 BM3 variant M11 V87F hydroxylated the aromatic ring at 4' position of all three drugs tested with high regioselectivity. Reference metabolites produced by P450 BM3 mutants allowed the characterisation of activity and regioselectivity of metabolism of all three NSAIDs by thirteen recombinant human P450s. In conclusion, engineered P450 BM3 mutants that are capable of benzylic or aromatic hydroxylation of Fenamic acid containing NSAIDs, with high selectivity and turnover numbers have been identified. This shows their potential use as a greener alternative for the generation of drug metabolites.