52079-10-4Relevant articles and documents
Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor
Adeniji, Adegoke,Uddin, Md. Jashim,Zang, Tianzhu,Tamae, Daniel,Wangtrakuldee, Phumvadee,Marnett, Lawrence J.,Penning, Trevor M.
, p. 7431 - 7444 (2016)
Type 5 17β-hydroxysteroid dehydrogenase, aldo-keto reductase 1C3 (AKR1C3) converts Δ4-androstene-3,17-dione and 5α-androstane-3,17-dione to testosterone (T) and 5α-dihydrotestosterone, respectively, in castration resistant prostate cancer (CRPC). In CRPC, AKR1C3 is implicated in drug resistance, and enzalutamide drug resistance can be surmounted by indomethacin a potent inhibitor of AKR1C3. We examined a series of naproxen analogues and find that (R)-2-(6-methoxynaphthalen-2-yl)butanoic acid (in which the methyl group of R-naproxen was replaced by an ethyl group) acts as a potent AKR1C3 inhibitor that displays selectivity for AKR1C3 over other AKR1C enzymes. This compound was devoid of inhibitory activity on COX isozymes and blocked AKR1C3 mediated production of T and induction of PSA in LNCaP-AKR1C3 cells as a model of a CRPC cell line. R-Profens are substrate selective COX-2 inhibitors and block the oxygenation of endocannabinoids and in the context of advanced prostate cancer R-profens could inhibit intratumoral androgen synthesis and act as analgesics for metastatic disease.
A Green Indirect Spectrophotometric Estimation of the Analgesic Naproxen in the Existence of the Another Analgesic Paracetamol
Al-Sarraj, Thura Zeyad,Al-Taee, Ammar Masood
, p. 193 - 198 (2022/01/22)
A novel and secure indirect spectrophotometric technique for estimation of naproxen as a coupled compound with paracetamol as a unharmed diazotized reagent than organic reagents. Naproxen was first converted into an active form to act as coupling agent by reflux with hydrobromic acid (HBr) and acetic acid (CH3COOH) to yield the Hydroxy Form of Naproxen (HFN). The diazotized complex absorb light in wavelength 500 nm. Beer's law linearity is 10 to 200 μg/20ml, (i.e. 0.5-10.0 ppm), the molar absorptivity (∈) is 2.14x104 l/mol.cm, Sandell's sensitivity index (SSI) is 0.0094 μg/cm which indicate a high sensitivity, RSD more than ±0.36 % indicate good precision and higher accuracy (relative error more than 0.82 %), and LOD = 0.024 μg/ml and LOQ = 0.079 μg/ml. The technique has been used effectively for estimation of naproxen in tablets.
Efficient demethylation of aromatic methyl ethers with HCl in water
Bomon, Jeroen,Bal, Mathias,Achar, Tapas Kumar,Sergeyev, Sergey,Wu, Xian,Wambacq, Ben,Lemière, Filip,Sels, Bert F.,Maes, Bert U. W.
supporting information, p. 1995 - 2009 (2021/03/26)
A green, efficient and cheap demethylation reaction of aromatic methyl ethers with mineral acid (HCl or H2SO4) as a catalyst in high temperature pressurized water provided the corresponding aromatic alcohols (phenols, catechols, pyrogallols) in high yield. 4-Propylguaiacol was chosen as a model, given the various applications of the 4-propylcatechol reaction product. This demethylation reaction could be easily scaled and biorenewable 4-propylguaiacol from wood and clove oil could also be applied as a feedstock. Greenness of the developed methodversusstate-of-the-art demethylation reactions was assessed by performing a quantitative and qualitative Green Metrics analysis. Versatility of the method was shown on a variety of aromatic methyl ethers containing (biorenewable) substrates, yielding up to 99% of the corresponding aromatic alcohols, in most cases just requiring simple extraction as work-up.
Naproxen impurity and preparation method thereof
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, (2021/02/06)
The invention provides a naproxen impurity R, and the structural formula of the naproxen impurity R is shown in the specification. The invention also provides a preparation method of the naproxen impurity R. The preparation method comprises the following steps of: demethylating naproxen racemate in an acidic medium, and further reacting the demethylated naproxen racemate with 3-bromo-2, 2-dimethyl-1-propanol in the presence of an acid-binding agent to obtain the naproxen impurity R. The naproxen impurity R disclosed by the invention is suitable for being used as an impurity reference substancefor researching the synthesis quality of naproxen and intermediates thereof.
Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2-Symmetric Biaryls
Coombs, Gavin,Sak, Marcus H.,Miller, Scott J.
supporting information, p. 2875 - 2880 (2020/01/24)
We have demonstrated that small, modular, tetrameric peptides featuring the Lewis-basic residue β-dimethylaminoalanine (Dmaa) are capable of atroposelectively coupling naphthols and ester-bearing quinones to yield non-C2-symmetric BINOL-type scaffolds with good yields and enantioselectivity. The study culminates in the asymmetric synthesis of backbone-substituted scaffolds similar to 3,3′-disubstituted BINOLs, such as (R)-TRIP, with good (94:6 e.r.) to excellent (>99.9:0.1 e.r.) enantioselectivity after recrystallization, and a diastereoselective net arylation of the minimally modified nonsteroidal anti-inflammatory drug (NSAID) naproxen.
Benchmarking of laboratory evolved unspecific peroxygenases for the synthesis of human drug metabolites
Gomez de Santos, Patricia,Cervantes, Fadia V.,Tieves, Florian,Plou, Francisco J.,Hollmann, Frank,Alcalde, Miguel
, p. 1827 - 1831 (2019/02/24)
By mimicking the role of human liver P450 monooxygenases, fungal unspecific peroxygenases (UPOs) can perform a range of highly selective oxyfunctionalization reactions on pharmacological compounds, including O-dealkylations and hydroxylations, thereby simulating drug metabolism. Here we have benchmarked human drug metabolite (HDM) synthesis by several evolved UPO mutants, focusing on dextromethorphan, naproxen and tolbutamide. The HDM from dextromethorphan was prepared at the semi-preparative scale as a proof of production. The structural analysis of mutations involved in the synthesis of HDMs highlights the heme access channel as the main feature on which to focus when designing evolved UPOs. These variants are becoming emergent tools for the cost-effective synthesis of HDMs from next-generation drugs.
Small Molecule Interactome Mapping by Photoaffinity Labeling Reveals Binding Site Hotspots for the NSAIDs
Gao, Jinxu,Mfuh, Adelphe,Amako, Yuka,Woo, Christina M.
supporting information, p. 4259 - 4268 (2018/04/05)
Many therapeutics elicit cell-type specific polypharmacology that is executed by a network of molecular recognition events between a small molecule and the whole proteome. However, measurement of the structures that underpin the molecular associations bet
Sulfur(VI) fluoride compounds and methods for the preparation thereof
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Page/Page column 100; 101, (2018/11/23)
This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.
2-BETA-NAPHTHYL-ACETIC ACID ANALOGS AS AKR1C3 INHIBITORS AND METHODS OF USING SAME
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Page/Page column 60; 61, (2017/08/01)
The invention includes 2-β-naphthyl-acetic acid derivatives, which are selective AKR1C3 inhibitors. In certain embodiments, the compounds of the invention are R-naproxen analogs. The invention further includes methods of treating cancer, such as prostate cancer and/or castration-resistant prostate cancer, using at least one compound of the invention.
NO- AND H2S- RELEASING COMPOUNDS
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Paragraph 0093 - 0095, (2016/10/11)
This disclosure relates to novel compounds containing an H2S releasing moiety and a nitric oxide (NO) releasing moiety covalently linked with a core (e.g., a salicylic acid moiety) and the use of such compounds in treating inflammatory diseases, including
